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Conserved domains on  [gi|1720407821|ref|XP_030109175|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X14 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 413-779 0e+00

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: 818.52  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 413 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSK 492
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 493 MKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 572
Cdd:cd05174    81 MKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 573 NIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 652
Cdd:cd05174   160 NIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 653 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDI 732
Cdd:cd05174   240 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDI 319

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 1720407821 733 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 779
Cdd:cd05174   320 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 243-421 2.50e-85

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: 268.36  E-value: 2.50e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:smart00145   6 EEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDP 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFG 402
Cdd:smart00145  86 KFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFG 165

                          170
                   ....*....|....*....
gi 1720407821  403 LIMEAYCRGSTHHMKVLMK 421
Cdd:smart00145 166 LLLEAYLRGCGTHLKELLK 184
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 79-219 1.56e-80

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: 255.31  E-value: 1.56e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTK----KKSKKADC 154
Cdd:cd08693    29 VGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGKRSRKnqtkKKKKKDDN 108

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720407821 155 PIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPH 219
Cdd:cd08693   109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESATALHISFPEYKPE 173
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 413-779 0e+00

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: 818.52  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 413 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSK 492
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 493 MKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 572
Cdd:cd05174    81 MKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 573 NIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 652
Cdd:cd05174   160 NIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 653 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDI 732
Cdd:cd05174   240 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDI 319

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 1720407821 733 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 779
Cdd:cd05174   320 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 243-421 2.50e-85

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: 268.36  E-value: 2.50e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:smart00145   6 EEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDP 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFG 402
Cdd:smart00145  86 KFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFG 165

                          170
                   ....*....|....*....
gi 1720407821  403 LIMEAYCRGSTHHMKVLMK 421
Cdd:smart00145 166 LLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 513-730 2.95e-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: 262.23  E-value: 2.95e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  513 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 577
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  578 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 644
Cdd:smart00146  81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  645 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 724
Cdd:smart00146 161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                   ....*.
gi 1720407821  725 ELSCSK 730
Cdd:smart00146 235 DWRSGK 240
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 79-219 1.56e-80

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: 255.31  E-value: 1.56e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTK----KKSKKADC 154
Cdd:cd08693    29 VGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGKRSRKnqtkKKKKKDDN 108

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720407821 155 PIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPH 219
Cdd:cd08693   109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESATALHISFPEYKPE 173
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 243-412 8.13e-79

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: 250.69  E-value: 8.13e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:cd00872     2 EEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFG 402
Cdd:cd00872    81 NFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRFG 160

                         170
                  ....*....|
gi 1720407821 403 LIMEAYCRGS 412
Cdd:cd00872   161 LLLEAYLRGC 170
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 511-727 1.28e-77

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: 250.32  E-value: 1.28e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 511 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAAF 587
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAMV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 588 N-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESG 642
Cdd:pfam00454  82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 643 QLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG 722
Cdd:pfam00454 162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                  ....*
gi 1720407821 723 LPELS 727
Cdd:pfam00454 236 LPDWS 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 237-421 1.62e-63

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: 210.26  E-value: 1.62e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 237 ERGRITEEEL-QLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLS 315
Cdd:pfam00613   1 KDLKPNEKERkELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 316 ALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVP 395
Cdd:pfam00613  80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                         170       180
                  ....*....|....*....|....*.
gi 1720407821 396 SVALRFGLIMEAYCRGSTHHMKVLMK 421
Cdd:pfam00613 160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
417-752 2.30e-38

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 154.94  E-value: 2.30e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  417 KVLMKQGE--ALSKLKALNDFVKVSSQKTTKPQTKEMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCVEQCTF 488
Cdd:COG5032   1698 KIRKKFKIdiSLLNLSRKLYISVLRSIRKRLKRLLELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEPEVSVV 1777

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  489 MDSKMKPLWIMYSseeaGSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIE 563
Cdd:COG5032   1778 KSHLQRPRRLTIR----GSDGKLySFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIE 1853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  564 VVLHSDTIANI------QLNKS-NMAATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTLS 615
Cdd:COG5032   1854 WVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFARS 1933

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  616 CAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERFR 694
Cdd:COG5032   1934 LAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSFR 2007

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720407821  695 GYCERAYTILRRHGLLFLHLFALMRAAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 752
Cdd:COG5032   2008 ELCETAFRALRKNADSLMNVLELFVRDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 79-145 1.23e-24

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 98.57  E-value: 1.23e-24
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720407821   79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARST 145
Cdd:smart00142  34 LYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARLCITIYAVKNPSKGSEFG 100
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 79-186 8.96e-22

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: 91.66  E-value: 8.96e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarstkKKSKKADCPIA 157
Cdd:pfam00792   5 LYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVPIG 73

                          90       100
                  ....*....|....*....|....*....
gi 1720407821 158 WANLMLFDYKDQLKTGERCLYMWPSVPDE 186
Cdd:pfam00792  74 WVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 413-779 0e+00

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: 818.52  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 413 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSK 492
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 493 MKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 572
Cdd:cd05174    81 MKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 573 NIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 652
Cdd:cd05174   160 NIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 653 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDI 732
Cdd:cd05174   240 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDI 319

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 1720407821 733 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 779
Cdd:cd05174   320 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 416-777 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: 657.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 416 MKVLMKQGEALSKLKALNDFVKVssQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKP 495
Cdd:cd05165     1 LKSLSRQVEALNKLKKLSDILKE--KKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 496 LWIMYSSEE--AGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAN 573
Cdd:cd05165    79 LWLVFENADplALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 574 IQLNKSNMAaTAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 652
Cdd:cd05165   159 IQKKKGKVA-TLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 653 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTN-NSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 731
Cdd:cd05165   238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*.
gi 1720407821 732 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 777
Cdd:cd05165   318 IEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 416-778 0e+00

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: 624.29  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 416 MKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKP 495
Cdd:cd05173     1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 496 LWIMYSSEEAGSaGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQ 575
Cdd:cd05173    81 LWIVYNNKLFGG-DSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 576 LNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN 655
Cdd:cd05173   160 LNSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGN 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 656 FKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYL 735
Cdd:cd05173   240 FKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYL 319

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 1720407821 736 KDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 778
Cdd:cd05173   320 KDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 416-761 6.08e-153

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: 448.94  E-value: 6.08e-153
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 416 MKVLMKQGEALSKLKALNDFVK-VSSQKttkpqtkemmhmcmRQETYMEALSHLQS------PLDPSTLLEEVCVEQCTF 488
Cdd:cd00891     1 REELLKQVKVLDELKEIAKKIKeEPSEE--------------RKEVLEKLLQKLELpkkftlPLDPRMEVKGLIVEKCKV 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 489 MDSKMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHS 568
Cdd:cd00891    67 MDSKKLPLWLVFKNADPG-GDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNS 145

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 569 DTIANIQlnKSNMAATAAFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHI 647
Cdd:cd00891   146 ETTAAIQ--KKYGGFGAAFKDTPISNWLKKHNPTEEeYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHI 223

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 648 DFGHFLGNFKTKFGINRERVPFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELS 727
Cdd:cd00891   224 DFGHFLGNFKKKFGIKRERAPFVFTPEMAYVM-GGE--DSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQ 300

                         330       340       350
                  ....*....|....*....|....*....|....
gi 1720407821 728 CSKDIQYLKDSLALGKTEEEALKHFRVKFNEALR 761
Cdd:cd00891   301 SIEDIEYLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 419-775 6.58e-121

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: 367.39  E-value: 6.58e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 419 LMKQGEALSKLKALNDFVKvssqkttkpQTKEmmhmCMRQETYMEALSHLQS---------PLDPSTLLEEVCVEQCTFM 489
Cdd:cd05166     4 FLKQHVLVQALTSIAEKVK---------SAKD----SARENALRRELEQLASfllensfrlPLDPALEVTGVDVRSCSYF 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 490 DSKMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSD 569
Cdd:cd05166    71 NSNALPLKLVFRNADPR-AEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAE 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 570 TIANIQlnkSNMAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHID 648
Cdd:cd05166   150 TLREIQ---TEHGLTGSFKDRPLADWLQKHNPSElEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHID 226

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 649 FGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSc 728
Cdd:cd05166   227 FGKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGD-KPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT- 304

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 1720407821 729 SKDIQYLKDSLALGKTEEEALKHFRVKFNEALReSWKTKVNWLAHNV 775
Cdd:cd05166   305 QDDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 415-777 1.25e-112

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: 346.66  E-value: 1.25e-112
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 415 HMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMK 494
Cdd:cd05175     4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 495 PLWIMYSSEEAGSA---GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 571
Cdd:cd05175    84 PLWLNWENPDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 572 ANIQLnKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 651
Cdd:cd05175   164 MQIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 652 FLGNFKTKFGINRERVPFILTYDFVHVIQQG--KTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCS 729
Cdd:cd05175   243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1720407821 730 KDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 777
Cdd:cd05175   323 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 466-775 5.82e-110

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: 339.53  E-value: 5.82e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 466 SHLQSPLDPSTLLEEVCVEQCTFMDSKMKPLWIMYS--SEEAGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL 543
Cdd:cd00894    53 ESFRVPYDPGLRAGALVIEKCKVMASKKKPLWLEFKcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESL 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 544 DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVA 622
Cdd:cd00894   133 DLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCVA 210

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 623 TYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYT 702
Cdd:cd00894   211 TFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYL 290

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720407821 703 ILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 775
Cdd:cd00894   291 ALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 457-777 4.87e-88

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: 281.87  E-value: 4.87e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 457 RQETYMEALSHLQS---------PLDPSTLLEEVCVEQCTFMDSKMKPLWI-MYSSEEAGSAGNVgiIFKNGDDLRQDML 526
Cdd:cd05176    29 RQVALQDGMERVQSffqknkcrlPLSPSLVAKELNIKACSFFSSNAVPLKVaLVNADPLGEEINV--MFKVGEDLRQDML 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 527 TLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNksnMAATAAFNKDALLNWLKSKNPGE-AL 605
Cdd:cd05176   107 ALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVE---YGVTGSFKDKPLAEWLRKYNPSEeEY 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 606 DRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTN 685
Cdd:cd05176   184 EKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEKP 263

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 686 NSeKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWK 765
Cdd:cd05176   264 TI-RFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQTTDAEATIFF-TRLIESSLGSVA 341

                         330
                  ....*....|..
gi 1720407821 766 TKVNWLAHNVSK 777
Cdd:cd05176   342 TKFNFFIHNLAQ 353
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 243-421 2.50e-85

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: 268.36  E-value: 2.50e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:smart00145   6 EEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDP 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFG 402
Cdd:smart00145  86 KFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFG 165

                          170
                   ....*....|....*....
gi 1720407821  403 LIMEAYCRGSTHHMKVLMK 421
Cdd:smart00145 166 LLLEAYLRGCGTHLKELLK 184
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 417-760 2.10e-82

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: 266.71  E-value: 2.10e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 417 KVLMKQGEALSKLKALNDFVKVSSQKTTKpQTKEMMHMCMRQETYMEALSH-LQSPLDPSTLLEEVCVEQCTFMDSKMKP 495
Cdd:cd00896     2 EALKRQQEFVDRLRSLMKEVKNEKGSRDK-KIERLRELLSDSELGLLLFFEpLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 496 LWIMYSSEEAGSagnVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIq 575
Cdd:cd00896    81 LKLTFKTLDGGE---YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 576 LNKSNmaataafnkdALLNWLKSKNPGEA-----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFG 650
Cdd:cd00896   157 LKKYG----------SILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFG 226

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 651 HFLGN----FKTKFGINRERVPFIltydfvhviqqGKTnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPEL 726
Cdd:cd00896   227 YILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDI 294

                         330       340       350
                  ....*....|....*....|....*....|....*.
gi 1720407821 727 SCSKD--IQYLKDSLALGKTEEEALKHFRVKFNEAL 760
Cdd:cd00896   295 ALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 513-730 2.95e-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: 262.23  E-value: 2.95e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  513 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 577
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  578 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 644
Cdd:smart00146  81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  645 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 724
Cdd:smart00146 161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                   ....*.
gi 1720407821  725 ELSCSK 730
Cdd:smart00146 235 DWRSGK 240
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 417-777 6.85e-82

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: 265.60  E-value: 6.85e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 417 KVLMKQGEALSKLKALNDFVKVSSqkttKPQTKEMMHMCMRQ-ETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKP 495
Cdd:cd05177     2 KEFSKETKLISILIDAAEKVKTAS----DTRRKEVLKREASRlEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAP 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 496 LWIMYSSEEAgSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQ 575
Cdd:cd05177    78 LKISFINANP-LAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIH 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 576 lNKSNMAATaaFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLG 654
Cdd:cd05177   157 -RESGLIGP--LKENTIEKWFHMHNKLKEdYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLG 233

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 655 NFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQY 734
Cdd:cd05177   234 HAQTFGSIKRDRAPFIFTSEMEYFITEGG-KKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKY 312

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 1720407821 735 LKDSLALGKTEEEALKHFRVKFNEALrESWKTKVNWLAHNVSK 777
Cdd:cd05177   313 VYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTLAQ 354
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 79-219 1.56e-80

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: 255.31  E-value: 1.56e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTK----KKSKKADC 154
Cdd:cd08693    29 VGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGKRSRKnqtkKKKKKDDN 108

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720407821 155 PIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPH 219
Cdd:cd08693   109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESATALHISFPEYKPE 173
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 243-412 8.13e-79

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: 250.69  E-value: 8.13e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:cd00872     2 EEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFG 402
Cdd:cd00872    81 NFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRFG 160

                         170
                  ....*....|
gi 1720407821 403 LIMEAYCRGS 412
Cdd:cd00872   161 LLLEAYLRGC 170
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 471-777 6.90e-78

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: 254.93  E-value: 6.90e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 471 PLDPSTLLEEVCVEQCTFMDSKMKPLWIMYSSEEAgSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPY 550
Cdd:cd00895    53 PLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDP-LGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIF 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 551 GCLPTGDRTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIG 629
Cdd:cd00895   132 RCFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTEdEYEKAVENFIYSCAGCCVATYVLGIC 208

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 630 DRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHGL 709
Cdd:cd00895   209 DRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHTH 287

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720407821 710 LFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 777
Cdd:cd00895   288 LFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYF-TRLIESSLGSVATKLNFFIHNLAQ 354
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 511-727 1.28e-77

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: 250.32  E-value: 1.28e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 511 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAAF 587
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAMV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 588 N-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESG 642
Cdd:pfam00454  82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 643 QLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG 722
Cdd:pfam00454 162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                  ....*
gi 1720407821 723 LPELS 727
Cdd:pfam00454 236 LPDWS 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 237-421 1.62e-63

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: 210.26  E-value: 1.62e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 237 ERGRITEEEL-QLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLS 315
Cdd:pfam00613   1 KDLKPNEKERkELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 316 ALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVP 395
Cdd:pfam00613  80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                         170       180
                  ....*....|....*....|....*.
gi 1720407821 396 SVALRFGLIMEAYCRGSTHHMKVLMK 421
Cdd:pfam00613 160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 243-393 1.02e-53

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: 182.41  E-value: 1.02e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:cd00864     2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNV-PKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSP 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720407821 323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMH 393
Cdd:cd00864    81 KYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 514-767 2.72e-50

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: 178.56  E-value: 2.72e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 514 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSdtianiqlnKS--NMAATAAFNkda 591
Cdd:cd05167    53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNS---------KSrdQIGRETDNG--- 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 592 LLNWLKSK--NPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGhFL------GNFKTkfgi 662
Cdd:cd05167   121 LYEYFLSKygDEStPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIfeispgGNLGF---- 195

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 663 nrERVPFILTYDFVHVIqqGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPelsC--SKDIQYLKDSLA 740
Cdd:cd05167   196 --ESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLP---CfrGQTIKNLRERFA 268

                         250       260
                  ....*....|....*....|....*..
gi 1720407821 741 LGKTEEEALKHFRVKFNEALrESWKTK 767
Cdd:cd05167   269 LEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 510-767 6.39e-48

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: 171.29  E-value: 6.39e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 510 NVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAniQLNKSNMAATAAFNk 589
Cdd:cd00893    27 LVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSID--SLKKKLDSFNKFVS- 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 590 daLLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERVPF 669
Cdd:cd00893   104 --LSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPF 179

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 670 ILTYDFVHVIqqgKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEAL 749
Cdd:cd00893   180 KLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELE 256

                         250
                  ....*....|....*...
gi 1720407821 750 KHFRVKFNEALReSWKTK 767
Cdd:cd00893   257 VYVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 511-767 4.61e-45

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: 163.42  E-value: 4.61e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 511 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVlhSDTIANIQLNKSNMAATaafnkd 590
Cdd:cd05168    31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETI--PDTVSIDSLKKRFPNFT------ 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 591 ALLNWLKSK---NPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERV 667
Cdd:cd05168   103 SLLDYFERTfgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 668 PFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG-LPELSCSKD--IQYLKDSLALGKT 744
Cdd:cd05168   181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257

                         250       260
                  ....*....|....*....|...
gi 1720407821 745 EEEALKHFRVKFNEALReSWKTK 767
Cdd:cd05168   258 EEECAQFVDSLIDKSLN-NWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 483-718 1.86e-43

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: 156.34  E-value: 1.86e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 483 VEQCTFMDSKMKPLWImyssEEAGSAGN-VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGL 561
Cdd:cd00142     5 VGILKVIHSKQRPKKI----TLIGADGKtYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 562 IEVVLHSDTIANiqlnksnmaataafnkdaLLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRE 640
Cdd:cd00142    81 IEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP 142

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720407821 641 SGQLFHIDFGHFLGNFKTKFGInrERVPFILTYDFVHVIQQGKTNNsekfeRFRGYCERAYTILRRHGLLFLHLFALM 718
Cdd:cd00142   143 SGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGVNG-----PFQISMVKIMEILREHADLIVPILEHS 213
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
417-752 2.30e-38

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 154.94  E-value: 2.30e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  417 KVLMKQGE--ALSKLKALNDFVKVSSQKTTKPQTKEMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCVEQCTF 488
Cdd:COG5032   1698 KIRKKFKIdiSLLNLSRKLYISVLRSIRKRLKRLLELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEPEVSVV 1777

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  489 MDSKMKPLWIMYSseeaGSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIE 563
Cdd:COG5032   1778 KSHLQRPRRLTIR----GSDGKLySFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIE 1853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  564 VVLHSDTIANI------QLNKS-NMAATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTLS 615
Cdd:COG5032   1854 WVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFARS 1933

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  616 CAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERFR 694
Cdd:COG5032   1934 LAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSFR 2007

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720407821  695 GYCERAYTILRRHGLLFLHLFALMRAAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 752
Cdd:COG5032   2008 ELCETAFRALRKNADSLMNVLELFVRDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 78-221 1.62e-35

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: 131.71  E-value: 1.62e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  78 WLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarsTKKKSKKaDCPIA 157
Cdd:cd08380    29 KLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLCLSIYAV---------SEPGSKK-EVPLG 98

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720407821 158 WANLMLFDYKDQLKTGERCLYMWPSVPDEkgellNPAGTVRGNPNTESAAALVIYLPEVaPHPV 221
Cdd:cd08380    99 WVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPCNNSNENSTRLLIELPEF-SKPV 156
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 81-205 2.25e-30

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: 117.20  E-value: 2.25e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  81 VQAGLFHGNEMLCKTVSSSEVNvCSEPVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarSTKKKSKKADCPIAWAN 160
Cdd:cd08398    30 VRTGIYHGGEPLCDNVNTQRVP-CSNPRWNEWLDYDIYIPDLPRSARLCLSICSV--------KGRKGAKEEHCPLAWGN 100

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1720407821 161 LMLFDYKDQLKTGERCLYMWPsVPDEKGELLNPAGTVRGNPNTES 205
Cdd:cd08398   101 INLFDYTDTLVSGKMALNLWP-VPHGLEDLLNPIGVTGSNPNKDT 144
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 247-393 6.90e-29

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: 113.19  E-value: 6.90e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 247 QLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDFSFPD 326
Cdd:cd00870    13 ELNKILKYPPTTKLTDEEKDLIWKFRFYLTNN-KKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELLSPYFTN 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720407821 327 CYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESY-------LDCELTKFLLGRALANRKIGHFLFWHLRSEMH 393
Cdd:cd00870    92 PVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLKVELE 165
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 243-393 1.17e-25

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: 104.08  E-value: 1.17e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 243 EEELQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 322
Cdd:cd00869     2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNE-PNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720407821 323 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMH 393
Cdd:cd00869    81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALD 151
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 79-145 1.23e-24

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 98.57  E-value: 1.23e-24
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720407821   79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARST 145
Cdd:smart00142  34 LYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARLCITIYAVKNPSKGSEFG 100
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 514-708 8.44e-23

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: 97.34  E-value: 8.44e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 514 IFKNGDDLRQDMLTLQMIQLMDVLWKQEG----LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIqlnksnmaataaFNK 589
Cdd:cd05164    33 LVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWVDNTTTLKPV------------LKK 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 590 DAllnWLKSKNPGEALDrAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTkFGINrERVP 668
Cdd:cd05164   101 WF---NETFPDPTQWYE-ARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFNKGKT-LPVP-EIVP 174

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1720407821 669 FILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRRHG 708
Cdd:cd05164   175 FRLTRNIINGMGPTGVEGL-----FRKSCEQVLRVFRKHK 209
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 79-186 8.96e-22

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: 91.66  E-value: 8.96e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarstkKKSKKADCPIA 157
Cdd:pfam00792   5 LYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVPIG 73

                          90       100
                  ....*....|....*....|....*....
gi 1720407821 158 WANLMLFDYKDQLKTGERCLYMWPSVPDE 186
Cdd:pfam00792  74 WVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 489-708 1.08e-20

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: 92.93  E-value: 1.08e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 489 MDSKMKP--LWIMysseeaGSAGNVgIIF--KNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTG 560
Cdd:cd05169    11 ITSKQRPrkLTIV------GSDGKE-YKFllKGHEDLRLDERVMQLFGLVNTLLKNDsetsRRNLSIQRYSVIPLSPNSG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 561 LIEVVLHSDTIA----------NIQLN--KSNMAATA-------------AFN-----------KDALlnWLKSKNPGEA 604
Cdd:cd05169    84 LIGWVPGCDTLHslirdyrekrKIPLNieHRLMLQMApdydnltliqkveVFEyalentpgddlRRVL--WLKSPSSEAW 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 605 LDRAIeEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFG-------HflgnfKTKFginRERVPFILTYDFV 676
Cdd:cd05169   162 LERRT-NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRMLV 232

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1720407821 677 HVIQQGKTNNSekferFRGYCERAYTILRRHG 708
Cdd:cd05169   233 NAMEVSGVEGT-----FRSTCEDVMRVLRENK 259
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 484-680 3.40e-20

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: 90.33  E-value: 3.40e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 484 EQCTFMDSKMKPLWI-MYSSEEAGSAgnvgIIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDR 558
Cdd:cd05172     6 PRVLVLSSKRRPKRItIRGSDEKEYK----FLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 559 TGLIEVVLHSDTIANIqlnksnmaataaFNKDALLNWLK--SKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNI 636
Cdd:cd05172    82 LGLIEWVDNTTPLKEI------------LENDLLRRALLslASSP-EAFLALRSNFARSLAAMSICGYILGIGDRHLSNF 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1720407821 637 MI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQ 680
Cdd:cd05172   149 LVdLSTGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 514-707 4.44e-19

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: 88.37  E-value: 4.44e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 514 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNKSN--------- 580
Cdd:cd05171    33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSksgaharyr 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 581 ------------MAATAAFNKDALLN-----------------WLKSKNPGEALDRaIEEFTLSCAGYCVATYVLGIGDR 631
Cdd:cd05171   113 pkdwtastcrkkMREKAKASAEERLKvfdeicknfkpvfrhffLEKFPDPSDWFER-RLAYTRSVATSSIVGYILGLGDR 191

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 632 HSDNIMI-RESGQLFHIDFG-HFlgnfktKFGIN---RERVPFILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRR 706
Cdd:cd05171   192 HLNNILIdQKTGELVHIDLGiAF------EQGKLlpiPETVPFRLTRDIVDGMGITGVEGV-----FRRCCEETLRVLRE 260


                  .
gi 1720407821 707 H 707
Cdd:cd05171   261 N 261
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 83-217 8.71e-19

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: 84.33  E-value: 8.71e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  83 AGLFHGNEMLCKTVSSSEVNVCSE----PVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTKKKSKKadcPIAW 158
Cdd:cd04012    35 CSLYHGGRLLCSPVTTKPVKITKSffprVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGGSNKQRMGPE---ELGW 111

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720407821 159 ANLMLFDYKDQLKTGERCLYMWPSvpdEKGELLNPAGTVrgNPNTESAAALVIYLPEVA 217
Cdd:cd04012   112 VSLPLFDFRGVLRQGSLLLGLWPP---SKDNPLGPAPPP--LFEQPDRVILQIDFPSSA 165
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 489-707 2.25e-16

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: 79.09  E-value: 2.25e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 489 MDSKMKPLWIMYsseeAGSAGN-VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQ----EGLDLRMTPYGCLPTGDRTGLIE 563
Cdd:cd00892    11 MPSLQKPKKITL----VGSDGKkYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEECGIIE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 564 VVLHSDTIANIqLNKsnmaataaFNKDALLNWLKSK--NPGEALdRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RE 640
Cdd:cd00892    87 WVPNTVTLRSI-LST--------LYPPVLHEWFLKNfpDPTAWY-EARNNYTRSTAVMSMVGYILGLGDRHGENILFdST 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720407821 641 SGQLFHIDFGHFLGNFKTkFGInRERVPFILTYDFVHVIqqGKTnnseKFE-RFRGYCERAYTILRRH 707
Cdd:cd00892   157 TGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAM--GVT----GVEgTFRRTCEVTLRVLREN 216
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 79-221 1.01e-14

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: 73.02  E-value: 1.01e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEvNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAV----VEKAKKARSTKKKSKKADC 154
Cdd:cd08399    32 VFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGALLNLQIYCGkapaLSSKKSAESPSSESKGKHQ 110

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720407821 155 PIAWANLMLFDYKDQLKTGERCLYMW--PSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVApHPV 221
Cdd:cd08399   111 LLYYVNLLLIDHRFLLRTGEYVLHMWqiSGKGEDQGSVNADKLTSATNPDKENSMSISILLDNYC-HPV 178
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 506-715 5.04e-09

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: 58.42  E-value: 5.04e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 506 GSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLW----KQEGLDLRMTPYGCLPTGDRTGLIEVV-------------LH 567
Cdd:cd05170    24 GSDGKRyPYLFKGLEDLHLDERIMQFLSIVNAMLasdnEHRRRRYRARHYSVTPLGPRSGLIQWVdgatplfslykrwQQ 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 568 SDTIANIQLNKSNMAATAA--------FNK---------------------DAL---LNWLKSKNPGEALDRAI------ 609
Cdd:cd05170   104 RRAAAQAQKNQDSGSTPPPvprpselfYNKlkpalkaagirkstsrrewplEVLrqvLEELVAETPRDLLARELwcssps 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 610 --------EEFTLSCAGYCVATYVLGIGDRHSDNIMIR-ESGQLFHIDF------GHFLgnfktkfginR--ERVPFILT 672
Cdd:cd05170   184 saewwrvtQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLT 253

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1720407821 673 YDFVHVIqqGKTNnsekFE-RFRGYCERAYTILRRHGLLFLHLF 715
Cdd:cd05170   254 QNIEHAL--GPTG----VEgTFRLSCEQVLKILRKGRETLLTLL 291
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 278-392 2.92e-08

Phosphoinositide 4-kinase(PI4K), 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. PI4K phosphorylates hydroxylgroup at position 4 on the inositol ring of phosphoinositide, the first commited step in the phosphatidylinositol cycle.


Pssm-ID: 238443  Cd Length: 175  Bit Score: 53.90  E-value: 2.92e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 278 HFPEALArlLLVTKWNKHEDVAQMLYLLCsWPELPVLSALELLDFSFP-DCYVGSFAIKSLRKLTDDELFQYLLQLVQVL 356
Cdd:cd00871    38 KIPEALP--FLVTGKSVDENSPDLKYLLY-WAPVSPVQALSLFTPQYPgHPLVLQYAVRVLESYPVETVFFYIPQIVQAL 114

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720407821 357 KYESylDCELTKFLLGRALANRKIGHFLFWHLRSEM 392
Cdd:cd00871   115 RYDK--MGYVEEYILETAKRSQLFAHQIIWNMQTNC 148
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 506-650 8.11e-08

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: 51.67  E-value: 8.11e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 506 GSAGNVGIIFKNGDDlRQDMLTLQMIQLMDVLWKQEGLDLrmTPYGCLPTGDRTG----LIEVVlhsdtianiqlnksnm 581
Cdd:cd13968    14 GECTTIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELV---------------- 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720407821 582 aataafnKDALLNWLKSKnpGEALDRAIEEFTLSCAGYCVATYV--LGIGDRHSDNIMIRESGQLFHIDFG 650
Cdd:cd13968    75 -------KGGTLIAYTQE--EELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 79-186 5.36e-07

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: 49.94  E-value: 5.36e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKarstkkkskkadCPIAW 158
Cdd:cd08397    32 LFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKA------------VPFGG 99

                          90       100
                  ....*....|....*....|....*...
gi 1720407821 159 ANLMLFDYKDQLKTGERCLYMWPSVPDE 186
Cdd:cd08397   100 TTLSLFNKDGTLRRGRQKLRVWPDVEAD 127
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 611-672 2.95e-04

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: 43.28  E-value: 2.95e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720407821 611 EFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFgHFLGNFKTKFGINRERVPFILT 672
Cdd:cd05163   140 QFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDF-LPSINSQGPLLDNNEPVPFRLT 201
HAD_sEH-N_like cd02603
N-terminal lipase phosphatase domain of human soluble epoxide hydrolase, Escherichia coli YihX ...
 237-355 9.01e-03

N-terminal lipase phosphatase domain of human soluble epoxide hydrolase, Escherichia coli YihX/HAD4 alpha-D-glucose 1-phosphate phosphatase, and related domains, may be inactive; This family includes the N-terminal phosphatase domain of human soluble epoxide hydrolase (sEH). sEH is a bifunctional enzyme with two distinct enzyme activities, the C-terminal domain has epoxide hydrolysis activity and the N-terminal domain (Ntermphos), which belongs to this family, has lipid phosphatase activity. The latter prefers mono-phosphate esters, and lysophosphatidic acids (LPAs) are the best natural substrates found to date. In addition this family includes Gallus gallus sEH and Xenopus sEH which appears to lack phosphatase activity, and Escherichia coli YihX/HAD4 which selectively hydrolyzes alpha-Glucose-1-P, phosphatase, has significant phosphatase activity against pyridoxal phosphate, and has low beta phosphoglucomutase activity. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.


Pssm-ID: 319790 [Multi-domain]  Cd Length: 195  Bit Score: 38.09  E-value: 9.01e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407821 237 ERGRITEEEL--QLREILERRGSGELYEHekdlVWKMRHEVQEHFPEALARLllvtkwnKHEDVAqmLYLLCSWPELPVL 314
Cdd:cd02603    49 ERGRITEEEFweELREELGRPLSAELFEE----LVLAAVDPNPEMLDLLEAL-------RAKGYK--VYLLSNTWPDHFK 115

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1720407821 315 SALELLD--FSFPDCYVGSFAIKsLRKlTDDELFQYLLQLVQV 355
Cdd:cd02603   116 FQLELLPrrGDLFDGVVESCRLG-VRK-PDPEIYQLALERLGV 156
 
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.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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