Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 320546077 1057 RHLFMEGDHKFKDNLG-KSDVHCFLLTDLLLVCKTIaKRGLGALKVIRQPYLTDQLIVQ-LAPNNTLNCVYLNEFQVATT 1134
Cdd:cd13244     1 RRLLLEGDLRLKEGKGsKVDVHCFLFTDMLLICKPV-KRKKDRLKVIRPPYLVDKLVVQeLKDPGGFLLVYLNEFHTAVA 79

                          90       100
                  ....*....|....*....|.
gi 320546077 1135 AFTLQCTEA---KNWYDALWR 1152
Cdd:cd13244    80 AYTFQTSSQedtRRWLDAIRK 100

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 320546077  616 DSSQQPDEEFIPATKGVTLLNALSHALRRRNLSFTQITItdnnptpsFLDAGPSLLPvsvdEQTDVESLAGHHLCITER 694
Cdd:cd17068     9 DDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNV--------FLDSSNTPLP----LEFDTYFLGGHTLRVKAK 75

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 320546077 1057 RHLFMEGDHKFKDNLG-KSDVHCFLLTDLLLVCKTIaKRGLGALKVIRQPYLTDQLIVQ-LAPNNTLNCVYLNEFQVATT 1134
Cdd:cd13244     1 RRLLLEGDLRLKEGKGsKVDVHCFLFTDMLLICKPV-KRKKDRLKVIRPPYLVDKLVVQeLKDPGGFLLVYLNEFHTAVA 79

                          90       100
                  ....*....|....*....|.
gi 320546077 1135 AFTLQCTEA---KNWYDALWR 1152
Cdd:cd13244    80 AYTFQTSSQedtRRWLDAIRK 100

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 320546077  813 AIWELVTTEVYYIHALQTVTDLFLACLeaVQEEGLLIDVDQARLFSNVRAVCEANIKFWTLwLYPMVAHSAITHEPLrca 892
Cdd:cd00160     4 VIKELLQTERNYVRDLKLLVEVFLKPL--DKELLPLSPEEVELLFGNIEEIYEFHRIFLKS-LEERVEEWDKSGPRI--- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320546077  893 ffQEGFLSFASIFAPYKIYCAEQSTCQFYCKELNHNNALFTSYLAWCESQkmCNRLRLADIVVRPMQRLTKYSLLLAAIK 972
Cdd:cd00160    78 --GDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELL 153

                         170       180
                  ....*....|....*....|....*...
gi 320546077  973 KHMSDV-EEIEAIDVMMHSVENFVGSVN 999
Cdd:cd00160   154 KHTPDGhEDREDLKKALEAIKEVASQVN 181

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 320546077  616 DSSQQPDEEFIPATKGVTLLNALSHALRRRNLSFTQITItdnnptpsFLDAGPSLLPvsvdEQTDVESLAGHHLCITER 694
Cdd:cd17068     9 DDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNV--------FLDSSNTPLP----LEFDTYFLGGHTLRVKAK 75

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 320546077 1057 RHLFMEGDHKFKDNLG-KSDVHCFLLTDLLLVCKTIaKRGLGALKVIRQPYLTDQLIVQ-LAPNNTLNCVYLNEFQVATT 1134
Cdd:cd13244     1 RRLLLEGDLRLKEGKGsKVDVHCFLFTDMLLICKPV-KRKKDRLKVIRPPYLVDKLVVQeLKDPGGFLLVYLNEFHTAVA 79

                          90       100
                  ....*....|....*....|.
gi 320546077 1135 AFTLQCTEA---KNWYDALWR 1152
Cdd:cd13244    80 AYTFQTSSQedtRRWLDAIRK 100

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 320546077  813 AIWELVTTEVYYIHALQTVTDLFLACLeaVQEEGLLIDVDQARLFSNVRAVCEANIKFWTLwLYPMVAHSAITHEPLrca 892
Cdd:cd00160     4 VIKELLQTERNYVRDLKLLVEVFLKPL--DKELLPLSPEEVELLFGNIEEIYEFHRIFLKS-LEERVEEWDKSGPRI--- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320546077  893 ffQEGFLSFASIFAPYKIYCAEQSTCQFYCKELNHNNALFTSYLAWCESQkmCNRLRLADIVVRPMQRLTKYSLLLAAIK 972
Cdd:cd00160    78 --GDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELL 153

                         170       180
                  ....*....|....*....|....*...
gi 320546077  973 KHMSDV-EEIEAIDVMMHSVENFVGSVN 999
Cdd:cd00160   154 KHTPDGhEDREDLKKALEAIKEVASQVN 181

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 320546077  616 DSSQQPDEEFIPATKGVTLLNALSHALRRRNLSFTQITItdnnptpsFLDAGPSLLPvsvdEQTDVESLAGHHLCITER 694
Cdd:cd17068     9 DDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNV--------FLDSSNTPLP----LEFDTYFLGGHTLRVKAK 75

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 320546077 1057 RHLFMEGDHKFKD---NLGKSDVHCFLLTDLLLVCKTIA-KRGLGALKV 1101
Cdd:cd01226     6 RYLLHEGDLLELDpddYKPIQKVHLFLLNDVLLIASWLPnRRGPVRYKF 54