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 1186128525 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDGKHQTNQTKGLLRAAAVGIYEQYLSEKASP 456
Cdd:cd08719     1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1186128525 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 1186128525 557 DSVQLHAYISDTvyadydpyavaGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILK 635
Cdd:cd06873     1 DKFKLTAVIINT-----------GIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLS 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1186128525 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 1186128525 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDGKHQTNQTKGLLRAAAVGIYEQYLSEKASP 456
Cdd:cd08719     1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1186128525 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 1186128525 557 DSVQLHAYISDTvyadydpyavaGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILK 635
Cdd:cd06873     1 DKFKLTAVIINT-----------GIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLS 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1186128525 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 1186128525 803 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAEAVPCRDKSIRMRTRVAGKTKLL 882
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 1186128525 883 AIMPDELKHIIGAETTRKGILRVFEMFQH 911
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 1186128525  584 DHGKTYALYAITVHRRNlnSEEMWKTYRRYSDFHDFHMRITEQFeSLSSILKLPGKKTF---NNMDRDFLEKRKKDLNAY 660
Cdd:smart00312   7 IGDGKHYYYVIEIETKT--GLEEWTVSRRYSDFLELHSKLKKHF-PRSILPPLPGKKLFgrlNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|....*.
gi 1186128525  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 1186128525 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQlevllsrqrdgkhqtnqtkgLLRAAAVGIYEQYLSEK 453
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDE--------------------ERLKKAKEIYNEFLAPG 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1186128525 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 1186128525 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDGKHQTNQTKGLLRAAAVGIYEQYLSEKASP 456
Cdd:cd08719     1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSAEQQLSELHLRQRGGEHQRSDVYEMLRAAALNIYDQYLSEKASP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1186128525 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 1186128525 557 DSVQLHAYISDTvyadydpyavaGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILK 635
Cdd:cd06873     1 DKFKLTAVIINT-----------GIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLS 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1186128525 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 1186128525 803 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAEAVPCRDKSIRMRTRVAGKTKLL 882
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 1186128525 883 AIMPDELKHIIGAETTRKGILRVFEMFQH 911
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 1186128525  584 DHGKTYALYAITVHRRNlnSEEMWKTYRRYSDFHDFHMRITEQFeSLSSILKLPGKKTF---NNMDRDFLEKRKKDLNAY 660
Cdd:smart00312   7 IGDGKHYYYVIEIETKT--GLEEWTVSRRYSDFLELHSKLKKHF-PRSILPPLPGKKLFgrlNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|....*.
gi 1186128525  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 1186128525 581 VCNDHGKTYALYAITVHRRNLNSeemWKTYRRYSDFHDFHMRITEQFESlSSILKLPGKKTFNNMDRDFLEKRKKDLNAY 660
Cdd:cd06093     9 KVKDGGKKYVVYIIEVTTQGGEE---WTVYRRYSDFEELHEKLKKKFPG-VILPPLPPKKLFGNLDPEFIEERRKQLEQY 84

                          90       100
                  ....*....|....*....|....*
gi 1186128525 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 1186128525 579 AGVCNDHGKTYALYAITVHRRNLNSEEM------WKTYRRYSDFHDFHMRITEQFESLSSI-LKLPGKKTFNNMDRDFLE 651
Cdd:cd06878    16 AEVTVEDDKEVPLYVIVVHVSEVGLNEDesissgWVVTRKLSEFHDLHRKLKECSSWLKKVeLPSLSKKWFKSIDKKFLD 95

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1186128525 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 1186128525 592 YAITVhRRNLNSEEMWKTYRRYSDFHDFHmriteqfESL--SSI-LKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLape 668
Cdd:cd06871    24 YIIRV-QRGPSPENSWQVIRRYNDFDLLN-------ASLqiSGIsLPLPPKKLIGNMDREFIAERQQGLQNYLNVIL--- 92

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1186128525 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 1186128525 605 EMWKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLL 665
Cdd:cd07277    30 DEWNVYRRYSEFYELHKKLKKKFPVVRS-FDFPPKKAIGNKDAKFVEERRKRLQVYLRRVV 89

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128525 584 DHGKTYALYAITVHRRNlnseEMWKTYRRYSDFHDFHMRITEQFESLSsiLKLPGKKTF-NNMDRDFLEKRKKDLNAYLQ 662
Cdd:cd06870    15 EKKKRFTVYKVVVSVGR----SSWFVFRRYAEFDKLYESLKKQFPASN--LKIPGKRLFgNNFDPDFIKQRRAGLDEFIQ 88

                  ....*....
gi 1186128525 663 -LLLAPEMM 670
Cdd:cd06870    89 rLVSDPKLL 97

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 1186128525 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYrvtaQQQLEvLLSRQRDGKHQTNQtkgllraaAVGIYEQYLSEKASP 456
Cdd:cd08721     1 ILYCESALFYFMEYMEQEGARNLLQFWLAADNF----QSQLA-AKEGQYDGQQAQND--------AMIIYDKYFSLQATE 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1186128525 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 1186128525 589 YALYAITVHRRNlnsEEMWKTYRRYSDFHDFHMRITEQFESLssILKLPGKKTF-NNMDRDFLEKRKKDLNAYLQLLLA- 666
Cdd:cd07276    20 FTVYKIRVENKV---GDSWFVFRRYTDFVRLNDKLKQMFPGF--RLSLPPKRWFkDNFDPDFLEERQLGLQAFVNNIMAh 94

                          90
                  ....*....|....*...
gi 1186128525 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 1186128525 587 KTYALYAITVhrrNLNSEEMWKTYRRYSDFHDFHMRITEQFEslsSILKLPGKKTFN-NMDRDFLEKRKKDLNAYLQLLL 665
Cdd:cd06872    16 KSFAVYSVAV---TDNENETWVVKRRFRNFETLHRRLKEVPK---YNLELPPKRFLSsSLDGAFIEERCKLLDKYLKDLL 89

                          90
                  ....*....|....*....
gi 1186128525 666 APEMMKASpalaHYVYDFL 684
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 1186128525 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTA-------------QQQLEVLLSRQRDGKHQTNQTKGLLRA 440
Cdd:cd08735     5 LEQILHDNSALPYFIQFMETRRAEHLIKFWLEAESFKSAAwsrirahslntvkHSSLEEPVSPSLDRKVLESKSTDSLSQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128525 441 A----------------AVGIYEQYLSEKASPRVTVDD----YLVAKLADTLNHEDPTpeIFDDIQRKVYELMLRDerFY 500
Cdd:cd08735    85 RltddddeksmksierdAVSIYTKYISPDAAKPIPITEeirnDIVAKICGEDGQVDPN--CFVEAQSFVFSAMEQD--HF 160

                  ....*....
gi 1186128525 501 PSFRQNALY 509
Cdd:cd08735   161 TEFLRSHFF 169

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 1186128525 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQqlevllsrqrdgkhqtnqtkgLLRAAAVGIYEQYLSEK 453
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESD---------------------LLPCKAEEIYKEFVQSD 59

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1186128525 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 1186128525 363 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLevllsrqRDGKHQTnqtkgllraaa 442
Cdd:cd08745     2 AQSFDKLMKSP--------AGRNVFREFLRTEYSEENMLFWLACEELKAEANKHV-------IDEKARL----------- 55

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1186128525 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 1186128525 601 LNSEEMWKTYRRYSDFHDFHMRITEQFESLSS-------ILKLPGKKTFNNMDRdFLEKRKKDLNAYL-QLLLAPEMMKA 672
Cdd:cd06890    23 LSDGKTRYLCRYYQDFYKLHIALLDLFPAEAGrnsskriLPYLPGPVTDVVNDS-ISLKRLNDLNEYLnELINLPAYIQT 101

                          90
                  ....*....|....*
gi 1186128525 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 1186128525 579 AGVCNDHGKTYALYAITVHRRNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSSILKLPGKKTFNNMDRDFLEKRKKDLN 658
Cdd:cd07279     8 ARTVKEGEKKYVVYQLAVVQTGDPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAERSRAFE 87

                          90       100
                  ....*....|....*....|...
gi 1186128525 659 AYLQLLLAPEMMKASPALAHYVY 681
Cdd:cd07279    88 QFLGHILSIPNLRDSKAFLDFLQ 110

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 1186128525 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRvtaQQQLEVLLSRQRDgkhqtnqtkgllraaavgIYEQYLSEK 453
Cdd:cd08737    10 LDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLK---KQPLQDVAKRVEE------------------IWQEFLAPG 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1186128525 454 ASPRVTVDDYLVAKLADtlNHEDPTPEIFDDIQRKVYELMLRDErfYPSF-RQNA 507
Cdd:cd08737    69 APSAINLDSHSYEKTSQ--NVKDPGRYTFEDAQEHIYKLMKSDS--YARFlRSNA 119

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 1186128525 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSrqrdgkhqtnqtkgllraaavGIYEQYLSEKASP 456
Cdd:cd08740    13 LLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVD---------------------SVYQQFLAPGATR 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1186128525 457 RVTVDDYLVAKLADTLnhEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRMLAE 515
Cdd:cd08740    72 WVNIDSKTMERTLEGL--KQPHRYVLDDAQMHIYMLMKKDS--YPRFLKSDLYKNLLAE 126