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 1034587498 1052 REQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGPEGGSEMFVYKQAFKTAD 1131
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034587498 1132 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPEIKLKWTSSIAQLLWRQAAHNK 1187
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 1034587498  594 LRRLQQVLQWLSGpgEEQLASFAMPGDTLSALQETELRFRAFSAEVQER------LAQAREALALEENATSQKV---LDI 664
Cdd:cd00176      6 LRDADELEAWLSE--KEELLSSTDYGDDLESVEALLKKHEALEAELAAHeerveaLNELGEQLIEEGHPDAEEIqerLEE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498  665 FEQRLEQVESG-------LHRALRLQRFFQQAHE---WVDEGFARLAGAGPGR--EAVLAAL----ALRRAPEPSAGTFQ 728
Cdd:cd00176     84 LNQRWEELRELaeerrqrLEEALDLQQFFRDADDleqWLEEKEAALASEDLGKdlESVEELLkkhkELEEELEAHEPRLK 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1034587498  729 EMRALALDLGSPAALREWGRCQARCQELERRIQQhVGEEASPRG 772
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 1034587498 1052 REQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGPEGGSEMFVYKQAFKTAD 1131
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034587498 1132 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPEIKLKWTSSIAQLLWRQAAHNK 1187
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 1034587498  894 QQRLVSELIACEQDYVATL-------SEPVPPPGPELTPELRgtwAAALSARERLRSFHRTHFLRELQGCA---THPLRI 963
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLkllvevfLKPLDKELLPLSPEEV---ELLFGNIEEIYEFHRIFLKSLEERVEewdKSGPRI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498  964 GACFLRHGDQFSLYAQYVKHRHK----LENGLAALSPLSKGSMEAGPY-----LPRALQQPLEQLTRYGRLLEELLREAg 1034
Cdd:cd00160     78 GDVFLKLAPFFKIYSEYCSNHPDalelLKKLKKFNKFFQEFLEKAESEcgrlkLESLLLKPVQRLTKYPLLLKELLKHT- 156

                          170
                   ....*....|....*....
gi 1034587498 1035 PELSSECRALGAAVQLLRE 1053
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 1034587498  594 LRRLQQVLQWLSGpgEEQLASFAMPGDTLSALQETELRFRAFSAEVQER------LAQAREALALEENATSQKV---LDI 664
Cdd:cd00176      6 LRDADELEAWLSE--KEELLSSTDYGDDLESVEALLKKHEALEAELAAHeerveaLNELGEQLIEEGHPDAEEIqerLEE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498  665 FEQRLEQVESG-------LHRALRLQRFFQQAHE---WVDEGFARLAGAGPGR--EAVLAAL----ALRRAPEPSAGTFQ 728
Cdd:cd00176     84 LNQRWEELRELaeerrqrLEEALDLQQFFRDADDleqWLEEKEAALASEDLGKdlESVEELLkkhkELEEELEAHEPRLK 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1034587498  729 EMRALALDLGSPAALREWGRCQARCQELERRIQQhVGEEASPRG 772
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 1034587498  566 LYQEVDEAIHQLVRLSNLHVQQQEQRQCLRRLQQVlqwlsgpgEEQLASFAMPGDTLSALQETELRFRAFSAEVQERLAQ 645
Cdd:COG4913    223 TFEAADALVEHFDDLERAHEALEDAREQIELLEPI--------RELAERYAAARERLAELEYLRAALRLWFAQRRLELLE 294

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498  646 AREALALEENATSQKVLDIFEQRLEQVE---SGLHRALR---------LQRFFQQAHEWVDEGFARLAGAgpgrEAVLAA 713
Cdd:COG4913    295 AELEELRAELARLEAELERLEARLDALReelDELEAQIRgnggdrleqLEREIERLERELEERERRRARL----EALLAA 370

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034587498  714 LALrrAPEPSAGTFQEMRALALDLgSPAALREWGRCQARCQELERRIQQHVGEEAS 769
Cdd:COG4913    371 LGL--PLPASAEEFAALRAEAAAL-LEALEEELEALEEALAEAEAALRDLRRELRE 423

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 1034587498 1052 REQEARGRDLLAVEAVRGCEIDLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGPEGGSEMFVYKQAFKTAD 1131
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034587498 1132 MGLTENIGDSGLCFELWFRRRRAREAYTLQATSPEIKLKWTSSIAQLLWRQAAHNK 1187
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 1034587498 1077 QGQLLHRDPFTVI----CGRKKCL-RHVFLFEHLLLFSKL--KGPEGGSEMFVYKQAFKTADMGLTENIGDSGLCFELWF 1149
Cdd:cd13241     14 QGKLLLQGTLLVSepsaGLLQKGKeRRVFLFEQIIIFSEIlgKKTQFSNPGYIYKNHIKVNKMSLEENVDGDPLRFALKS 93

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1034587498 1150 R-RRRAREAYTLQATSPEIKLKWTSSIAQLLWRQ 1182
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 1034587498  898 VSELIACEQDYVATLS-------EPVPPPGPELTPELR---GTWaaalsarERLRSFHRTHFLRELQGCATHPLRIGACF 967
Cdd:pfam00621    2 IKELLQTERSYVRDLEilvevflPPNSKPLSESEEEIKtifSNI-------EEIYELHRQLLLEELLKEWISIQRIGDIF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498  968 LRHGDQFSLYAQYVKHRhklENGLAALSPLSKGSMEAGPYLPRALQQPLEQ--------------LTRYGRLLEELLReA 1033
Cdd:pfam00621   75 LKFAPGFKVYSTYCSNY---PKALKLLKKLLKKNPKFRAFLEELEANPECRgldlnsflikpvqrIPRYPLLLKELLK-H 150

                          170       180
                   ....*....|....*....|
gi 1034587498 1034 GPELSSECRALGAAVQLLRE 1053
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 1034587498 1070 CEIDLKEQGQLLHRDPFTVICgrKKCLRHVFLFEHLLLFSKLKGPEGgsemFVYKQAFKTADMGLTENIGDSGLCFE-LW 1148
Cdd:cd13243     42 EGPELTTYGDLVLEGTFRMAG--AKNERLLFLFDKMLLITKKREDGI----LQYKTHIMCSNLMLSESIPKEPLSFQvLP 115

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1034587498 1149 FRRRRAReaYTLQATSPEIKLKWTSSIAQLL 1179
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 1034587498   897 LVSELIACEQDYVATL-------SEPVPPPGPELTPELRGTWAAALsarERLRSFHRThFLRELQGC----ATHPLRIGA 965
Cdd:smart00325    1 VLKELLQTERNYVRDLkllvevfLKPLKKELKLLSPNELETLFGNI---EEIYEFHRD-FLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498   966 CFLRHGDQFSLYAQYVKHR---HKLENGLAALSPLSKGSMEAGP-------YLPRALQQPLEQLTRYGRLLEELLREagP 1035
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHpdaLELLKKLKKNPRFQKFLKEIESspqcrrlTLESLLLKPVQRLTKYPLLLKELLKH--T 154

                           170
                    ....*....|....*....
gi 1034587498  1036 ELSSECR-ALGAAVQLLRE 1053
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 1034587498  1077 QGQLLHRDPFTvicGRKKCLRHVFLFEHLLLFSKLKGPEGGSEmfvYKQAFKTADMGLTENIGDSGL----CFELWFRRR 1152
Cdd:smart00233    4 EGWLYKKSGGG---KKSWKKRYFVLFNSTLLYYKSKKDKKSYK---PKGSIDLSGCTVREAPDPDSSkkphCFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*..
gi 1034587498  1153 RAreaYTLQATSPEIKLKWTSSIAQLL 1179
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 1034587498 1077 QGQLLHRDPFTvICGRKKclRHVFLFEHLLLFSKlkgpeggSEMFVYKQAFKTADMGLTENI-----GDSGLCFELWFRR 1151
Cdd:cd00821      2 EGYLLKRGGGG-LKSWKK--RWFVLFEGVLLYYK-------SKKDSSYKPKGSIPLSGILEVeevspKERPHCFELVTPD 71

                           90       100
                   ....*....|....*....|....
gi 1034587498 1152 RRAreaYTLQATSPEIKLKWTSSI 1175
Cdd:cd00821     72 GRT---YYLQADSEEERQEWLKAL 92

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034587498 1077 QGQLLHRDPFTVIcGRKKclRHVFLFEHLLLFSKLKGPEGGSEMfVYKQAFKTADMGLTENIGDSG--LCFELWFRRRRA 1154
Cdd:pfam00169    4 EGWLLKKGGGKKK-SWKK--RYFVLFDGSLLYYKDDKSGKSKEP-KGSISLSGCEVVEVVASDSPKrkFCFELRTGERTG 79

                           90       100
                   ....*....|....*....|.
gi 1034587498 1155 REAYTLQATSPEIKLKWTSSI 1175
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAI 100