Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) 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. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 174 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLSGRQRDGKQQTNQTKGLLRAAAVGIYEQYLSEKASP 253
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568977697 254 RVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDERFYPSFRQNALYVR 308
Cdd:cd08719   81 RVPLDDSLVKKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDERFYPAFKKSPAYVK 135

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697  600 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAETVPCRDKAIRMRTRIAGKTKLF 679
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 568977697  680 AIMPDELKHIIGAETTRKGILRVFEMFQH 708
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQN 109

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) 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. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 174 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLSGRQRDGKQQTNQTKGLLRAAAVGIYEQYLSEKASP 253
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568977697 254 RVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDERFYPSFRQNALYVR 308
Cdd:cd08719   81 RVPLDDSLVKKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDERFYPAFKKSPAYVK 135

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697  600 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAETVPCRDKAIRMRTRIAGKTKLF 679
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 568977697  680 AIMPDELKHIIGAETTRKGILRVFEMFQH 708
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQN 109

Domain associated with PX domains; unpubl. observations

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568977697    13 SPKDEEGFLRDLCEVLLYLLLPPGDFQSKIMRYFVREILARGILLPLINQLSDPDYINQYVIWMIRDSN 81
Cdd:smart00313 108 SPSNELTYRRQLVEMLLKFLLPEDSLCSRLHRCLLREVLAMQVILPLITHLSDPDTINLCIILLFSSSR 176

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697  396 RNLNTEEMWKTYRRYSDFHDFHMRITEQFENLSsILKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLTPEMMKASPalah 475
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSE---- 75

                  ....*..
gi 568977697  476 CVYDFLE 482
Cdd:pfam00787  76 VLLEFLE 82

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 568977697  171 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQlevlsgrqrdgkqqtnqtkgLLRAAAVGIYEQYLSEK 250
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDE--------------------ERLKKAKEIYNEFLAPG 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568977697  251 ASPRVTVDDYLVAKLADTLNHEdPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRM 309
Cdd:pfam00615  62 SPKEINLDSDLREEIRENLEKE-PTRDLFDEAQAEVYELMEKDS--YPRFLKSPLYLRL 117

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) 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. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 174 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLSGRQRDGKQQTNQTKGLLRAAAVGIYEQYLSEKASP 253
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568977697 254 RVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDERFYPSFRQNALYVR 308
Cdd:cd08719   81 RVPLDDSLVKKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDERFYPAFKKSPAYVK 135

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697  600 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAETVPCRDKAIRMRTRIAGKTKLF 679
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 568977697  680 AIMPDELKHIIGAETTRKGILRVFEMFQH 708
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQN 109

Domain associated with PX domains; unpubl. observations

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568977697    13 SPKDEEGFLRDLCEVLLYLLLPPGDFQSKIMRYFVREILARGILLPLINQLSDPDYINQYVIWMIRDSN 81
Cdd:smart00313 108 SPSNELTYRRQLVEMLLKFLLPEDSLCSRLHRCLLREVLAMQVILPLITHLSDPDTINLCIILLFSSSR 176

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 568977697 175 LVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEvlsgrqrdgkqqtnqtkglLRAAAVGIYEQYLSEKASPR 254
Cdd:cd07440    1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDEE-------------------LKSKAKEIYDKYISKDAPKE 61

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568977697 255 VTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVR 308
Cdd:cd07440   62 INIPESIREEIEENLEEPYPDPDCFDEAQEHILNLLEKD--SYPRFLKSDLYLK 113

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697  396 RNLNTEEMWKTYRRYSDFHDFHMRITEQFENLSsILKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLTPEMMKASPalah 475
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSE---- 75

                  ....*..
gi 568977697  476 CVYDFLE 482
Cdd:pfam00787  76 VLLEFLE 82

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 376 AGVCNDHGKTYALYAITVHRRNLNTEEM------WKTYRRYSDFHDFHMRITEQFENLSSI-LKLPGKKTFNNMDRDFLE 448
Cdd:cd06878   16 AEVTVEDDKEVPLYVIVVHVSEVGLNEDesissgWVVTRKLSEFHDLHRKLKECSSWLKKVeLPSLSKKWFKSIDKKFLD 95

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568977697 449 KRKKDLNAYLQLLLTPEMMKASPALahcvYDFL 481
Cdd:cd06878   96 KSKNQLQKYLQFILEDETLCQSEAL----YSFL 124

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 568977697  171 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQlevlsgrqrdgkqqtnqtkgLLRAAAVGIYEQYLSEK 250
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDE--------------------ERLKKAKEIYNEFLAPG 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568977697  251 ASPRVTVDDYLVAKLADTLNHEdPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRM 309
Cdd:pfam00615  62 SPKEINLDSDLREEIRENLEKE-PTRDLFDEAQAEVYELMEKDS--YPRFLKSPLYLRL 117

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568977697 402 EMWKTYRRYSDFHDFHMRITEQFENLSSiLKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLL 462
Cdd:cd07277   30 DEWNVYRRYSEFYELHKKLKKKFPVVRS-FDFPPKKAIGNKDAKFVEERRKRLQVYLRRVV 89

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 371 DPYAVAGVCNDHGKTYALYAITVHRRNLNTE----EMWKTYRRYSDFHDFHMRITEqFENLSSILKLPGKKTFNNMDRDF 446
Cdd:cd06877    7 IPYVEMRRDPSNGERIYVFCIEVERNDRRAKghepQHWSVLRRYNEFYVLESKLTE-FHGEFPDAPLPSRRIFGPKSYEF 85

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568977697 447 LEKRKKDLNAYLQLLLTPEMMKASPALahcvYDFL 481
Cdd:cd06877   86 LESKREIFEEFLQKLLQKPELRGSELL----YDFL 116

Regulator of G protein signaling (RGS) domain 2 found in the A-kinase anchoring protein, D-AKAP2; The RGS (Regulator of G-protein Signaling) domain is an essential part of the D-AKAP2 (A-kinase anchoring 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. D-AKAP2 contains two RGS domains which play an important role in spatiotemporal localization of cAMP-dependent PKA (cyclic AMP-dependent protein kinase) that regulates many different signaling pathways by phosphorylation of target proteins. This cd contains the second RGS domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 174 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYrvtaQQQLEVLSGrQRDGKQQTNQtkgllraaAVGIYEQYLSEKASP 253
Cdd:cd08721    1 ILYCESALFYFMEYMEQEGARNLLQFWLAADNF----QSQLAAKEG-QYDGQQAQND--------AMIIYDKYFSLQATE 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568977697 254 RVTVDDYLVAKLADTLNHED-PTPEIFDDIQRKVYELMlrDERFYPSFRQNALYVR 308
Cdd:cd08721   68 PLGFDDKTRLEVESNICREGgPLPSCFEAPLLQALTTL--EQHYLPGFLSSQLYYK 121

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 568977697 171 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevlsgrqRDGKQqtnqtkglLRAAAVGIYEQYLSEK 250
Cdd:cd08706    1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKI------------PDKKQ--------LVQEAREIYDTFLSSK 60

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568977697 251 ASPRVTVDDYlvAKLADTLnHEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 306
Cdd:cd08706   61 ASSPVNIDSQ--AQLAEEM-LEEPHPDMFQKQQLQIFNLMKFDS--YSRFLKSPLY 111

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 568977697 160 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEgyrvtaqqqlevlsgrqrDGKQQTNqtKGLLRAAA 239
Cdd:cd08746   51 GQSFDKLMLTP--------AGRNAFREFLRTEFSEENMLFWMACE------------------ELKKEAN--KSVIEEKA 102

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568977697 240 VGIYEQYLSEKASPRVTVDdylvAKLADTLNHE--DPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 306
Cdd:cd08746  103 RIIYEDYISILSPKEVSLD----SRVREVINRNmlEPSQHTFDDAQLQIYTLMHRDS--YPRFMNSAIY 165

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 384 KTYALYAITVhrrNLNTEEMWKTYRRYSDFHDFHMRITEqFENLSsiLKLPGKKTFN-NMDRDFLEKRKKDLNAYLQLLL 462
Cdd:cd06872   16 KSFAVYSVAV---TDNENETWVVKRRFRNFETLHRRLKE-VPKYN--LELPPKRFLSsSLDGAFIEERCKLLDKYLKDLL 89

                         90
                 ....*....|....*....
gi 568977697 463 TPEMMKASpalaHCVYDFL 481
Cdd:cd06872   90 VIEKVAES----HEVWSFL 104

Regulator of G protein signaling (RGS) domain 1 found in the A-kinase anchoring protein, D-AKAP2; The RGS (Regulator of G-protein Signaling) domain is an essential part of the D-AKAP2 (A-kinase anchoring 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. D-AKAP2 contains two RGS domains which play an important role in spatiotemporal localization of cAMP-dependent PKA (cyclic AMP-dependent protein kinase) that regulates many different signaling pathways by phosphorylation of target proteins. This cd contains the first RGS domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 171 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTA-------------QQQLEVLSGRQRDGKQQTNQTKGLLRA 237
Cdd:cd08735    5 LEQILHDNSALPYFIQFMETRRAEHLIKFWLEAESFKSAAwsrirahslntvkHSSLEEPVSPSLDRKVLESKSTDSLSQ 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 238 A----------------AVGIYEQYLSEKASPRVTVDD----YLVAKLADTLNHEDPTpeIFDDIQRKVYELMLRDerFY 297
Cdd:cd08735   85 RltddddeksmksierdAVSIYTKYISPDAAKPIPITEeirnDIVAKICGEDGQVDPN--CFVEAQSFVFSAMEQD--HF 160

                 ....*....
gi 568977697 298 PSFRQNALY 306
Cdd:cd08735  161 TEFLRSHFF 169

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 382 HGKTYALYAITVHRRNlnTEEMWKTYRRYSDFHDFHMRITEQFENLssilKLPGKKTFNNMDR----DFLEKRKKDLNAY 457
Cdd:cd06883   12 SPEKYYIYVVKVTREN--QTEPSFVFRTFEEFQELHNKLSLLFPSL----KLPSFPARVVLGRshikQVAERRKIELNSY 85

                         90       100
                 ....*....|....*....|....*.
gi 568977697 458 LQllltpEMMKASPALAHC--VYDFL 481
Cdd:cd06883   86 LK-----SLFNASPEVAESdlVYTFF 106

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 398 LNTEEMWKTYRRYSDFHDFHMRITEQFENLSS-------ILKLPGKKTFNNMDRdFLEKRKKDLNAYL-QLLLTPEMMKA 469
Cdd:cd06890   23 LSDGKTRYLCRYYQDFYKLHIALLDLFPAEAGrnsskriLPYLPGPVTDVVNDS-ISLKRLNDLNEYLnELINLPAYIQT 101

                         90
                 ....*....|....*
gi 568977697 470 SPAlahcVYDFLENK 484
Cdd:cd06890  102 SEV----VRDFFANR 112

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568977697 376 AGVCNDHGKTYALYAITVHRRNLNTEEMWKTYRRYSDFHDFHMRITEQFENLSSILKLPGKKTFNNMDRDFLEKRKKDLN 455
Cdd:cd07279    8 ARTVKEGEKKYVVYQLAVVQTGDPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAERSRAFE 87

                         90       100
                 ....*....|....*....|....*.
gi 568977697 456 AYLQLLLTPEMMKASPALAhcvyDFL 481
Cdd:cd07279   88 QFLGHILSIPNLRDSKAFL----DFL 109

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 568977697 171 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRvtaQQQLEVLSGRQRDgkqqtnqtkgllraaavgIYEQYLSEK 250
Cdd:cd08737   10 LDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLK---KQPLQDVAKRVEE------------------IWQEFLAPG 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568977697 251 ASPRVTVDDYLVAKLADtlNHEDPTPEIFDDIQRKVYELMLRDErfYPSF-RQNA 304
Cdd:cd08737   69 APSAINLDSHSYEKTSQ--NVKDPGRYTFEDAQEHIYKLMKSDS--YARFlRSNA 119

Regulator of G protein signaling (RGS) domain found in the RZ protein; The RGS (Regulator of G-protein Signaling) domain is an essential part 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 RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in reassociation of the alpha-subunit with the beta-gamma-dimer and 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 RZ subfamily of RGS proteins includes RGS17, RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568977697 242 IYEQYLSeKASPRVTVDDYLVAKLADTlNHEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 306
Cdd:cd08718   56 IYEDYIS-ILSPKEVSLDSRVREVINR-NMLEPSPHTFDDAQLQIYTLMHRDS--YPRFLNSAIY 116

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 568977697 160 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEgyrvtaqqqlevlsgrqrDGKQQtnQTKGLLRAAA 239
Cdd:cd08744    2 SQNFDKMMKTP--------AGRNLFREFLRTEYSEENLLFWLACE------------------DLKKE--QNKKVIEEKA 53

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568977697 240 VGIYEQYLSEKASPRVTVDdylvAKLADTLNHE--DPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 306
Cdd:cd08744   54 RLIYEDYISILSPKEVSLD----SRVREVINRNllDPNPHMYEDAQLQIYTLMHRDS--FPRFLNSQIY 116

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 568977697 171 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRvtaqqqlevlsgrqrdgKQQTNQtkgLLRAAAVGIYEQYLSEK 250
Cdd:cd08712    1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYK-----------------KSKTPQ---QIHLKAKAIYEKFIQTD 60