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 1190447024   16 EPAKQARIPGSELVENYTVYVIQVTVGSHQWTVKHRYSDFHDLHEKLIAEKKIDKNLLPPKKIIGKNSKSLVEKRQKDLE 95
Cdd:cd06875      1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1190447024   96 VYLQTLLTKFPVAAPKVLSHFLHFHLYEINGITAAL 131
Cdd:cd06875     81 IYLQTLLSFFQKTMPRELAHFLDFHKYEIIGLTQNL 116

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 1190447024   16 EPAKQARIPGSELVENYTVYVIQVTVGSHQWTVKHRYSDFHDLHEKLIAEKKIDKNLLPPKKIIGKNSKSLVEKRQKDLE 95
Cdd:cd06875      1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1190447024   96 VYLQTLLTKFPVAAPKVLSHFLHFHLYEINGITAAL 131
Cdd:cd06875     81 IYLQTLLSFFQKTMPRELAHFLDFHKYEIIGLTQNL 116

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  291 LTTLDMSHNSISQIDDSVKLiPKIEFLDLSHNGVMVVENLQHLYNLIHLDLSYNKLT----------SLEGIhtkLGNIK 360
Cdd:cd21340     48 LTHLYLQNNQIEKIENLENL-VNLKKLYLGGNRISVVEGLENLTNLEELHIENQRLPpgekltfdprSLAAL---SNSLR 123

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1190447024  361 TLNLAGNLLESLSGLNKLYSLVNLDLSNNNIEQIKEIKN-IGSLPCLEEVVLSSNPLSIIPDYRTKVLA 428
Cdd:cd21340    124 VLNISGNNIDSLEPLAPLRNLEQLDASNNQISDLEELLDlLSSWPSLRELDLTGNPVCKKPKYRDKIIL 192

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   38 QVTVGSHQWTVKHRYSDFHDLHEKLIAEKKIDK-NLLPPKKIIGKNSKSLVEKRQKDLEVYLQTLLTKFPVAAPKVLSHF 116
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIiPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEF 80

                   ....
gi 1190447024  117 LHFH 120
Cdd:pfam00787   81 LESD 84

type III secretion system effector E3 ubiquitin transferase SlrP;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  290 ALTTLDMSHNSISQIDDSvkLIPKIEFLDLSHNGVMVVEnlQHL-YNLIHLDLSYNKLTSLEGihTKLGNIKTLNLAGNL 368
Cdd:PRK15370   263 ALQSLDLFHNKISCLPEN--LPEELRYLSVYDNSIRTLP--AHLpSGITHLNVQSNSLTALPE--TLPPGLKTLEAGENA 336

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1190447024  369 LESLSGlNKLYSLVNLDLSNNNIEQIKEIKNigslPCLEEVVLSSNPLSIIPD 421
Cdd:PRK15370   337 LTSLPA-SLPPELQVLDVSKNQITVLPETLP----PTITTLDVSRNALTNLPE 384

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 1190447024   16 EPAKQARIPGSELVENYTVYVIQVTVGSHQWTVKHRYSDFHDLHEKLIAEKKIDKNLLPPKKIIGKNSKSLVEKRQKDLE 95
Cdd:cd06875      1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1190447024   96 VYLQTLLTKFPVAAPKVLSHFLHFHLYEINGITAAL 131
Cdd:cd06875     81 IYLQTLLSFFQKTMPRELAHFLDFHKYEIIGLTQNL 116

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  291 LTTLDMSHNSISQIDDSVKLiPKIEFLDLSHNGVMVVENLQHLYNLIHLDLSYNKLT----------SLEGIhtkLGNIK 360
Cdd:cd21340     48 LTHLYLQNNQIEKIENLENL-VNLKKLYLGGNRISVVEGLENLTNLEELHIENQRLPpgekltfdprSLAAL---SNSLR 123

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1190447024  361 TLNLAGNLLESLSGLNKLYSLVNLDLSNNNIEQIKEIKN-IGSLPCLEEVVLSSNPLSIIPDYRTKVLA 428
Cdd:cd21340    124 VLNISGNNIDSLEPLAPLRNLEQLDASNNQISDLEELLDlLSSWPSLRELDLTGNPVCKKPKYRDKIIL 192

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   20 QARIPGSELVE----NYTVYVIQVTV-GSHQWTVKHRYSDFHDLHEKLIaEKKIDKNL--LPPKKIIGKNSKSLVEKRQK 92
Cdd:cd06093      1 SVSIPDYEKVKdggkKYVVYIIEVTTqGGEEWTVYRRYSDFEELHEKLK-KKFPGVILppLPPKKLFGNLDPEFIEERRK 79

                           90       100
                   ....*....|....*....|....*
gi 1190447024   93 DLEVYLQTLLTKFPVAAPKVLSHFL 117
Cdd:cd06093     80 QLEQYLQSLLNHPELRNSEELKEFL 104

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   38 QVTVGSHQWTVKHRYSDFHDLHEKLIAEKKIDK-NLLPPKKIIGKNSKSLVEKRQKDLEVYLQTLLTKFPVAAPKVLSHF 116
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIiPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEF 80

                   ....
gi 1190447024  117 LHFH 120
Cdd:pfam00787   81 LESD 84

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 1190447024   23 IPGSELVEN-----YTVYVIQVTVGSHQWTVKHRYSDFHDLHEKLiaEKKIDKNLLPPKKIIGKNSKSLvEKRQKDLEVY 97
Cdd:cd06880      5 IPSYRLEVDesekpYTVFTIEVLVNGRRHTVEKRYSEFHALHKKL--KKSIKTPDFPPKRVRNWNPKVL-EQRRQGLEAY 81

                           90       100
                   ....*....|....*....|....*.
gi 1190447024   98 LQTLLTKFPVaaPKVLSHFL---HFH 120
Cdd:cd06880     82 LQGLLKINEL--PKQLLDFLgvrHFP 105

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 1190447024   32 YTVYVIQVTV-----GSHQWTVKHRYSDFHDLHeKLIAEK--KIDKNLLPPKKIIGKNSKSLVEKRQKDLEVYLQTLLTK 104
Cdd:cd06873     22 YAVYAISVTRiypngQEESWHVYRRYSDFHDLH-MRLKEKfpNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNP 100

                           90
                   ....*....|....*.
gi 1190447024  105 FPVAA-PKVLSHFLHF 119
Cdd:cd06873    101 EVLDAnPGLQEIVLDF 116

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 1190447024   32 YTVYVIQVTVGSHQWTVKHRYSDFHDLHEKLiaeKKI--DKNL-LPPKKIIGKN-SKSLVEKRQKDLEVYLQTLltkfpV 107
Cdd:cd06870     20 FTVYKVVVSVGRSSWFVFRRYAEFDKLYESL---KKQfpASNLkIPGKRLFGNNfDPDFIKQRRAGLDEFIQRL-----V 91

                   ....*...
gi 1190447024  108 AAPKVLSH 115
Cdd:cd06870     92 SDPKLLNH 99

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1190447024   32 YTVYVIQVTV--GSHQ---WTVKHRYSDFHDLHEKLIAE-KKIDKNLLPPKKIIGKN--SKSLVEKRQKDLEVYLQTLL 102
Cdd:cd06876     38 FVVYLIEVQRlnNDDQssgWVVARRYSEFLELHKYLKKRyPGVLKLDFPQKRKISLKysKTLLVEERRKALEKYLQELL 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; 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. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   30 ENYTVYVIQV-----TVGSH---QWTVKHRYSDFHDLHEKLI---AEKKIDKnlLPPKKIIGKNSKSLVEKRQKDLEVYL 98
Cdd:cd06877     20 ERIYVFCIEVerndrRAKGHepqHWSVLRRYNEFYVLESKLTefhGEFPDAP--LPSRRIFGPKSYEFLESKREIFEEFL 97

                   ....*.
gi 1190447024   99 QTLLTK 104
Cdd:cd06877     98 QKLLQK 103

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  333 LYNLIHLDLSYNKLTSLEGIHTkLGNIKTLNLAGNLLESLSGLNKLYSLVNLDLSNNNIEqikEIKNIGSLPCLEEVVLS 412
Cdd:cd21340      1 LKRITHLYLNDKNITKIDNLSL-CKNLKVLYLYDNKITKIENLEFLTNLTHLYLQNNQIE---KIENLENLVNLKKLYLG 76

                   ....*..
gi 1190447024  413 SNPLSII 419
Cdd:cd21340     77 GNRISVV 83

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; 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 SNX1, SNX2, and similar proteins. They harbor 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. SNX1 and SNX2 are components 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   27 ELVENYTVY-VIQVTVGSH----QWTVKHRYSDFHDLHEKLIAekkidKNL------LPPKKIIG--KNSKSLVEKRQKD 93
Cdd:cd06859     13 DGMSAYVVYrVTTKTNLPDfkksEFSVLRRYSDFLWLYERLVE-----KYPgrivppPPEKQAVGrfKVKFEFIEKRRAA 87

                   ....*.
gi 1190447024   94 LEVYLQ 99
Cdd:cd06859     88 LERFLR 93

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; 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. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1190447024   32 YTVYviQVTVGSHQWTVKHRYSDFHDLHEKLIaEKKIDKNL--LPPKKIIGKNSKSLVEKRQKDLEVYLqTLLTKFPV 107
Cdd:cd06866     18 HVEY--EVSSKRFKSTVYRRYSDFVWLHEYLL-KRYPYRMVpaLPPKRIGGSADREFLEARRRGLSRFL-NLVARHPV 91

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1190447024  358 NIKTLNLAGNLLESLSGLNKLYSLVNLDLSNNN-IEQIKEIKN 399
Cdd:pfam12799    2 NLEVLDLSNNQITDIPPLAKLPNLETLDLSGNNkITDLSDLAN 44

Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  290 ALTTLDMSHNSISqiDDSVKLI-------PKIEFLDLSHN-----GVM-VVENLQHLYNLIHLDLSYNKLTS--LEGIHT 354
Cdd:COG5238    209 TVTTLWLKRNPIG--DEGAEILaealkgnKSLTTLDLSNNqigdeGVIaLAEALKNNTTVETLYLSGNQIGAegAIALAK 286

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  355 KLG---NIKTLNLAGN---------LLESLSGlNKlySLVNLDLSNNNI---EQIKEIKNIGSLPCLEEVVLSSNPLSii 419
Cdd:COG5238    287 ALQgntTLTSLDLSVNrigdegaiaLAEGLQG-NK--TLHTLNLAYNGIgaqGAIALAKALQENTTLHSLDLSDNQIG-- 361

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1190447024  420 pDYRTKVLAQFGERAS---EVCL-DNIITTEKeldTVEVLKAIQKAKEAKYKLNNSDKKISEDSRLTAA 484
Cdd:COG5238    362 -DEGAIALAKYLEGNTtlrELNLgKNNIGKQG---AEALIDALQTNRLHTLILDGNLIGAEAQQRLEQL 426

Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  289 RALTTLDMSHNSISQ-----IDDSVKLIPKIEFLDLSHN-----GVMV-VENLQHLYNLIHLDLSYNKLTSLEGI----H 353
Cdd:COG5238    264 TTVETLYLSGNQIGAegaiaLAKALQGNTTLTSLDLSVNrigdeGAIAlAEGLQGNKTLHTLNLAYNGIGAQGAIalakA 343

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1190447024  354 TKLG-NIKTLNLAGNLL--ESLSGLNKLY----SLVNLDLSNNNI 391
Cdd:COG5238    344 LQENtTLHSLDLSDNQIgdEGAIALAKYLegntTLRELNLGKNNI 388

Leucine rich repeat;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  335 NLIHLDLSYNKLTSLEGIH-TKLGNIKTLNLAGNLLESLSG--LNKLYSLVNLDLSNNNI 391
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAfKGLSNLKVLDLSNNLLTTLSPgaFSGLPSLRYLDLSGNRL 61

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   18 AKQARIPGSELVENYTVYVIQVTV-GSHQWTVKHRYSDFHDLHEKLIA----EKKIDKN--LLP--PKKIIGKNSKSLVE 88
Cdd:cd06882      6 ATIADIEEKRGFTNYYVFVIEVKTkGGSKYLIYRRYRQFFALQSKLEErfgpEAGSSAYdcTLPtlPGKIYVGRKAEIAE 85

                           90
                   ....*....|....
gi 1190447024   89 KRQKDLEVYLQTLL 102
Cdd:cd06882     86 RRIPLLNRYMKELL 99

Leucine-rich repeat;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024  317 LDLSHNGVMVVENL-QHLYNLIHLDLSYNKLTSLEGIhTKLGNIKTLNLAGN-LLESLSGLNK-LYSLVNLDLSNNNIEQ 393
Cdd:pfam14580   24 LDLRGYKIPIIENLgATLDQFDTIDFSDNEIRKLDGF-PLLRRLKTLLLNNNrICRIGEGLGEaLPNLTELILTNNNLQE 102

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1190447024  394 IKEIKNIGSLPCLEEVVLSSNPLSIIPDYRTKVLAQF 430
Cdd:pfam14580  103 LGDLDPLASLKKLTFLSLLRNPVTNKPHYRLYVIYKV 139

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1190447024  335 NLIHLDLSYNKLTSLEGIHtKLGNIKTLNLAGN-LLESLSGLNK 377
Cdd:pfam12799    2 NLEVLDLSNNQITDIPPLA-KLPNLETLDLSGNnKITDLSDLAN 44

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 1190447024   32 YTVYVIQVTVGSHQWTVKH---RYSDFHDLHEKLIAEKKIDKNL----LPPKKII----GKNSKSLVEKRQKDLEVYLQT 100
Cdd:cd07280     22 YVVWKITIETKDLIGSSIVaykRYSEFVQLREALLDEFPRHKRNeipqLPPKVPWydsrVNLNKAWLEKRRRGLQYFLNC 101

                           90
                   ....*....|....*..
gi 1190447024  101 LLTKFPVAAPKVLSHFL 117
Cdd:cd07280    102 VLLNPVFGGSPVVKEFL 118

The phosphoinositide binding Phox Homology domain of Phospholipase D; 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. Phospholipase D (PLD) catalyzes the hydrolysis of the phosphodiester bond of phosphatidylcholine to generate membrane-bound phosphatidic acid and choline. Members of this subfamily contain PX and Pleckstrin Homology (PH) domains in addition to the catalytic domain. PLD activity has been detected in viruses, bacteria, yeast, plants, and mammals, but the PX domain is not present in PLDs from viruses and bacteria. PLDs are implicated in many cellular functions like signaling, cytoskeletal reorganization, vesicular transport, stress responses, and the control of differentiation, proliferation, and survival. Vertebrates contain two PLD isozymes, PLD1 and PLD2. PLD1 is located mainly in intracellular membranes while PLD2 is associated with plasma membranes. 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   29 VENYTVYVIQVTVGSHQWTVKHRYSDFHDLHEKL---------------------------IAEKKIDKNLLP--PKKII 79
Cdd:cd06895     20 LLNPNLYTIELQHGQFTWTIKRRYKHFQELHQALklyrallriplptrrhkeerlslkrsrKPEREKKNRRLPslPALPD 99

                           90       100
                   ....*....|....*....|....
gi 1190447024   80 GKNSKSLVEKRQKDLEVYLQTLLT 103
Cdd:cd06895    100 ILVSEEQLDSRKKQLENYLQNLLK 123

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1190447024   46 WTVKHRYSDFHDLHEKLiAE-----KKIDKNlLPPKKIIGKNSKSLVEKRQKDLEVYLQTLLT 103
Cdd:cd06878     50 WVVTRKLSEFHDLHRKL-KEcsswlKKVELP-SLSKKWFKSIDKKFLDKSKNQLQKYLQFILE 110

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; 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. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   32 YTVYVIQVtvGSHQwtVKHRYSDFHDLHEKL-----------IAEK-KIDKNLLPPKKiiGKNSKSLVEKRQKDLEVYLQ 99
Cdd:cd06867     18 YIVYVIRL--GGSE--VKRRYSEFESLRKNLtrlyptliippIPEKhSLKDYAKKPSK--AKNDAKIIERRKRMLQRFLN 91

                   ....
gi 1190447024  100 TLLT 103
Cdd:cd06867     92 RCLQ 95

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; 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. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1190447024   15 AEPAKQARIPGSELVENYTVYVIQVTVGSHQW---------TVKHRYSDFHDLHEKLIA-----------EKKIDknlLP 74
Cdd:cd06864      6 TEAEKRTGGSAMNLKETYTVYLIETKIVEHESeeglskklsSLWRRYSEFELLRNYLVVtypyvivpplpEKRAM---FM 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1190447024   75 PKKIIGKN-SKSLVEKRQKDLEVYLQTlltkfpVAAPKVLS---HFLHF 119
Cdd:cd06864     83 WQKLSSDTfDPDFVERRRAGLENFLLR------VAGHPELCqdkIFLEF 125