Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (PH) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1138 TEKTCRGYLIKMGGKIKTWKKRWFVFDRNKRTFSYYADKHEAKLKGVIYFQAIEEVYYDHLKNANKSPNPLLTFSVKTHD 1217
Cdd:cd14673     1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                          90       100
                  ....*....|....*....|....*
gi 188528897 1218 RIYYMVAPSPEAMRIWMDVIVTGAE 1242
Cdd:cd14673    81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 188528897  1030 RIEEMER-----LLKQAHAEKTRLLESREREMEAKKRAleeEKRRREILEKRLQE------ETSQRQKLIEKEVKIREK 1097
Cdd:pfam17380  452 RLEEQERqqqveRLRQQEEERKRKKLELEKEKRDRKRA---EEQRRKILEKELEErkqamiEEERKRKLLEKEMEERQK 527

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (PH) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1138 TEKTCRGYLIKMGGKIKTWKKRWFVFDRNKRTFSYYADKHEAKLKGVIYFQAIEEVYYDHLKNANKSPNPLLTFSVKTHD 1217
Cdd:cd14673     1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                          90       100
                  ....*....|....*....|....*
gi 188528897 1218 RIYYMVAPSPEAMRIWMDVIVTGAE 1242
Cdd:cd14673    81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  1141 TCRGYLIKMGGKIK-TWKKRWFVFDRNkrTFSYYADK---HEAKLKGVIYFQAIEEVYYDHLKNANKsPNPL-LTFSVKT 1215
Cdd:pfam00169    2 VKEGWLLKKGGGKKkSWKKRYFVLFDG--SLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKR-KFCFeLRTGERT 78

                           90       100
                   ....*....|....*....|..
gi 188528897  1216 HDRIYYMVAPSPEAMRIWMDVI 1237
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAI 100

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  577 EQRTQELAAMEDARMVILNNLEELEQKIKDINDQMDESSR---ELDMECALLDGEQKSETAELMKEKEILDHLNRKITEL 653
Cdd:COG1196   277 EELELELEEAQAEEYELLAELARLEQDIARLEERRRELEErleELEEELAELEEELEELEEELEELEEELEEAEEELEEA 356

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  654 EKNIVGEKTKEKVKLDAEREKLERLQELYSEQKTQLDNCpESMREQLQQQLKRDADLLDVESKHFE---DLEFQQLEHES 730
Cdd:COG1196   357 EAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAA-AELAAQLEELEEAEEALLERLERLEEeleELEEALAELEE 435

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 188528897  731 RLDEEKENLTQQLLREVAEYQRNIVARKEKISALKKQASHIVQQAQREQD 780
Cdd:COG1196   436 EEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEE 485

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   572 EDIGEEQRTQELAAMEDARMVILNNLEELEQKIKdindqmdessRELDMECALLDGEQKSETAELMKEKEILDHLNRKIT 651
Cdd:pfam02463  167 LKRKKKEALKKLIEETENLAELIIDLEELKLQEL----------KLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNE 236

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   652 ELEKNIVGEKTKEKVKLDAEREKLERLQELYSEQKTQLDNCPESMREQLQQQLKRDADLLDVESKhFEDLEFQQLEHESR 731
Cdd:pfam02463  237 ERIDLLQELLRDEQEEIESSKQEIEKEEEKLAQVLKENKEEEKEKKLQEEELKLLAKEEEELKSE-LLKLERRKVDDEEK 315

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 188528897   732 LDEEKENLTQQLLREVAEYQRNIVARKEKISALKKQASH--IVQQAQREQDHFVKEKNNLIMMLQREKENLCNLEKKY 807
Cdd:pfam02463  316 LKESEKEKKKAEKELKKEKEEIEELEKELKELEIKREAEeeEEEELEKLQEKLEQLEEELLAKKKLESERLSSAAKLK 393

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  597 LEELEQKIKDINDQMDESSRELDMEC--ALLDgEQKSETAELMKEKEILDHLNRKITELEKNIVGEKTKEKVKLDAEREK 674
Cdd:cd00176     9 ADELEAWLSEKEELLSSTDYGDDLESveALLK-KHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQERLEELNQR 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  675 LERLQELYSEQKTQLdncpesmrEQLQQQLKRDADLLDVESKhFEDLEFQQLEHESRLDEEKenlTQQLLREVAEYQRNI 754
Cdd:cd00176    88 WEELRELAEERRQRL--------EEALDLQQFFRDADDLEQW-LEEKEAALASEDLGKDLES---VEELLKKHKELEEEL 155

                         170       180       190
                  ....*....|....*....|....*....|..
gi 188528897  755 VARKEKISALKKQASHIVQQAQREQDHFVKEK 786
Cdd:cd00176   156 EAHEPRLKSLNELAEELLEEGHPDADEEIEEK 187

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 188528897  1029 ARIEEMERLLKQAHAEKTRllesREREMEAKKRALEEEKRRREILEKRL----QEETSQRQKLIEKEVKIREKQRA 1100
Cdd:TIGR02169  681 ERLEGLKRELSSLQSELRR----IENRLDELSQELSDASRKIGEIEKEIeqleQEEEKLKERLEELEEDLSSLEQE 752

Uncharacterized family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes an uncharacterized family of proteins similar to stomatin, prohibitin, flotillin, HflK/C (SPFH) and podocin. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Many superfamily members are associated with lipid rafts. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Microdomains formed from flotillin proteins may in addition be dynamic units with their own regulatory functions. Flotillins have been implicated in signal transduction, vesicle trafficking, cytoskeleton rearrangement and are known to interact with a variety of proteins. Stomatin interacts with and regulates members of the degenerin/epithelia Na+ channel family in mechanosensory cells of Caenorhabditis elegans and vertebrate neurons and participates in trafficking of Glut1 glucose transporters. Prohibitin may act as a chaperone for the stabilization of mitochondrial proteins. Prokaryotic HflK/C plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection. Flotillins have been implicated in the progression of prion disease, in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's disease and, in cancer invasion and metastasis. Mutations in the podocin gene give rise to autosomal recessive steroid resistant nephritic syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1032 EEMErllkqahAEKTRLLESRER--------EMEAKKRALEEEKRR--------REILEKrlqeETSQRQKLIEKEVKI- 1094
Cdd:cd03406   169 EAME-------AEKTKLLIAEQHqkvvekeaETERKRAVIEAEKDAevakiqmqQKIMEK----EAEKKISEIEDEMHLa 237

                  ....*...
gi 188528897 1095 REKQRAQA 1102
Cdd:cd03406   238 REKARADA 245

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (PH) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1138 TEKTCRGYLIKMGGKIKTWKKRWFVFDRNKRTFSYYADKHEAKLKGVIYFQAIEEVYYDHLKNANKSPNPLLTFSVKTHD 1217
Cdd:cd14673     1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                          90       100
                  ....*....|....*....|....*
gi 188528897 1218 RIYYMVAPSPEAMRIWMDVIVTGAE 1242
Cdd:cd14673    81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1144 GYLIKMGGKIKTWKKRWFVFdRNKRTFsYYADKHEA--KLKGVIyfqAIEEvyYDHLKNANKSPnpllTFSVKTHDRIYY 1221
Cdd:cd13282     3 GYLTKLGGKVKTWKRRWFVL-KNGELF-YYKSPNDVirKPQGQI---ALDG--SCEIARAEGAQ----TFEIVTEKRTYY 71

                          90       100
                  ....*....|....*....|....
gi 188528897 1222 MVAPSPEAMRIWMDVIVTGAEGYT 1245
Cdd:cd13282    72 LTADSENDLDEWIRVIQNVLRRQA 95

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1142 CRGYLIKMGGKIKTWKKRWFVFDRNKrtFSYYADKHEAKLKGVIYFQAIEEVYYdhLKNAnKSPNpllTFSVKTHDRIYY 1221
Cdd:cd13298     8 KSGYLLKRSRKTKNWKKRWVVLRPCQ--LSYYKDEKEYKLRRVINLSELLAVAP--LKDK-KRKN---VFGIYTPSKNLH 79

                          90
                  ....*....|....*.
gi 188528897 1222 MVAPSPEAMRIWMDVI 1237
Cdd:cd13298    80 FRATSEKDANEWVEAL 95

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1144 GYLIKMGGKIKTWKKRWFVFDRNKrtFSYYADKHEAKLKGVIYFQAIEEVYYDHlknankSPNPLLTFSVKTHDRIYYMV 1223
Cdd:cd10573     7 GYLTKLGGIVKNWKTRWFVLRRNE--LKYFKTRGDTKPIRVLDLRECSSVQRDY------SQGKVNCFCLVFPERTFYMY 78

                          90
                  ....*....|....
gi 188528897 1224 APSPEAMRIWMDVI 1237
Cdd:cd10573    79 ANTEEEADEWVKLL 92

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1144 GYLIKMGGKIKTWKKRWFVFdRNKRtFSYYADKHEAKLKGVIYFQAIEEVYYDHLKnanKSPNpllTFSVKTHDRIYYMV 1223
Cdd:cd13255    10 GYLEKKGERRKTWKKRWFVL-RPTK-LAYYKNDKEYRLLRLIDLTDIHTCTEVQLK---KHDN---TFGIVTPARTFYVQ 81

                          90
                  ....*....|....
gi 188528897 1224 APSPEAMRIWMDVI 1237
Cdd:cd13255    82 ADSKAEMESWISAI 95

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1144 GYLIKMGGK-IKTWKKRWFVFDRNKrtFSYYADKHEA--KLKGVIYFQAIEEVYYDHLKNANKspnpllTFSVKT-HDRI 1219
Cdd:cd00821     3 GYLLKRGGGgLKSWKKRWFVLFEGV--LLYYKSKKDSsyKPKGSIPLSGILEVEEVSPKERPH------CFELVTpDGRT 74

                          90
                  ....*....|....*...
gi 188528897 1220 YYMVAPSPEAMRIWMDVI 1237
Cdd:cd00821    75 YYLQADSEEERQEWLKAL 92

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1144 GYLIKMGGKIKTWKKRWFVFDRNkrTFSYYADKHEAKLKGVIYFQAIeEVYYDHLKNAN------KSPNPLLTFSVKT-- 1215
Cdd:cd01252     7 GWLLKLGGRVKSWKRRWFILTDN--CLYYFEYTTDKEPRGIIPLENL-SVREVEDKKKPfcfelySPSNGQVIKACKTds 83

                          90       100       110
                  ....*....|....*....|....*....|
gi 188528897 1216 --------HDrIYYMVAPSPEAMRIWMDVI 1237
Cdd:cd01252    84 dgkvvegnHT-VYRISAASEEERDEWIKSI 112

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   577 EQRTQELAAMEDARMVILNNLEELEQKIKDINDQMdessRELDMECALLDGE---QKSETAELMKEKEI----LDHLNRK 649
Cdd:TIGR02168  242 EELQEELKEAEEELEELTAELQELEEKLEELRLEV----SELEEEIEELQKElyaLANEISRLEQQKQIlrerLANLERQ 317

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   650 ITELEKNIV-GEKTKEKVKLDAER--EKLERLQELYSEQKTQLDNCPESMREQLQQQLKRDADLLDVESKHFE------- 719
Cdd:TIGR02168  318 LEELEAQLEeLESKLDELAEELAEleEKLEELKEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQlelqias 397

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   720 -DLEFQQLE-HESRLDEEKENLTQ-------------------------QLLREVAEYQRNIVARKEKISALKKQASHIV 772
Cdd:TIGR02168  398 lNNEIERLEaRLERLEDRRERLQQeieellkkleeaelkelqaeleeleEELEELQEELERLEEALEELREELEEAEQAL 477

                          250       260
                   ....*....|....*....|....*...
gi 188528897   773 QQAQREqdhfVKEKNNLIMMLQREKENL 800
Cdd:TIGR02168  478 DAAERE----LAQLQARLDSLERLQENL 501

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   595 NNLEELEQKIKDINDQMDESSRELDMECALLDgEQKSETAELMKEKEILDH----LNRKITELEknivgektKEKVKLDA 670
Cdd:TIGR02168  239 EELEELQEELKEAEEELEELTAELQELEEKLE-ELRLEVSELEEEIEELQKelyaLANEISRLE--------QQKQILRE 309

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   671 EREKLERLQELYSEQKTQLdncpESMREQLQQQLKRDADLLDVESKHFEDLEfQQLEHESRLDEEKENLTQQLLREVAEY 750
Cdd:TIGR02168  310 RLANLERQLEELEAQLEEL----ESKLDELAEELAELEEKLEELKEELESLE-AELEELEAELEELESRLEELEEQLETL 384

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 188528897   751 QRNIVARKEKISALKKQASHI---VQQAQREQDHFVKEKNNLIMMLQR 795
Cdd:TIGR02168  385 RSKVAQLELQIASLNNEIERLearLERLEDRRERLQQEIEELLKKLEE 432

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   595 NNLEELEQKIKDINDQMDESSRELDMECALLDGEQKSETAELMKEKEILDHLNRKITELEKNIvgekTKEKVKLDAEREK 674
Cdd:TIGR04523  394 NDLESKIQNQEKLNQQKDEQIKKLQQEKELLEKEIERLKETIIKNNSEIKDLTNQDSVKELII----KNLDNTRESLETQ 469

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   675 LERLQELYSEQKTQLdncpesmrEQLQQQLKRDADLLDVESKHFEDLE----------------FQQLEHE--------- 729
Cdd:TIGR04523  470 LKVLSRSINKIKQNL--------EQKQKELKSKEKELKKLNEEKKELEekvkdltkkisslkekIEKLESEkkekeskis 541

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   730 ---SRLDEEKENLTQQLLR-EVAEYQRNIVARKEKISALKK---QASHIVQQAQREQDHFVKEKNNLIMMLQREKENLCN 802
Cdd:TIGR04523  542 dleDELNKDDFELKKENLEkEIDEKNKEIEELKQTQKSLKKkqeEKQELIDQKEKEKKDLIKEIEEKEKKISSLEKELEK 621

                   ....*...
gi 188528897   803 LEKKYSSL 810
Cdd:TIGR04523  622 AKKENEKL 629

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  576 EEQRTQELAAMEDArmvILNNLEELEQKIKDINDQMDESSRELDM---ECALLDGEQKSETAELMKEKEILDHLNRKITE 652
Cdd:COG1196   307 LEERRRELEERLEE---LEEELAELEEELEELEEELEELEEELEEaeeELEEAEAELAEAEEALLEAEAELAEAEEELEE 383

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  653 LEKNIVGEKTKEKVKLDAEREKLERLQELYSEQKTQldncpESMREQLQQQLKRDADLLDVESKHFEDLEFQQLEHESRL 732
Cdd:COG1196   384 LAEELLEALRAAAELAAQLEELEEAEEALLERLERL-----EEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEE 458

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 188528897  733 DEEKENLtQQLLREVAEYQRNIVARKEKISALKKQASHIVQQAQREQ 779
Cdd:COG1196   459 EALLELL-AELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYE 504

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  576 EEQRTQELAAMEDARmvILNNLEELEQKIKDINDQMDESS---RELDMECALLDGEQKSETAELMKEKEILDHLNRKITE 652
Cdd:COG1196   222 LKELEAELLLLKLRE--LEAELEELEAELEELEAELEELEaelAELEAELEELRLELEELELELEEAQAEEYELLAELAR 299

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  653 LEKnivgEKTKEKVKLDAEREKLERLQELYSEQKTQLdncpesmrEQLQQQLKRDADLLDVESKHFEDLEFQQLEHESRL 732
Cdd:COG1196   300 LEQ----DIARLEERRRELEERLEELEEELAELEEEL--------EELEEELEELEEELEEAEEELEEAEAELAEAEEAL 367

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 188528897  733 DEEKENLTQQLLREVAEYQRNIVARKEKISALKKQASHIVQQAQREQD 780
Cdd:COG1196   368 LEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLER 415

putative mechanosensitive channel protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  581 QELAAMEDARMVILNNL--EELEQKIKDINDQMDESSRELdmecalldgEQKSETAelmkeKEILDHLN----------R 648
Cdd:PRK10929   86 QQLNNERDEPRSVPPNMstDALEQEILQVSSQLLEKSRQA---------QQEQDRA-----REISDSLSqlpqqqtearR 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  649 KITELEKNIVG------------------EKTKEKVKLDA---------EREKLERLQ-ELYSEQKTQLDNCPESMREQL 700
Cdd:PRK10929  152 QLNEIERRLQTlgtpntplaqaqltalqaESAALKALVDElelaqlsanNRQELARLRsELAKKRSQQLDAYLQALRNQL 231

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897  701 QQQLKRDADlldveskhfedlefQQLEHESRLDEEKENLTQQLL------REVAEYQRNIVARKEKISALKKQA-SHIVQ 773
Cdd:PRK10929  232 NSQRQREAE--------------RALESTELLAEQSGDLPKSIVaqfkinRELSQALNQQAQRMDLIASQQRQAaSQTLQ 297

                         250       260
                  ....*....|....*....|.
gi 188528897  774 QAQ-----REQDHFVKEKNNL 789
Cdd:PRK10929  298 VRQalntlREQSQWLGVSNAL 318

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897 1144 GYLIKMGGKIKT-WKKRWFVFDRnkRTFSYYADKHEAKLKGVIYFQAIEEVYY------DHLKNANKSPnplltFSVKTH 1216
Cdd:cd01251     6 GYLEKTGPKQTDgFRKRWFTLDD--RRLMYFKDPLDAFPKGEIFIGSKEEGYSvreglpPGIKGHWGFG-----FTLVTP 78

                          90       100
                  ....*....|....*....|.
gi 188528897 1217 DRIYYMVAPSPEAMRIWMDVI 1237
Cdd:cd01251    79 DRTFLLSAETEEERREWITAI 99

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   592 VILNNLEELEQKIKDINDQMDESSRELDMECALLDgeqksETAELMKEKEI-LDHLNRKITELEKNIVGEKTKEKVKLDA 670
Cdd:TIGR02169  227 ELLKEKEALERQKEAIERQLASLEEELEKLTEEIS-----ELEKRLEEIEQlLEELNKKIKDLGEEEQLRVKEKIGELEA 301

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188528897   671 EREKLERLQELYSEQKTQLDNcpesmrEQLQQQLKRDADLLDVESKHfEDLEFQQLEHESRLDE-----EKENLTQQLLR 745
Cdd:TIGR02169  302 EIASLERSIAEKERELEDAEE------RLAKLEAEIDKLLAEIEELE-REIEEERKRRDKLTEEyaelkEELEDLRAELE 374

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 188528897   746 EV----AEYQRNIVARKEKISALKKQASHIvqqaQREQDHFVKEKNNLIMMLQREKENLCNLEKK 806
Cdd:TIGR02169  375 EVdkefAETRDELKDYREKLEKLKREINEL----KRELDRLQEELQRLSEELADLNAAIAGIEAK 435