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 2077113093   11 EPLRSAQVLGSELVETYTVYIIQVSVGSHQWTVKHRYSDFHDLHEKLVSEKKIDKNLLPPKKIIGKNSKSLVEKRQKELE 90
Cdd:cd06875      1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2077113093   91 VYLQTLLVKFPVTVPKVLSHFLHFHFYEINGITAAL 126
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 2077113093   11 EPLRSAQVLGSELVETYTVYIIQVSVGSHQWTVKHRYSDFHDLHEKLVSEKKIDKNLLPPKKIIGKNSKSLVEKRQKELE 90
Cdd:cd06875      1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2077113093   91 VYLQTLLVKFPVTVPKVLSHFLHFHFYEINGITAAL 126
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 2077113093  284 RNLTTLDMSHNNIPQIDDSVKLiPKIEFLDLSHNGVSLVENLQHLYNLVHLDLSYNKLTSLEG-------VHTKLGNIKT 356
Cdd:cd21340     46 TNLTHLYLQNNQIEKIENLENL-VNLKKLYLGGNRISVVEGLENLTNLEELHIENQRLPPGEKltfdprsLAALSNSLRV 124

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2077113093  357 LNLAGNQLESLYGLNKLYSLVNLDLSSNKIEQIDEVKN-IGSLPCLEKVVLSSNPLSIIPDYRTKVLA 423
Cdd:cd21340    125 LNISGNNIDSLEPLAPLRNLEQLDASNNQISDLEELLDlLSSWPSLRELDLTGNPVCKKPKYRDKIIL 192

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093   37 GSHQWTVKHRYSDFHDLHEKLVSEKKIDK-NLLPPKKIIGKNSKSLVEKRQKELEVYLQTLLVKFPVTVPKVLSHFLHFH 115
Cdd:pfam00787    5 SLEEWSVRRRYSDFVELHKKLLRKFPSVIiPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 84

leucine-rich repeat receptor-like protein kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  285 NLTTLDMSHNNIPQ-IDDSVKLIPKIEFLDLSHNGVS--LVENLQHLYNLVHLDLSYNKLT-SLEGVHTKLGNIKTLNLA 360
Cdd:PLN00113   476 RLENLDLSRNQFSGaVPRKLGSLSELMQLKLSENKLSgeIPDELSSCKKLVSLDLSHNQLSgQIPASFSEMPVLSQLDLS 555

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2077113093  361 GNQL--ESLYGLNKLYSLVNLDLSSNKIEqidevkniGSLP 399
Cdd:PLN00113   556 QNQLsgEIPKNLGNVESLVQVNISHNHLH--------GSLP 588

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 2077113093   11 EPLRSAQVLGSELVETYTVYIIQVSVGSHQWTVKHRYSDFHDLHEKLVSEKKIDKNLLPPKKIIGKNSKSLVEKRQKELE 90
Cdd:cd06875      1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2077113093   91 VYLQTLLVKFPVTVPKVLSHFLHFHFYEINGITAAL 126
Cdd:cd06875     81 IYLQTLLSFFQKTMPRELAHFLDFHKYEIIGLTQNL 116

Leucine-rich repeat (LRR) protein [Transcription];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  280 IPTWRNLTTLDMSHNNIPQIDDSVKLIPKIEFLDLSHNGVS-LVENLQHLYNLVHLDLSYNKLTSLEGVHTKLGNIKTLN 358
Cdd:COG4886    132 LANLTNLKELDLSNNQLTDLPEPLGNLTNLKSLDLSNNQLTdLPEELGNLTNLKELDLSNNQITDLPEPLGNLTNLEELD 211

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2077113093  359 LAGNQLESL-YGLNKLYSLVNLDLSSNKIEQIDEvknIGSLPCLEKVVLSSNPLSIIPD 416
Cdd:COG4886    212 LSGNQLTDLpEPLANLTNLETLDLSNNQLTDLPE---LGNLTNLEELDLSNNQLTDLPP 267

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 2077113093   22 ELVETYTVYIIQVSV-GSHQWTVKHRYSDFHDLHEKLVSEKKIDKNL-LPPKKIIGKNSKSLVEKRQKELEVYLQTLLVK 99
Cdd:cd06093     12 DGGKKYVVYIIEVTTqGGEEWTVYRRYSDFEELHEKLKKKFPGVILPpLPPKKLFGNLDPEFIEERRKQLEQYLQSLLNH 91

                           90
                   ....*....|...
gi 2077113093  100 FPVTVPKVLSHFL 112
Cdd:cd06093     92 PELRNSEELKEFL 104

Leucine-rich repeat (LRR) protein [Transcription];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  282 TWRNLTTLDMSHNNIPQIDDSVKLIPKIEFLDLSHNgvslvENLQHLYNLVHLDLSYNKLTSLEGVHTKLGNIKTLNLAG 361
Cdd:COG4886     71 LLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLSGN-----EELSNLTNLESLDLSGNQLTDLPEELANLTNLKELDLSN 145

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2077113093  362 NQLESLY-GLNKLYSLVNLDLSSNKIEQIDEvkNIGSLPCLEKVVLSSNPLSIIPD 416
Cdd:COG4886    146 NQLTDLPePLGNLTNLKSLDLSNNQLTDLPE--ELGNLTNLKELDLSNNQITDLPE 199

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093   37 GSHQWTVKHRYSDFHDLHEKLVSEKKIDK-NLLPPKKIIGKNSKSLVEKRQKELEVYLQTLLVKFPVTVPKVLSHFLHFH 115
Cdd:pfam00787    5 SLEEWSVRRRYSDFVELHKKLLRKFPSVIiPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 84

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093   21 SELVETYTVYIIQVSVGSHQWTVKHRYSDFHDLHEKLVSEkkIDKNL---LPPKKII--GKNSKSLVEKRQKELEVYLQT 95
Cdd:cd06897      9 SVSPKPYTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESE--VGIEPpypLPPKSWFlsTSSNPKLVEERRVGLEAFLRA 86

                   ..
gi 2077113093   96 LL 97
Cdd:cd06897     87 LL 88

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2077113093   26 TYTVYIIQV-----SVGSHQWTVKHRYSDFHDLHEKLVsEK--KIDKNLLPPKKIIGKNSKSLVEKRQKELEVYLQTLL 97
Cdd:cd06873     21 TYAVYAISVtriypNGQEESWHVYRRYSDFHDLHMRLK-EKfpNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLL 98

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 2077113093   27 YTVYIIQV--------SVGshqWTVKHRYSDFHDLHEKLVSE-KKIDKNLLPPKKIIGKN--SKSLVEKRQKELEVYLQT 95
Cdd:cd06876     38 FVVYLIEVqrlnnddqSSG---WVVARRYSEFLELHKYLKKRyPGVLKLDFPQKRKISLKysKTLLVEERRKALEKYLQE 114

                   ...
gi 2077113093   96 LLV 98
Cdd:cd06876    115 LLK 117

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 2077113093   15 SAQVLGSELV----ETYTVYIIQVS-VGSHQWTVKHRYSDFHDLHEKLvseKKIDK-NL-LPPKKIIGKN-SKSLVEKRQ 86
Cdd:cd06872      2 SCRVLGAEIVksgsKSFAVYSVAVTdNENETWVVKRRFRNFETLHRRL---KEVPKyNLeLPPKRFLSSSlDGAFIEERC 78

                           90
                   ....*....|..
gi 2077113093   87 KELEVYLQTLLV 98
Cdd:cd06872     79 KLLDKYLKDLLV 90

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 2077113093   25 ETYTVYIIQV-----SVGSH---QWTVKHRYSDFHDLHEKLVS---EKKIDKnlLPPKKIIGKNSKSLVEKRQKELEVYL 93
Cdd:cd06877     20 ERIYVFCIEVerndrRAKGHepqHWSVLRRYNEFYVLESKLTEfhgEFPDAP--LPSRRIFGPKSYEFLESKREIFEEFL 97

                   ....*.
gi 2077113093   94 QTLLVK 99
Cdd:cd06877     98 QKLLQK 103

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093   17 QVLGSELVETYTVYIIQVSvGSHQWTVkhRYSDFHDLHEKLVSE---KKIDKnlLPPKKIIGKNSKSLVEKRQKeLEVYL 93
Cdd:cd06885      8 QELSDEGGSTYVAYNIHIN-GVLHCSV--RYSQLHGLNEQLKKEfgnRKLPP--FPPKKLLPLTPAQLEERRLQ-LEKYL 81

                           90
                   ....*....|....*....
gi 2077113093   94 QTLlvkfpVTVPKVLSHFL 112
Cdd:cd06885     82 QAV-----VQDPRIANSDI 95

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 2077113093  284 RNLTTLDMSHNNIPQ-----IDDSVKLIPKIEFLDLSHN------GVSLVENLQHLYNLVHLDLSYNKLTSLEGV----H 348
Cdd:COG5238    264 TTVETLYLSGNQIGAegaiaLAKALQGNTTLTSLDLSVNrigdegAIALAEGLQGNKTLHTLNLAYNGIGAQGAIalakA 343

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2077113093  349 TKLG-NIKTLNLAGNQL--ESLYGLNKLY----SLVNLDLSSNKI 386
Cdd:COG5238    344 LQENtTLHSLDLSDNQIgdEGAIALAKYLegntTLRELNLGKNNI 388

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 2077113093   27 YTVYIiqVSVGSHQWTVKHRYSDFHDLHEKLVsEKKIDKNL--LPPKKIIGKNSKSLVEKRQKELEVYLqTLLVKFPV 102
Cdd:cd06866     18 HVEYE--VSSKRFKSTVYRRYSDFVWLHEYLL-KRYPYRMVpaLPPKRIGGSADREFLEARRRGLSRFL-NLVARHPV 91

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 2077113093  285 NLTTLDMSHNNI-----PQIDDSVKLIPKIEFLDLSHN-----GVS-LVENLQHLYNLVHLDLSYNKLTS--LEGVHTKL 351
Cdd:COG5238    209 TVTTLWLKRNPIgdegaEILAEALKGNKSLTTLDLSNNqigdeGVIaLAEALKNNTTVETLYLSGNQIGAegAIALAKAL 288

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  352 G---NIKTLNLAGNQL-----ESLY-GLNKLYSLVNLDLSSNKI---EQIDEVKNIGSLPCLEKVVLSSNPLSiipDYRT 419
Cdd:COG5238    289 QgntTLTSLDLSVNRIgdegaIALAeGLQGNKTLHTLNLAYNGIgaqGAIALAKALQENTTLHSLDLSDNQIG---DEGA 365

                   ....*.
gi 2077113093  420 KVLAQF 425
Cdd:COG5238    366 IALAKY 371

Leucine rich repeat;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  284 RNLTTLDMSHNNIPQIDDSVklipkiefldlshngvslvenLQHLYNLVHLDLSYNKLTSLEGVH-TKLGNIKTLNLAGN 362
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGA---------------------FKGLSNLKVLDLSNNLLTTLSPGAfSGLPSLRYLDLSGN 59

                   ..
gi 2077113093  363 QL 364
Cdd:pfam13855   60 RL 61

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 2077113093  353 NIKTLNLAGNQLESLYGLNKLYSLVNLDLSSN-KIEQIDEVKN 394
Cdd:pfam12799    2 NLEVLDLSNNQITDIPPLAKLPNLETLDLSGNnKITDLSDLAN 44

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093    7 EDGEEPLRS--AQVLGSELVETYTVyiiqvsvgSHQWTVKHRYSDFHDLHEKLvSE-----KKIDKNlLPPKKIIGKNSK 79
Cdd:cd06878     22 DDKEVPLYVivVHVSEVGLNEDESI--------SSGWVVTRKLSEFHDLHRKL-KEcsswlKKVELP-SLSKKWFKSIDK 91

                           90
                   ....*....|....*...
gi 2077113093   80 SLVEKRQKELEVYLQTLL 97
Cdd:cd06878     92 KFLDKSKNQLQKYLQFIL 109

Leucine-rich repeat;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  289 LDMSHNNIPQIDDSVKLIPKIEFLDLSHNGVSLVENLQHLYNLVHLDLSYNKLTSL-EGVHTKLGNIKTLNLAGNQLESL 367
Cdd:pfam14580   24 LDLRGYKIPIIENLGATLDQFDTIDFSDNEIRKLDGFPLLRRLKTLLLNNNRICRIgEGLGEALPNLTELILTNNNLQEL 103

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2077113093  368 YGLNKLYSLVNLDLSSnkieqidevknigslpclekvvLSSNPLSIIPDYRTKVLAQF 425
Cdd:pfam14580  104 GDLDPLASLKKLTFLS----------------------LLRNPVTNKPHYRLYVIYKV 139

Leucine-rich repeat (LRR) protein [Transcription];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  285 NLTTLDMSHNNIPQIDDSVKLIPKIEFLDLSHNGVSLVENLQHLYNLVHLDLSYNKLTSLEGVHT-----KLGNIKTLNL 359
Cdd:COG4886     24 LILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGltdlgDLTNLTELDL 103

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2077113093  360 AGNQleslyGLNKLYSLVNLDLSSNKIEQIDEvkNIGSLPCLEKVVLSSNPLSIIPD 416
Cdd:COG4886    104 SGNE-----ELSNLTNLESLDLSGNQLTDLPE--ELANLTNLKELDLSNNQLTDLPE 153

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 2077113093   27 YTVYIIQVSV-GSHQWTVKHRYSDFHDLHEKLVS----EKKIDKN--LLP--PKKIIGKNSKSLVEKRQKELEVYLQTLL 97
Cdd:cd06882     20 YYVFVIEVKTkGGSKYLIYRRYRQFFALQSKLEErfgpEAGSSAYdcTLPtlPGKIYVGRKAEIAERRIPLLNRYMKELL 99

leucine-rich repeat receptor-like protein kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077113093  285 NLTTLDMSHNNIPQ-IDDSVKLIPKIEFLDLSHNGVS--LVENLQHLYNLVHLDLSYNKLT-SLEGVHTKLGNIKTLNLA 360
Cdd:PLN00113   476 RLENLDLSRNQFSGaVPRKLGSLSELMQLKLSENKLSgeIPDELSSCKKLVSLDLSHNQLSgQIPASFSEMPVLSQLDLS 555

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2077113093  361 GNQL--ESLYGLNKLYSLVNLDLSSNKIEqidevkniGSLP 399
Cdd:PLN00113   556 QNQLsgEIPKNLGNVESLVQVNISHNHLH--------GSLP 588

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 2077113093   27 YTVYIIQVSVGSH----------------QWTVKHRYSDFHDLHEKLVSE---KKIDKNLLPPKKI----IGKNSKSLVE 83
Cdd:cd06893     21 YTLYTVQYETILDvqseqnpnaaseqplaTHTVNRRFREFLTLQTRLEENpkfRKIMNVKGPPKRLfdlpFGNMDKDKIE 100

                           90
                   ....*....|...
gi 2077113093   84 KRQKELEVYLQTL 96
Cdd:cd06893    101 ARRGLLETFLRQL 113

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2077113093   25 ETYTVYIIQVS-VGSHQWT-VKHRYSDFHDLHEKLvSEKKIDKNL--LPPKKIIGK-NSKSLVEKRQKELEVYLQTLL 97
Cdd:cd06883     14 EKYYIYVVKVTrENQTEPSfVFRTFEEFQELHNKL-SLLFPSLKLpsFPARVVLGRsHIKQVAERRKIELNSYLKSLF 90

leucine-rich repeat receptor-like protein kinase; Provisional

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2077113093  276 VTAVIP----TWRNLTTLDMSHNNIP-QIDDSVKLIPKIEFLDLSHNGVS--LVENLQHLYNLVHLDLSYNKL 341
Cdd:PLN00113   511 LSGEIPdelsSCKKLVSLDLSHNQLSgQIPASFSEMPVLSQLDLSQNQLSgeIPKNLGNVESLVQVNISHNHL 583