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 767945103 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDGKHQTNQTKGLLRAAAVGIYEQYLSEKASP 456
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767945103 457 RVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDERFYPSFRQNALYVR 511
Cdd:cd08719   81 RVPLDDSLVKKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDERFYPAFKKSPAYVK 135

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains 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. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 557 DSVQLHAYISDTvyadydpyavaGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILK 635
Cdd:cd06873    1 DKFKLTAVIINT-----------GIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLS 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767945103 636 LPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 687
Cdd:cd06873   69 FPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

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 767945103 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDGKHQTNQTKGLLRAAAVGIYEQYLSEKASP 456
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767945103 457 RVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDERFYPSFRQNALYVR 511
Cdd:cd08719   81 RVPLDDSLVKKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDERFYPAFKKSPAYVK 135

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains 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. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 557 DSVQLHAYISDTvyadydpyavaGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILK 635
Cdd:cd06873    1 DKFKLTAVIINT-----------GIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLS 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767945103 636 LPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 687
Cdd:cd06873   69 FPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

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 767945103  749 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAEAVPCRDKSIRMRTRVAGKTKLL 828
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 767945103  829 AIMPDELKHIIGAETTRKGILRVFEMFQH 857
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQN 109

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103   584 DHGKTYALYAITVHRRNlnSEEMWKTYRRYSDFHDFHMRITEQFeSLSSILKLPGKKTF---NNMDRDFLEKRKKDLNAY 660
Cdd:smart00312   7 IGDGKHYYYVIEIETKT--GLEEWTVSRRYSDFLELHSKLKKHF-PRSILPPLPGKKLFgrlNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|....*.
gi 767945103   661 LQLLL-APEMMKASPAlahyVYDFLE 685
Cdd:smart00312  84 LQSLLnHPELINHSEV----VLEFLE 105

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 767945103  374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQlevllsrqrdgkhqtnqtkgLLRAAAVGIYEQYLSEK 453
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDE--------------------ERLKKAKEIYNEFLAPG 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 767945103  454 ASPRVTVDDYLVAKLADTLNHEdPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRM 512
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 767945103 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDGKHQTNQTKGLLRAAAVGIYEQYLSEKASP 456
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767945103 457 RVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDERFYPSFRQNALYVR 511
Cdd:cd08719   81 RVPLDDSLVKKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDERFYPAFKKSPAYVK 135

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains 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. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 557 DSVQLHAYISDTvyadydpyavaGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILK 635
Cdd:cd06873    1 DKFKLTAVIINT-----------GIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLS 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767945103 636 LPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 687
Cdd:cd06873   69 FPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

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 767945103  749 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAEAVPCRDKSIRMRTRVAGKTKLL 828
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 767945103  829 AIMPDELKHIIGAETTRKGILRVFEMFQH 857
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQN 109

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103   584 DHGKTYALYAITVHRRNlnSEEMWKTYRRYSDFHDFHMRITEQFeSLSSILKLPGKKTF---NNMDRDFLEKRKKDLNAY 660
Cdd:smart00312   7 IGDGKHYYYVIEIETKT--GLEEWTVSRRYSDFLELHSKLKKHF-PRSILPPLPGKKLFgrlNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|....*.
gi 767945103   661 LQLLL-APEMMKASPAlahyVYDFLE 685
Cdd:smart00312  84 LQSLLnHPELINHSEV----VLEFLE 105

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and 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. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 581 VCNDHGKTYALYAITVHRRNLNSeemWKTYRRYSDFHDFHMRITEQFESlSSILKLPGKKTFNNMDRDFLEKRKKDLNAY 660
Cdd:cd06093    9 KVKDGGKKYVVYIIEVTTQGGEE---WTVYRRYSDFEELHEKLKKKFPG-VILPPLPPKKLFGNLDPEFIEERRKQLEQY 84

                         90       100
                 ....*....|....*....|....*
gi 767945103 661 LQLLLAPEMMKASPALahyvYDFLE 685
Cdd:cd06093   85 LQSLLNHPELRNSEEL----KEFLE 105

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 767945103 579 AGVCNDHGKTYALYAITVHRRNLNSEEM------WKTYRRYSDFHDFHMRITEQFESLSSI-LKLPGKKTFNNMDRDFLE 651
Cdd:cd06878   16 AEVTVEDDKEVPLYVIVVHVSEVGLNEDesissgWVVTRKLSEFHDLHRKLKECSSWLKKVeLPSLSKKWFKSIDKKFLD 95

                         90       100       110
                 ....*....|....*....|....*....|...
gi 767945103 652 KRKKDLNAYLQLLLAPEMMKASPALahyvYDFL 684
Cdd:cd06878   96 KSKNQLQKYLQFILEDETLCQSEAL----YSFL 124

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; 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. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 592 YAITVhRRNLNSEEMWKTYRRYSDFHDFHmriteqfESL--SSI-LKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLape 668
Cdd:cd06871   24 YIIRV-QRGPSPENSWQVIRRYNDFDLLN-------ASLqiSGIsLPLPPKKLIGNMDREFIAERQQGLQNYLNVIL--- 92

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767945103 669 mmkASPALAHY--VYDFLENKAYSKGKGDFA 697
Cdd:cd06871   93 ---MNPILASClpVKKFLDPNNYSANFTEIA 120

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 767945103 605 EMWKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLL 665
Cdd:cd07277   30 DEWNVYRRYSEFYELHKKLKKKFPVVRS-FDFPPKKAIGNKDAKFVEERRKRLQVYLRRVV 89

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 584 DHGKTYALYAITVHRRNLNSEEM-WKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKK--TFNNMDRDFLEKRKKDLNAY 660
Cdd:cd06876   33 EEGKEFVVYLIEVQRLNNDDQSSgWVVARRYSEFLELHKYLKKRYPGVLK-LDFPQKRkiSLKYSKTLLVEERRKALEKY 111

                 ....*....
gi 767945103 661 LQ-LLLAPE 668
Cdd:cd06876  112 LQeLLKIPE 120

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 767945103 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYrvtaQQQLEvLLSRQRDGKHQTNQtkgllraaAVGIYEQYLSEKASP 456
Cdd:cd08721    1 ILYCESALFYFMEYMEQEGARNLLQFWLAADNF----QSQLA-AKEGQYDGQQAQND--------AMIIYDKYFSLQATE 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767945103 457 RVTVDDYLVAKLADTLNHED-PTPEIFDDIQRKVYELMlrDERFYPSFRQNALYVR 511
Cdd:cd08721   68 PLGFDDKTRLEVESNICREGgPLPSCFEAPLLQALTTL--EQHYLPGFLSSQLYYK 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 589 YALYAITVHRRNlnsEEMWKTYRRYSDFHDFHMRITEQFESLssILKLPGKKTF-NNMDRDFLEKRKKDLNAYLQLLLA- 666
Cdd:cd07276   20 FTVYKIRVENKV---GDSWFVFRRYTDFVRLNDKLKQMFPGF--RLSLPPKRWFkDNFDPDFLEERQLGLQAFVNNIMAh 94

                         90
                 ....*....|....*...
gi 767945103 667 PEMMKASPalahyVYDFL 684
Cdd:cd07276   95 KDIAKCKL-----VREFF 107

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 767945103 587 KTYALYAITVhrrNLNSEEMWKTYRRYSDFHDFHMRITEQFEslsSILKLPGKKTFN-NMDRDFLEKRKKDLNAYLQLLL 665
Cdd:cd06872   16 KSFAVYSVAV---TDNENETWVVKRRFRNFETLHRRLKEVPK---YNLELPPKRFLSsSLDGAFIEERCKLLDKYLKDLL 89

                         90
                 ....*....|....*....
gi 767945103 666 APEMMKASpalaHYVYDFL 684
Cdd:cd06872   90 VIEKVAES----HEVWSFL 104

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 767945103 363 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAqqqlevllsrqrdgkhqtnqTKGLLRAAA 442
Cdd:cd08746   51 GQSFDKLMLTP--------AGRNAFREFLRTEFSEENMLFWMACEELKKEA--------------------NKSVIEEKA 102

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767945103 443 VGIYEQYLSEKASPRVTVDdylvAKLADTLNHE--DPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 509
Cdd:cd08746  103 RIIYEDYISILSPKEVSLD----SRVREVINRNmlEPSQHTFDDAQLQIYTLMHRDS--YPRFMNSAIY 165

Regulator of G protein signaling (RGS) domain found in the RGS1 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS1 protein. RGS1 is a 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. RGS 1 is expressed predominantly in hematopoietic compartments, including T and B lymphocytes, and may play a major role in chemokine-mediated homing of lymphocytes to secondary lymphoid organs. In addition, RGS1 interacts with calmodulin and 14-3-3 protein outside of the GPCR pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQqlevllsrqrdgkhqtnqtkgLLRAAAVGIYEQYLSEK 453
Cdd:cd08715    1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESD---------------------LLPCKAEEIYKEFVQSD 59

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 767945103 454 ASPRVTVDDYLVAKLADTLnhEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRM 512
Cdd:cd08715   60 AAKQINIDFRTRESTAKKI--KAPTPTCFDEAQKVIYILMERDS--YPRFLKSDIYLNL 114

Regulator of G protein signaling (RGS) domain found in the RGS19 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS19 protein (also known as GAIP), 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 RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, resulting in a reassociation of the alpha-subunit with the beta-gamma-dimer and an 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 includes RGS17, RGS20, and its splice variant Ret-RGS. RGS19 participates in regulation of dopamine receptor D2R and D3R, as well as beta-adrenergic receptors .

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 363 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLevllsrqRDGKHQTnqtkgllraaa 442
Cdd:cd08745    2 AQSFDKLMKSP--------AGRNVFREFLRTEYSEENMLFWLACEELKAEANKHV-------IDEKARL----------- 55

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767945103 443 vgIYEQYLSEKASPRVTVDdylvAKLADTLNH--EDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 509
Cdd:cd08745   56 --IYEDYISILSPKEVSLD----SRVREGINRkmQEPSSHTFDDAQLQIYTLMHRDS--YPRFLNSPIY 116

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 767945103 601 LNSEEMWKTYRRYSDFHDFHMRITEQFESLSS-------ILKLPGKKTFNNMDRdFLEKRKKDLNAYL-QLLLAPEMMKA 672
Cdd:cd06890   23 LSDGKTRYLCRYYQDFYKLHIALLDLFPAEAGrnsskriLPYLPGPVTDVVNDS-ISLKRLNDLNEYLnELINLPAYIQT 101

                         90
                 ....*....|....*
gi 767945103 673 SPAlahyVYDFLENK 687
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 767945103 579 AGVCNDHGKTYALYAITVHRRNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSSILKLPGKKTFNNMDRDFLEKRKKDLN 658
Cdd:cd07279    8 ARTVKEGEKKYVVYQLAVVQTGDPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAERSRAFE 87

                         90       100
                 ....*....|....*....|...
gi 767945103 659 AYLQLLLAPEMMKASPALAHYVY 681
Cdd:cd07279   88 QFLGHILSIPNLRDSKAFLDFLQ 110

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 is a 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). 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 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. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQleVLLSRQRDgkhqtnqtkgllraaavgIYEQYLSEK 453
Cdd:cd08713    1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQS--KMASRAKK------------------IFAEYIAIQ 60

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767945103 454 ASPRVTVDDYLVAKLADTLnhEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 509
Cdd:cd08713   61 SCKEVNLDSYTREHTKENL--QNPTRGCFDLAQKRIYGLMEKDS--YPRFLRSDLY 112

Regulator of G protein signaling (RGS) domain found in the RGS11 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS11 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). 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. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS7, and RGS9, 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. RGS11 is expressed exclusively in retinal ON-bipolar neurons in which it forms complexes with G-beta-5 and R7AP (RGS7 anchor protein ) and plays crucial roles in processing the light responses of retinal neurons.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767945103 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSrqrdgkhqtnqtkgllraaavGIYEQYLSEKASP 456
Cdd:cd08740   13 LLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVD---------------------SVYQQFLAPGATR 71

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 767945103 457 RVTVDDYLVAKLADTLnhEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRMLAE 515
Cdd:cd08740   72 WVNIDSKTMERTLEGL--KQPHRYVLDDAQMHIYMLMKKDS--YPRFLKSDLYKNLLAE 126