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 1186128483 477 DSVQLHAYISDTGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMD 555
Cdd:cd06873     1 DKFKLTAVIINTGIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLSFPGKKTFNNLD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1186128483 556 RDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 596
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 1186128483 712 WLRRNIKNLLQQLIRATYGDTINRKIVDHVDWMTSPEQVADSVKRFRDAFWPNGILAEAVPCRDKSIRMRTRVAGKTKLL 791
Cdd:pfam08628   1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAEPPPERTEEEKLRTRKEARKLLL 80

                          90       100
                  ....*....|....*....|....*....
gi 1186128483 792 AIMPDELKHIIGAETTRKGILRVFEMFQH 820
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 1186128483 477 DSVQLHAYISDTGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMD 555
Cdd:cd06873     1 DKFKLTAVIINTGIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLSFPGKKTFNNLD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1186128483 556 RDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 596
Cdd:cd06873    80 RAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483  18 NIIDEPLQQVIQFSLRDYVQYWYYTLSDDESFLLEIRQTLQNALIQFATRSKEIDWQPYFTTRIVDDFGTHLRVFRKAQQ 97
Cdd:pfam02194   2 PEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAEE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483  98 KITEKDDQvkGTAEDLVDTFFEVEVEMEKEVCRDLVCTSPKDEEGFLRDLCEVLLYLLLPPGDFQNKIMRYFVREILARG 177
Cdd:pfam02194  82 AVRGKKLN--ELDLALASKYLALKPHPALSPVLLSSSQSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACL 159

                         170       180
                  ....*....|....*....|..
gi 1186128483 178 ILLPLINQLSDPDYINQYVIWM 199
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 1186128483  293 PLDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevllsrqrdgkhqtnQTKGLLRAAAVGIYEQYLSE 372
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKA--------------------EDDEERIAKAREIYDKFLSP 60

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483  373 KASPRVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVRM 432
Cdd:smart00315  61 NAPKEVNLDSDLREKIEENLESEEPPPDLFDEAQREVYELLEKD--SFPRFLESDYYLRF 118

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483 508 RNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPAlah 587
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEV--- 76

                  ....*..
gi 1186128483 588 yVYDFLE 594
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 1186128483 493 DHGKTYALYAITVHRRN----LNSEEMWKTYRRYSDFHDFHMRITEQFEsLSSILKLPGKKT-----FNNMDRDFLEKRK 563
Cdd:COG5391   146 DSRDKHTSYEIITVTNLpsfqLRESRPLVVRRRYSDFESLHSILIKLLP-LCAIPPLPSKKSnseyyGDRFSDEFIEERR 224

                          90
                  ....*....|....*
gi 1186128483 564 KDLNAYLQLL-LAPE 577
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 1186128483 477 DSVQLHAYISDTGVCNDHGKTYALYAITVHRRNLN-SEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMD 555
Cdd:cd06873     1 DKFKLTAVIINTGIVKEHGKTYAVYAISVTRIYPNgQEESWHVYRRYSDFHDLHMRLKEKFPNLS-KLSFPGKKTFNNLD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1186128483 556 RDFLEKRKKDLNAYLQLLLAPEMMKASPALAHYVYDFLENK 596
Cdd:cd06873    80 RAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVLDFLEPG 120

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483  18 NIIDEPLQQVIQFSLRDYVQYWYYTLSDDESFLLEIRQTLQNALIQFATRSKEIDWQPYFTTRIVDDFGTHLRVFRKAQQ 97
Cdd:pfam02194   2 PEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAEE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483  98 KITEKDDQvkGTAEDLVDTFFEVEVEMEKEVCRDLVCTSPKDEEGFLRDLCEVLLYLLLPPGDFQNKIMRYFVREILARG 177
Cdd:pfam02194  82 AVRGKKLN--ELDLALASKYLALKPHPALSPVLLSSSQSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACL 159

                         170       180
                  ....*....|....*....|..
gi 1186128483 178 ILLPLINQLSDPDYINQYVIWM 199
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 1186128483  293 PLDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevllsrqrdgkhqtnQTKGLLRAAAVGIYEQYLSE 372
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKA--------------------EDDEERIAKAREIYDKFLSP 60

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483  373 KASPRVTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVRM 432
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 1186128483 298 LVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEvllsrqrdgkhqtnqtkglLRAAAVGIYEQYLSEKASPR 377
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDEE-------------------LKSKAKEIYDKYISKDAPKE 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1186128483 378 VTVDDYLVAKLADTLNHEDPTPEIFDDIQRKVYELMLRDerFYPSFRQNALYVR 431
Cdd:cd07440    62 INIPESIREEIEENLEEPYPDPDCFDEAQEHILNLLEKD--SYPRFLKSDLYLK 113

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483 508 RNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSsILKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLAPEMMKASPAlah 587
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEV--- 76

                  ....*..
gi 1186128483 588 yVYDFLE 594
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 1186128483 476 DDSVQLHAYIsdTGVCNDHGKTYalYAITVhRRNLNSEEMWKTYRRYSDFHDFHmriteqfESL--SSI-LKLPGKKTFN 552
Cdd:cd06871     3 DDTVPLTCVI--EASQNIQSHTE--YIIRV-QRGPSPENSWQVIRRYNDFDLLN-------ASLqiSGIsLPLPPKKLIG 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1186128483 553 NMDRDFLEKRKKDLNAYLQLLLapemmkASPALAHY--VYDFLENKAYSKGKGDFA 606
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 1186128483 493 DHGKTYALYAITVHrrnlNSEEMWKTYRRYSDFHDFHMRITEQFeslsSILK--LPGKKTFNNMDRDFLEKRKKDLNAYL 570
Cdd:cd06875    12 ETVEGYTVYIIEVK----VGSVEWTVKHRYSDFAELHDKLVAEH----KVDKdlLPPKKLIGNKSPSFVEKRRKELEIYL 83

                          90       100
                  ....*....|....*....|....*
gi 1186128483 571 QLLLApEMMKASP-ALAHyvydFLE 594
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 1186128483 479 VQLHAYISDTgvcNDHGKTYALYAITVHRRNLNSEEM-WKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKK--TFNNMD 555
Cdd:cd06876    22 VSIQSYISDV---EEEGKEFVVYLIEVQRLNNDDQSSgWVVARRYSEFLELHKYLKKRYPGVLK-LDFPQKRkiSLKYSK 97

                          90       100
                  ....*....|....*....|...
gi 1186128483 556 RDFLEKRKKDLNAYLQ-LLLAPE 577
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 1186128483 493 DHGKTYALYAITVHRRNlnseEMWKTYRRYSDFHDFHMRITEQFESLSsiLKLPGKKTF-NNMDRDFLEKRKKDLNAYLQ 571
Cdd:cd06870    15 EKKKRFTVYKVVVSVGR----SSWFVFRRYAEFDKLYESLKKQFPASN--LKIPGKRLFgNNFDPDFIKQRRAGLDEFIQ 88

                  ....*....
gi 1186128483 572 -LLLAPEMM 579
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 1186128483 297 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYrvtaQQQLEvLLSRQRDGKHQTNQtkgllraaAVGIYEQYLSEKASP 376
Cdd:cd08721     1 ILYCESALFYFMEYMEQEGARNLLQFWLAADNF----QSQLA-AKEGQYDGQQAQND--------AMIIYDKYFSLQATE 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1186128483 377 RVTVDDYLVAKLADTLNHED-PTPEIFDDIQRKVYELMlrDERFYPSFRQNALYVR 431
Cdd:cd08721    68 PLGFDDKTRLEVESNICREGgPLPSCFEAPLLQALTTL--EQHYLPGFLSSQLYYK 121

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 1186128483 496 KTYALYAITVhrrNLNSEEMWKTYRRYSDFHDFHMRITEQFEslsSILKLPGKKTFN-NMDRDFLEKRKKDLNAYLQLLL 574
Cdd:cd06872    16 KSFAVYSVAV---TDNENETWVVKRRFRNFETLHRRLKEVPK---YNLELPPKRFLSsSLDGAFIEERCKLLDKYLKDLL 89

                          90
                  ....*....|....*....
gi 1186128483 575 APEMMKASpalaHYVYDFL 593
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 1186128483 283 AANFGKLCTVPldsilvdnVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAqqqlevllsrqrdgkhqtnqTKGLLRAAA 362
Cdd:cd08746    51 GQSFDKLMLTP--------AGRNAFREFLRTEFSEENMLFWMACEELKKEA--------------------NKSVIEEKA 102

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1186128483 363 VGIYEQYLSEKASPRVTVDdylvAKLADTLNHE--DPTPEIFDDIQRKVYELMLRDErfYPSFRQNALY 429
Cdd:cd08746   103 RIIYEDYISILSPKEVSLD----SRVREVINRNmlEPSQHTFDDAQLQIYTLMHRDS--YPRFMNSAIY 165

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 1186128483 294 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTA-------------QQQLEVLLSRQRDGKHQTNQTKGLLRA 360
Cdd:cd08735     5 LEQILHDNSALPYFIQFMETRRAEHLIKFWLEAESFKSAAwsrirahslntvkHSSLEEPVSPSLDRKVLESKSTDSLSQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1186128483 361 A----------------AVGIYEQYLSEKASPRVTVDD----YLVAKLADTLNHEDPTpeIFDDIQRKVYELMLRDerFY 420
Cdd:cd08735    85 RltddddeksmksierdAVSIYTKYISPDAAKPIPITEeirnDIVAKICGEDGQVDPN--CFVEAQSFVFSAMEQD--HF 160

                  ....*....
gi 1186128483 421 PSFRQNALY 429
Cdd:cd08735   161 TEFLRSHFF 169

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 1186128483 294 LDSILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTaqqqlevllsrqrdgkhqtnQTKGLLRAAAVGIYEQYLSEK 373
Cdd:cd08741     1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKM--------------------QDKTQMQEKAKEIYMTFLSSK 60

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1186128483 374 ASPRVTVDDYlvAKLADTLnHEDPTPEIFDDIQRKVYELMLRD--ERFYPS 422
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 1186128483 494 HGKTYALYAITVHRRNlnSEEMWKTYRRYSDFHDFHMRITEQFESlssiLKLPGKKTFNNMDR----DFLEKRKKDLNAY 569
Cdd:cd06883    12 SPEKYYIYVVKVTREN--QTEPSFVFRTFEEFQELHNKLSLLFPS----LKLPSFPARVVLGRshikQVAERRKIELNSY 85

                          90       100
                  ....*....|....*....|....*.
gi 1186128483 570 LQlllapEMMKASPALAHY--VYDFL 593
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 1186128483 512 SEEMWKTYRRYSDFHDFHMRITEQFESLSSiLKLPGKKTFNNMDRDFLEKRKKDLNAYLQLLLapEMMKASPA 584
Cdd:cd06874    28 LDETWTVFRRYSRFRELHKTMKLKYPEVAA-LEFPPKKLFGNKSERVAKERRRQLETYLRNFF--SVCLKLPA 97

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 1186128483 490 VCNDHGKTYALYAITVHRRNLNSEEMWKTYRRYSDFHDFHMRITEQFESLSSILKLPGKKTFNNMDRDFLEKRKKDLNAY 569
Cdd:cd07279    10 TVKEGEKKYVVYQLAVVQTGDPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAERSRAFEQF 89

                          90       100
                  ....*....|....*....|.
gi 1186128483 570 LQLLLAPEMMKASPALAHYVY 590
Cdd:cd07279    90 LGHILSIPNLRDSKAFLDFLQ 110

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 1186128483 297 ILVDNVALQFFMDYMQQTGGQAHLFFWMTVEGYRVTAQQQLEVLLSrqrdgkhqtnqtkgllraaavGIYEQYLSEKASP 376
Cdd:cd08740    13 LLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVD---------------------SVYQQFLAPGATR 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1186128483 377 RVTVDDYLVAKLADTLnhEDPTPEIFDDIQRKVYELMLRDErfYPSFRQNALYVRMLAE 435
Cdd:cd08740    72 WVNIDSKTMERTLEGL--KQPHRYVLDDAQMHIYMLMKKDS--YPRFLKSDLYKNLLAE 126