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Conserved domains on  [gi|226246569|ref|NP_001139672|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Mus musculus]

Protein Classification

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform( domain architecture ID 18341701)

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform phosphorylates PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-1095 0e+00

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


:

Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 766.72  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  729 LQDFTQQVHVIEMLQKVTIDIKSLSAEKYDVSSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKK 808
Cdd:cd00894     1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  809 KPLWLEFKCADPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00894    81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  889 AQIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHI 968
Cdd:cd00894   161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  969 LGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00894   241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 226246569 1049 EYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd00894   321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 2.16e-113

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


:

Pssm-ID: 176044  Cd Length: 178  Bit Score: 348.83  E-value: 2.16e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALL 429
Cdd:cd08399     1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  430 NLQIYCCKTPSLSSKASAETPGSESKGKAQLLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQGSFNADKLTSATNPD 509
Cdd:cd08399    81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                         170
                  ....*....|....*...
gi 226246569  510 KENSMSISILLDNYCHPI 527
Cdd:cd08399   161 KENSMSISILLDNYCHPV 178
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 2.53e-113

PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma) which contains the adaptor-binding domain (ABD). This is a globular domain with an alpha/beta sandwich topology, common to all catalytic subunits of PIK3s, and it is similar to ubiquitin-like domains. This domain interacts with the regulatory subunit of the p101 type.


:

Pssm-ID: 466155  Cd Length: 195  Bit Score: 349.45  E-value: 2.53e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569     1 MELENYEQPVVLREDNLRRRRRMKPRSAAGSLSSMELIPIEFVLPTSQRISKTPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710    4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    81 TSVAAEFYHRLGPDQFLLLYQKKGQWYEIYDRYQVVQTLDCLHYWKLMHKSPGQIHVVQRHVPSEETLAFQKQLTSLIGY 160
Cdd:pfam19710   84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                          170       180       190
                   ....*....|....*....|....*....|..
gi 226246569   161 DVTDISNVHDDELEFTRRRLVTPRMAEVAGRD 192
Cdd:pfam19710  164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.25e-89

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


:

Pssm-ID: 238444  Cd Length: 171  Bit Score: 284.98  E-value: 1.25e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLarrEIWdqSALDVGLTM 628
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLL---KRW--PKLKPEQAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872    76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                         170
                  ....*....|....*..
gi 226246569  709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872   156 -SQRFGLLLEAYLRGCG 171
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 1.88e-31

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


:

Pssm-ID: 197540  Cd Length: 108  Bit Score: 118.97  E-value: 1.88e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    203 TSKPLPDYLSKKIANNCIFIVIHR--GTTSQTIKVSADDTPGTILQSFFTKMakkKSLMNISESQSEqDFVLRVCGRDEY 280
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLekDQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                            90       100       110
                    ....*....|....*....|....*....|..
gi 226246569    281 LVGETPLKNFQWVRQCLKNGDEIHLVLDTPPD 312
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
 
Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-1095 0e+00

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 766.72  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  729 LQDFTQQVHVIEMLQKVTIDIKSLSAEKYDVSSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKK 808
Cdd:cd00894     1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  809 KPLWLEFKCADPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00894    81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  889 AQIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHI 968
Cdd:cd00894   161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  969 LGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00894   241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 226246569 1049 EYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd00894   321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 2.16e-113

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176044  Cd Length: 178  Bit Score: 348.83  E-value: 2.16e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALL 429
Cdd:cd08399     1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  430 NLQIYCCKTPSLSSKASAETPGSESKGKAQLLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQGSFNADKLTSATNPD 509
Cdd:cd08399    81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                         170
                  ....*....|....*...
gi 226246569  510 KENSMSISILLDNYCHPI 527
Cdd:cd08399   161 KENSMSISILLDNYCHPV 178
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 2.53e-113

PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma) which contains the adaptor-binding domain (ABD). This is a globular domain with an alpha/beta sandwich topology, common to all catalytic subunits of PIK3s, and it is similar to ubiquitin-like domains. This domain interacts with the regulatory subunit of the p101 type.


Pssm-ID: 466155  Cd Length: 195  Bit Score: 349.45  E-value: 2.53e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569     1 MELENYEQPVVLREDNLRRRRRMKPRSAAGSLSSMELIPIEFVLPTSQRISKTPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710    4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    81 TSVAAEFYHRLGPDQFLLLYQKKGQWYEIYDRYQVVQTLDCLHYWKLMHKSPGQIHVVQRHVPSEETLAFQKQLTSLIGY 160
Cdd:pfam19710   84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                          170       180       190
                   ....*....|....*....|....*....|..
gi 226246569   161 DVTDISNVHDDELEFTRRRLVTPRMAEVAGRD 192
Cdd:pfam19710  164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.25e-89

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 284.98  E-value: 1.25e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLarrEIWdqSALDVGLTM 628
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLL---KRW--PKLKPEQAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872    76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                         170
                  ....*....|....*..
gi 226246569  709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872   156 -SQRFGLLLEAYLRGCG 171
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 830-1046 3.56e-82

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 267.24  E-value: 3.56e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    830 IIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQ------------- 892
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKetrrRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILkeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    893 -----------QSTVGNTGAFKDEVLNHWLKEKCPIE-EKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNL 960
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPsEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    961 FHIDFGHILGNYKSFLGiNKERVPFVLTPDFLFVMGSSGkktspHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMP 1040
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVMGDSG-----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 226246569   1041 QLTSKE 1046
Cdd:smart00146  235 DWRSGK 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 543-733 2.26e-77

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 251.87  E-value: 2.26e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   543 VRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARreiWDQsaL 622
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--I 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   623 DVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSE 702
Cdd:pfam00613   76 DPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSE 155

                          170       180       190
                   ....*....|....*....|....*....|.
gi 226246569   703 IaQSRHYQQRFAVILEAYLRGCGTAMLQDFT 733
Cdd:pfam00613  156 I-HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 545-732 6.20e-73

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 239.85  E-value: 6.20e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    545 AEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLK-HPKAYPKLFSSVKWGQQEIVAKTYQLLarrEIWDqsALD 623
Cdd:smart00145    1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLL---LSWA--PLD 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    624 VGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:smart00145   76 PEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL 155

                           170       180
                    ....*....|....*....|....*....
gi 226246569    704 aQSRHYQQRFAVILEAYLRGCGTAMLQDF 732
Cdd:smart00145  156 -HDPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 828-1044 2.20e-72

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 240.31  E-value: 2.20e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL-PYGCISTGDKIGMIEIVKDATTIAQIQQ----STVGNTGAF 902
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDeygeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   903 KD-----------------------EVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMIS-ETG 958
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDkTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   959 NLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMGSSGkktspHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTG 1038
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGPSG-----DEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 226246569  1039 MPQLTS 1044
Cdd:pfam00454  236 LPDWSI 241
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
729-1085 1.82e-43

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 173.43  E-value: 1.82e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  729 LQDFTQQVHV-IEMLQKVtidIKSLSAEKYDVSSQVISQLKQKLESLQ----------NSNLP--ESFRVPYDPGLKAGT 795
Cdd:COG5032  1688 LKELIKKSPRkIRKKFKI---DISLLNLSRKLYISVLRSIRKRLKRLLelrlkkvspkLLLFHafLEIKLPGQYLLDKPF 1764

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  796 LVIEK-----CKVMASKKKPLWLEFKCADptvlsNETIGIIFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLP 866
Cdd:COG5032  1765 VLIERfepevSVVKSHLQRPRRLTIRGSD-----GKLYSFIVKGGDDLRQDELALQLIRLMNKILkkdkETRRRDLWIRP 1839

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  867 YGCISTGDKIGMIEIVKDATTIAQI------------------QQSTVGNTGAFKDE-----------VLNHWLKEKCPI 917
Cdd:COG5032  1840 YKVIPLSPGSGIIEWVPNSDTLHSIlreyhkrknisidqekklAARLDNLKLLLKDEfftkatlksppVLYDWFSESFPN 1919

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  918 EEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-SETGNLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMG 996
Cdd:COG5032  1920 PEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMG 1998

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  997 SSGKKTSphfqkFQDVCVRAYLALRHHTNLLIILFSMML------------MTGMPQLTSKEDIEYIRDALTvgksEEDA 1064
Cdd:COG5032  1999 VSGVEGS-----FRELCETAFRALRKNADSLMNVLELFVrdpliewrrlpcFREIQNNEIVNVLERFRLKLS----EKDA 2069

                         410       420
                  ....*....|....*....|....*
gi 226246569 1065 KKYFL----DQIEVCRdKGWTVQFN 1085
Cdd:COG5032  2070 EKFVDllinKSVESLI-TQATDPFQ 2093
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 1.88e-31

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 118.97  E-value: 1.88e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    203 TSKPLPDYLSKKIANNCIFIVIHR--GTTSQTIKVSADDTPGTILQSFFTKMakkKSLMNISESQSEqDFVLRVCGRDEY 280
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLekDQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                            90       100       110
                    ....*....|....*....|....*....|..
gi 226246569    281 LVGETPLKNFQWVRQCLKNGDEIHLVLDTPPD 312
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.93e-28

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 109.69  E-value: 2.93e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   203 TSKPLPDYLsKKIANNCIFIVIH--RGTTSQTIKVSADDTPGTILQSFFTKmakKKSLMNISESQSeqDFVLRVCGRDEY 280
Cdd:pfam00794    1 ASTVSPEPL-PKLINNKLLISVHleGDQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGDVTD--DYVLKVCGRDEY 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 226246569   281 LVGETPLKNFQWVRQCLKNGDEIHLVLDTPPD 312
Cdd:pfam00794   75 LLGDHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 349-444 1.65e-26

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 104.35  E-value: 1.65e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    349 VFTVSLWDCDRKFRVKIRGIDIPVLPRNTDL-TVFVEANIQHGQQVLC-QRRTSPKPFAEEVLWNVWLEFGIKIKDLPKG 426
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLClPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|....*...
gi 226246569    427 ALLNLQIYCCKTPSLSSK 444
Cdd:smart00142   81 ARLCITIYAVKNPSKGSE 98
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 381-486 1.28e-09

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 57.38  E-value: 1.28e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   381 VFVEANIQHGQQVLCQR-RTSPKPFAEE-VLWNVWLEFGIKIKDLPKGALLNLQIYCCKTPslsskasaetpgsesKGKA 458
Cdd:pfam00792    5 LYVECQLYHGGKPLCLPvSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------------EKSF 69

                           90       100
                   ....*....|....*....|....*...
gi 226246569   459 QLLYYVNLLLIDHRFLLRHGDYVLHMWQ 486
Cdd:pfam00792   70 VPIGWVNTSLFDKKGILRQGKQKLRLWP 97
 
Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-1095 0e+00

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 766.72  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  729 LQDFTQQVHVIEMLQKVTIDIKSLSAEKYDVSSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKK 808
Cdd:cd00894     1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  809 KPLWLEFKCADPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00894    81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  889 AQIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHI 968
Cdd:cd00894   161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  969 LGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00894   241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 226246569 1049 EYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd00894   321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 729-1091 0e+00

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 600.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  729 LQDFTQQVHVIEMLQKVTIDIKSLSAEKydvsSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKK 808
Cdd:cd05165     1 LKSLSRQVEALNKLKKLSDILKEKKKSK----EKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKK 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  809 KPLWLEFKCADPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd05165    77 RPLWLVFENADPLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTI 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  889 AQIQQSTVGN-TGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGH 967
Cdd:cd05165   157 ANIQKKKGKVaTLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  968 ILGNYKSFLGINKERVPFVLTPDFLFVMG-SSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKE 1046
Cdd:cd05165   237 FLGNFKKKFGIKRERVPFVLTHDFVYVIArGQDNTKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVK 316

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 226246569 1047 DIEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05165   317 DIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNV 361
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 730-1077 0e+00

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624 [Multi-domain]  Cd Length: 334  Bit Score: 532.53  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  730 QDFTQQVHVIEMLQKVTIDIKSLSAEKydvssqVISQLKQKLESLQnsnLPESFRVPYDPGLKAGTLVIEKCKVMASKKK 809
Cdd:cd00891     2 EELLKQVKVLDELKEIAKKIKEEPSEE------RKEVLEKLLQKLE---LPKKFTLPLDPRMEVKGLIVEKCKVMDSKKL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  810 PLWLEFKCADPTvlsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd00891    73 PLWLVFKNADPG---GDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTA 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  890 QIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHIL 969
Cdd:cd00891   150 AIQKKYGGFGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFL 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  970 GNYKSFLGINKERVPFVLTPDFLFVMGssGKKtSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 1049
Cdd:cd00891   230 GNFKKKFGIKRERAPFVFTPEMAYVMG--GED-SENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIE 306

                         330       340
                  ....*....|....*....|....*...
gi 226246569 1050 YIRDALTVGKSEEDAKKYFLDQIEVCRD 1077
Cdd:cd00891   307 YLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 730-1089 1.30e-123

Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. They are activated by a variety of stimuli including chemokines, cytokines, lysophosphatidic acid (LPA), insulin, and tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 382.79  E-value: 1.30e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  730 QDFTQQVHVIEMLQKVTIDIKSLSaekydvSSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKKK 809
Cdd:cd05166     2 EEFLKQHVLVQALTSIAEKVKSAK------DSARENALRRELEQLASFLLENSFRLPLDPALEVTGVDVRSCSYFNSNAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  810 PLWLEFKCADPtvlSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd05166    76 PLKLVFRNADP---RAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLR 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  890 QIQQStVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHIL 969
Cdd:cd05166   153 EIQTE-HGLTGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFL 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  970 GNYKSFLGINKERVPFVLTPDFLFVMgSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSkEDIE 1049
Cdd:cd05166   232 GDAQMFGNFKRDRVPFVLTSDMAYVI-NGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQ-DDLR 309

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 226246569 1050 YIRDALTVGKSEEDAKKYFLDQIEVCRdKGWTVQFNWFLH 1089
Cdd:cd05166   310 YVQDALLPELTDAEATAHFTRMIEESL-SSKFTQLNFFIH 348
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 2.16e-113

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176044  Cd Length: 178  Bit Score: 348.83  E-value: 2.16e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALL 429
Cdd:cd08399     1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  430 NLQIYCCKTPSLSSKASAETPGSESKGKAQLLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQGSFNADKLTSATNPD 509
Cdd:cd08399    81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                         170
                  ....*....|....*...
gi 226246569  510 KENSMSISILLDNYCHPI 527
Cdd:cd08399   161 KENSMSISILLDNYCHPV 178
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 732-1091 2.50e-113

Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kbeta can be activated by G-protein-coupled receptors. Deletion of PI3Kbeta in mice results in early lethality at around day three of development. PI3Kbeta plays an important role in regulating sustained integrin activation and stable platelet agrregation, especially under conditions of high shear stress. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270717 [Multi-domain]  Cd Length: 362  Bit Score: 355.81  E-value: 2.50e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  732 FTQQVHVIEMLQKVT--IDIKSLSAEKYDVSSQVISQLKQKLESLQNSNLpesfRVPYDPGLKAGTLVIEKCKVMASKKK 809
Cdd:cd05173     4 LSKQVEALNKLKTLNslIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDL----QSPLNPSIILSELNVEKCKYMDSKMK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  810 PLWLEFkcaDPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd05173    80 PLWIVY---NNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIA 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  890 QIQ--QSTVGNTGAFKDEVLNHWLKEkCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGH 967
Cdd:cd05173   157 DIQlnSSNVAAAAAFNKDALLNWLKE-YNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGH 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  968 ILGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKED 1047
Cdd:cd05173   236 ILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKD 315

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 226246569 1048 IEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05173   316 IQYLKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTV 359
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 2.53e-113

PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma) which contains the adaptor-binding domain (ABD). This is a globular domain with an alpha/beta sandwich topology, common to all catalytic subunits of PIK3s, and it is similar to ubiquitin-like domains. This domain interacts with the regulatory subunit of the p101 type.


Pssm-ID: 466155  Cd Length: 195  Bit Score: 349.45  E-value: 2.53e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569     1 MELENYEQPVVLREDNLRRRRRMKPRSAAGSLSSMELIPIEFVLPTSQRISKTPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710    4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    81 TSVAAEFYHRLGPDQFLLLYQKKGQWYEIYDRYQVVQTLDCLHYWKLMHKSPGQIHVVQRHVPSEETLAFQKQLTSLIGY 160
Cdd:pfam19710   84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                          170       180       190
                   ....*....|....*....|....*....|..
gi 226246569   161 DVTDISNVHDDELEFTRRRLVTPRMAEVAGRD 192
Cdd:pfam19710  164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 786-1091 4.50e-112

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 352.82  E-value: 4.50e-112
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  786 PYDPGLKAGTLVIEKCKVMASKKKPLWLEFKCADPtvlSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 865
Cdd:cd05174    59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEA---GAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMT 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  866 PYGCISTGDKIGMIEIVKDATTIAQIQ--QSTVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCVATFVLG 943
Cdd:cd05174   136 PYGCLSTGDKTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNP-GDALDQAIEEFTLSCAGYCVATYVLG 214

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  944 IGDRHNDNIMISETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHH 1023
Cdd:cd05174   215 IGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRH 294

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 226246569 1024 TNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05174   295 GLLFLHLFALMKAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 362
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 724-1091 5.03e-102

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 326.24  E-value: 5.03e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  724 CGTaMLQDFTQQVHVIEMLQKVTiDIksLSAEKYDVSSQVisQLKQKLESLQNSNLPES---FRVPYDPGLKAGTLVIEK 800
Cdd:cd05175     1 CGM-YLKHLSRQVEAMEKLINLT-DI--LKQEKKDETQKV--QMKFLVEQMRRPDFMDAlqgFLSPLNPAHQLGNLRLEE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  801 CKVMASKKKPLWLEFKcaDPTVLSN---ETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIG 877
Cdd:cd05175    75 CRIMSSAKRPLWLNWE--NPDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVG 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  878 MIEIVKDATTIAQIQqSTVGNTGA--FKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMIS 955
Cdd:cd05175   153 LIEVVRNSHTIMQIQ-CKGGLKGAlqFNSHTLHQWLKDKNK-GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVK 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  956 ETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSP--HFQKFQDVCVRAYLALRHHTNLLIILFSM 1033
Cdd:cd05175   231 DDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKtrEFERFQEMCYKAYLAIRQHANLFINLFSM 310

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 226246569 1034 MLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05175   311 MLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTI 368
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 730-1089 3.61e-91

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 296.12  E-value: 3.61e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  730 QDFTQQVHVIEMLQKVTIDIKSLSAEKYDVSsqvisqLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKKK 809
Cdd:cd05176     2 EELEKQTRLVQLLGRVAEKVRQASGSARQVA------LQDGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  810 PLWLEFKCADPTvlsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd05176    76 PLKVALVNADPL---GEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLR 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  890 QIQQStVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHIL 969
Cdd:cd05176   153 KIQVE-YGVTGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFL 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  970 GNYKSFLGINKERVPFVLTPDFLFVMgSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 1049
Cdd:cd05176   232 GHAQMFGSFKRDRAPFVLTSDMAYVI-NGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLK 310

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 226246569 1050 YIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTvQFNWFLH 1089
Cdd:cd05176   311 YVFDALQPQTTDAEATIFFTRLIESSLGSVAT-KFNFFIH 349
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.25e-89

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 284.98  E-value: 1.25e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLarrEIWdqSALDVGLTM 628
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLL---KRW--PKLKPEQAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872    76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                         170
                  ....*....|....*..
gi 226246569  709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872   156 -SQRFGLLLEAYLRGCG 171
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 730-1073 5.23e-84

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 276.77  E-value: 5.23e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  730 QDFTQQVHVIEMLQKVTIDIKSLS-AEKYDVSSQVISQLKQKLESLQnsnlpeSFRVPYDPGLKAGTLVIEKCKVMASKK 808
Cdd:cd05177     2 KEFSKETKLISILIDAAEKVKTASdTRRKEVLKREASRLEDFFQDVV------SCCLPLNPALRVKGIDADACSYFTSNA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  809 KPLWLEFKCADPTvlsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd05177    76 APLKISFINANPL---AKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTL 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  889 AQIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHI 968
Cdd:cd05177   153 AKIHRES-GLIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKF 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  969 LGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSpHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd05177   232 LGHAQTFGSIKRDRAPFIFTSEMEYFITEGGKKPQ-RFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDL 310

                         330       340
                  ....*....|....*....|....*
gi 226246569 1049 EYIRDALTVGKSEEDAKKYFLDQIE 1073
Cdd:cd05177   311 KYVYNNLRPQDTDLEATSYFTKKIK 335
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 730-1089 1.77e-83

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 275.34  E-value: 1.77e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  730 QDFTQQVHVIEMLQKVTIDIKSLSAEkydvSSQVIsqLKQKLESL-QNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKK 808
Cdd:cd00895     2 EEFDRQCWLVNVLAKLAQQVREAAPS----ARQGI--LREGLEEVkQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  809 KPLWLEFKCADPTvlsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00895    76 VPLKLSFQNVDPL---GENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETL 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  889 AQIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHI 968
Cdd:cd00895   153 RKIQVEH-GVTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRF 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  969 LGNYKSFLGINKERVPFVLTPDFLFVMgSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00895   232 LGHAQMFGNIKRDRAPFVFTSDMAYVI-NGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDL 310

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|.
gi 226246569 1049 EYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTvQFNWFLH 1089
Cdd:cd00895   311 KYVYDALRPQDTEADATTYFTRLIESSLGSVAT-KLNFFIH 350
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 830-1046 3.56e-82

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 267.24  E-value: 3.56e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    830 IIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQ------------- 892
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKetrrRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILkeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    893 -----------QSTVGNTGAFKDEVLNHWLKEKCPIE-EKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNL 960
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPsEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    961 FHIDFGHILGNYKSFLGiNKERVPFVLTPDFLFVMGSSGkktspHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMP 1040
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVMGDSG-----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 226246569   1041 QLTSKE 1046
Cdd:smart00146  235 DWRSGK 240
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 794-1037 1.41e-81

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 264.97  E-value: 1.41e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  794 GTLVIEKCKVMASKKKPLWLEFKCADptvlsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTG 873
Cdd:cd00142     1 NALDVGILKVIHSKQRPKKITLIGAD-----GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLS 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  874 DKIGMIEIVKDATTIaqiqqstvgntgafkdEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIM 953
Cdd:cd00142    76 ENSGLIEIVKDAQTI----------------EDLLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIM 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  954 ISETGNLFHIDFGHILGNYKSFLGinKERVPFVLTPDFLFVMGSSGkktspHFQKFQDVCVRAYLALRHHTNLLIILFSM 1033
Cdd:cd00142   140 IEPSGNIFHIDFGFIFSGRKLAEG--VETVPFRLTPMLENAMGTAG-----VNGPFQISMVKIMEILREHADLIVPILEH 212


                  ....
gi 226246569 1034 MLMT 1037
Cdd:cd00142   213 SLRD 216
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 739-1073 1.98e-79

Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class III PI3Ks, also called Vps34 (vacuolar protein sorting 34), contain an N-terminal lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They phosphorylate only the substrate PtdIns. They interact with a regulatory subunit, Vps15, to form a membrane-associated complex. Class III PI3Ks are involved in protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 264.01  E-value: 1.98e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  739 IEMLQKVTIDIKSLSAEKYDVSSQvISQLKQKLESLQNSNL--PESFRVPYDPGLKAGTLVIEKCKVMASKKKPLWLEFK 816
Cdd:cd00896     8 QEFVDRLRSLMKEVKNEKGSRDKK-IERLRELLSDSELGLLlfFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPLKLTFK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  817 CADPtvlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQqSTV 896
Cdd:cd00896    87 TLDG-----GEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADIL-KKY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  897 GNTGAFkdeVLNHWLKEKCPIEEKFQAaVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHILGN-YKSF 975
Cdd:cd00896   161 GSILNF---LRKHNPDESGPYGIKPEV-MDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRdPKPF 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  976 LginkerVPFVLTPDFLFVMGssGKKtSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMP--QLTSKEDIEYIRD 1053
Cdd:cd00896   237 P------PPMKLCKEMVEAMG--GAN-SEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPdiALEPDKAVLKVQE 307

                         330       340
                  ....*....|....*....|
gi 226246569 1054 ALTVGKSEEDAKKYFLDQIE 1073
Cdd:cd00896   308 KFRLDLSDEEAEQYFQNLID 327
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 543-733 2.26e-77

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 251.87  E-value: 2.26e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   543 VRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARreiWDQsaL 622
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--I 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   623 DVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSE 702
Cdd:pfam00613   76 DPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSE 155

                          170       180       190
                   ....*....|....*....|....*....|.
gi 226246569   703 IaQSRHYQQRFAVILEAYLRGCGTAMLQDFT 733
Cdd:pfam00613  156 I-HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 545-732 6.20e-73

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 239.85  E-value: 6.20e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    545 AEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLK-HPKAYPKLFSSVKWGQQEIVAKTYQLLarrEIWDqsALD 623
Cdd:smart00145    1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLL---LSWA--PLD 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    624 VGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:smart00145   76 PEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL 155

                           170       180
                    ....*....|....*....|....*....
gi 226246569    704 aQSRHYQQRFAVILEAYLRGCGTAMLQDF 732
Cdd:smart00145  156 -HDPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 828-1044 2.20e-72

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 240.31  E-value: 2.20e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL-PYGCISTGDKIGMIEIVKDATTIAQIQQ----STVGNTGAF 902
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDeygeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   903 KD-----------------------EVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMIS-ETG 958
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDkTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   959 NLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMGSSGkktspHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTG 1038
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGPSG-----DEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 226246569  1039 MPQLTS 1044
Cdd:pfam00454  236 LPDWSI 241
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 799-1095 1.13e-62

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 215.54  E-value: 1.13e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  799 EKCKVMASKKK-PLWLEFKCADPTVLSNETIGI------------IFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 865
Cdd:cd05167     8 KSGKPLQSAAKaPFLVTFKVKDCGVDELEHEGTeseatkevwqaaIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLF 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  866 PYGCISTGDKIGMIEIVKDATTIAQIQQSTVGNtgafkdevLNHWLKEKCPIEE--KFQAAVERFVYSCAGYCVATFVLG 943
Cdd:cd05167    88 PYRVVATGPGCGVIEVIPNSKSRDQIGRETDNG--------LYEYFLSKYGDEStpAFQKARRNFIKSMAGYSLVSYLLQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  944 IGDRHNDNIMISETGNLFHIDFGHIL-----GNyksflgINKERVPFVLTPDFLFVMGssGKKTSPHFQKFQDVCVRAYL 1018
Cdd:cd05167   160 IKDRHNGNIMIDDDGHIIHIDFGFIFeispgGN------LGFESAPFKLTKEMVDLMG--GSMESEPFKWFVELCVRGYL 231

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 226246569 1019 ALRHHTNLLIILFSMMLMTGMPQLTsKEDIEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd05167   232 AVRPYAEAIVSLVELMLDSGLPCFR-GQTIKNLRERFALEMSEREAANFMIKLIADSYLKIRTKGYDMFQYYQNGIP 307
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 549-703 4.28e-59

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


Pssm-ID: 238440  Cd Length: 152  Bit Score: 199.36  E-value: 4.28e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREIwdqsaLDVGLTM 628
Cdd:cd00864     1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAP-----LSPEDAL 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 226246569  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:cd00864    76 ELLSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEI 150
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 830-1094 9.59e-56

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 195.17  E-value: 9.59e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  830 IIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQQSTvGNTGAFKDevLNH 909
Cdd:cd00893    30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKL-DSFNKFVS--LSD 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  910 WLKEKCPiEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHILGNYKSFLGInkERVPFVLTP 989
Cdd:cd00893   107 FFDDNFG-DEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPFKLSS 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  990 DFLFVMGssGKKTSPhFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKYFL 1069
Cdd:cd00893   184 EYIEVLG--GVDSEL-FKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVYVL 260

                         250       260
                  ....*....|....*....|....*
gi 226246569 1070 DQIEVCRDKGWTVQFNWFLHLVLGI 1094
Cdd:cd00893   261 SLINKSLDNWRTRWYDKYQYFSQGI 285
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 828-1094 1.82e-55

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 194.62  E-value: 1.82e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQQSTVGNTGafkdeVL 907
Cdd:cd05168    31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTS-----LL 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  908 NHWLKE-KCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHILGNYKSflGINKERVPFV 986
Cdd:cd05168   106 DYFERTfGDPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPG--GLGFETAPFK 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  987 LTPDFLFVMGSsgkKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTG-MPQLTS--KEDIEYIRDALTVGKSEED 1063
Cdd:cd05168   184 LTQEYVEVMGG---LESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGggEFTIEQLRERFKLNLTEEE 260

                         250       260       270
                  ....*....|....*....|....*....|.
gi 226246569 1064 AKKYFLDQIEVCRDKGWTVQFNWFLHLVLGI 1094
Cdd:cd05168   261 CAQFVDSLIDKSLNNWRTRQYDNFQYLTNGI 291
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
729-1085 1.82e-43

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 173.43  E-value: 1.82e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  729 LQDFTQQVHV-IEMLQKVtidIKSLSAEKYDVSSQVISQLKQKLESLQ----------NSNLP--ESFRVPYDPGLKAGT 795
Cdd:COG5032  1688 LKELIKKSPRkIRKKFKI---DISLLNLSRKLYISVLRSIRKRLKRLLelrlkkvspkLLLFHafLEIKLPGQYLLDKPF 1764

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  796 LVIEK-----CKVMASKKKPLWLEFKCADptvlsNETIGIIFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLP 866
Cdd:COG5032  1765 VLIERfepevSVVKSHLQRPRRLTIRGSD-----GKLYSFIVKGGDDLRQDELALQLIRLMNKILkkdkETRRRDLWIRP 1839

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  867 YGCISTGDKIGMIEIVKDATTIAQI------------------QQSTVGNTGAFKDE-----------VLNHWLKEKCPI 917
Cdd:COG5032  1840 YKVIPLSPGSGIIEWVPNSDTLHSIlreyhkrknisidqekklAARLDNLKLLLKDEfftkatlksppVLYDWFSESFPN 1919

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  918 EEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-SETGNLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMG 996
Cdd:COG5032  1920 PEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMG 1998

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  997 SSGKKTSphfqkFQDVCVRAYLALRHHTNLLIILFSMML------------MTGMPQLTSKEDIEYIRDALTvgksEEDA 1064
Cdd:COG5032  1999 VSGVEGS-----FRELCETAFRALRKNADSLMNVLELFVrdpliewrrlpcFREIQNNEIVNVLERFRLKLS----EKDA 2069

                         410       420
                  ....*....|....*....|....*
gi 226246569 1065 KKYFL----DQIEVCRdKGWTVQFN 1085
Cdd:COG5032  2070 EKFVDllinKSVESLI-TQATDPFQ 2093
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 352-527 7.90e-38

C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes of PI3Ks. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains members with the first C2 repeat, C2A, and a type-I topology, as well as some with a single C2 repeat.


Pssm-ID: 176026  Cd Length: 156  Bit Score: 139.03  E-value: 7.90e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  352 VSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPK-PFAEEVLWNVWLEFGIKIKDLPKGALLN 430
Cdd:cd08380     1 KSLWDINFNLRIKIHGITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKvPFSTSVTWNEWLTFDILISDLPREARLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  431 LQIYCCKTPslsskasaetpgseSKGKAQLLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQGsfnadklTSATNPDK 510
Cdd:cd08380    81 LSIYAVSEP--------------GSKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIA-------CTPCNNSN 139

                         170
                  ....*....|....*..
gi 226246569  511 ENSMSISILLDNYCHPI 527
Cdd:cd08380   140 ENSTRLLIELPEFSKPV 156
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 548-703 1.52e-32

Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III phosphorylate phosphoinositol (PtdIns) only. The prototypical PI3K class III, yeast Vps34, is involved in trafficking proteins from Golgi to the vacuole.


Pssm-ID: 238442  Cd Length: 166  Bit Score: 124.36  E-value: 1.52e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  548 PNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARreiWDQsaLDVGLT 627
Cdd:cd00870     7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPK---WAK--IDIEDA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  628 MQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYH-------DSALARFLLKRGLRNKRIGHFLFWFLR 700
Cdd:cd00870    82 LELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDlsplprlDSPLADFLIERALKNPKLANFLYWYLK 161


                  ...
gi 226246569  701 SEI 703
Cdd:cd00870   162 VEL 164
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 1.88e-31

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 118.97  E-value: 1.88e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    203 TSKPLPDYLSKKIANNCIFIVIHR--GTTSQTIKVSADDTPGTILQSFFTKMakkKSLMNISESQSEqDFVLRVCGRDEY 280
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLekDQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                            90       100       110
                    ....*....|....*....|....*....|..
gi 226246569    281 LVGETPLKNFQWVRQCLKNGDEIHLVLDTPPD 312
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 553-719 2.44e-31

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 121.03  E-value: 2.44e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  553 KQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARreiWdqSALDVGLTMQLLD 632
Cdd:cd00869     5 EKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQ---W--APLRPLIALELLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  633 CNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSrHYQQR 712
Cdd:cd00869    80 PKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDC-YFSSA 158


                  ....*..
gi 226246569  713 FAVILEA 719
Cdd:cd00869   159 YQDLGAA 165
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 802-1035 9.72e-29

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 115.06  E-value: 9.72e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  802 KVMASKKKPLWLEFKCadptvlSNETIGI-IFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKI 876
Cdd:cd05164     9 RILASLQKPKKITILG------SDGKEYPfLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  877 GMIEIVKDATTiaqiqqstvgntgaFKDeVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-S 955
Cdd:cd05164    83 GLIEWVDNTTT--------------LKP-VLKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdT 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  956 ETGNLFHIDFGHILGNYKSFLgiNKERVPFVLTPDFLFVMGSSGKKTsphfqKFQDVCVRAYLALRHHTNLLIILFSMML 1035
Cdd:cd05164   148 KTGEVVHIDFGMIFNKGKTLP--VPEIVPFRLTRNIINGMGPTGVEG-----LFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.93e-28

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 109.69  E-value: 2.93e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   203 TSKPLPDYLsKKIANNCIFIVIH--RGTTSQTIKVSADDTPGTILQSFFTKmakKKSLMNISESQSeqDFVLRVCGRDEY 280
Cdd:pfam00794    1 ASTVSPEPL-PKLINNKLLISVHleGDQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGDVTD--DYVLKVCGRDEY 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 226246569   281 LVGETPLKNFQWVRQCLKNGDEIHLVLDTPPD 312
Cdd:pfam00794   75 LLGDHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 349-444 1.65e-26

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 104.35  E-value: 1.65e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569    349 VFTVSLWDCDRKFRVKIRGIDIPVLPRNTDL-TVFVEANIQHGQQVLC-QRRTSPKPFAEEVLWNVWLEFGIKIKDLPKG 426
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLClPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|....*...
gi 226246569    427 ALLNLQIYCCKTPSLSSK 444
Cdd:smart00142   81 ARLCITIYAVKNPSKGSE 98
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 803-1028 2.02e-26

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 108.82  E-value: 2.02e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  803 VMASKKKPLWLEFKCADptvlsNETIGIIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKIGM 878
Cdd:cd05172    10 VLSSKRRPKRITIRGSD-----EKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPacrqRRLRIRTYQVIPMTSRLGL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  879 IEIVKDATTIAQIqqstvgntgaFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMIS-ET 957
Cdd:cd05172    85 IEWVDNTTPLKEI----------LENDLLRRALLSLASSPEAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVDlST 154

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 226246569  958 GNLFHIDFGHILGNYKSFLGInKERVPFVLTPDFLFVMGssgkktsPHFQK--FQDVCVRAYLALRHHTNLLI 1028
Cdd:cd05172   155 GRLIGIDFGHAFGSATQFLPI-PELVPFRLTRQLLNLLQ-------PLDARglLRSDMVHVLRALRAGRDLLL 219
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 808-966 7.60e-23

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 95.20  E-value: 7.60e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  808 KKPLWLEFKCadptvlsnETIGIIFKHGDD--------LRQDMLILQILRIMEsiwetesldlcLLPYGCISTGD----K 875
Cdd:cd13968     7 AKVFWAEGEC--------TTIGVAVKIGDDvnneegedLESEMDILRRLKGLE-----------LNIPKVLVTEDvdgpN 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  876 IGMIEIVKDATTIAQIQqstvgntgafkdevlnhwlkekcpIEEKFQAAVERFVYSCAGYCVATFV--LGIGDRHNDNIM 953
Cdd:cd13968    68 ILLMELVKGGTLIAYTQ------------------------EEELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNIL 123

                         170
                  ....*....|...
gi 226246569  954 ISETGNLFHIDFG 966
Cdd:cd13968   124 LSEDGNVKLIDFG 136
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 799-1034 9.64e-21

Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to as Mei-41 (Drosophila), Esr1/Mec1p (Saccharomyces cerevisiae), Rad3 (Schizosaccharomyces pombe), and FRAP-related protein (human). ATR contains a UME domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. Together with its downstream effector kinase, Chk1, ATR plays a central role in regulating the replication checkpoint. ATR stabilizes replication forks by promoting the association of DNA polymerases with the fork. Preventing fork collapse is essential in preserving genomic integrity. ATR also plays a role in normal cell growth and in response to DNA damage. ATR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 92.57  E-value: 9.64e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  799 EKCKVMASKKKPLWLEFKCADptvlsNETIGIIFKHGDDLRQDM----LILQILRIMESIWETESLDLCLLPYGCISTGD 874
Cdd:cd00892     6 DEVEIMPSLQKPKKITLVGSD-----GKKYPFLCKPKDDLRKDArmmeFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  875 KIGMIEIVKDATTIAQIQQStvgntgaFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI 954
Cdd:cd00892    81 ECGIIEWVPNTVTLRSILST-------LYPPVLHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILF 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  955 SE-TGNLFHIDFGHILGNYKSfLGInKERVPFVLTPDFLFVMGSSGKKTSphfqkFQDVCVRAYLALRHHTNLLI-ILFS 1032
Cdd:cd00892   154 DStTGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAMGVTGVEGT-----FRRTCEVTLRVLRENRETLMsVLET 226


                  ..
gi 226246569 1033 MM 1034
Cdd:cd00892   227 FV 228
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 352-523 1.94e-20

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 89.68  E-value: 1.94e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  352 VSLWDCDRKFRVKIRGIDiPVLPRNTDLTVFVEANIQHGQQVLC-QRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALLN 430
Cdd:cd08693     1 KSLWDIEEKFSITLHKIS-NLNAAERTMKVGVQAGLFHGGESLCkTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  431 LQIYccktPSLSSKASAETPGSESKGKAQLLYY----VNLLLIDHRFLLRHGDYVLHMWQIsgkAEEQGSFNADKL-TSA 505
Cdd:cd08693    80 FAIY----EVSKKAKGKRSRKNQTKKKKKKDDNpiawVNTMVFDYKGQLKTGDHTLYMWTY---AEDQSEDLLNPLgTVE 152

                         170
                  ....*....|....*...
gi 226246569  506 TNPDKENSMSISILLDNY 523
Cdd:cd08693   153 SNPNTESATALHISFPEY 170
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 831-999 9.88e-16

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 78.74  E-value: 9.88e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  831 IFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQQSTVGNTGAFKDEV 906
Cdd:cd05171    33 LVKGGDDLRQDAVMEQVFELVNQLLkrdkETRKRKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSKSGAHARYR 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  907 LNHWLKEKC----------PIEEKFQAAVE---------RFV----YSCAG--------YC--VAT-----FVLGIGDRH 948
Cdd:cd05171   113 PKDWTASTCrkkmrekakaSAEERLKVFDEicknfkpvfRHFflekFPDPSdwferrlaYTrsVATssivgYILGLGDRH 192

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 226246569  949 NDNIMI-SETGNLFHIDFGHILGNYKsFLGInKERVPFVLTPDFLFVMGSSG 999
Cdd:cd05171   193 LNNILIdQKTGELVHIDLGIAFEQGK-LLPI-PETVPFRLTRDIVDGMGITG 242
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 802-988 1.80e-11

Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic domain, and a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. It is also called FRAP (FK506 binding protein 12-rapamycin associated protein). TOR is a central component of the eukaryotic growth regulatory network. It controls the expression of many genes transcribed by all three RNA polymerases. It associates with other proteins to form two distinct complexes, TORC1 and TORC2. TORC1 is involved in diverse growth-related functions including protein synthesis, nutrient use and transport, autophagy and stress responses. TORC2 is involved in organizing cytoskeletal structures. TOR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The TOR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 65.97  E-value: 1.80e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  802 KVMASKKKPLWLEFKCADptvlsnetiGIIFK-----HgDDLRQDMLILQILR----IMESIWETESLDLCLLPYGCIST 872
Cdd:cd05169     9 EVITSKQRPRKLTIVGSD---------GKEYKfllkgH-EDLRLDERVMQLFGlvntLLKNDSETSRRNLSIQRYSVIPL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  873 GDKIGMIEIVKDATTIAQI---------------QQSTVGNTGAF-------KDEVLNH--------------WLKEKCP 916
Cdd:cd05169    79 SPNSGLIGWVPGCDTLHSLirdyrekrkiplnieHRLMLQMAPDYdnltliqKVEVFEYalentpgddlrrvlWLKSPSS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  917 ieekfQAAVER---FVYSCAGYCVATFVLGIGDRHNDNIMISE-TGNLFHIDFGhilgnyKSF-LGINK----ERVPFVL 987
Cdd:cd05169   159 -----EAWLERrtnFTRSLAVMSMVGYILGLGDRHPSNIMLDRlTGKVIHIDFG------DCFeVAMHRekfpEKVPFRL 227


                  .
gi 226246569  988 T 988
Cdd:cd05169   228 T 228
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 382-485 4.03e-10

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175979  Cd Length: 171  Bit Score: 60.06  E-value: 4.03e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  382 FVEANIQHGQQVLCQRRTSP-----KPFAEEVLWNVWLEFGIKIKDLPKGALLNLQIYCCKTPSlsskasaetPGSESKG 456
Cdd:cd04012    32 YLSCSLYHGGRLLCSPVTTKpvkitKSFFPRVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSP---------DGGSNKQ 102

                          90       100       110
                  ....*....|....*....|....*....|.
gi 226246569  457 K--AQLLYYVNLLLIDHRFLLRHGDYVLHMW 485
Cdd:cd04012   103 RmgPEELGWVSLPLFDFRGVLRQGSLLLGLW 133
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 381-486 1.28e-09

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 57.38  E-value: 1.28e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569   381 VFVEANIQHGQQVLCQR-RTSPKPFAEE-VLWNVWLEFGIKIKDLPKGALLNLQIYCCKTPslsskasaetpgsesKGKA 458
Cdd:pfam00792    5 LYVECQLYHGGKPLCLPvSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------------EKSF 69

                           90       100
                   ....*....|....*....|....*...
gi 226246569   459 QLLYYVNLLLIDHRFLLRHGDYVLHMWQ 486
Cdd:pfam00792   70 VPIGWVNTSLFDKKGILRQGKQKLRLWP 97
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 353-527 3.11e-08

C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, alpha isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176043  Cd Length: 158  Bit Score: 54.03  E-value: 3.11e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  353 SLWDCDRKFRVKI--------RGIDipvlprntdlTVFVEANIQHGQQVLCQRRTSPKPFAEEVLWNVWLEFGIKIKDLP 424
Cdd:cd08398     2 SLWKINSNLRIKIlcatyvnvNDID----------KIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLP 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  425 KGALLNLQIyCcktpSLSSKASAETPGSEskgkaqlLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQgsFNADKLTs 504
Cdd:cd08398    72 RSARLCLSI-C----SVKGRKGAKEEHCP-------LAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDL--LNPIGVT- 136

                         170       180
                  ....*....|....*....|...
gi 226246569  505 ATNPDKEnSMSISILLDNYCHPI 527
Cdd:cd08398   137 GSNPNKD-TPCLELEFDRFSCVV 158
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 832-999 1.56e-07

Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C-terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The SMG-1 catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270714  Cd Length: 304  Bit Score: 54.57  E-value: 1.56e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  832 FKHGDDLRQDMLILQILRI----MESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI-----------AQIQQSTV 896
Cdd:cd05170    34 FKGLEDLHLDERIMQFLSIvnamLASDNEHRRRRYRARHYSVTPLGPRSGLIQWVDGATPLfslykrwqqrrAAAQAQKN 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  897 GNTGAFKDEVL-------------------------NHW----LKE--------------------KCPIEEKFQAAVER 927
Cdd:cd05170   114 QDSGSTPPPVPrpselfynklkpalkaagirkstsrREWplevLRQvleelvaetprdllarelwcSSPSSAEWWRVTQR 193

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  928 FVYSCAGYCVATFVLGIGDRHNDNIMIS-ETGNLFHIDF------GHILgnyksflginK--ERVPFVLTPDFLFVMGSS 998
Cdd:cd05170   194 FARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIEHALGPT 263


                  .
gi 226246569  999 G 999
Cdd:cd05170   264 G 264
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 375-485 2.44e-05

C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. These are the only domains identified in the class III PI3Ks present in this cd. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176042  Cd Length: 159  Bit Score: 45.70  E-value: 2.44e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226246569  375 RNTDLtvFVEANIQHGQQVLC-QRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALLNLQIYccktpslsskasaETPGSE 453
Cdd:cd08397    28 PNSDL--FVTCQVFDDGKPLTlPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIW-------------DVSGTG 92

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 226246569  454 SK---GKAqllyyvNLLLIDHRFLLRHGDYVLHMW 485
Cdd:cd08397    93 KAvpfGGT------TLSLFNKDGTLRRGRQKLRVW 121
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 927-989 1.40e-03

Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs to the the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. It contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain and has a large molecular weight. Unlike most PIKK proteins, however, it contains an inactive PI3K-like pseudokinase domain, which lacks the conserved residues necessary for ATP binding and catalytic activity. TRRAP also contains many motifs that may be critical for protein-protein interactions. TRRAP is a common component of many histone acetyltransferase (HAT) complexes, and is responsible for the recruitment of these complexes to chromatin during transcription, replication, and DNA repair. TRRAP also exists in non-HAT complexes such as the p400 and MRN complexes, which are implicated in ATP-dependent remodeling and DNA repair, respectively. The TRRAP pseudokinase domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270707  Cd Length: 252  Bit Score: 41.74  E-value: 1.40e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 226246569  927 RFVYSCAGYCVATFVLGIGDRHNDNIMISE-TGNLFHIDFGHILGNYKSFLGINkERVPFVLTP 989
Cdd:cd05163   140 QFTLQLALSSFMTYVLSLGNRTPHRILISRsTGNVFMTDFLPSINSQGPLLDNN-EPVPFRLTP 202
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
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