NCBI Conserved Domain Search

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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.

Pssm-ID: 269944 [Multi-domain] Cd Length: 140 Bit Score: 176.26 E-value: 4.39e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  551 KEGWLTKRSRNRKdPKKEANYRDRYVRMTTECLSYYITNKAN-AVPKDSMKLKDVTIVEAVTDGTFGERKYFFQVGSKGD 629
Cdd:cd01238     1 LEGLLVKRSQGKK-RFGPVNYKERWFVLTKSSLSYYEGDGEKrGKEKGSIDLSKVRCVEEVKDEAFFERKYPFQVVYDDY 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 196014388  630 LLYAHAMNPTDRDEWVLALRQCCQRLKLNMDrRYHPGAYTD-KWSCCQAVDLSQNGCQHAFD 690
Cdd:cd01238    80 TLYVFAPSEEDRDEWIAALRKVCRNNSNLHD-KYHPGFWTGgKWSCCGQTSKSAPGCQPAFD 140

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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.

Pssm-ID: 269944 [Multi-domain] Cd Length: 140 Bit Score: 175.88 E-value: 6.16e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  700 KKGWVVKRSRGRgKSKNAANYRERFVVLTEEFLSYY---GNEAGEYKDCINMKHVSIVEPVNDGT-LERDFVFQVGSKGD 775
Cdd:cd01238     1 LEGLLVKRSQGK-KRFGPVNYKERWFVLTKSSLSYYegdGEKRGKEKGSIDLSKVRCVEEVKDEAfFERKYPFQVVYDDY 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 196014388  776 ILYICAPNEEEREDWIVALRfVTQQLHNKMEDRFHPGGFTRSKWTCCDYPSLDEDGCQRAFD 837
Cdd:cd01238    80 TLYVFAPSEEDRDEWIAALR-KVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPGCQPAFD 140

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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.

Pssm-ID: 269944 [Multi-domain] Cd Length: 140 Bit Score: 165.48 E-value: 3.14e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  403 KEGWLVKRSRNRNAInKDANYRSRYVRLTKDYLIYYL--NEKLNNYKDCIHLKYATIVESVKDHTFEKKKNVFQIGQKND 480
Cdd:cd01238     1 LEGLLVKRSQGKKRF-GPVNYKERWFVLTKSSLSYYEgdGEKRGKEKGSIDLSKVRCVEEVKDEAFFERKYPFQVVYDDY 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 196014388  481 FLYLLAQSDSHREDWLNAIRNACmRLRNKMDKKFHPGALTKGeRWSCCSHLS-SAEGCEDAFD 542
Cdd:cd01238    80 TLYVFAPSEEDRDEWIAALRKVC-RNNSNLHDKYHPGFWTGG-KWSCCGQTSkSAPGCQPAFD 140

Domain of unknown function (DUF4698); This family of proteins is found in eukaryotes. Proteins in this family are typically between 464 and 550 amino acids in length.

Pssm-ID: 464857 Cd Length: 484 Bit Score: 138.79 E-value: 2.26e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388   994 IQKFMQYTQHRRIRTLGNAEDVSKDKISD------DAKIRAWIEEFGGIEEDDRQRKKKLRPQSAP--VKNTPGTAGIER 1065
Cdd:pfam15769  243 LQKLLEMVRESARRTLKMMENELQRKAPSilsllkDSAPKAKQTTHKSSERSSSTSGESHRPKSQKkiKSLTHIDIFIKS 322

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  1066 YQDLASRMRQKFIDVAKENEELLHDQLDRIEMKRSQKCELRFFAIEPKTYVHRDLGKMRHKIKKIEIRQANKSVHrpWYI 1145
Cdd:pfam15769  323 KSGLCSEMRAKFYEVAQEAAFCLHDKLEILERRQEERSLQKFLSLVLVSNFHKDLEKMRQAVVMVKGDAEEIADH--WFF 400

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  1146 NLVDTLPESIREDRQCSQTLERISSHA-KID-GIVPSsvQLIRVLSGLRHWEICSPDISAAIEFVREKIVEMPDYEYEEW 1223
Cdd:pfam15769  401 DLLSKLPEDVKNNRPAKKILKKLQKFGeNLDlRIRPH--VFLKVLQDLRTWELCSPDVAVAIEFVREHIIHMPQEDYEAW 478


                   ...
gi 196014388  1224 LRS 1226
Cdd:pfam15769  479 LQS 481

Domain of unknown function (DUF4698); This family of proteins is found in eukaryotes. Proteins in this family are typically between 464 and 550 amino acids in length.

Pssm-ID: 464857 Cd Length: 484 Bit Score: 86.40 E-value: 3.09e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388   280 LHRKHYRSRKSSSIQVRPFSPYYSSV-ASSPIQSDREHIFRQLCVIQWLLEATALELGYIMVPISACWKLNESNDGKMSR 358
Cdd:pfam15769   61 EEEPKKSKKKKAKSTLRPFTPLHSSLlSPSLPEAHVEPLFRQLCALHWLLEALTLEPTHTMKPVISCWNLKDPGGSKSTI 140

                           90       100
                   ....*....|....*....|..
gi 196014388   359 KRQEKDnkKALDNKWDALCNNP 380
Cdd:pfam15769  141 KKINKE--KSIEQRWEHFVTAS 160

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 76.43 E-value: 1.22e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388    698 VVKKGWVVKRSRGRGKSknaanYRERFVVLTEEFLSYY----GNEAGEYKDCINMKHVSIVEPVNDGTLERDFVFQV-GS 772
Cdd:smart00233    1 VIKEGWLYKKSGGGKKS-----WKKRYFVLFNSTLLYYkskkDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIkTS 75

                            90       100
                    ....*....|....*....|....*..
gi 196014388    773 KGDILYICAPNEEEREDWIVALRFVTQ 799
Cdd:smart00233   76 DRKTLLLQAESEEEREKWVEALRKAIA 102

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 72.21 E-value: 4.27e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388   698 VVKKGWVVKRSRGRGKsknaaNYRERFVVLTEEFLSYY----GNEAGEYKDCINMKHVSIVEPVNDGTLERDFVFQV--- 770
Cdd:pfam00169    1 VVKEGWLLKKGGGKKK-----SWKKRYFVLFDGSLLYYkddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELrtg 75

                           90       100
                   ....*....|....*....|....*...
gi 196014388   771 -GSKGDILYICAPNEEEREDWIVALRFV 797
Cdd:pfam00169   76 eRTGKRTYLLQAESEEERKDWIKAIQSA 103

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 69.50 E-value: 3.44e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388    549 VIKEGWLTKRSRNRKDpkkeaNYRDRYVRMTTECLSYYITNKAN--AVPKDSMKLKDVTIVEaVTDGTFGERKYFFQV-G 625
Cdd:smart00233    1 VIKEGWLYKKSGGGKK-----SWKKRYFVLFNSTLLYYKSKKDKksYKPKGSIDLSGCTVRE-APDPDSSKKPHCFEIkT 74

                            90       100
                    ....*....|....*....|....*...
gi 196014388    626 SKGDLLYAHAMNPTDRDEWVLALRQCCQ 653
Cdd:smart00233   75 SDRKTLLLQAESEEEREKWVEALRKAIA 102

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 68.73 E-value: 6.23e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388    401 ILKEGWLVKRSRNRNAinkdaNYRSRYVRLTKDYLIYYLNEKLN---NYKDCIHLKYATIVESVkDHTFEKKKNVFQIGQ 477
Cdd:smart00233    1 VIKEGWLYKKSGGGKK-----SWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAP-DPDSSKKPHCFEIKT 74

                            90       100
                    ....*....|....*....|....*..
gi 196014388    478 KNDFLYLL-AQSDSHREDWLNAIRNAC 503
Cdd:smart00233   75 SDRKTLLLqAESEEEREKWVEALRKAI 101

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.

Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 64.49 E-value: 1.50e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  700 KKGWVVKRSRGRGKSknaanYRERFVVLTEEFLSYYGNE---AGEYKDCINMKHVSIVEPVNDGtlERDFVFQV-GSKGD 775
Cdd:cd00821     1 KEGYLLKRGGGGLKS-----WKKRWFVLFEGVLLYYKSKkdsSYKPKGSIPLSGILEVEEVSPK--ERPHCFELvTPDGR 73

                          90
                  ....*....|....*....
gi 196014388  776 ILYICAPNEEEREDWIVAL 794
Cdd:cd00821    74 TYYLQADSEEERQEWLKAL 92

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 62.97 E-value: 7.88e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388   401 ILKEGWLVKRSRNRNAinkdaNYRSRYVRLTKDYLIYYLNEKLNNYKD---CIHLKYATIVESVKdHTFEKKKNVFQI-- 475
Cdd:pfam00169    1 VVKEGWLLKKGGGKKK-----SWKKRYFVLFDGSLLYYKDDKSGKSKEpkgSISLSGCEVVEVVA-SDSPKRKFCFELrt 74

                           90       100       110
                   ....*....|....*....|....*....|
gi 196014388   476 --GQKNDFLYLLAQSDSHREDWLNAIRNAC 503
Cdd:pfam00169   75 geRTGKRTYLLQAESEEERKDWIKAIQSAI 104

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first 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.

Pssm-ID: 270113 Cd Length: 108 Bit Score: 61.62 E-value: 2.84e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  399 QKILKEGWLVKRSRNRNainkdaNYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKYATIVESVKDhtFEKKKNVFQI-GQ 477
Cdd:cd13301     1 PGIIKEGYLVKKGHVVN------NWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTITSPCLE--YGKRPLVFKLtTA 72

                          90       100
                  ....*....|....*....|....*
gi 196014388  478 KNDFLYLLAQSDSHREDWLNAIRNA 502
Cdd:cd13301    73 KGQEHFFQACSREERDAWAKDITKA 97

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.

Pssm-ID: 270110 Cd Length: 106 Bit Score: 60.33 E-value: 7.57e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  399 QKILKEGWLVKRSRNRnainkdANYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKYATIVESVKDHtfeKKKNVFQIGQK 478
Cdd:cd13298     4 DRVLKSGYLLKRSRKT------KNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVAPLKDK---KRKNVFGIYTP 74

                          90       100
                  ....*....|....*....|...
gi 196014388  479 NDFLYLLAQSDSHREDWLNAIRN 501
Cdd:cd13298    75 SKNLHFRATSEKDANEWVEALRE 97

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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.

Pssm-ID: 269950 Cd Length: 107 Bit Score: 59.99 E-value: 8.71e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  551 KEGWLTKRSRNRKDPKKEANYRDRYVRMTTECLSYYITNKANavPKDSMKLKDVTIVEAVTDGTFGeRKYFFQVGSKGDL 630
Cdd:cd01244     1 KEGYLIKRAQGRKKKFGRKNFKKRYFRLTNEALSYSKSKGKQ--PLCSIPLEDILAVERVEEESFK-MKNMFQIVQPDRT 77

                          90       100
                  ....*....|....*....|...
gi 196014388  631 LYAHAMNPTDRDEWVLALRQCCQ 653
Cdd:cd01244    78 LYLQAKNVVELNEWLSALRKVCL 100

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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.

Pssm-ID: 269950 Cd Length: 107 Bit Score: 59.61 E-value: 1.18e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  700 KKGWVVKRSRGRGKSKNAANYRERFVVLTEEFLSYYGNEAGEYKDCINMKHVSIVEPVNDGTLERDFVFQVGSKGDILYI 779
Cdd:cd01244     1 KEGYLIKRAQGRKKKFGRKNFKKRYFRLTNEALSYSKSKGKQPLCSIPLEDILAVERVEEESFKMKNMFQIVQPDRTLYL 80

                          90       100
                  ....*....|....*....|....*..
gi 196014388  780 CAPNEEEREDWIVALRFVTQQLHNKME 806
Cdd:cd01244    81 QAKNVVELNEWLSALRKVCLCNPNRLP 107

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 58.73 E-value: 2.47e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388   549 VIKEGWLTKRSRNRKDpkkeaNYRDRYVRMTTECLSYYITNKAN--AVPKDSMKLKDVTIVEAVTDGTfGERKYFFQV-- 624
Cdd:pfam00169    1 VVKEGWLLKKGGGKKK-----SWKKRYFVLFDGSLLYYKDDKSGksKEPKGSISLSGCEVVEVVASDS-PKRKFCFELrt 74

                           90       100       110
                   ....*....|....*....|....*....|
gi 196014388   625 --GSKGDLLYAHAMNPTDRDEWVLALRQCC 652
Cdd:pfam00169   75 geRTGKRTYLLQAESEEERKDWIKAIQSAI 104

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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.

Pssm-ID: 269950 Cd Length: 107 Bit Score: 58.84 E-value: 2.54e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  403 KEGWLVKRSRNRNAINKDANYRSRYVRLTKDYLIYYLNEKLNNYKDcIHLKYATIVESVKDHTFeKKKNVFQIGQKNDFL 482
Cdd:cd01244     1 KEGYLIKRAQGRKKKFGRKNFKKRYFRLTNEALSYSKSKGKQPLCS-IPLEDILAVERVEEESF-KMKNMFQIVQPDRTL 78

                          90       100
                  ....*....|....*....|....*...
gi 196014388  483 YLLAQSDSHREDWLNAIRNACMRLRNKM 510
Cdd:cd01244    79 YLQAKNVVELNEWLSALRKVCLCNPNRL 106

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.

Pssm-ID: 270110 Cd Length: 106 Bit Score: 55.71 E-value: 2.59e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  698 VVKKGWVVKRSRGRGksknaaNYRERFVVLTEEFLSYYGNEAgEYK--DCINMKHVSIVEPVNDGtlERDFVFQVGSKGD 775
Cdd:cd13298     6 VLKSGYLLKRSRKTK------NWKKRWVVLRPCQLSYYKDEK-EYKlrRVINLSELLAVAPLKDK--KRKNVFGIYTPSK 76

                          90       100
                  ....*....|....*....|
gi 196014388  776 ILYICAPNEEEREDWIVALR 795
Cdd:cd13298    77 NLHFRATSEKDANEWVEALR 96

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.

Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 54.47 E-value: 6.09e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  403 KEGWLVKRSRNRNAinkdaNYRSRYVRLTKDYLIYYLNEKLNNY--KDCIHLKYATIVESVKDhtfEKKKNVFQI-GQKN 479
Cdd:cd00821     1 KEGYLLKRGGGGLK-----SWKKRWFVLFEGVLLYYKSKKDSSYkpKGSIPLSGILEVEEVSP---KERPHCFELvTPDG 72

                          90       100
                  ....*....|....*....|
gi 196014388  480 DFLYLLAQSDSHREDWLNAI 499
Cdd:cd00821    73 RTYYLQADSEEERQEWLKAL 92

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(m) binds inositol tetrakisphosphate (IP4). 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.

Pssm-ID: 241521 Cd Length: 133 Bit Score: 52.64 E-value: 6.00e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  693 TELSTVVKKGWVVKRSRGRgKSKNAANYRERFVVLTEEFLSYYGNEAGEYKDCINMKHVSIVEPVNDGTLERDFVFQVGS 772
Cdd:cd13370    11 VSESVHLKEGEMHKRAQGR-TRIGKKNFKKRWFCLTSRELTYHKQKGKEAIFTIPVKNILAVEKLEESAFNKKNMFQVIH 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 196014388  773 KGDILYICAPNEEEREDWIVALRFVTQQLHNKMEdRFHPGGF 814
Cdd:cd13370    90 SEKPLYVQANNCVEANEWIEVLSRVSRCNQKRLS-FYHPSAY 130

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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.

Pssm-ID: 270080 Cd Length: 103 Bit Score: 51.58 E-value: 7.41e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  696 STVVKKGWVVKRSRGRGKSKNAanyrerFVVL--TEEFLSYYGNE-AGEYKDCINMKhVSIVEPVNDGTLERDFVFQV-- 770
Cdd:cd13260     1 KGIDKKGYLLKKGGKNKKWKNL------YFVLegKEQHLYFFDNEkRTKPKGLIDLS-YCSLYPVHDSLFGRPNCFQIvv 73

                          90       100
                  ....*....|....*....|....*..
gi 196014388  771 --GSKGDILYICAPNEEEREDWIVALR 795
Cdd:cd13260    74 raLNESTITYLCADTAELAQEWMRALR 100

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.

Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 51.39 E-value: 7.55e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  551 KEGWLTKRSRNRKDpkkeaNYRDRYVRMTTECLSYY-ITNKANAVPKDSMKLKDVTIVEAVTDgtfGERKYFFQV-GSKG 628
Cdd:cd00821     1 KEGYLLKRGGGGLK-----SWKKRWFVLFEGVLLYYkSKKDSSYKPKGSIPLSGILEVEEVSP---KERPHCFELvTPDG 72

                          90       100
                  ....*....|....*....|
gi 196014388  629 DLLYAHAMNPTDRDEWVLAL 648
Cdd:cd00821    73 RTYYLQADSEEERQEWLKAL 92

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(m) binds inositol tetrakisphosphate (IP4). 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.

Pssm-ID: 241521 Cd Length: 133 Bit Score: 52.25 E-value: 8.25e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  546 DTKVIKEGWLTKRSRNRKDPKKEaNYRDRYVRMTTECLSYYITNKANAVPkdSMKLKDVTIVEAVTDGTFgERKYFFQVG 625
Cdd:cd13370    13 ESVHLKEGEMHKRAQGRTRIGKK-NFKKRWFCLTSRELTYHKQKGKEAIF--TIPVKNILAVEKLEESAF-NKKNMFQVI 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 196014388  626 SKGDLLYAHAMNPTDRDEWVLALrqcCQRLKLNMDR--RYHPGAY 668
Cdd:cd13370    89 HSEKPLYVQANNCVEANEWIEVL---SRVSRCNQKRlsFYHPSAY 130

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or 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.

Pssm-ID: 270175 Cd Length: 138 Bit Score: 50.63 E-value: 3.44e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  696 STVVKKGWVVKRSRGRGKSKNAANYRERFVVLTEEFLSYYGNEAGEYKDCINMKHVSIVEPVNDGTLERDFVFQV----- 770
Cdd:cd13369    13 SVTVKEGYLHKRKAEGVGLVTRFTFKKRYFWLSSETLSYSKSPDWQVRSSIPVQRICAVERVDENAFQQPNVMQVvtqdg 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 196014388  771 GSKGDILYICAPNEEEREDWIVALRFVTqqLHN-KMEDRFHPGGF 814
Cdd:cd13369    93 EGQVHTTYIQCKNVNELNQWLSALRKVS--LSNeRMLPACHPGAF 135

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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.

Pssm-ID: 270083 Cd Length: 114 Bit Score: 48.92 E-value: 7.56e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  399 QKILKEGWLVKRsrnRNAINkdaNYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKYATivesVKDHTF---EKKKNVFQI 475
Cdd:cd13263     1 ERPIKSGWLKKQ---GSIVK---NWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNK----VKEVPFnpeEPGKFLFEI 70

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 196014388  476 ----GQKN-----DFLYLLAQSDSHREDWLNAIRNA 502
Cdd:cd13263    71 ipggGGDRmtsnhDSYLLMANSQAEMEEWVKVIRRV 106

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. 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.

Pssm-ID: 241522 Cd Length: 125 Bit Score: 49.26 E-value: 9.48e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  692 STELSTVVKKGWVVKRSRGRgKSKNAANYRERFVVLTEEFLSYYGNEaGEYKDC-INMKHVSIVEPVNDGTLERDFVFQV 770
Cdd:cd13371    10 SIEQPILLKEGFMIKRAQGR-KRFGMKNFKKRWFRLTNHEFTYHKSK-GDHPLCsIPIENILAVERLEEESFKMKNMFQV 87

                          90       100
                  ....*....|....*....|....*....
gi 196014388  771 GSKGDILYICAPNEEEREDWIVALRFVTQ 799
Cdd:cd13371    88 IQPERALYIQANNCVEAKDWIDILTKVSQ 116

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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.

Pssm-ID: 270095 Cd Length: 106 Bit Score: 48.47 E-value: 1.00e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  403 KEGWLVKRSRnrnaINKDanYRSRYVRLTKDYLIYYLNEKLNNYK---DCIHLKYATIVESVKDHTfeKKKNVFQIGQKN 479
Cdd:cd13276     1 KAGWLEKQGE----FIKT--WRRRWFVLKQGKLFWFKEPDVTPYSkprGVIDLSKCLTVKSAEDAT--NKENAFELSTPE 72

                          90       100
                  ....*....|....*....|....*..
gi 196014388  480 DFLYLLAQSDSHREDWLNAIRNACMRL 506
Cdd:cd13276    73 ETFYFIADNEKEKEEWIGAIGRAIVKH 99

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.

Pssm-ID: 270110 Cd Length: 106 Bit Score: 48.39 E-value: 1.07e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  548 KVIKEGWLTKRSRNRKdpkkeaNYRDRYVRMTTECLSYYiTNKANAVPKDSMKLKDVT----IVEAVTDGTFG----ERK 619
Cdd:cd13298     5 RVLKSGYLLKRSRKTK------NWKKRWVVLRPCQLSYY-KDEKEYKLRRVINLSELLavapLKDKKRKNVFGiytpSKN 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 196014388  620 YFFQvgskgdllyahAMNPTDRDEWVLALRQ 650
Cdd:cd13298    78 LHFR-----------ATSEKDANEWVEALRE 97

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. 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.

Pssm-ID: 241522 Cd Length: 125 Bit Score: 48.88 E-value: 1.34e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  393 PKTARGQKILKEGWLVKRSRNRNAINKDaNYRSRYVRLTKDYLIYYlNEKLNNYKDCIHLKYATIVESVKDHTFeKKKNV 472
Cdd:cd13371     8 HKSIEQPILLKEGFMIKRAQGRKRFGMK-NFKKRWFRLTNHEFTYH-KSKGDHPLCSIPIENILAVERLEEESF-KMKNM 84

                          90       100
                  ....*....|....*....|....*
gi 196014388  473 FQIGQKNDFLYLLAQSDSHREDWLN 497
Cdd:cd13371    85 FQVIQPERALYIQANNCVEAKDWID 109

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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.

Pssm-ID: 241529 Cd Length: 116 Bit Score: 47.63 E-value: 2.95e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  399 QKILKEGWLvKRSRnrnAINKdaNYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKyATIVESVKDHTFEKKKNVFQI--- 475
Cdd:cd13378     1 EGVLKAGWL-KKQR---SIMK--NWQQRWFVLRGDQLFYYKDEEETKPQGCISLQ-GSQVNELPPNPEEPGKHLFEIlpg 73

                          90       100       110
                  ....*....|....*....|....*....|...
gi 196014388  476 GQKN--------DFLYLLAQSDSHREDWLNAIR 500
Cdd:cd13378    74 GAGDrekvpmnhEAFLLMANSQSDMEDWVKAIR 106

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(m) binds inositol tetrakisphosphate (IP4). 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.

Pssm-ID: 241521 Cd Length: 133 Bit Score: 47.24 E-value: 5.16e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  401 ILKEGWLVKRSRNRNAINKDaNYRSRYVRLTKDYLIYYlNEKLNNYKDCIHLKYATIVESVKDHTFeKKKNVFQIGQKND 480
Cdd:cd13370    16 HLKEGEMHKRAQGRTRIGKK-NFKKRWFCLTSRELTYH-KQKGKEAIFTIPVKNILAVEKLEESAF-NKKNMFQVIHSEK 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 196014388  481 FLYLLAQSDSHREDWLNAIRNACMRLRNKMdKKFHPGALTKG 522
Cdd:cd13370    93 PLYVQANNCVEANEWIEVLSRVSRCNQKRL-SFYHPSAYLGG 133

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. 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.

Pssm-ID: 270099 Cd Length: 139 Bit Score: 46.55 E-value: 8.95e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  688 AFDYSTElstVVKKGWVVKRSRGRGKsknaANYRERFVVLTEEFLSYYG-NEAGEY--KDCINM--KHV-----SIVEPV 757
Cdd:cd13281     5 DLDITTK---VQLHGILWKKPFGHQS----AKWSKRFFIIKEGFLLYYSeSEKKDFekTRHFNIhpKGViplggCSIEAV 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 196014388  758 NDGTleRDFVFQVGS---KGDILyICAPNEEEREDWIVALR 795
Cdd:cd13281    78 EDPG--KPYAISISHsdfKGNII-LAADSEFEQEKWLDMLR 115

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first 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.

Pssm-ID: 270113 Cd Length: 108 Bit Score: 45.44 E-value: 1.06e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  547 TKVIKEGWLTKRSRNRKdpkkeaNYRDRYVRMTTECLSYYiTNKANAVPKDSMKLKDVTIVEAVTDgtFGERKYFFQVGS 626
Cdd:cd13301     1 PGIIKEGYLVKKGHVVN------NWKARWFVLKEDGLEYY-KKKTDSSPKGMIPLKGCTITSPCLE--YGKRPLVFKLTT 71

                          90       100       110
                  ....*....|....*....|....*....|....
gi 196014388  627 -KGDLLYAHAMNPTDRDEWVLALR---QCCQRLK 656
Cdd:cd13301    72 aKGQEHFFQACSREERDAWAKDITkaiTCLEGGK 105

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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.

Pssm-ID: 270096 Cd Length: 111 Bit Score: 45.35 E-value: 1.39e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  402 LKEGWLVKRsrNRNAINKDANYRSRYVRLTKDYLIYYlNEKLNNYKDCIHLKYATI--VESVKDHTFekkknvfqiGQKN 479
Cdd:cd13277     4 VKEGYLLKR--RKKTLGSTGGWKLRYGVLDGNILELY-ESRGGQLLESIKLRNAQIerQPNLPDDKY---------GTRH 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 196014388  480 DFL---------------YLLAQSDSHREDWLNAIRNACM 504
Cdd:cd13277    72 GFLinehkksglssttkyYLCAETDKERDEWVSALSEYID 111

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.

Pssm-ID: 459937 Cd Length: 30 Bit Score: 42.90 E-value: 1.57e-05

                           10        20
                   ....*....|....*....|....*..
gi 196014388   662 RYHPGAYTD-KWSCCQAVDLSQNGCQH 687
Cdd:pfam00779    1 KYHPGAFVDgKWLCCKQTDKNAPGCSP 27

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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.

Pssm-ID: 270078 Cd Length: 123 Bit Score: 45.39 E-value: 1.98e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  419 KDANYRSRYVRLTKDYLIYYlneKLNNYKDCIHLKYATIVE--SVKDHTFEKKKNVFQIGQKNDF---LYLLAQSDSHRE 493
Cdd:cd13258    32 KSEVFKERWFKLKGNLLFYF---RTNEFGDCSEPIGAIVLEncRVQMEEITEKPFAFSIVFNDEPekkYIFSCRSEEQCE 108

                          90
                  ....*....|....*
gi 196014388  494 DWLNAIRNA---CMR 505
Cdd:cd13258   109 QWIEALRQAsyeYLR 123

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. 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.

Pssm-ID: 241281 Cd Length: 114 Bit Score: 43.85 E-value: 5.68e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  699 VKKGWVVKRSrgrGKSKNAaNYRERFVVLTEE-FLSYYGNeAGEYKDCINMKHVSIVE----------PVNDGTLERDFV 767
Cdd:cd01250     5 IKQGYLYKRS---SKSLNK-EWKKKYVTLCDDgRLTYHPS-LHDYMENVHGKEIDLLRttvkvpgkrpPRASSKSAFEFI 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 196014388  768 FqVGSKGDILYICAPNEEEREDWIVAlrfVTQQLHN 803
Cdd:cd01250    80 I-VSLDGKQWHFEAASSEERDEWVQA---IEQQILA 111

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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.

Pssm-ID: 270096 Cd Length: 111 Bit Score: 43.43 E-value: 5.78e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  699 VKKGWVVKRsrGRGKSKNAANYRERFVVLTEEFLSYYGNEAGEYKDCINMKHVSI--VEPVND---GTlERDFVFQVGSK 773
Cdd:cd13277     4 VKEGYLLKR--RKKTLGSTGGWKLRYGVLDGNILELYESRGGQLLESIKLRNAQIerQPNLPDdkyGT-RHGFLINEHKK 80

                          90       100
                  ....*....|....*....|....*.
gi 196014388  774 GDIL-----YICAPNEEEREDWIVAL 794
Cdd:cd13277    81 SGLSsttkyYLCAETDKERDEWVSAL 106

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first 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.

Pssm-ID: 270113 Cd Length: 108 Bit Score: 43.52 E-value: 6.67e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  696 STVVKKGWVVKRsrgrGKSKNaaNYRERFVVLTEEFLSYY-GNEAGEYKDCINMKHVSIVEPVNDGTlERDFVFQVGS-K 773
Cdd:cd13301     1 PGIIKEGYLVKK----GHVVN--NWKARWFVLKEDGLEYYkKKTDSSPKGMIPLKGCTITSPCLEYG-KRPLVFKLTTaK 73

                          90       100       110
                  ....*....|....*....|....*....|....
gi 196014388  774 GDILYICAPNEEEREDWIVALRFVTQQLHNKMED 807
Cdd:cd13301    74 GQEHFFQACSREERDAWAKDITKAITCLEGGKRF 107

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. 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.

Pssm-ID: 270114 Cd Length: 109 Bit Score: 42.88 E-value: 1.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  400 KILKEGWLVKRSRNRNainkdaNYRSRYVRLTKD--YLIYYLNEKLNNYKDCIHLKyATIVESVKDHTFEKKK----NVF 473
Cdd:cd13302     6 IIVKQGCLLKQGHRRK------NWKVRKFVLRDDpaYLHYYDPAKGEDPLGAIHLR-GCVVTAVEDNSNPRKGsvegNLF 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 196014388  474 QIGQKNDFLYLL-AQSDSHREDWLNAIRNA 502
Cdd:cd13302    79 EIITADEVHYYLqAATPAERTEWIKAIQMA 108

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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.

Pssm-ID: 270073 Cd Length: 94 Bit Score: 41.99 E-value: 1.37e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  699 VKKGWVVKRSrGRGKSKNaanYRERFVVLTEEFLSYYGNEAGEY-KDCINMKHVSIVEPVNDG-----TLERDFVFQvgs 772
Cdd:cd13253     1 IKSGYLDKQG-GQGNNKG---FQKRWVVFDGLSLRYFDSEKDAYsKRIIPLSAISTVRAVGDNkfelvTTNRTFVFR--- 73

                          90       100
                  ....*....|....*....|..
gi 196014388  773 kgdilyicAPNEEEREDWIVAL 794
Cdd:cd13253    74 --------AESDDERNLWCSTL 87

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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.

Pssm-ID: 270092 Cd Length: 110 Bit Score: 41.90 E-value: 2.47e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  691 YSTELSTVVKKGWVVKRSRGRGksknaaNYRERFVVLTEEFLSYYGNEAG-EYKDCINMKHVSIVE--PVNDGTLERdfv 767
Cdd:cd13273     1 YDELILDVIKKGYLWKKGHLLP------TWTERWFVLKPNSLSYYKSEDLkEKKGEIALDSNCCVEslPDREGKKCR--- 71

                          90       100
                  ....*....|....*....|....*...
gi 196014388  768 FQVGSKGDILYICAPNEEEREDWIVALR 795
Cdd:cd13273    72 FLVKTPDKTYELSASDHKTRQEWIAAIQ 99

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and 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). TAPP1 and TAPP2 contain 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. 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.

Pssm-ID: 270090 Cd Length: 114 Bit Score: 41.96 E-value: 2.59e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  696 STVVKKGWVVKRSRGRgksknaANYRERFVVLTEEFLSYYGNEAG-EYKDCINMKHVSIV-EPVNDGTLERDFVFQVGSK 773
Cdd:cd13271     6 RNVIKSGYCVKQGAVR------KNWKRRFFILDDNTISYYKSETDkEPLRTIPLREVLKVhECLVKSLLMRDNLFEIITT 79

                          90       100
                  ....*....|....*....|
gi 196014388  774 GDILYICAPNEEEREDWIVA 793
Cdd:cd13271    80 SRTFYIQADSPEEMHSWIKA 99

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.

Pssm-ID: 269977 [Multi-domain] Cd Length: 96 Bit Score: 40.77 E-value: 3.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  700 KKGWVVKRsrgrGKSKNaaNYRERFVVLTEEFLSYYgNEAGEYK--DCINMKHVSIVEPvnDGTLERDFVFQVGSKGDIL 777
Cdd:cd10573     5 KEGYLTKL----GGIVK--NWKTRWFVLRRNELKYF-KTRGDTKpiRVLDLRECSSVQR--DYSQGKVNCFCLVFPERTF 75

                          90
                  ....*....|....*...
gi 196014388  778 YICAPNEEEREDWIVALR 795
Cdd:cd10573    76 YMYANTEEEADEWVKLLK 93

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.

Pssm-ID: 270075 Cd Length: 110 Bit Score: 41.24 E-value: 4.16e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  401 ILKEGWLVKRSRNRNAinkdanYRSRYVRLTKDYLIYYLNEKlnNYKdCIHLKYATIVESVKDHTFEKKKNVFQIGQKND 480
Cdd:cd13255     6 VLKAGYLEKKGERRKT------WKKRWFVLRPTKLAYYKNDK--EYR-LLRLIDLTDIHTCTEVQLKKHDNTFGIVTPAR 76

                          90       100
                  ....*....|....*....|....*..
gi 196014388  481 FLYLLAQSDSHREDWLNAIRNACMRLR 507
Cdd:cd13255    77 TFYVQADSKAEMESWISAINLARQALR 103

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. 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.

Pssm-ID: 241522 Cd Length: 125 Bit Score: 41.56 E-value: 4.27e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  549 VIKEGWLTKRSRNRKDPKKEaNYRDRYVRMTTECLSYYITNKANavPKDSMKLKDVTIVEAVTDGTFgERKYFFQVGSKG 628
Cdd:cd13371    16 LLKEGFMIKRAQGRKRFGMK-NFKKRWFRLTNHEFTYHKSKGDH--PLCSIPIENILAVERLEEESF-KMKNMFQVIQPE 91

                          90       100
                  ....*....|....*....|....*
gi 196014388  629 DLLYAHAMNPTDRDEWVLALRQCCQ 653
Cdd:cd13371    92 RALYIQANNCVEAKDWIDILTKVSQ 116

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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.

Pssm-ID: 270073 Cd Length: 94 Bit Score: 40.45 E-value: 4.70e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  402 LKEGWLVKRSRNRNainkDANYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKYATIVESVKDHTFEKKKN--VFQigqkn 479
Cdd:cd13253     1 IKSGYLDKQGGQGN----NKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTnrTFV----- 71

                          90       100
                  ....*....|....*....|...
gi 196014388  480 dflyLLAQSDSHREDWLNAIRNA 502
Cdd:cd13253    72 ----FRAESDDERNLWCSTLQAA 90

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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.

Pssm-ID: 270073 Cd Length: 94 Bit Score: 40.45 E-value: 4.93e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  550 IKEGWLTKRSRNRKDpkkeANYRDRYVRMTTECLSYYiTNKANAVPKDSMKLKDVTIVEAVTDGTF----GERKYFFQvg 625
Cdd:cd13253     1 IKSGYLDKQGGQGNN----KGFQKRWVVFDGLSLRYF-DSEKDAYSKRIIPLSAISTVRAVGDNKFelvtTNRTFVFR-- 73

                          90       100
                  ....*....|....*....|....*.
gi 196014388  626 skgdllyahAMNPTDRDEWVLALRQC 651
Cdd:cd13253    74 ---------AESDDERNLWCSTLQAA 90

Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is proposed to function in sterol transport and regulation of nuclear fusion during mating and of pseudohyphal growth as well as sphingolipid metabolism. Osh3 contains a N-GOLD (Golgi dynamics) domain, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. GOLD domains are thought to mediate protein-protein interactions, but their role in ORPs are unknown. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 241443 Cd Length: 90 Bit Score: 40.32 E-value: 5.57e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  702 GWVVKRSRGRGKSknaanYRERFVVLTEEF--LSYYGNEAGEYKDCINMKHVSIVepvndgTLERDFVFQVGSKGDILYI 779
Cdd:cd13289     4 GWLLKKRRKKMQG-----FARRYFVLNFKYgtLSYYFNPNSPVRGQIPLRLASIS------ASPRRRTIHIDSGSEVWHL 72

                          90
                  ....*....|....*...
gi 196014388  780 CAPNEEEREDWIVALRFV 797
Cdd:cd13289    73 KALNDEDFQAWMKALRKF 90

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or 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.

Pssm-ID: 270175 Cd Length: 138 Bit Score: 41.39 E-value: 6.32e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  549 VIKEGWLTKRSRNRKDPKKEANYRDRYVRMTTECLSYyiTNKANAVPKDSMKLKDVTIVEAVTDGTFgERKYFFQV---- 624
Cdd:cd13369    15 TVKEGYLHKRKAEGVGLVTRFTFKKRYFWLSSETLSY--SKSPDWQVRSSIPVQRICAVERVDENAF-QQPNVMQVvtqd 91

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 196014388  625 -GSKGDLLYAHAMNPTDRDEWVLALRQ---CCQRlklnMDRRYHPGAY 668
Cdd:cd13369    92 gEGQVHTTYIQCKNVNELNQWLSALRKvslSNER----MLPACHPGAF 135

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. 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.

Pssm-ID: 270114 Cd Length: 109 Bit Score: 40.57 E-value: 7.00e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  697 TVVKKGWVVKRSRGRgksknaANYRERFVVLTEE--FLSYYGNEAGE-------YKDCInmkhVSIVEPVNDGTL--ERD 765
Cdd:cd13302     6 IIVKQGCLLKQGHRR------KNWKVRKFVLRDDpaYLHYYDPAKGEdplgaihLRGCV----VTAVEDNSNPRKgsVEG 75

                          90       100       110
                  ....*....|....*....|....*....|....
gi 196014388  766 FVFQVGSKGDI-LYICAPNEEEREDWIVALRFVT 798
Cdd:cd13302    76 NLFEIITADEVhYYLQAATPAERTEWIKAIQMAS 109

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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.

Pssm-ID: 270109 Cd Length: 126 Bit Score: 40.50 E-value: 8.30e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  698 VVKKGWVVKRSRGRGKSKNAANyRERFVVLTEEFLSYYGNEAGEYKD---------CinmkhvSIVEPVNDGTLER-DFV 767
Cdd:cd13297    13 VIERGWLYKEGGKGGARGNLTK-KKRWFVLTGNSLDYYKSSEKNSLKlgtlvlnslC------SVVPPDEKMAKETgYWT 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 196014388  768 FQVGSKGDILYICAPNEEEREDWIVALRFVT 798
Cdd:cd13297    86 FTVHGRKHSFRLYTKLQEEAMRWVNAIQDVI 116

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.

Pssm-ID: 269954 Cd Length: 119 Bit Score: 40.38 E-value: 8.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  700 KKGWVVKRSrGRGKSknaanYRERFVVLTEEFLSYYGN-EAGEYKDCINMKHVSIVEpVNDGTleRDFVFQVGSKG---- 774
Cdd:cd01252     5 REGWLLKLG-GRVKS-----WKRRWFILTDNCLYYFEYtTDKEPRGIIPLENLSVRE-VEDKK--KPFCFELYSPSngqv 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 196014388  775 -----------------DILYICAPNEEEREDWIVALRFVTQQ 800
Cdd:cd01252    76 ikacktdsdgkvvegnhTVYRISAASEEERDEWIKSIKASISR 118

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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.

Pssm-ID: 270078 Cd Length: 123 Bit Score: 40.39 E-value: 8.96e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  707 RSRGRGKSKNAANYRERFVVLTEEFLSYYG-NEAGEYKD---CINMKHVSIV-EPVNDGTLERDFVFQVGSKGDILYICA 781
Cdd:cd13258    23 AERQMGGPKKSEVFKERWFKLKGNLLFYFRtNEFGDCSEpigAIVLENCRVQmEEITEKPFAFSIVFNDEPEKKYIFSCR 102

                          90
                  ....*....|....
gi 196014388  782 pNEEEREDWIVALR 795
Cdd:cd13258   103 -SEEQCEQWIEALR 115

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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.

Pssm-ID: 275424 Cd Length: 124 Bit Score: 39.56 E-value: 1.83e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  398 GQKILKEGWLVKRSRnrnainKDAnyRSRYVRLTKDYLIYYLNEKLNNYKDCIH---LKYATivesVKDHTFEKKKNVFQ 474
Cdd:cd13389    11 GRKLIKEGELMKVSR------KEM--QPRYFFLFNDCLLYTTPVQSSGMLKLNNelpLSGMK----VKLPEDEEYSNEFQ 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 196014388  475 I-GQKNDFLyLLAQSDSHREDWLNAIRNACMRLRNK 509
Cdd:cd13389    79 IiSTKRSFT-LIASSEEERDEWVKALSRAIEEHTKK 113

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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.

Pssm-ID: 270080 Cd Length: 103 Bit Score: 38.86 E-value: 2.54e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  401 ILKEGWLVKRSrnrnaiNKDANYRSRYVRL--TKDYLIYYLNEKLNNYKDCIHLKYATIVeSVKDHTFEkKKNVFQIGQK 478
Cdd:cd13260     3 IDKKGYLLKKG------GKNKKWKNLYFVLegKEQHLYFFDNEKRTKPKGLIDLSYCSLY-PVHDSLFG-RPNCFQIVVR 74

                          90       100
                  ....*....|....*....|....*....
gi 196014388  479 NDFL----YLLAQSDSHREDWLNAIRNAC 503
Cdd:cd13260    75 ALNEstitYLCADTAELAQEWMRALRAFC 103

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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.

Pssm-ID: 270095 Cd Length: 106 Bit Score: 38.45 E-value: 3.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  551 KEGWLTKRSRNRKDpkkeanYRDRYVRMTTECLSYYITNKA--NAVPKDSMKLKDVTIVEAVTDGTfgERKYFFQVGSKG 628
Cdd:cd13276     1 KAGWLEKQGEFIKT------WRRRWFVLKQGKLFWFKEPDVtpYSKPRGVIDLSKCLTVKSAEDAT--NKENAFELSTPE 72

                          90       100
                  ....*....|....*....|
gi 196014388  629 DLLYAHAMNPTDRDEWVLAL 648
Cdd:cd13276    73 ETFYFIADNEKEKEEWIGAI 92

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.

Pssm-ID: 128417 Cd Length: 36 Bit Score: 36.21 E-value: 3.31e-03

                            10        20
                    ....*....|....*....|....*
gi 196014388    663 YHPGAYTD-KWSCCQAVDLSQNGCQ 686
Cdd:smart00107    8 YHPSFWVDgKWLCCQQSEKNAPGCT 32

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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.

Pssm-ID: 270092 Cd Length: 110 Bit Score: 38.43 E-value: 3.60e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  401 ILKEGWLVKRSRNRnainkdANYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKYATIVESVKDHtfEKKKNVFQIGQKND 480
Cdd:cd13273     8 VIKKGYLWKKGHLL------PTWTERWFVLKPNSLSYYKSEDLKEKKGEIALDSNCCVESLPDR--EGKKCRFLVKTPDK 79

                          90       100
                  ....*....|....*....|..
gi 196014388  481 FLYLLAQSDSHREDWLNAIRNA 502
Cdd:cd13273    80 TYELSASDHKTRQEWIAAIQTA 101

Pleckstrin homology domain-containing family O Pleckstrin homology domain; The PLEKHO family members are PLEKHO1 (also called CKIP-1/Casein kinase 2-interacting protein 1/CK2-interacting protein 1) and PLEKHO2 (PLEKHQ1/PH domain-containing family Q member 1). They both contain a single PH domain. PLEKHO1 acts as a scaffold protein that functions in plasma membrane recruitment, transcriptional activity modulation, and posttranscriptional modification regulation. As an adaptor protein it is involved in signaling pathways, apoptosis, differentiation, cytoskeleton, and bone formation. Not much is know about PLEKHO2. 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.

Pssm-ID: 270127 Cd Length: 102 Bit Score: 38.26 E-value: 3.92e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  403 KEGWLVKRSRNRNAINKDanyrsRYVRLTKDYLIYYLNE----KLNNYKDCIHLKYAtivesvKDHTFEKKKNVF----- 473
Cdd:cd13317     7 KAGWIKKSSGGLLGIWKD-----RYVVLKGTQLLVYEKEekvfDLEDYELCEYLRCS------KSRASKKNKSRFtlirs 75

                          90       100
                  ....*....|....*....|....*..
gi 196014388  474 -QIGQKNDFLYLLAQSDSHREDWLNAI 499
Cdd:cd13317    76 kQPGNKAPDLKFQAVSPEEKESWINAL 102

Protein kinase D (PKD/PKCmu) pleckstrin homology (PH) domain; Protein Kinase C family is composed of three members, PKD1 (PKCmu), PKD2 and PKD3 (PKCnu). Like the C-type protein kinases (PKCs), PKDs are activated by diacylglycerol (DAG). They are involved in vesicular transport, cell proliferation, survival, migration and immune responses. PKD consists of tandem C1 domains, followed by a PH domain and a kinase domain. While the PKD PH domain has not been shown to bind phosphorylated inositol lipids and is not required for membrane translocation, it is required for nuclear export. 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.

Pssm-ID: 269945 Cd Length: 127 Bit Score: 38.52 E-value: 4.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  394 KTARGQKILKEGWLVKRSrnrnaiNKDANYRSRYVRLTKDYLIYYLNEKLNNYKDCIHLKYATIVESVK---------DH 464
Cdd:cd01239     1 TKRRSSKVLKEGWMVHYT------NKDPLRKRHYWRLDTKCITLFQNETTSRYYKEIPLSEILSVEPADnpslppgtpPH 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 196014388  465 TFE--KKKNVFQIGQKNDFLYLLAQSDSHRE---------DWLNAIRNACM 504
Cdd:cd01239    75 CFEirTANLVYYVGEDPDGESGPPKLIPPPEsgsgtesarMWETAIRQALM 125

Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is proposed to function in sterol transport and regulation of nuclear fusion during mating and of pseudohyphal growth as well as sphingolipid metabolism. Osh3 contains a N-GOLD (Golgi dynamics) domain, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. GOLD domains are thought to mediate protein-protein interactions, but their role in ORPs are unknown. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 241443 Cd Length: 90 Bit Score: 37.62 E-value: 4.21e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  550 IKEGWLTKRSRnrkdpKKEANYRDRYVRMT--TECLSYYITNKANAvpKDSMKLKDVTIVEAVTDGTFgerkyffQVGSK 627
Cdd:cd13289     1 YLEGWLLKKRR-----KKMQGFARRYFVLNfkYGTLSYYFNPNSPV--RGQIPLRLASISASPRRRTI-------HIDSG 66

                          90       100
                  ....*....|....*....|....
gi 196014388  628 GDLLYAHAMNPTDRDEWVLALRQC 651
Cdd:cd13289    67 SEVWHLKALNDEDFQAWMKALRKF 90

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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.

Pssm-ID: 270053 Cd Length: 110 Bit Score: 38.03 E-value: 4.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  422 NYRSRYVRLTKDYLIYYLNEK-----LNNY---KDCIHLKYATIvESVKDHTfeKKKNVFQIGQKNDFLYLLaQSDSHRE 493
Cdd:cd13233    21 NWSTSWVVLTSSHLLFYKDAKsaaksGNPYskpESSVDLRGASI-EWAKEKS--SRKNVFQISTVTGTEFLL-QSDNDTE 96

                          90
                  ....*....|.
gi 196014388  494 --DWLNAIRNA 502
Cdd:cd13233    97 irEWFDAIKAV 107

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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.

Pssm-ID: 270070 Cd Length: 98 Bit Score: 37.58 E-value: 6.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  700 KKGWVVKRSRGRGKSknaanYRERFVVLTEEFLSYYGNEAGEykdciNMKHV------SIVEPVNDgtLERDFVFQVGSK 773
Cdd:cd13250     1 KEGYLFKRSSNAFKT-----WKRRWFSLQNGQLYYQKRDKKD-----EPTVMvedlrlCTVKPTED--SDRRFCFEVISP 68

                          90       100       110
                  ....*....|....*....|....*....|
gi 196014388  774 GDILYICAPNEEEREDWIVALRFVTQQLHN 803
Cdd:cd13250    69 TKSYMLQAESEEDRQAWIQAIQSAIASALN 98

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. 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.

Pssm-ID: 241281 Cd Length: 114 Bit Score: 37.69 E-value: 6.28e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  401 ILKEGWLVKRSrnRNAINKDanYRSRYVRLTKD-YLIYYLNekLNNYKDCIH-----LKYATIVESVKDHTFEKKKNVFQ 474
Cdd:cd01250     4 PIKQGYLYKRS--SKSLNKE--WKKKYVTLCDDgRLTYHPS--LHDYMENVHgkeidLLRTTVKVPGKRPPRASSKSAFE 77

                          90       100
                  ....*....|....*....|....*...
gi 196014388  475 ---IGQKNDFLYLLAQSDSHREDWLNAI 499
Cdd:cd01250    78 fiiVSLDGKQWHFEAASSEERDEWVQAI 105

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.

Pssm-ID: 269977 [Multi-domain] Cd Length: 96 Bit Score: 37.30 E-value: 7.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  551 KEGWLTKRSRNRKdpkkeaNYRDRYVRMTTECLSYYiTNKANAVPKDSMKLKDVTIVEAvtDGTFGeRKYFFQVGSKGDL 630
Cdd:cd10573     5 KEGYLTKLGGIVK------NWKTRWFVLRRNELKYF-KTRGDTKPIRVLDLRECSSVQR--DYSQG-KVNCFCLVFPERT 74

                          90
                  ....*....|....*....
gi 196014388  631 LYAHAMNPTDRDEWVLALR 649
Cdd:cd10573    75 FYMYANTEEEADEWVKLLK 93

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.

Pssm-ID: 270075 Cd Length: 110 Bit Score: 37.39 E-value: 7.62e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  545 LDTKVIKEGWLTKRSRNRKDPKKeanyrdRYVRMTTECLSYYITNKANAVpkdsMKLKDVTIVEAVT-------DGTFG- 616
Cdd:cd13255     2 ISEAVLKAGYLEKKGERRKTWKK------RWFVLRPTKLAYYKNDKEYRL----LRLIDLTDIHTCTevqlkkhDNTFGi 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 196014388  617 ---ERKYFFQVGSKgdllyahamnpTDRDEWVLALRQCCQRLK 656
Cdd:cd13255    72 vtpARTFYVQADSK-----------AEMESWISAINLARQALR 103

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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.

Pssm-ID: 270118 Cd Length: 113 Bit Score: 37.38 E-value: 8.30e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  544 TLDTKVIKEGWLTKRSrnrKDPKKEANYRDRYVRMTTECLsYYITNKANAVPKDSMKLKDVTIV---EAVTDGTFG---- 616
Cdd:cd13308     4 TLPRDVIHSGTLTKKG---GSQKTLQNWQLRYVIIHQGCV-YYYKNDQSAKPKGVFSLNGYNRRaaeERTSKLKFVfkii 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 196014388  617 -----ERKYFFQvgskgdllyahAMNPTDRDEWVLALR 649
Cdd:cd13308    80 hlspdHRTWYFA-----------AKSEDEMSEWMEYIR 106

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) domain; There are 2 types of ORPs found in Cryptosporidium: CpORP1 and CpORP2. Cryptosporium differs from other apicomplexans like Plasmodium, Toxoplasma, and Eimeria which possess only a single long-type ORP consisting of an N-terminal PH domain followed by a C-terminal ligand binding (LB) domain. CpORP2 is like this, but CpORP1 differs and has a truncated N-terminus resulting in only having a LB domain present. The exact functions of these proteins are largely unknown though CpORP1 is thought to be involved in lipid transport across the parasitophorous vacuole membrane. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 241447 Cd Length: 88 Bit Score: 36.54 E-value: 8.97e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 196014388  404 EGWLVKRSrnrNAINKdanYRSRYVRLTKDYLIYYLNEKLNNyKDCIHLKYATIVESVKDHTfekkKNVFQIGQKNdfLY 483
Cdd:cd13293     2 EGYLKKWT---NIFNS---WKPRYFILYPGILCYSKQKGGPK-KGTIHLKICDIRLVPDDPL----RIIINTGTNQ--LH 68

                          90
                  ....*....|....*....
gi 196014388  484 LLAQSDSHREDWLNAIRNA 502
Cdd:cd13293    69 LRASSVEEKLKWYNALKYA 87