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 50843837 1244 REQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGPEGGSEMFVYKQAFKTAD 1323
Cdd:cd13242    1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 50843837 1324 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPEIKLKWTSSIAQLLWRQAAHNK 1379
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 50843837  786 LRRLQQVLQWLSGpgEEQLASFAMPGDTLSALQETELRFRAFSAEVQER------LAQAREALALEENATSQKV---LDI 856
Cdd:cd00176    6 LRDADELEAWLSE--KEELLSSTDYGDDLESVEALLKKHEALEAELAAHeerveaLNELGEQLIEEGHPDAEEIqerLEE 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837  857 FEQRLEQVESG-------LHRALRLQRFFQQAHE---WVDEGFARLAGAGPGR--EAVLAAL----ALRRAPEPSAGTFQ 920
Cdd:cd00176   84 LNQRWEELRELaeerrqrLEEALDLQQFFRDADDleqWLEEKEAALASEDLGKdlESVEELLkkhkELEEELEAHEPRLK 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 50843837  921 EMRALALDLGSPAALREWGRCQARCQELERRIQQhVGEEASPRG 964
Cdd:cd00176  164 SLNELAEELLEEGHPDADEEIEEKLEELNERWEE-LLELAEERQ 206

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 50843837 1244 REQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGPEGGSEMFVYKQAFKTAD 1323
Cdd:cd13242    1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 50843837 1324 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPEIKLKWTSSIAQLLWRQAAHNK 1379
Cdd:cd13242   81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

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 50843837 1086 QQRLVSELIACEQDYVATL-------SEPVPPPGPELTPELRgtwAAALSARERLRSFHRTHFLRELQGCA---THPLRI 1155
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLkllvevfLKPLDKELLPLSPEEV---ELLFGNIEEIYEFHRIFLKSLEERVEewdKSGPRI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837 1156 GACFLRHGDQFSLYAQYVKHRHK----LENGLAALSPLSKGSMEAGPY-----LPRALQQPLEQLTRYGRLLEELLREAg 1226
Cdd:cd00160   78 GDVFLKLAPFFKIYSEYCSNHPDalelLKKLKKFNKFFQEFLEKAESEcgrlkLESLLLKPVQRLTKYPLLLKELLKHT- 156

                        170
                 ....*....|....*....
gi 50843837 1227 PELSSECRALGAAVQLLRE 1245
Cdd:cd00160  157 PDGHEDREDLKKALEAIKE 175

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 50843837  786 LRRLQQVLQWLSGpgEEQLASFAMPGDTLSALQETELRFRAFSAEVQER------LAQAREALALEENATSQKV---LDI 856
Cdd:cd00176    6 LRDADELEAWLSE--KEELLSSTDYGDDLESVEALLKKHEALEAELAAHeerveaLNELGEQLIEEGHPDAEEIqerLEE 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837  857 FEQRLEQVESG-------LHRALRLQRFFQQAHE---WVDEGFARLAGAGPGR--EAVLAAL----ALRRAPEPSAGTFQ 920
Cdd:cd00176   84 LNQRWEELRELaeerrqrLEEALDLQQFFRDADDleqWLEEKEAALASEDLGKdlESVEELLkkhkELEEELEAHEPRLK 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 50843837  921 EMRALALDLGSPAALREWGRCQARCQELERRIQQhVGEEASPRG 964
Cdd:cd00176  164 SLNELAEELLEEGHPDADEEIEEKLEELNERWEE-LLELAEERQ 206

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837  758 LYQEVDEAIHQLVRLSNLHVQQQEQRQCLRRLQQVlqwlsgpgEEQLASFAMPGDTLSALQETELRFRAFSAEVQERLAQ 837
Cdd:COG4913  223 TFEAADALVEHFDDLERAHEALEDAREQIELLEPI--------RELAERYAAARERLAELEYLRAALRLWFAQRRLELLE 294

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837  838 AREALALEENATSQKVLDIFEQRLEQVE---SGLHRALR---------LQRFFQQAHEWVDEGFARLAGAgpgrEAVLAA 905
Cdd:COG4913  295 AELEELRAELARLEAELERLEARLDALReelDELEAQIRgnggdrleqLEREIERLERELEERERRRARL----EALLAA 370

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 50843837  906 LALrrAPEPSAGTFQEMRALALDLgSPAALREWGRCQARCQELERRIQQHVGEEAS 961
Cdd:COG4913  371 LGL--PLPASAEEFAALRAEAAAL-LEALEEELEALEEALAEAEAALRDLRRELRE 423

Laminin Domain I; coiled-coil structure. It has been suggested that the domains I and II from laminin A, B1 and B2 may come together to form a triple helical coiled-coil structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837    738 ILMRLRSTPSSKLEGQGPATLYQEVDEAIHQL--VRLSNLHVQQQEQRQCLRR----LQQVLQWLSGPGEEqlaSFAMPG 811
Cdd:pfam06008  100 EINEKVATLGENDFALPSSDLSRMLAEAQRMLgeIRSRDFGTQLQNAEAELKAaqdlLSRIQTWFQSPQEE---NKALAN 176

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837    812 DTLSALQETELRFRAFSAEVQERLAQAREALALeeNATSQKVLDIFEQRLEQVESglhRALRLQRFFQQAHEWVDEGFAR 891
Cdd:pfam06008  177 ALRDSLAEYEAKLSDLRELLREAAAKTRDANRL--NLANQANLREFQRKKEEVSE---QKNQLEETLKTARDSLDAANLL 251

                   ..
gi 50843837    892 LA 893
Cdd:pfam06008  252 LQ 253

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 50843837 1244 REQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGPEGGSEMFVYKQAFKTAD 1323
Cdd:cd13242    1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 50843837 1324 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPEIKLKWTSSIAQLLWRQAAHNK 1379
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 50843837 1269 QGQLLHRDPFTVI----CGRKKCL-RHVFLFEHLLLFSKL--KGPEGGSEMFVYKQAFKTADMGLTENIGDSGLCFELWF 1341
Cdd:cd13241   14 QGKLLLQGTLLVSepsaGLLQKGKeRRVFLFEQIIIFSEIlgKKTQFSNPGYIYKNHIKVNKMSLEENVDGDPLRFALKS 93

                         90       100       110
                 ....*....|....*....|....*....|....
gi 50843837 1342 R-RRRAREAYTLQATSPEIKLKWTSSIAQLLWRQ 1374
Cdd:cd13241   94 RdPNNPSETFILQAASPEVRQEWVDTINQILDTQ 127

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 50843837   1090 VSELIACEQDYVATLS-------EPVPPPGPELTPELR---GTWaaalsarERLRSFHRTHFLRELQGCATHPLRIGACF 1159
Cdd:pfam00621    2 IKELLQTERSYVRDLEilvevflPPNSKPLSESEEEIKtifSNI-------EEIYELHRQLLLEELLKEWISIQRIGDIF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837   1160 LRHGDQFSLYAQYVKHRhklENGLAALSPLSKGSMEAGPYLPRALQQPLEQ--------------LTRYGRLLEELLReA 1225
Cdd:pfam00621   75 LKFAPGFKVYSTYCSNY---PKALKLLKKLLKKNPKFRAFLEELEANPECRgldlnsflikpvqrIPRYPLLLKELLK-H 150

                          170       180
                   ....*....|....*....|
gi 50843837   1226 GPELSSECRALGAAVQLLRE 1245
Cdd:pfam00621  151 TPPDHPDYEDLKKALEAIKE 170

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 50843837 1262 CEIDLKEQGQLLHRDPFTVICgrKKCLRHVFLFEHLLLFSKLKGPEGgsemFVYKQAFKTADMGLTENIGDSGLCFE-LW 1340
Cdd:cd13243   42 EGPELTTYGDLVLEGTFRMAG--AKNERLLFLFDKMLLITKKREDGI----LQYKTHIMCSNLMLSESIPKEPLSFQvLP 115

                         90       100       110
                 ....*....|....*....|....*....|.
gi 50843837 1341 FRRRRAReaYTLQATSPEIKLKWTSSIAQLL 1371
Cdd:cd13243  116 FDNPKLQ--YTLQAKNQEQKRLWTQEIKRLI 144

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 50843837    1089 LVSELIACEQDYVATL-------SEPVPPPGPELTPELRGTWAAALsarERLRSFHRThFLRELQGC----ATHPLRIGA 1157
Cdd:smart00325    1 VLKELLQTERNYVRDLkllvevfLKPLKKELKLLSPNELETLFGNI---EEIYEFHRD-FLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837    1158 CFLRHGDQFSLYAQYVKHR---HKLENGLAALSPLSKGSMEAGP-------YLPRALQQPLEQLTRYGRLLEELLREagP 1227
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHpdaLELLKKLKKNPRFQKFLKEIESspqcrrlTLESLLLKPVQRLTKYPLLLKELLKH--T 154

                           170
                    ....*....|....*....
gi 50843837    1228 ELSSECR-ALGAAVQLLRE 1245
Cdd:smart00325  155 PEDHEDReDLKKALKAIKE 173

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 50843837    1269 QGQLLHRDPFTvicGRKKCLRHVFLFEHLLLFSKLKGPEGGSEmfvYKQAFKTADMGLTENIGDSGL----CFELWFRRR 1344
Cdd:smart00233    4 EGWLYKKSGGG---KKSWKKRYFVLFNSTLLYYKSKKDKKSYK---PKGSIDLSGCTVREAPDPDSSkkphCFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*..
gi 50843837    1345 RAreaYTLQATSPEIKLKWTSSIAQLL 1371
Cdd:smart00233   78 KT---LLLQAESEEEREKWVEALRKAI 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837 1269 QGQLLHRDPFTvICGRKKclRHVFLFEHLLLFSKlkgpeggSEMFVYKQAFKTADMGLTENI-----GDSGLCFELWFRR 1343
Cdd:cd00821    2 EGYLLKRGGGG-LKSWKK--RWFVLFEGVLLYYK-------SKKDSSYKPKGSIPLSGILEVeevspKERPHCFELVTPD 71

                         90       100
                 ....*....|....*....|....
gi 50843837 1344 RRAreaYTLQATSPEIKLKWTSSI 1367
Cdd:cd00821   72 GRT---YYLQADSEEERQEWLKAL 92

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50843837   1269 QGQLLHRDPFTVIcGRKKclRHVFLFEHLLLFSKLKGPEGGSEMfVYKQAFKTADMGLTENIGDSG--LCFELWFRRRRA 1346
Cdd:pfam00169    4 EGWLLKKGGGKKK-SWKK--RYFVLFDGSLLYYKDDKSGKSKEP-KGSISLSGCEVVEVVASDSPKrkFCFELRTGERTG 79

                           90       100
                   ....*....|....*....|.
gi 50843837   1347 REAYTLQATSPEIKLKWTSSI 1367
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAI 100