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 225543507 1242 QEQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEDLLLFSKLKGSEGGSETFVYKQAFKTAD 1321
Cdd:cd13242     1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 225543507 1322 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPETKLKWTSSIAQLLWRQAAHNK 1377
Cdd:cd13242    81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

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 225543507  784 LRQVQQVLQWLSGpGEEQLASFSmPGNSLSVLQETELRFRAFSTEVQERLVQAREALALEEDLTS---------QKVLDI 854
Cdd:cd00176     6 LRDADELEAWLSE-KEELLSSTD-YGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEeghpdaeeiQERLEE 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 225543507  855 FEQR-------LEQAESGLHRALRLQRFFQQAHE---WVDEGSARLA 891
Cdd:cd00176    84 LNQRweelrelAEERRQRLEEALDLQQFFRDADDleqWLEEKEAALA 130

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 225543507 1242 QEQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEDLLLFSKLKGSEGGSETFVYKQAFKTAD 1321
Cdd:cd13242     1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 225543507 1322 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPETKLKWTSSIAQLLWRQAAHNK 1377
Cdd:cd13242    81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507  1088 VSELIACEQEYVTTLN-------EPVPLPGPELTPELR---CTWaaalsvrERLRSFHGTHFLQELQGCAAHPLRIGACF 1157
Cdd:pfam00621    2 IKELLQTERSYVRDLEilvevflPPNSKPLSESEEEIKtifSNI-------EEIYELHRQLLLEELLKEWISIQRIGDIF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507  1158 LRHGDQFNLYAQFVKHRHKLESGLAALT---PSVKGSMESSPCLPRALQQPLE--------QLARYGQLLEELLReAGPE 1226
Cdd:pfam00621   75 LKFAPGFKVYSTYCSNYPKALKLLKKLLkknPKFRAFLEELEANPECRGLDLNsflikpvqRIPRYPLLLKELLK-HTPP 153

                          170
                   ....*....|....*..
gi 225543507  1227 LSSERQALRAAVQLLQE 1243
Cdd:pfam00621  154 DHPDYEDLKKALEAIKE 170

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 225543507   1267 QGQLLHRDPFTvicGRKKCLRHVFLFEDLLLFSKlkgSEGGSETFVYKQAFKTADMGLTENIGDSGL----CFELWFRRR 1342
Cdd:smart00233    4 EGWLYKKSGGG---KKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDPDSSkkphCFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*..
gi 225543507   1343 RAreaYTLQATSPETKLKWTSSIAQLL 1369
Cdd:smart00233   78 KT---LLLQAESEEEREKWVEALRKAI 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 225543507  784 LRQVQQVLQWLSGpGEEQLASFSmPGNSLSVLQETELRFRAFSTEVQERLVQAREALALEEDLTS---------QKVLDI 854
Cdd:cd00176     6 LRDADELEAWLSE-KEELLSSTD-YGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEeghpdaeeiQERLEE 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 225543507  855 FEQR-------LEQAESGLHRALRLQRFFQQAHE---WVDEGSARLA 891
Cdd:cd00176    84 LNQRweelrelAEERRQRLEEALDLQQFFRDADDleqWLEEKEAALA 130

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 225543507 1242 QEQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEDLLLFSKLKGSEGGSETFVYKQAFKTAD 1321
Cdd:cd13242     1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 225543507 1322 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPETKLKWTSSIAQLLWRQAAHNK 1377
Cdd:cd13242    81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. 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 225543507 1267 QGQLLHRDPFTVI----CGRKKCL-RHVFLFEDLLLFSKL--KGSEGGSETFVYKQAFKTADMGLTENIGDSGLCFELWF 1339
Cdd:cd13241    14 QGKLLLQGTLLVSepsaGLLQKGKeRRVFLFEQIIIFSEIlgKKTQFSNPGYIYKNHIKVNKMSLEENVDGDPLRFALKS 93

                          90       100       110
                  ....*....|....*....|....*....|....
gi 225543507 1340 R-RRRAREAYTLQATSPETKLKWTSSIAQLLWRQ 1372
Cdd:cd13241    94 RdPNNPSETFILQAASPEVRQEWVDTINQILDTQ 127

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507 1084 QQRLVSELIACEQEYVTTLN-------EPVPLPGPELTPELRCTWAAALsvrERLRSFHgTHFLQELQGCAA----HPLR 1152
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKllvevflKPLDKELLPLSPEEVELLFGNI---EEIYEFH-RIFLKSLEERVEewdkSGPR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507 1153 IGACFLRHGDQFNLYAQFVKHRH----------KLESGLAALTPSVKGSMESSPcLPRALQQPLEQLARYGQLLEELLRE 1222
Cdd:cd00160    77 IGDVFLKLAPFFKIYSEYCSNHPdalellkklkKFNKFFQEFLEKAESECGRLK-LESLLLKPVQRLTKYPLLLKELLKH 155

                         170       180
                  ....*....|....*....|.
gi 225543507 1223 AgPELSSERQALRAAVQLLQE 1243
Cdd:cd00160   156 T-PDGHEDREDLKKALEAIKE 175

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 225543507   1087 LVSELIACEQEYVTTLN-------EPVPLPGPELTPELRCTWAAALsvrERLRSFHgTHFLQELQGCAAHPL----RIGA 1155
Cdd:smart00325    1 VLKELLQTERNYVRDLKllvevflKPLKKELKLLSPNELETLFGNI---EEIYEFH-RDFLDELEERIEEWDdsveRIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507   1156 CFLRHGDQFNLYAQFVKHRHKLESGLAALTPS------VKGSMESSPC----LPRALQQPLEQLARYGQLLEELLREAgP 1225
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKKNprfqkfLKEIESSPQCrrltLESLLLKPVQRLTKYPLLLKELLKHT-P 155

                           170
                    ....*....|....*...
gi 225543507   1226 ELSSERQALRAAVQLLQE 1243
Cdd:smart00325  156 EDHEDREDLKKALKAIKE 173

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 225543507 1260 CEIDLKEQGQLLHRDPFTVICgrKKCLRHVFLFEDLLLFSKLKGSEGgsetFVYKQAFKTADMGLTENIGDSGLCFE-LW 1338
Cdd:cd13243    42 EGPELTTYGDLVLEGTFRMAG--AKNERLLFLFDKMLLITKKREDGI----LQYKTHIMCSNLMLSESIPKEPLSFQvLP 115

                          90       100       110
                  ....*....|....*....|....*....|.
gi 225543507 1339 FRRRRAReaYTLQATSPETKLKWTSSIAQLL 1369
Cdd:cd13243   116 FDNPKLQ--YTLQAKNQEQKRLWTQEIKRLI 144

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507  1267 QGQLLHRDPFTVIcGRKKclRHVFLFEDLLLFSKlKGSEGGSETFVYKQAFKTADMGLTENIGDSG--LCFELWFRRRRA 1344
Cdd:pfam00169    4 EGWLLKKGGGKKK-SWKK--RYFVLFDGSLLYYK-DDKSGKSKEPKGSISLSGCEVVEVVASDSPKrkFCFELRTGERTG 79

                           90       100
                   ....*....|....*....|.
gi 225543507  1345 REAYTLQATSPETKLKWTSSI 1365
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAI 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543507 1267 QGQLLHRDPFTvICGRKKclRHVFLFEDLLLFSKLKGSeggsetfVYKQAFKTADMGLTENI-----GDSGLCFELWFRR 1341
Cdd:cd00821     2 EGYLLKRGGGG-LKSWKK--RWFVLFEGVLLYYKSKKD-------SSYKPKGSIPLSGILEVeevspKERPHCFELVTPD 71

                          90       100
                  ....*....|....*....|....
gi 225543507 1342 RRAreaYTLQATSPETKLKWTSSI 1365
Cdd:cd00821    72 GRT---YYLQADSEEERQEWLKAL 92

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of vertebrate BCRs. 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
                  ....*....|....*....|....*....|....*....|....
gi 225543507 1266 EQGQLLhRDPFTV--ICGRKKcLRHVFLFEDLLLFSKLKGSEGG 1307
Cdd:cd13367    22 EHRQLL-KDSFMVelVEGARK-LRHVFLFTDLLLCAKLKKQIGG 63

PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 225543507  1287 RHVFLFEDLLLFSKLKGSEGGSETFVYKQAFKTADM 1322
Cdd:pfam16453   33 REVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGM 68