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 193211594  899 HFQLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFVVRTGRHKSVRRIFLFEELLLFSKPRHGPTGVDTFAYKRSFKMAD 978
Cdd:cd13242     1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 193211594  979 LGLTECCGNSNLRFEIWFRRRKARDTFVLQASSLAIKQAWTADISHLLWRQAVHNK 1034
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 193211594  447 QALELVQTLEARESGLHQIEVWLQQVGWPALEEagepSLDMLLQAQGSFQELYQVAQEQV----RQGEKFLQPLtgweAA 522
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLE----SVEALLKKHEALEAELAAHEERVealnELGEQLIEEG----HP 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 193211594  523 ELDPPGARFLALRAQLTEFSRALAQRCQRLADAERLFQLFREA---LTWAEEGQRVLAELEqerPGVVLQQLQLHWTRH 598
Cdd:cd00176    73 DAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDAddlEQWLEEKEAALASED---LGKDLESVEELLKKH 148

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 193211594  899 HFQLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFVVRTGRHKSVRRIFLFEELLLFSKPRHGPTGVDTFAYKRSFKMAD 978
Cdd:cd13242     1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 193211594  979 LGLTECCGNSNLRFEIWFRRRKARDTFVLQASSLAIKQAWTADISHLLWRQAVHNK 1034
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 193211594  733 LQLVLAEMVATEREYVRALEYTMENYFPELDRPDVPqGLRGQRAHLFGNLEKLRDFHcHFFLRELEACT----RHPPRVA 808
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFH-RIFLKSLEERVeewdKSGPRIG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  809 YAFLRHRVQFGMYALYSKNKPRSDALMSSY--GHTFFKD---KQQALGDHLDLASYLLKPIQRMGKYALLLQELARACGG 883
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEfleKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                         170
                  ....*....|....*.
gi 193211594  884 PTQELSALREAQSLVH 899
Cdd:cd00160   159 GHEDREDLKKALEAIK 174

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 193211594    924 QGQLVRQDEfVVRTGRHKsvRRIFLFEELLLFSKPRHGPTGvdtFAYKRSFKMADLGLTEC----CGNSNLRFEIWFRRR 999
Cdd:smart00233    4 EGWLYKKSG-GGKKSWKK--RYFVLFNSTLLYYKSKKDKKS---YKPKGSIDLSGCTVREApdpdSSKKPHCFEIKTSDR 77

                            90       100
                    ....*....|....*....|...
gi 193211594   1000 KardTFVLQASSLAIKQAWTADI 1022
Cdd:smart00233   78 K---TLLLQAESEEEREKWVEAL 97

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 193211594  447 QALELVQTLEARESGLHQIEVWLQQVGWPALEEagepSLDMLLQAQGSFQELYQVAQEQV----RQGEKFLQPLtgweAA 522
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLE----SVEALLKKHEALEAELAAHEERVealnELGEQLIEEG----HP 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 193211594  523 ELDPPGARFLALRAQLTEFSRALAQRCQRLADAERLFQLFREA---LTWAEEGQRVLAELEqerPGVVLQQLQLHWTRH 598
Cdd:cd00176    73 DAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDAddlEQWLEEKEAALASED---LGKDLESVEELLKKH 148

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  193 GMATLPGTRDVQGRAVLLLCAHspAWLQSECSSQELIRLLLYL--RSIPRPEVQALGLTVLVDAR-----ICAPSSSLFS 265
Cdd:cd00170     9 GGIGYLGGRDKEGRPVLVFRAG--WDPPKLLDLEELLRYLVYLleKALRELEEQVEGFVVIIDLKgfslsNLSDLSLLKK 86

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 193211594  266 GLSQLQEAAPGAVYQVLLV------------GSTLLKE--------VPSGLQleqlpsqSLLTHIPTAGLPTSLGG 321
Cdd:cd00170    87 LLKILQDHYPERLKKIYIVnapwifsalwkiVKPFLSEktrkkivfLGSDLE-------ELLEYIDPDQLPKELGG 155

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 193211594  899 HFQLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFVVRTGRHKSVRRIFLFEELLLFSKPRHGPTGVDTFAYKRSFKMAD 978
Cdd:cd13242     1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 193211594  979 LGLTECCGNSNLRFEIWFRRRKARDTFVLQASSLAIKQAWTADISHLLWRQAVHNK 1034
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 193211594  733 LQLVLAEMVATEREYVRALEYTMENYFPELDRPDVPqGLRGQRAHLFGNLEKLRDFHcHFFLRELEACT----RHPPRVA 808
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFH-RIFLKSLEERVeewdKSGPRIG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  809 YAFLRHRVQFGMYALYSKNKPRSDALMSSY--GHTFFKD---KQQALGDHLDLASYLLKPIQRMGKYALLLQELARACGG 883
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLkkFNKFFQEfleKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                         170
                  ....*....|....*.
gi 193211594  884 PTQELSALREAQSLVH 899
Cdd:cd00160   159 GHEDREDLKKALEAIK 174

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 193211594  914 IQGCDVNLKEQGQLVRQDEFVVRTG------RHKSvRRIFLFEELLLFSKP--RHGPTGVDTFAYKRSFKMADLGLTECC 985
Cdd:cd13241     4 LQGFDGKITAQGKLLLQGTLLVSEPsagllqKGKE-RRVFLFEQIIIFSEIlgKKTQFSNPGYIYKNHIKVNKMSLEENV 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 193211594  986 GNSNLRFEIWFR-RRKARDTFVLQASSLAIKQAWTADISHLLWRQ 1029
Cdd:cd13241    83 DGDPLRFALKSRdPNNPSETFILQAASPEVRQEWVDTINQILDTQ 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  913 AIQGCDVNLKEQGQLVRQDEFVVRTGRHK-----------SVRRIFLFEELLLFSKPRHGPTGVDTFAYKRSFKMADLGL 981
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKghtkklarfkpMQRHIFLYEKAVLFCKKRGENGEAPSYSYKNSLNTTAVGL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 193211594  982 TECCGNSNLRFEIWFRRRKarDTFVLQASSLAIKQAWTADISHLLWRQ 1029
Cdd:cd01227    81 TENVKGDTKKFEIWLNGRE--EVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

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 193211594  917 CDVNLKEQGQLVRQDEFvvRTGRHKSVRRIFLFEELLLFSKPRHGptgvDTFAYKRSFKMADLGLTECCGNSNLRFEIW- 995
Cdd:cd13243    42 EGPELTTYGDLVLEGTF--RMAGAKNERLLFLFDKMLLITKKRED----GILQYKTHIMCSNLMLSESIPKEPLSFQVLp 115

                          90       100       110
                  ....*....|....*....|....*....|.
gi 193211594  996 FRRRKARDTFvlQASSLAIKQAWTADISHLL 1026
Cdd:cd13243   116 FDNPKLQYTL--QAKNQEQKRLWTQEIKRLI 144

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 193211594    924 QGQLVRQDEfVVRTGRHKsvRRIFLFEELLLFSKPRHGPTGvdtFAYKRSFKMADLGLTEC----CGNSNLRFEIWFRRR 999
Cdd:smart00233    4 EGWLYKKSG-GGKKSWKK--RYFVLFNSTLLYYKSKKDKKS---YKPKGSIDLSGCTVREApdpdSSKKPHCFEIKTSDR 77

                            90       100
                    ....*....|....*....|...
gi 193211594   1000 KardTFVLQASSLAIKQAWTADI 1022
Cdd:smart00233   78 K---TLLLQAESEEEREKWVEAL 97

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 193211594  447 QALELVQTLEARESGLHQIEVWLQQVGWPALEEagepSLDMLLQAQGSFQELYQVAQEQV----RQGEKFLQPLtgweAA 522
Cdd:cd00176     1 KLQQFLRDADELEAWLSEKEELLSSTDYGDDLE----SVEALLKKHEALEAELAAHEERVealnELGEQLIEEG----HP 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 193211594  523 ELDPPGARFLALRAQLTEFSRALAQRCQRLADAERLFQLFREA---LTWAEEGQRVLAELEqerPGVVLQQLQLHWTRH 598
Cdd:cd00176    73 DAEEIQERLEELNQRWEELRELAEERRQRLEEALDLQQFFRDAddlEQWLEEKEAALASED---LGKDLESVEELLKKH 148

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  193 GMATLPGTRDVQGRAVLLLCAHspAWLQSECSSQELIRLLLYL--RSIPRPEVQALGLTVLVDAR-----ICAPSSSLFS 265
Cdd:cd00170     9 GGIGYLGGRDKEGRPVLVFRAG--WDPPKLLDLEELLRYLVYLleKALRELEEQVEGFVVIIDLKgfslsNLSDLSLLKK 86

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 193211594  266 GLSQLQEAAPGAVYQVLLV------------GSTLLKE--------VPSGLQleqlpsqSLLTHIPTAGLPTSLGG 321
Cdd:cd00170    87 LLKILQDHYPERLKKIYIVnapwifsalwkiVKPFLSEktrkkivfLGSDLE-------ELLEYIDPDQLPKELGG 155

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  375 QQTEVLMQQVLDSPWLAWlqcQGGRELTWLKQEVPE-----VTLSPDYRTAMDKADELYDRVDGLLHQLTLQSNQRIQAL 449
Cdd:COG4913   267 ARERLAELEYLRAALRLW---FAQRRLELLEAELEElraelARLEAELERLEARLDALREELDELEAQIRGNGGDRLEQL 343

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193211594  450 E-----LVQTLEARESGLHQIEVWLQQVGWPALEEAGEpsldmllqaqgsFQELYQVAQEQVRQGEKFLQPLtgweAAEL 524
Cdd:COG4913   344 EreierLERELEERERRRARLEALLAALGLPLPASAEE------------FAALRAEAAALLEALEEELEAL----EEAL 407

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 193211594  525 DPPGARFLALRAQLTEFS---RALAQRCQRL-ADAERLFQLFREALTWAEEGQRVLAELEQERPG 585
Cdd:COG4913   408 AEAEAALRDLRRELRELEaeiASLERRKSNIpARLLALRDALAEALGLDEAELPFVGELIEVRPE 472