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 17864088 557 DSVQLHAYISDTGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMD 635
Cdd:cd06873   1 DKFKLTAVIINTGIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLSFPGKKTFNNLD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 17864088 636 RDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 676
Cdd:cd06873  80 RAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 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 17864088   792 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAEAVPCRDKSIRMRTRVAGKTKLL 871
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 17864088   872 AIMPDELKHIIGAETTRKGILRVFEMFQH 900
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQN 109

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 17864088 557 DSVQLHAYISDTGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMD 635
Cdd:cd06873   1 DKFKLTAVIINTGIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLSFPGKKTFNNLD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 17864088 636 RDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 676
Cdd:cd06873  80 RAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088    98 NIIDEPLQQVIQFSLRDYVQYWYYTLSDDESFLLEIRQTLQNALIQFATRSKEIDWQPYFTTRIVDDFGTHLRVFRKAQQ 177
Cdd:pfam02194   2 PEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAEE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088   178 KITEKDDQvkGTAEDLVDTFFEVEVEMEKEVCRDLVCTSPKDEEGFLRDLCEVLLYLLLPPGDFQNKIMRYFVREILARG 257
Cdd:pfam02194  82 AVRGKKLN--ELDLALASKYLALKPHPALSPVLLSSSQSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACL 159

                         170       180
                  ....*....|....*....|..
gi 17864088   258 ILLPLINQLSDPDYINQYVIWM 279
Cdd:pfam02194 160 VLLPVINKLSDPDFINELIVKL 181

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088    373 PLDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevllsrqrdgkhqtnQTKGLLRAAAVGIYEQYLSE 452
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKA--------------------EDDEERIAKAREIYDKFLSP 60

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088    453 KASPRVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVRM 512
Cdd:smart00315  61 NAPKEVNLDSDLREKIEENLESEEPPPDLFDEAQREVYELLEKD--SFPRFLESDYYLRF 118

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088   588 RNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPAlah 667
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEV--- 76

                  ....*..
gi 17864088   668 yVYDFLE 674
Cdd:pfam00787  77 -LLEFLE 82

Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088 573 DHGKTYALYAITVHRRN----LNSEEMWKTYRRYSDFHDFHMRITEQFEsLSSILKLPGKKT-----FNNMDRDFLEKRK 643
Cdd:COG5391 146 DSRDKHTSYEIITVTNLpsfqLRESRPLVVRRRYSDFESLHSILIKLLP-LCAIPPLPSKKSnseyyGDRFSDEFIEERR 224

                        90
                ....*....|....*
gi 17864088 644 KDLNAYLQLL-LAPE 657
Cdd:COG5391 225 QSLQNFLRRVsTHPL 239

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 17864088 557 DSVQLHAYISDTGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMD 635
Cdd:cd06873   1 DKFKLTAVIINTGIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLSFPGKKTFNNLD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 17864088 636 RDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 676
Cdd:cd06873  80 RAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088    98 NIIDEPLQQVIQFSLRDYVQYWYYTLSDDESFLLEIRQTLQNALIQFATRSKEIDWQPYFTTRIVDDFGTHLRVFRKAQQ 177
Cdd:pfam02194   2 PEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAEE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088   178 KITEKDDQvkGTAEDLVDTFFEVEVEMEKEVCRDLVCTSPKDEEGFLRDLCEVLLYLLLPPGDFQNKIMRYFVREILARG 257
Cdd:pfam02194  82 AVRGKKLN--ELDLALASKYLALKPHPALSPVLLSSSQSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACL 159

                         170       180
                  ....*....|....*....|..
gi 17864088   258 ILLPLINQLSDPDYINQYVIWM 279
Cdd:pfam02194 160 VLLPVINKLSDPDFINELIVKL 181

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088    373 PLDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevllsrqrdgkhqtnQTKGLLRAAAVGIYEQYLSE 452
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKA--------------------EDDEERIAKAREIYDKFLSP 60

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088    453 KASPRVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVRM 512
Cdd:smart00315  61 NAPKEVNLDSDLREKIEENLESEEPPPDLFDEAQREVYELLEKD--SFPRFLESDYYLRF 118

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 17864088 378 LVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEvllsrqrdgkhqtnqtkglLRAAAVGIYEQYLSEKASPR 457
Cdd:cd07440   1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDEE-------------------LKSKAKEIYDKYISKDAPKE 61

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 17864088 458 VTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVR 511
Cdd:cd07440  62 INIPESIREEIEENLEEPYPDPDCFDEAQEHILNLLEKD--SYPRFLKSDLYLK 113

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088   588 RNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPAlah 667
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEV--- 76

                  ....*..
gi 17864088   668 yVYDFLE 674
Cdd:pfam00787  77 -LLEFLE 82

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 17864088 556 DDSVQLHAYIsdTGVCNDHGKTYalYAITVhRRNLNSEEMWKTYRRYSDFHDFHmriteqfESL--SSI-LKLPGKKTFN 632
Cdd:cd06871   3 DDTVPLTCVI--EASQNIQSHTE--YIIRV-QRGPSPENSWQVIRRYNDFDLLN-------ASLqiSGIsLPLPPKKLIG 70

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17864088 633 NMDRDFLEKRKKDLNAYLQLLLapemmkASPALAHY--VYDFLENKAYSKGKGDFA 686
Cdd:cd06871  71 NMDREFIAERQQGLQNYLNVIL------MNPILASClpVKKFLDPNNYSANFTEIA 120

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; 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. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. 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. 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 17864088 573 DHGKTYALYAITVHrrnlNSEEMWKTYRRYSDFHDFHMRITEQFeslsSILK--LPGKKTFNNMDRDFLEKRKKDLNAYL 650
Cdd:cd06875  12 ETVEGYTVYIIEVK----VGSVEWTVKHRYSDFAELHDKLVAEH----KVDKdlLPPKKLIGNKSPSFVEKRRKELEIYL 83

                        90       100
                ....*....|....*....|....*
gi 17864088 651 QLLLApEMMKASP-ALAHyvydFLE 674
Cdd:cd06875  84 QTLLS-FFQKTMPrELAH----FLD 103

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 17864088 559 VQLHAYISDTgvcNDHGKTYALYAITVHRRNLNSEEM-WKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKK--TFNNMD 635
Cdd:cd06876  22 VSIQSYISDV---EEEGKEFVVYLIEVQRLNNDDQSSgWVVARRYSEFLELHKYLKKRYPGVLK-LDFPQKRkiSLKYSK 97

                        90       100
                ....*....|....*....|...
gi 17864088 636 RDFLEKRKKDLNAYLQ-LLLAPE 657
Cdd:cd06876  98 TLLVEERRKALEKYLQeLLKIPE 120

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 17864088 573 DHGKTYALYAITVHRRNlnseEMWKTYRRYSDFHDFHMRITEQFESLSsiLKLPGKKTF-NNMDRDFLEKRKKDLNAYLQ 651
Cdd:cd06870  15 EKKKRFTVYKVVVSVGR----SSWFVFRRYAEFDKLYESLKKQFPASN--LKIPGKRLFgNNFDPDFIKQRRAGLDEFIQ 88

                ....*....
gi 17864088 652 -LLLAPEMM 659
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 17864088 377 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYrvtaQQQLEvLLSRQRDGKHQTNQtkgllraaAVGIYEQYLSEKASP 456
Cdd:cd08721   1 ILYCESALFYFMEYMEQEGARNLLQFWLAADNF----QSQLA-AKEGQYDGQQAQND--------AMIIYDKYFSLQATE 67

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17864088 457 RVTVDDYLVAKLADTLNHED-PTPEIFDDIQRKVYELMlrDERFYPSFRQNALYVR 511
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 17864088 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYR-VTAQQQLevllsrqrdgkhqtnqtkgllRAAAVGIYEQYLSE 452
Cdd:cd08706   1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKkIPDKKQL---------------------VQEAREIYDTFLSS 59

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17864088 453 KASPRVTVDDYlvAKLADTLnHEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 509
Cdd:cd08706  60 KASSPVNIDSQ--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 17864088 363 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAqqqlevllsrqrdgkhqtnqTKGLLRAAA 442
Cdd:cd08746  51 GQSFDKLMLTP--------AGRNAFREFLRTEFSEENMLFWMACEELKKEA--------------------NKSVIEEKA 102

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17864088 443 VGIYEQYLSEKASPRVTVDdylvAKLADTLNHE--DPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 509
Cdd:cd08746 103 RIIYEDYISILSPKEVSLD----SRVREVINRNmlEPSQHTFDDAQLQIYTLMHRDS--YPRFMNSAIY 165

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; 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. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. 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 YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088 575 GKTYALYAITVHRRNLNSEEMwKTYRRYSDFHDFHMRITEQF--ESLSSILKLPGKKTF----NNMDRDFLEKRKKDLNA 648
Cdd:cd07280  19 GGAYVVWKITIETKDLIGSSI-VAYKRYSEFVQLREALLDEFprHKRNEIPQLPPKVPWydsrVNLNKAWLEKRRRGLQY 97

                        90       100
                ....*....|....*....|..
gi 17864088 649 YLQ-LLLAPEMMkASPALAHYV 669
Cdd:cd07280  98 FLNcVLLNPVFG-GSPVVKEFL 118

Regulator of G protein signaling (RGS) domain found in the RGS10 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS10 protein. RGS10 is a member of the RA/RGS subfamily of RGS proteins 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. RGS10 belong to the R12 RGS subfamily, which includes RGS12 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS10 exists in 2 splice isoforms. RGS10A is specifically expressed in osteoclasts and is a key component in the RANKL signaling mechanism for osteoclast differentiation, whereas RGS10B expressed in brain and in immune tissues and has been implicated in diverse processes including: promoting of dopaminergic neuron survival via regulation of the microglial inflammatory response, modulation of presynaptic and postsynaptic G-protein signalling, as well as a possible role in regulation of gene expression.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevllsrqrdgkhqtnQTKGLLRAAAVGIYEQYLSEK 453
Cdd:cd08741   1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKM--------------------QDKTQMQEKAKEIYMTFLSSK 60

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 17864088 454 ASPRVTVDDYlvAKLADTLnHEDPTPEIFDDIQRKVYELMLRD--ERFYPS 502
Cdd:cd08741  61 ASSQVNVEGQ--SRLNEKI-LEEPHPLMFQKLQDQIFNLMKYDsySRFLKS 108

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 17864088 574 HGKTYALYAITVHRRNlnSEEMWKTYRRYSDFHDFHMRITEQFESlssiLKLPGKKTFNNMDR----DFLEKRKKDLNAY 649
Cdd:cd06883  12 SPEKYYIYVVKVTREN--QTEPSFVFRTFEEFQELHNKLSLLFPS----LKLPSFPARVVLGRshikQVAERRKIELNSY 85

                        90       100
                ....*....|....*....|....*.
gi 17864088 650 LQlllapEMMKASPALAHY--VYDFL 673
Cdd:cd06883  86 LK-----SLFNASPEVAESdlVYTFF 106

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; 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. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17864088 592 SEEMWKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLapEMMKASPA 664
Cdd:cd06874  28 LDETWTVFRRYSRFRELHKTMKLKYPEVAA-LEFPPKKLFGNKSERVAKERRRQLETYLRNFF--SVCLKLPA 97

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 17864088 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRvtaQQQLEVLLSRQRDgkhqtnqtkgllraaavgIYEQYLSEK 453
Cdd:cd08737  10 LDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLK---KQPLQDVAKRVEE------------------IWQEFLAPG 68

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 17864088 454 ASPRVTVDDYLVAKLADtlNHEDPTPEIFDDIQRKVYELMLRDErfYPSF-RQNA 507
Cdd:cd08737  69 APSAINLDSHSYEKTSQ--NVKDPGRYTFEDAQEHIYKLMKSDS--YARFlRSNA 119

Regulator of G protein signaling (RGS) domain found in the RGS12 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS12 protein. RGS12 is a member of the RA/RGS subfamily of RGS proteins 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. RGS12 belong to the R12 RGS subfamily, which includes RGS10 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS12 exist in multiple splice variants: RGS12s (short) contains the core RGS/RBD/GoLoco domains, while RGS12L (long) has additional N-terminal PDZ and PTB domains. RGS12 splice variants show distinct expression patterns, suggesting that they have discrete functions during mouse embryogenesis. RGS12 also may play a critical role in coordinating Ras-dependent signals that are required for promoting and maintaining neuronal differentiation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17864088 374 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSRQRDgkhqtnqtkgllraaavgIYEQYLSEK 453
Cdd:cd08742   1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAHDKKELSYRARE------------------IFSKFLCSK 62

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17864088 454 ASPRVTVDDYlvAKLADTLNHEdPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 509
Cdd:cd08742  63 ATTPVNIDSQ--AQLADDILNA-PHPDMFKEQQLQIFNLMKFDS--YTRFLKSPLY 113