DIX domain; The DIX domain is present in Dishevelled and axin. This domain is involved in homo- and hetero-oligomerization. It is involved in the homo- oligomerization of mouse axin. The axin DIX domain also interacts with the dishevelled DIX domain. The DIX domain has also been called the DAX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442621813  613 ETIVVFSFCEEPVPYRIKI--PGTQPTLRQFKDYLPRRGHFRFFFKThcEDPDSPVIQEEIVNDSDILPLFGDKAMGLV 689
Cdd:pfam00778   1 ETKVIYYLCDEPVPYRIKIhkPGGQITLGDFKELLPKKGNYRYFFKT--LDPEFGTVKEEITDDDDILPLWEGKIVAKV 77

DIX domain; The DIX domain is present in Dishevelled and axin. This domain is involved in homo- and hetero-oligomerization. It is involved in the homo- oligomerization of mouse axin. The axin DIX domain also interacts with the dishevelled DIX domain. The DIX domain has also been called the DAX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442621813  613 ETIVVFSFCEEPVPYRIKI--PGTQPTLRQFKDYLPRRGHFRFFFKThcEDPDSPVIQEEIVNDSDILPLFGDKAMGLV 689
Cdd:pfam00778   1 ETKVIYYLCDEPVPYRIKIhkPGGQITLGDFKELLPKKGNYRYFFKT--LDPEFGTVKEEITDDDDILPLWEGKIVAKV 77

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813   55 LNHLLEDRDGVELFKKYVEEEAPayNDHLNFYFACEGLKQQTDPEKIKQIIGAIY-RFLR---KSQLSISDDLRAQIKA- 129
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFS--EENLEFWLACEEFKKADPDEERLKKAKEIYnEFLApgsPKEINLDSDLREEIREn 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 442621813  130 IKTNPeiplSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:pfam00615  80 LEKEP----TRDLFDEAQAEVYELMEKDSYPRFLKSPLY 114

Axin beta-catenin binding motif; This motif is found on the scaffolding protein Axin which is a component of the beta-catenin destruction complex. It competes with the tumour suppressor adenomatous polyposis coli protein (APC) for binding to beta-catenin.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 442621813  449 DNDQDILDQHVSRVWKDqTPHRSPGTMSPCPPIPSR 484
Cdd:pfam08833   1 DNPQSILDEHVSRVWKT-PGCQSPGRHSPRSRSPDS 35

DIX domain; The DIX domain is present in Dishevelled and axin. This domain is involved in homo- and hetero-oligomerization. It is involved in the homo- oligomerization of mouse axin. The axin DIX domain also interacts with the dishevelled DIX domain. The DIX domain has also been called the DAX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442621813  613 ETIVVFSFCEEPVPYRIKI--PGTQPTLRQFKDYLPRRGHFRFFFKThcEDPDSPVIQEEIVNDSDILPLFGDKAMGLV 689
Cdd:pfam00778   1 ETKVIYYLCDEPVPYRIKIhkPGGQITLGDFKELLPKKGNYRYFFKT--LDPEFGTVKEEITDDDDILPLWEGKIVAKV 77

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813   55 LNHLLEDRDGVELFKKYVEEEAPayNDHLNFYFACEGLKQQTDPEKIKQIIGAIY-RFLR---KSQLSISDDLRAQIKA- 129
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFS--EENLEFWLACEEFKKADPDEERLKKAKEIYnEFLApgsPKEINLDSDLREEIREn 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 442621813  130 IKTNPeiplSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:pfam00615  80 LEKEP----TRDLFDEAQAEVYELMEKDSYPRFLKSPLY 114

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  59 LEDRDGVELFKKYVE-EEAPaynDHLNFYFACEGLKQQT-DPEKIKQIIGAIYR-FLRKS---QLSISDDLRAQIKAIKT 132
Cdd:cd07440    1 LRDPYGLEYFRQFLKsEHCE---ENLEFWLAVEKFKKTTsSDEELKSKAKEIYDkYISKDapkEINIPESIREEIEENLE 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 442621813 133 NPEIPlsPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd07440   78 EPYPD--PDCFDEAQEHILNLLEKDSYPRFLKSDLY 111

Regulator of G protein signaling (RGS) domain found in the R12 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R12 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling, controlled by RGS domain, accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP that results in reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R12 RGS subfamily includes RGS10, RGS12 and RGS14 all of which are highly selective for G-alpha-i1 over G-alpha-q.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  55 LNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKIKQIIGAIY-RFL-RKSQLSISDDLRAQI-KAIK 131
Cdd:cd08706    1 FERLLQDPVGVKYFTEFLKKEFSEEN--ILFWQACEKFKKIPDKKQLVQEAREIYdTFLsSKASSPVNIDSQAQLaEEML 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442621813 132 TNPeiplSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08706   79 EEP----HPDMFQKQQLQIFNLMKFDSYSRFLKSPLY 111

Regulator of G protein signaling (RGS) domain found in the RGS2 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS2 protein. RGS2 is a member of R4/RGS subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G- alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS2 plays important roles in the regulation of blood pressure and the pathogenesis of human hypertension, as well as in bone formation in osteoblasts. Outside of the GPCR pathway RGS2 interacts with calmodulin, beta- COP, tubulin, PKG1-alpha, and TRPV6.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  55 LNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKIKQIIGAIY-RFLRK-SQLSISDDLRAQIKAIKT 132
Cdd:cd08709    1 FDELLASKYGVAAFRAFLKSEFSEEN--IEFWLACEDFKKTKSPQKLTSKAKKIYtDFIEKeAPKEINIDFQTKTLIAQN 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 442621813 133 NPEIPLSphIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08709   79 IQEATSG--CFTAAQKRVYSLMENNSYPRFLESEFY 112

Regulator of G protein signaling (RGS) domain found in the RGS18 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS18 protein. RGS18 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS18 is a member of the R4/RGS subfamily and is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  58 LLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKIKQIIGAIY-RFLRK-SQLSISDDLRAQiKAIKTNPE 135
Cdd:cd08712    4 LLSHKDGLEAFTRFLKTEFSEEN--IEFWIACEDYKKSKTPQQIHLKAKAIYeKFIQTdAPKEVNLDFHTK-EVTTNSIE 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 442621813 136 IPlSPHIFDPMQRHVEVTIRDNIYPTFLCSEMYI 169
Cdd:cd08712   81 QP-TLTSFDAAQSRVYQLMEQDSYPRFLKSDIYL 113

Regulator of G protein signaling (RGS) domain found in the RGS20 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS20 protein (also known as RGSZ1), a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP resulting in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins include RGS17, RGS19 (former GAIP), and the splice variant of RGS20, Ret-RGS. RGS20 is expressed exclusively in brain, with the highest concentrations in the temporal lobe and the caudate nucleus and may play a role in signaling regulation in these brain regions. RGS20 acts as a GAP of both G-alpha-z and G-alpha-I and controls signaling in the mu opioid receptor pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  26 EESRVKKM-----TEGVADTSKNSSPSYLN---WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTD 97
Cdd:cd08746   17 EDERNRRTsyefrAEGIPNCEESPKPTLEEvcaWGQSFDKLMLTPAGRNAFREFLRTEFSEEN--MLFWMACEELKKEAN 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 442621813  98 PEKIKQIIGAIYR----FLRKSQLSISDDLRAQIKAIKTNPeiplSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08746   95 KSVIEEKARIIYEdyisILSPKEVSLDSRVREVINRNMLEP----SQHTFDDAQLQIYTLMHRDSYPRFMNSAIY 165

Regulator of G protein signaling (RGS) domain found in the RGS17 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS17 protein, a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of the G-protein signaling controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. The RZ subfamily of RGS proteins includes RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS. RGS17 is a relatively non-selective GAP for G-alpha-z and other G-alpha-i/o proteins. RGS17 blocks dopamine receptor-mediated inhibition of cAMP accumulation; it also blocks thyrotropin releasing hormone-stimulated Ca++ mobilization. RGS17, like other members of RZ subfamily, can act either as a GAP or as G-protein effector antogonist.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  51 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKIKQIIGAIYR----FLRKSQLSISDDLRAQ 126
Cdd:cd08744    1 WSQNFDKMMKTPAGRNLFREFLRTEYSEEN--LLFWLACEDLKKEQNKKVIEEKARLIYEdyisILSPKEVSLDSRVREV 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 442621813 127 IKAIKTNPeiplSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08744   79 INRNLLDP----NPHMYEDAQLQIYTLMHRDSFPRFLNSQIY 116

Regulator of G protein signaling (RGS) domain found in the RGS5 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS5 protein. RGS5 is member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Two splice isoforms of RGS5 has been found: RGS5L (long) which is expressed in smooth muscle cells (pericytes) and heart and RGS5S (short) which is highly expressed in the ciliary body of the eye, kidney, brain, spleen, skeletal muscle, and small intestine. Outside of the GPCR pathway, RGS5 interacts with the 14-3-3 protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  55 LNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKIKQIIGAIYRFLRKSQLSISDDLRAQIKAIKTNP 134
Cdd:cd08717    1 LDKLLQNSYGLASFKSFLKSEFSEEN--IEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKN 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 442621813 135 EIPLSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08717   79 LVEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFY 112

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  51 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKIKQIIGAIYRFLRK-SQLSISDDLRAQIKA 129
Cdd:cd08737    6 WGFSLDEVLKDPVGRDQFLRFLESEFSSEN--LRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPgAPSAINLDSHSYEKT 83

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 442621813 130 iKTNPEIPlSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08737   84 -SQNVKDP-GRYTFEDAQEHIYKLMKSDSYARFLRSNAY 120

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 25 (SNX25) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX25 (Sorting Nexin 25) protein, a member of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. SNX25 is a member of the Dopamine receptors (DAR) signalplex and regulates the trafficking of D1 and D2 DARs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442621813  58 LLEDRDGVELFKKYVEEEAPayNDHLNFYFACEGLKQqTDPEKIKQIIGAI-YRFLR--KSQLSISDDLRAQIKAIKTNP 134
Cdd:cd08720    1 ILANVFGRKYLSQFLERMDS--QALIGFWEAVEELRS-ANKSEWHQLGAEIfYTFIVepTAEIKVDKSLRKRIEQFLLGD 77

                         90       100       110
                 ....*....|....*....|....*....|....
gi 442621813 135 EiplSPHIFDPMQRHVEVTIRDNIYPTFLCSEMY 168
Cdd:cd08720   78 K---GPEVFYEVQENVVETLEEKYYPSFVVSDQY 108