Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 655 AINGYVGNINELGKMVLQGSFNVWLGHRKGATKmkDFARFKPMQRHLFLYEKAVMFCKRRFESGEGadryPSYSFKHCLK 734
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTK--KLARFKPMQRHIFLYEKAVLFCKKRGENGEA----PSYSYKNSLN 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1039795992 735 MEDVGITEHVKGDNRKFEIRYSEKEEIYIVQAPNVDVKMLWLKEIRKILVQQ 786
Cdd:cd01227    75 TTAVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039795992   20 FPGSLHLVLVLRPTSFLqRTFTDIGFRFSQEDFMLKLPVVMLSSVSDLLTYIDDKQLTPELGGTLQ 85
Cdd:smart00516  94 YPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 655 AINGYVGNINELGKMVLQGSFNVWLGHRKGATKmkDFARFKPMQRHLFLYEKAVMFCKRRFESGEGadryPSYSFKHCLK 734
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTK--KLARFKPMQRHIFLYEKAVLFCKKRGENGEA----PSYSYKNSLN 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1039795992 735 MEDVGITEHVKGDNRKFEIRYSEKEEIYIVQAPNVDVKMLWLKEIRKILVQQ 786
Cdd:cd01227    75 TTAVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992  474 VLNELIQTERAYVRELFTVLLGYRSEMDNPQMFdlmppLLRNKKDVLFGNMAEIYEFHNnIFMSRLEDCS----DAPERV 549
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFHR-DFLDELEERIeewdDSVERI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992  550 GPCFLERKDDFQMYAKYCQNKPRSELIWRKYSEC----AFFQECQRKLKH-RLGLDSYLLKPVQRITKYQLLLKELLKYS 624
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNprfqKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHT 154

                          170       180
                   ....*....|....*....|....*.
gi 1039795992  625 KEG-EGTTKLKEALDSMLELLKSVND 649
Cdd:smart00325 155 PEDhEDREDLKKALKAIKELANQVNE 180

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039795992   20 FPGSLHLVLVLRPTSFLqRTFTDIGFRFSQEDFMLKLPVVMLSSVSDLLTYIDDKQLTPELGGTLQ 85
Cdd:smart00516  94 YPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992  686 TKMKDFARFKPMQRHLFLYEKAVMFCKRRfesgegaDRYPSYSFKHCLKMEDVGITEHVKGDNRK----FEIRYSEKEEI 761
Cdd:smart00233   8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSK-------KDKKSYKPKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDRKTL 80

                           90       100
                   ....*....|....*....|..
gi 1039795992  762 YIvQAPNVDVKMLWLKEIRKIL 783
Cdd:smart00233  81 LL-QAESEEEREKWVEALRKAI 101

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 219 QLWKFEQDFQEELLTKARIV---ILRGHKLASNHHYA-------LDLICQRCNELRYLSDilvneirTKRVQLSRTFKVH 288
Cdd:cd00176    37 ALLKKHEALEAELAAHEERVealNELGEQLIEEGHPDaeeiqerLEELNQRWEELRELAE-------ERRQRLEEALDLQ 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 289 RLLQQARQC---CDQGECLLASQGMDKfqTKEDAQKALQDVDNFlQMAMPFINYDIESLQYEFDVLLSPELKAQMQNIQL 365
Cdd:cd00176   110 QFFRDADDLeqwLEEKEAALASEDLGK--DLESVEELLKKHKEL-EEELEAHEPRLKSLNELAEELLEEGHPDADEEIEE 186

                         170
                  ....*....|.
gi 1039795992 366 KLENIRSAFQN 376
Cdd:cd00176   187 KLEELNERWEE 197

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039795992  20 FPGSLHLVLVLRPTSFLqRTFTDIGFRFSQEDFMLKLpVVMLSSVSDLLTYIDDKQLTPELGGT 83
Cdd:cd00170    95 YPERLKKIYIVNAPWIF-SALWKIVKPFLSEKTRKKI-VFLGSDLEELLEYIDPDQLPKELGGT 156

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 655 AINGYVGNINELGKMVLQGSFNVWLGHRKGATKmkDFARFKPMQRHLFLYEKAVMFCKRRFESGEGadryPSYSFKHCLK 734
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTK--KLARFKPMQRHIFLYEKAVLFCKKRGENGEA----PSYSYKNSLN 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1039795992 735 MEDVGITEHVKGDNRKFEIRYSEKEEIYIVQAPNVDVKMLWLKEIRKILVQQ 786
Cdd:cd01227    75 TTAVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992  474 VLNELIQTERAYVRELFTVLLGYRSEMDNPQMFdlmppLLRNKKDVLFGNMAEIYEFHNnIFMSRLEDCS----DAPERV 549
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFHR-DFLDELEERIeewdDSVERI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992  550 GPCFLERKDDFQMYAKYCQNKPRSELIWRKYSEC----AFFQECQRKLKH-RLGLDSYLLKPVQRITKYQLLLKELLKYS 624
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNprfqKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHT 154

                          170       180
                   ....*....|....*....|....*.
gi 1039795992  625 KEG-EGTTKLKEALDSMLELLKSVND 649
Cdd:smart00325 155 PEDhEDREDLKKALKAIKELANQVNE 180

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 648 NDSMHQTAINGYVGNINELGKMVLQGSFNVWLGHRKGatkmkdfarfkpmQRHLFLYEKAVMFCK-RRFESGEGAdryps 726
Cdd:cd13242     8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKC-------------LRHVFLFEDLILFSKpKKTPGGKDV----- 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039795992 727 YSFKHCLKMEDVGITEHVKGDNRKFEI--RYSEKEEIYIVQAPNVDVKMLWLKEIRKILVQQ 786
Cdd:cd13242    70 YIYKHSIKTSDIGLTENVGDSGLKFEIwfRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQ 131

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 656 INGYVGNINELGKMVLQGSFNVWlghrKGATKMKDFARfkPMQRHLFLYEKAVMFCKRRFESGEGADrypSYSFKHCLKM 735
Cdd:cd13239     2 IENYPAPLQALGEPIRQGHFTVW----EEAPEVKTSSR--GHHRHVFLFKNCVVICKPKRDSRTDTV---TYVFKNKMKL 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039795992 736 EDVGITEHVKGDNRKFEIRYSEKEEI--YIVQAPNVDVKMLWLKEIRKIlvQQK 787
Cdd:cd13239    73 SDIDVKDTVEGDDRSFGLWHEHRGSVrkYTLQARSAIIKSSWLKDLRDL--QQR 124

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039795992   20 FPGSLHLVLVLRPTSFLqRTFTDIGFRFSQEDFMLKLPVVMLSSVSDLLTYIDDKQLTPELGGTLQ 85
Cdd:smart00516  94 YPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992  686 TKMKDFARFKPMQRHLFLYEKAVMFCKRRfesgegaDRYPSYSFKHCLKMEDVGITEHVKGDNRK----FEIRYSEKEEI 761
Cdd:smart00233   8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSK-------KDKKSYKPKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDRKTL 80

                           90       100
                   ....*....|....*....|..
gi 1039795992  762 YIvQAPNVDVKMLWLKEIRKIL 783
Cdd:smart00233  81 LL-QAESEEEREKWVEALRKAI 101

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 633 LKEALDSMLELLKSVND-------SMHQTAINGYVGNINEL-----GKMVLQGSFNVwLGHRKgatkmkdfarfkpmQRH 700
Cdd:cd13243     4 VEEALDTMTQVAWHINDmkrkhehAVRVQEIQSLLDGWEGPelttyGDLVLEGTFRM-AGAKN--------------ERL 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 701 LFLYEKAVMFCKRRFESGegadrypsYSFKHCLKMEDVGITEHVKGDNRKFEIR-YSEKEEIYIVQAPNVDVKMLWLKEI 779
Cdd:cd13243    69 LFLFDKMLLITKKREDGI--------LQYKTHIMCSNLMLSESIPKEPLSFQVLpFDNPKLQYTLQAKNQEQKRLWTQEI 140

                  ....
gi 1039795992 780 RKIL 783
Cdd:cd13243   141 KRLI 144

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 219 QLWKFEQDFQEELLTKARIV---ILRGHKLASNHHYA-------LDLICQRCNELRYLSDilvneirTKRVQLSRTFKVH 288
Cdd:cd00176    37 ALLKKHEALEAELAAHEERVealNELGEQLIEEGHPDaeeiqerLEELNQRWEELRELAE-------ERRQRLEEALDLQ 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039795992 289 RLLQQARQC---CDQGECLLASQGMDKfqTKEDAQKALQDVDNFlQMAMPFINYDIESLQYEFDVLLSPELKAQMQNIQL 365
Cdd:cd00176   110 QFFRDADDLeqwLEEKEAALASEDLGK--DLESVEELLKKHKEL-EEELEAHEPRLKSLNELAEELLEEGHPDADEEIEE 186

                         170
                  ....*....|.
gi 1039795992 366 KLENIRSAFQN 376
Cdd:cd00176   187 KLEELNERWEE 197

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039795992  20 FPGSLHLVLVLRPTSFLqRTFTDIGFRFSQEDFMLKLpVVMLSSVSDLLTYIDDKQLTPELGGT 83
Cdd:cd00170    95 YPERLKKIYIVNAPWIF-SALWKIVKPFLSEKTRKKI-VFLGSDLEELLEYIDPDQLPKELGGT 156

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. 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.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. 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 kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

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gi 1039795992 684 GATKMKDFARFKPMQRHLFLYEKAVMFCKRRFESgegadrypSYSFKHCLKMEDVGITEHVKGDNRKFEIRYS------- 756
Cdd:cd01223    23 GELKIKSHEDQKKKDRYAFLFDKVLLICKSLRGD--------QYEYKEIINLSEYRIEDDPSRRTLKRDKRWSyqfllvh 94

                          90       100
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gi 1039795992 757 -EKEEIYIVQAPNVDVKMLWLKEIRK 781
Cdd:cd01223    95 kQGKTAYTLYAKTEELKKKWMEAIEM 120