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 1911117033 1281 REQETRGRDLLAVEAVRGCEADLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGSEGGSETFVYKQAFKTAD 1360
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1911117033 1361 MGLTENIGDSGLCFELWFRRRRAREAYTLQAASPEIKLKWTSSIAQLLWRQAAHNK 1416
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 1911117033  813 RLHRLQQPCSppclpQVLQWLSGpGEEQLTSFAAPGDcLSALQETELRFQAFSAEVQER------LAQARDALALEEDTA 886
Cdd:cd00176      1 KLQQFLRDAD-----ELEAWLSE-KEELLSSTDYGDD-LESVEALLKKHEALEAELAAHeerveaLNELGEQLIEEGHPD 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033  887 SQKV---LDIFEQRLEQVESG-------LHRALRLQRFFQQAHE---WVDEGSARLAGAGPGR--EAVLAAL----ALRR 947
Cdd:cd00176     74 AEEIqerLEELNQRWEELRELaeerrqrLEEALDLQQFFRDADDleqWLEEKEAALASEDLGKdlESVEELLkkhkELEE 153

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033  948 APEPSTGTFQEMRALALDLGSPAALREWGRCRARCQELERRiQQQLGEEASPRGHRRRRA 1007
Cdd:cd00176    154 ELEAHEPRLKSLNELAEELLEEGHPDADEEIEEKLEELNER-WEELLELAEERQKKLEEA 212

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 1911117033 1281 REQETRGRDLLAVEAVRGCEADLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGSEGGSETFVYKQAFKTAD 1360
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1911117033 1361 MGLTENIGDSGLCFELWFRRRRAREAYTLQAASPEIKLKWTSSIAQLLWRQAAHNK 1416
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 1911117033 1127 VSELIACEQEYVATLS-------EPVPPPGSELTPELR---GTWaaalsvrERLRSFHRTHFLRELQGCATHPLRIGACF 1196
Cdd:pfam00621    2 IKELLQTERSYVRDLEilvevflPPNSKPLSESEEEIKtifSNI-------EEIYELHRQLLLEELLKEWISIQRIGDIF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033 1197 LRHGDQFSLYAQYVKHRHK----LENALAALgPPTKGSTESAPHLPRALQQPLE--------QLARYGRLLEELLReAGP 1264
Cdd:pfam00621   75 LKFAPGFKVYSTYCSNYPKalklLKKLLKKN-PKFRAFLEELEANPECRGLDLNsflikpvqRIPRYPLLLKELLK-HTP 152

                          170
                   ....*....|....*...
gi 1911117033 1265 ELSSERQALGAAVQLLRE 1282
Cdd:pfam00621  153 PDHPDYEDLKKALEAIKE 170

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 1911117033  813 RLHRLQQPCSppclpQVLQWLSGpGEEQLTSFAAPGDcLSALQETELRFQAFSAEVQER------LAQARDALALEEDTA 886
Cdd:cd00176      1 KLQQFLRDAD-----ELEAWLSE-KEELLSSTDYGDD-LESVEALLKKHEALEAELAAHeerveaLNELGEQLIEEGHPD 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033  887 SQKV---LDIFEQRLEQVESG-------LHRALRLQRFFQQAHE---WVDEGSARLAGAGPGR--EAVLAAL----ALRR 947
Cdd:cd00176     74 AEEIqerLEELNQRWEELRELaeerrqrLEEALDLQQFFRDADDleqWLEEKEAALASEDLGKdlESVEELLkkhkELEE 153

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033  948 APEPSTGTFQEMRALALDLGSPAALREWGRCRARCQELERRiQQQLGEEASPRGHRRRRA 1007
Cdd:cd00176    154 ELEAHEPRLKSLNELAEELLEEGHPDADEEIEEKLEELNER-WEELLELAEERQKKLEEA 212

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033 1306 QGQLLHRDPFTVIcGRKKclRHVFLFEHLLLFSKlKGSEGGSETFVYKQAFKTADMGLTENIGDSG--LCFELWFRRRRA 1383
Cdd:pfam00169    4 EGWLLKKGGGKKK-SWKK--RYFVLFDGSLLYYK-DDKSGKSKEPKGSISLSGCEVVEVVASDSPKrkFCFELRTGERTG 79

                           90       100
                   ....*....|....*....|.
gi 1911117033 1384 REAYTLQAASPEIKLKWTSSI 1404
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAI 100

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 1911117033 1281 REQETRGRDLLAVEAVRGCEADLKEQGQLLHRDPFTVICGRKKCLRHVFLFEHLLLFSKLKGSEGGSETFVYKQAFKTAD 1360
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1911117033 1361 MGLTENIGDSGLCFELWFRRRRAREAYTLQAASPEIKLKWTSSIAQLLWRQAAHNK 1416
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 1911117033 1306 QGQLLHRDPFTVI----CGRKKCL-RHVFLFEHLLLFSKL--KGSEGGSETFVYKQAFKTADMGLTENIGDSGLCFELWF 1378
Cdd:cd13241     14 QGKLLLQGTLLVSepsaGLLQKGKeRRVFLFEQIIIFSEIlgKKTQFSNPGYIYKNHIKVNKMSLEENVDGDPLRFALKS 93

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1911117033 1379 R-RRRAREAYTLQAASPEIKLKWTSSIAQLLWRQ 1411
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 1911117033 1123 QQRLVSELIACEQEYVATL-------SEPVPPPGSELTPELRGTWAAALsvrERLRSFHRTHFLRELQGCA---THPLRI 1192
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLkllvevfLKPLDKELLPLSPEEVELLFGNI---EEIYEFHRIFLKSLEERVEewdKSGPRI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033 1193 GACFLRHGDQFSLYAQYVKHRHKLENALAALgppTKGST---------ESAPH---LPRALQQPLEQLARYGRLLEELLR 1260
Cdd:cd00160     78 GDVFLKLAPFFKIYSEYCSNHPDALELLKKL---KKFNKffqeflekaESECGrlkLESLLLKPVQRLTKYPLLLKELLK 154

                          170       180
                   ....*....|....*....|..
gi 1911117033 1261 EAgPELSSERQALGAAVQLLRE 1282
Cdd:cd00160    155 HT-PDGHEDREDLKKALEAIKE 175

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 1911117033 1301 ADLKEQGQLLHRDPFTVICG-------RKKCLRHVFLFEHLLLFSKLK-GSEGGSETFVYKQAFKTADMGLTENIGDSGL 1372
Cdd:cd13239      7 APLQALGEPIRQGHFTVWEEapevktsSRGHHRHVFLFKNCVVICKPKrDSRTDTVTYVFKNKMKLSDIDVKDTVEGDDR 86

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1911117033 1373 CFELWFRRRRAREAYTLQAASPEIKLKWTSSIAQLLWR 1410
Cdd:cd13239     87 SFGLWHEHRGSVRKYTLQARSAIIKSSWLKDLRDLQQR 124

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 1911117033  1126 LVSELIACEQEYVATL-------SEPVPPPGSELTPELRGTWAAALsvrERLRSFHRThFLRELQGC----ATHPLRIGA 1194
Cdd:smart00325    1 VLKELLQTERNYVRDLkllvevfLKPLKKELKLLSPNELETLFGNI---EEIYEFHRD-FLDELEERieewDDSVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1911117033  1195 CFLRHGDQFSLYAQYVKH-------------RHKLENALAALG--PPTKGSTesaphLPRALQQPLEQLARYGRLLEELL 1259
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNhpdalellkklkkNPRFQKFLKEIEssPQCRRLT-----LESLLLKPVQRLTKYPLLLKELL 151

                           170       180
                    ....*....|....*....|...
gi 1911117033  1260 REAgPELSSERQALGAAVQLLRE 1282
Cdd:smart00325  152 KHT-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 1911117033  1306 QGQLLHRDPFTvicGRKKCLRHVFLFEHLLLFSKlkgSEGGSETFVYKQAFKTADMGLTENIGDSGL----CFELWFRRR 1381
Cdd:smart00233    4 EGWLYKKSGGG---KKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDPDSSkkphCFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*..
gi 1911117033  1382 RAreaYTLQAASPEIKLKWTSSIAQLL 1408
Cdd:smart00233   78 KT---LLLQAESEEEREKWVEALRKAI 101

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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 1911117033 1307 GQLLHRDPFTVICGRKKC-LRHVFLFEHLLLFSKLKGSEGGSETFVYKQAFKTADMGLtENIGDSGLCFELWFRRRRAR- 1384
Cdd:cd13325      7 GRLLRHDWFTVTDGEGKAkERYLFLFKSRILITKVRRISEDRSVFILKDIIRLPEVNV-KQHPDDERTFELQPKLPAFGi 85

                           90       100
                   ....*....|....*....|..
gi 1911117033 1385 EAYTLQAASPEIKLKWTSSIAQ 1406
Cdd:cd13325     86 LPIDFKAHKDEIKDYWLNEIEE 107