Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 340 IREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEI 419
Cdd:cd08722    1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDFNRRILNPDLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 662236845 420 QRIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08722   81 KQILEGGPEKIVKLRTSRPLFEAYEHVYSLLESVFCPLFCHSDEYFI 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845  130 SSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLIRRIHKVDIPSIITKKLLKAAMKHIEVIVKAR 209
Cdd:pfam02194   1 SPEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845  210 QKVKN---TEFLQQAALEEYGPELHVALR--------SRRDELHYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSV 278
Cdd:pfam02194  81 EAVRGkklNELDLALASKYLALKPHPALSpvllsssqSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 662236845  279 FLPSLDFLADPDTVNHLLIIF 299
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 340 IREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEI 419
Cdd:cd08722    1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDFNRRILNPDLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 662236845 420 QRIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08722   81 KQILEGGPEKIVKLRTSRPLFEAYEHVYSLLESVFCPLFCHSDEYFI 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845  130 SSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLIRRIHKVDIPSIITKKLLKAAMKHIEVIVKAR 209
Cdd:pfam02194   1 SPEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845  210 QKVKN---TEFLQQAALEEYGPELHVALR--------SRRDELHYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSV 278
Cdd:pfam02194  81 EAVRGkklNELDLALASKYLALKPHPALSpvllsssqSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 662236845  279 FLPSLDFLADPDTVNHLLIIF 299
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

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 662236845  798 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 871
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 662236845  872 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 902
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

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 662236845   595 VGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNY---EFLKSKREEFQEYLQKLLQHPELSN-SQLL 670
Cdd:smart00312  21 TKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNfseEFIEKRRRGLEKYLQSLLNHPELINhSEVV 100

                   ....*
gi 662236845   671 ADFLS 675
Cdd:smart00312 101 LEFLE 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 662236845  346 LLFRfmNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDemlslheeLQKIYKTYCLDESIDKIRFDPFIVEEIQriaeg 425
Cdd:pfam00615  13 RLFR--QFLESEFSEENLEFWLACEEFKKADPDEERLKK--------AKEIYNEFLAPGSPKEINLDSDLREEIR----- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 662236845  426 pyiDVVKLQTMRCLFEAY-EHVLSLLENVFTPMFCHSDeYFRQL 468
Cdd:pfam00615  78 ---ENLEKEPTRDLFDEAqAEVYELMEKDSYPRFLKSP-LYLRL 117

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 340 IREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEI 419
Cdd:cd08722    1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDFNRRILNPDLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 662236845 420 QRIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08722   81 KQILEGGPEKIVKLRTSRPLFEAYEHVYSLLESVFCPLFCHSDEYFI 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845  130 SSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLIRRIHKVDIPSIITKKLLKAAMKHIEVIVKAR 209
Cdd:pfam02194   1 SPEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845  210 QKVKN---TEFLQQAALEEYGPELHVALR--------SRRDELHYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSV 278
Cdd:pfam02194  81 EAVRGkklNELDLALASKYLALKPHPALSpvllsssqSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 662236845  279 FLPSLDFLADPDTVNHLLIIF 299
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

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 662236845  798 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 871
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 662236845  872 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 902
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

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 662236845 342 EQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDrilrpelSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEIQR 421
Cdd:cd07440    2 RDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKK-------TTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEE 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 662236845 422 IAEGPYIDvvklqtMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd07440   75 NLEEPYPD------PDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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 662236845 557 KISIpyVDFFEDPSSERKEkkerIPVFCIDVER--NDRRAVGhepehWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 634
Cdd:cd06876   21 RVSI--QSYISDVEEEGKE----FVVYLIEVQRlnNDDQSSG-----WVVARRYSEFLELHKYLKKRYPGVLKLDFPQKR 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 662236845 635 IIGPKNYE--FLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 675
Cdd:cd06876   90 KISLKYSKtlLVEERRKALEKYLQELLKIPEVCEDEEFRKFLS 132

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 662236845 572 ERKEKKERIPVFCIDVERNdrravghEPEHWSVYRRYLEFYVLESKLTEfhgAFPDAQ--LPSKRIIGPK-NYEFLKSKR 648
Cdd:cd07276   12 EVMEERARFTVYKIRVENK-------VGDSWFVFRRYTDFVRLNDKLKQ---MFPGFRlsLPPKRWFKDNfDPDFLEERQ 81

                         90       100
                 ....*....|....*....|....*.
gi 662236845 649 EEFQEYLQKLLQHPELSNSQLLADFL 674
Cdd:cd07276   82 LGLQAFVNNIMAHKDIAKCKLVREFF 107

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 662236845 583 FCIDVERndrravGHEPEH-WSVYRRYLEFYVLESKLtEFHGAfpDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQH 661
Cdd:cd06871   24 YIIRVQR------GPSPENsWQVIRRYNDFDLLNASL-QISGI--SLPLPPKKLIGNMDREFIAERQQGLQNYLNVILMN 94

                         90       100
                 ....*....|....*....|....
gi 662236845 662 PELSNSQLLADFLSPNGGETQFLD 685
Cdd:cd06871   95 PILASCLPVKKFLDPNNYSANFTE 118

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 662236845 570 SSERKEKKERIPVFCIDVerndrrAVGHEpeHWSVYRRYLEFYVLESKLTEfhgAFPDAQL--PSKRIIGpKNY--EFLK 645
Cdd:cd06870   10 SDEDREKKKRFTVYKVVV------SVGRS--SWFVFRRYAEFDKLYESLKK---QFPASNLkiPGKRLFG-NNFdpDFIK 77

                         90       100
                 ....*....|....*....|....*....
gi 662236845 646 SKREEFQEYLQKLLQHPELSNSQLLADFL 674
Cdd:cd06870   78 QRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

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 662236845 574 KEKKERIPVFCIDVERNDRRAvghEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQE 653
Cdd:cd06873   16 KEHGKTYAVYAISVTRIYPNG---QEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQ 92

                         90       100
                 ....*....|....*....|....*..
gi 662236845 654 YLQKLLQHPELSNS----QLLADFLSP 676
Cdd:cd06873   93 YLQSLLNPEVLDANpglqEIVLDFLEP 119

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; 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 fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 662236845 602 WSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRII--GPKNYEFLKSKREEFQEYLQKLLQHPE--LSNSQLLADFLS 675
Cdd:cd06897   29 YTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFlsTSSNPKLVEERRVGLEAFLRALLNDEDsrWRNSPAVKEFLN 106

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; 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. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 662236845 603 SVYRRYLEF-YVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 675
Cdd:cd07285   33 SVNHRYKHFdWLYERLLVKFGLAIPIPSLPDKQVTGRFEEEFIKMRMERLQAWMTRMCRHPVISESEVFQQFLN 106

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; 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. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 600 EHWSVYRRYLEFYVLESKLTEFHG--AFPDAQLPSKRIIG----------PKNYEFLKSKREEFQEYLQKLLQHPELSNS 667
Cdd:cd07281   35 KHFTVKRRFSDFLGLYEKLSEKHSqnGFIVPPPPEKSLIGmtkvkvgkedSSSAEFLERRRAALERYLQRIVSHPSLLQD 114

                 ....*..
gi 662236845 668 QLLADFL 674
Cdd:cd07281  115 PDVREFL 121

The phosphoinositide binding Phox Homology domain of SNX-like proteins; 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 592 RRAVGHEPEHWSVYRRYLEFYVLESKL-TEFHGAFPDAQlPSKRI---IGPKNYEFLKSKREEFQEYLQKLLQHPELSNS 667
Cdd:cd06865   32 TNIPSYTHGEFTVRRRFRDVVALADRLaEAYRGAFVPPR-PDKSVvesQVMQSAEFIEQRRVALEKYLNRLAAHPVIGLS 110

                 ....*...
gi 662236845 668 QLLADFLS 675
Cdd:cd06865  111 DELRVFLT 118

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 662236845 344 QDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELqKIYKTYCLDESI------DKIRFDpfIVE 417
Cdd:cd08721    5 ESALFYFMEYMEQEGARNLLQFWLAADNFQSQLAAKEGQYDGQQAQNDAM-IIYDKYFSLQATeplgfdDKTRLE--VES 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 662236845 418 EIQRiAEGPYIDvvklqtmrCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08721   82 NICR-EGGPLPS--------CFEAPLLQALTTLEQHYLPGFLSSQLYYK 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 582 VFCIDVERNDRRAVghepehwsVYRRYLEFYVLESKLTEFHGAfPDaqLPSKRIIGpKNYEFLKSKREEFQEYLQKLLQH 661
Cdd:cd06880   21 VFTIEVLVNGRRHT--------VEKRYSEFHALHKKLKKSIKT-PD--FPPKRVRN-WNPKVLEQRRQGLEAYLQGLLKI 88

                         90
                 ....*....|...
gi 662236845 662 PELsnSQLLADFL 674
Cdd:cd06880   89 NEL--PKQLLDFL 99

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; 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. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 662236845 598 EPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 675
Cdd:cd06861   33 EVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 600 EHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLL 659
Cdd:cd06874   30 ETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFGNKSERVAKERRRQLETYLRNFF 89

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 544 VSTPNTPRNLAAWKISIpyvdfFEDPSSERKEKKERIPVFCIDVER--NDRRAVGHEPEHWSVYRRYLEFYVLESKLTEF 621
Cdd:COG5391  118 PPLSTSHTILDYFISST-----VSNPQSLTLLVDSRDKHTSYEIITvtNLPSFQLRESRPLVVRRRYSDFESLHSILIKL 192

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 622 HGAFPDAQLPSKRIIGPKNY-----EFLKSKREEFQEYLQKLLQHPELSNSQ----------LLADFLSPNG--GETQFL 684
Cdd:COG5391  193 LPLCAIPPLPSKKSNSEYYGdrfsdEFIEERRQSLQNFLRRVSTHPLLSNYKnsksweshstLLSSFIENRKsvPTPLSL 272

                 ..
gi 662236845 685 DK 686
Cdd:COG5391  273 DL 274

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 662236845 602 WSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPK----NYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFL 674
Cdd:cd06860   37 YSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLldrfSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; 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. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662236845 585 IDVERNDRRAVGHEP--EHWSVYRRYLEFYVLESKLTEFHG--AFPDAQLPSKRI----IGPKNYEFLKSKREEFQEYLQ 656
Cdd:cd06893   32 LDVQSEQNPNAASEQplATHTVNRRFREFLTLQTRLEENPKfrKIMNVKGPPKRLfdlpFGNMDKDKIEARRGLLETFLR 111

                         90       100
                 ....*....|....*....|.
gi 662236845 657 KLLQHPELSNSQLLADFLSPN 677
Cdd:cd06893  112 QLCSIPEISNSEEVQEFLAYG 132

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 662236845 604 VYRRYLEFYVLESKLTEfhgAFPDA------QLPSKRIIGPK----NYEFLKSKREEFQEYLQKLLQHPELSNSQLLADF 673
Cdd:cd07280   41 AYKRYSEFVQLREALLD---EFPRHkrneipQLPPKVPWYDSrvnlNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEF 117

                 ...
gi 662236845 674 LSP 676
Cdd:cd07280  118 LLP 120