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 1676318464  14 EPAKEARVVGSELVDTYTVYIIQVTDGSHEWTVKHRYSDFHDLHEKLVAERKIDKNLLPPKKIIGKNSRSLVEKREKDLE 93
Cdd:cd06875     1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1676318464  94 VYLQKLLAAFPGVTPRVLAHFLHFHFYEINGITAAL 129
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 1676318464  14 EPAKEARVVGSELVDTYTVYIIQVTDGSHEWTVKHRYSDFHDLHEKLVAERKIDKNLLPPKKIIGKNSRSLVEKREKDLE 93
Cdd:cd06875     1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1676318464  94 VYLQKLLAAFPGVTPRVLAHFLHFHFYEINGITAAL 129
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 1676318464 289 LTTLDLSHNSVSEIdESVKLIPKIEFLDLSHNGLLVVDNLQHLYNLVHLDLSYNKLSSLEGL-------HTKLGNIKTLN 361
Cdd:cd21340    48 LTHLYLQNNQIEKI-ENLENLVNLKKLYLGGNRISVVEGLENLTNLEELHIENQRLPPGEKLtfdprslAALSNSLRVLN 126

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1676318464 362 LAGNLLESLSGLHKLYSLVNLDLRDNRIEQMEEV-RSIGSLPCLEHVSLLNNPLSIIPDYRTKVLA 426
Cdd:cd21340   127 ISGNNIDSLEPLAPLRNLEQLDASNNQISDLEELlDLLSSWPSLRELDLTGNPVCKKPKYRDKIIL 192

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464  36 QVTDGSHEWTVKHRYSDFHDLHEKLvaERKIDKNL---LPPKKIIGKNSRSLVEKREKDLEVYLQKLLAAFPGVTPRVLA 112
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKL--LRKFPSVIippLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLL 78

                  ....*.
gi 1676318464 113 HFLHFH 118
Cdd:pfam00787  79 EFLESD 84

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464 275 LEGPVTAVIPTWQALTTLDLSHNSVS-EIDESVKLIPKIEFLDLSHNGLL--VVDNLQHLYNLVHLDLSYNKLSSleGLH 351
Cdd:PLN00113  272 LSGPIPPSIFSLQKLISLDLSDNSLSgEIPELVIQLQNLEILHLFSNNFTgkIPVALTSLPRLQVLQLWSNKFSG--EIP 349

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1676318464 352 TKLG--------NIKTLNLAGNLLESLSGLHKLYSLVnldLRDNRIEQmEEVRSIGSLPCLEHVSLLNNPLS 415
Cdd:PLN00113  350 KNLGkhnnltvlDLSTNNLTGEIPEGLCSSGNLFKLI---LFSNSLEG-EIPKSLGACRSLRRVRLQDNSFS 417

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 1676318464  14 EPAKEARVVGSELVDTYTVYIIQVTDGSHEWTVKHRYSDFHDLHEKLVAERKIDKNLLPPKKIIGKNSRSLVEKREKDLE 93
Cdd:cd06875     1 EPETKIRIPSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPSFVEKRRKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1676318464  94 VYLQKLLAAFPGVTPRVLAHFLHFHFYEINGITAAL 129
Cdd:cd06875    81 IYLQTLLSFFQKTMPRELAHFLDFHKYEIIGLTQNL 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464 281 AVIPTWQALTTLDLSHNSVSEIDESVKLIPKIEFLDLSHNGLLVV-DNLQHLYNLVHLDLSYNKLSSLEGLHTKLGNIKT 359
Cdd:COG4886   153 EPLGNLTNLKSLDLSNNQLTDLPEELGNLTNLKELDLSNNQITDLpEPLGNLTNLEELDLSGNQLTDLPEPLANLTNLET 232

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1676318464 360 LNLAGNLLESLSGLHKLYSLVNLDLRDNRIeqmEEVRSIGSLPCLEHVSLLNNPLSII 417
Cdd:COG4886   233 LDLSNNQLTDLPELGNLTNLEELDLSNNQL---TDLPPLANLTNLKTLDLSNNQLTDL 287

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464 283 IPTWQALTTLDLSHNSVSEIDESVKLIPKIEFLDLSHNGLLVVDN-LQHLYNLVHLDLSYNKLSSLEGLHTKLGNIKTLN 361
Cdd:COG4886   132 LANLTNLKELDLSNNQLTDLPEPLGNLTNLKSLDLSNNQLTDLPEeLGNLTNLKELDLSNNQITDLPEPLGNLTNLEELD 211

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1676318464 362 LAGNLLESLS-GLHKLYSLVNLDLRDNRIEQMEEvrsIGSLPCLEHVSLLNNPLSIIPD 419
Cdd:COG4886   212 LSGNQLTDLPePLANLTNLETLDLSNNQLTDLPE---LGNLTNLEELDLSNNQLTDLPP 267

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464 283 IPTWQALTTLDLSHNSVSEIDESVKLIPKIEFLDLSHNGL-LVVDNLQHLYNLVHLDLSYNKLSSLEGLHTKLGNIKTLN 361
Cdd:COG4886   109 LSNLTNLESLDLSGNQLTDLPEELANLTNLKELDLSNNQLtDLPEPLGNLTNLKSLDLSNNQLTDLPEELGNLTNLKELD 188

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1676318464 362 LAGNLLESLSG-LHKLYSLVNLDLRDNRIEQMEEvrSIGSLPCLEHVSLLNNPLSIIPD 419
Cdd:COG4886   189 LSNNQITDLPEpLGNLTNLEELDLSGNQLTDLPE--PLANLTNLETLDLSNNQLTDLPE 245

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464  28 DTYTVYIIQVTDGSHEWTVKHRYSDFHDLHEKLVAERKIDKNL-LPPKKIIGKNSRSLVEKREKDLEVYLQKLLAAFPGV 106
Cdd:cd07277    16 DAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFdFPPKKAIGNKDAKFVEERRKRLQVYLRRVVNTLIQT 95

                  ....*.
gi 1676318464 107 TPRVLA 112
Cdd:cd07277    96 SPELTA 101

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 1676318464  29 TYTVYIIQVT----DGSHE-WTVKHRYSDFHDLHEKLVaER--KIDKNLLPPKKIIGKNSRSLVEKREKDLEVYLQKLLA 101
Cdd:cd06873    21 TYAVYAISVTriypNGQEEsWHVYRRYSDFHDLHMRLK-EKfpNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLN 99

                          90
                  ....*....|....*....
gi 1676318464 102 -----AFPGVTPrVLAHFL 115
Cdd:cd06873   100 pevldANPGLQE-IVLDFL 117

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 1676318464  24 SELVDTYTVYIIQVTDGSHEWTVKHRYSDFHDLHEKLvaERKIDKNL---LPPKKII--GKNSRSLVEKREKDLEVYLQK 98
Cdd:cd06897     9 SVSPKPYTVYNIQVRLPLRSYTVSRRYSEFVALHKQL--ESEVGIEPpypLPPKSWFlsTSSNPKLVEERRVGLEAFLRA 86

                  ..
gi 1676318464  99 LL 100
Cdd:cd06897    87 LL 88

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 1676318464  23 GSELVDTYTVYIIQVTDGS---HEWTVKHRYSDFHDLHEKL-VAERKIdknLLPPKKIIGKNSRSLVEKREKDLEVYLQK 98
Cdd:cd06871    14 ASQNIQSHTEYIIRVQRGPspeNSWQVIRRYNDFDLLNASLqISGISL---PLPPKKLIGNMDREFIAERQQGLQNYLNV 90

                  ...
gi 1676318464  99 LLA 101
Cdd:cd06871    91 ILM 93

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 1676318464  19 ARVVGSELV----DTYTVYIIQVTDGS-HEWTVKHRYSDFHDLHEKLvaeRKIDK-NL-LPPKKIIGKN-SRSLVEKREK 90
Cdd:cd06872     3 CRVLGAEIVksgsKSFAVYSVAVTDNEnETWVVKRRFRNFETLHRRL---KEVPKyNLeLPPKRFLSSSlDGAFIEERCK 79

                          90
                  ....*....|.
gi 1676318464  91 DLEVYLQKLLA 101
Cdd:cd06872    80 LLDKYLKDLLV 90

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 1676318464  14 EPAKearvVGsELVDTYTVY-IIQVTDGSH----EWTVKHRYSDFHDLHEKLVAerkidKNL------LPPKKIIG--KN 80
Cdd:cd06859     7 DPVK----VG-DGMSAYVVYrVTTKTNLPDfkksEFSVLRRYSDFLWLYERLVE-----KYPgrivppPPEKQAVGrfKV 76

                          90
                  ....*....|....*...
gi 1676318464  81 SRSLVEKREKDLEVYLQK 98
Cdd:cd06859    77 KFEFIEKRRAALERFLRR 94

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 1676318464  28 DTYTVYIIQV-----TDGSHE---WTVKHRYSDFHDLHEKLVaERKIDKNL--LPPKKIIGKNSRSLVEKREKDLEVYLQ 97
Cdd:cd06877    20 ERIYVFCIEVerndrRAKGHEpqhWSVLRRYNEFYVLESKLT-EFHGEFPDapLPSRRIFGPKSYEFLESKREIFEEFLQ 98

                  ...
gi 1676318464  98 KLL 100
Cdd:cd06877    99 KLL 101

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 1676318464  25 ELVD----TYTVYIIQVtDGSHEWTVkhRYSDFHDLHEKLVAE---RKIDKnlLPPKKIIGKNSRSLVEKREKdLEVYLQ 97
Cdd:cd06885     9 ELSDeggsTYVAYNIHI-NGVLHCSV--RYSQLHGLNEQLKKEfgnRKLPP--FPPKKLLPLTPAQLEERRLQ-LEKYLQ 82

                          90
                  ....*....|....*...
gi 1676318464  98 KLlaafpGVTPRVLAHFL 115
Cdd:cd06885    83 AV-----VQDPRIANSDI 95

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 1676318464  30 YTVYIiqVTDGSHEWTVKHRYSDFHDLHEKLVAE---RKIDknLLPPKKIIGKNSRSLVEKREKDLEVYL 96
Cdd:cd06866    18 HVEYE--VSSKRFKSTVYRRYSDFVWLHEYLLKRypyRMVP--ALPPKRIGGSADREFLEARRRGLSRFL 83

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 1676318464  27 VDTYTVYIIQVTDG-----SHEWTVKHRYSDFHDLHEKLVAERKIDKNLLPP---KKIIG----------KNSRSLVEKR 88
Cdd:cd07281    15 MNAYVVYKVTTQTSllmfrSKHFTVKRRFSDFLGLYEKLSEKHSQNGFIVPPppeKSLIGmtkvkvgkedSSSAEFLERR 94

                          90
                  ....*....|...
gi 1676318464  89 EKDLEVYLQKLLA 101
Cdd:cd07281    95 RAALERYLQRIVS 107

Leucine-rich repeat;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464 292 LDLSHNSVSEIDESVKLIPKIEFLDLSHNGLLVVDNLQHLYNLVHLDLSYNKLSSL-EGLHTKLGNIKTLNLAGNLLESL 370
Cdd:pfam14580  24 LDLRGYKIPIIENLGATLDQFDTIDFSDNEIRKLDGFPLLRRLKTLLLNNNRICRIgEGLGEALPNLTELILTNNNLQEL 103

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1676318464 371 SGLHKLyslvnldlrdnrieqmeevrsiGSLPCLEHVSLLNNPLSIIPDYRTKVLAQF 428
Cdd:pfam14580 104 GDLDPL----------------------ASLKKLTFLSLLRNPVTNKPHYRLYVIYKV 139

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464  18 EARVVGSE---LVDTYTVYIIQVT-DGSHEWT-VKHRYSDFHDLHEKLvaeRKIDKNL----LPPKKIIGK-NSRSLVEK 87
Cdd:cd06883     1 EVSVFGFQkrySPEKYYIYVVKVTrENQTEPSfVFRTFEEFQELHNKL---SLLFPSLklpsFPARVVLGRsHIKQVAER 77

                          90       100
                  ....*....|....*....|
gi 1676318464  88 REKDLEVYLQKLLAAFPGVT 107
Cdd:cd06883    78 RKIELNSYLKSLFNASPEVA 97

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 1676318464  21 VVGSELVDT---YTVYIIQVTDGSHE-WTVKHRYSDFHDLHEKLVAERKIDKNLLPPKKIIGKN-SRSLVEKREKDLEVY 95
Cdd:cd07276     8 ILGYEVMEErarFTVYKIRVENKVGDsWFVFRRYTDFVRLNDKLKQMFPGFRLSLPPKRWFKDNfDPDFLEERQLGLQAF 87

                  ....*.
gi 1676318464  96 LQKLLA 101
Cdd:cd07276    88 VNNIMA 93

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX2 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. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1676318464  43 EWTVKHRYSDFHDLHEKLVAERKIDKNLLPP---KKIIG----------KNSRSLVEKREKDLEVYLQK 98
Cdd:cd07282    36 EFSVRRRFSDFLGLHSKLASKYLHVGYIVPPapeKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQR 104

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 1676318464 310 PKIEFLDLSHNGLLVVDNLQHLYNLVHLDLSYN-KLSSLEGL 350
Cdd:pfam12799   1 PNLEVLDLSNNQITDIPPLAKLPNLETLDLSGNnKITDLSDL 42

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 1676318464  13 AEPAKEARVVGSELVDTYTVYIIQVTDGSHEW---------TVKHRYSDFHDLHEKLVAerKIDKNLLPP---KKI--IG 78
Cdd:cd06864     6 TEAEKRTGGSAMNLKETYTVYLIETKIVEHESeeglskklsSLWRRYSEFELLRNYLVV--TYPYVIVPPlpeKRAmfMW 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1676318464  79 KNSRS------LVEKREKDLEVYLQKlLAAFPgvtprVLA---HFLHF 117
Cdd:cd06864    84 QKLSSdtfdpdFVERRRAGLENFLLR-VAGHP-----ELCqdkIFLEF 125

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 1676318464  30 YTVYIIQV-TDGSHEWTVKHRYSDFHDLHEKLVAERKIDKN------LLP--PKKIIGKNSRSLVEKREKDLEVYLQKLL 100
Cdd:cd06882    20 YYVFVIEVkTKGGSKYLIYRRYRQFFALQSKLEERFGPEAGssaydcTLPtlPGKIYVGRKAEIAERRIPLLNRYMKELL 99

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 1676318464  19 ARVVGSELVDTY------TVYIIQVTDGSHEWTVKHRYSDFHDLHEKL---------------------------VAERK 65
Cdd:cd06895     6 ARITDVERSGTTrhllnpNLYTIELQHGQFTWTIKRRYKHFQELHQALklyrallriplptrrhkeerlslkrsrKPERE 85

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1676318464  66 IDKNLLP--PKKIIGKNSRSLVEKREKDLEVYLQKLL 100
Cdd:cd06895    86 KKNRRLPslPALPDILVSEEQLDSRKKQLENYLQNLL 122

The phosphoinositide binding Phox Homology domain of Five SH protein; 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. Five SH (FISH), also called Tks5, is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. FISH contains an N-terminal PX domain and five Src homology 3 (SH3) domains. FISH binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. This subfamily also includes proteins with a different number of SH3 domains than FISH, such as Tks4, which contains four SH3 domains instead of five. The Tks4 adaptor protein is required for the formation of functional podosomes. It has overlapping, but not identical, functions as FISH. 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 1676318464  32 VYIIQVT--DGSHEwTVKHRYSDFHDLHEKLVAERKID---KN-------LLPPKKIIGK-NSRSLVEKREKDLEVYLQK 98
Cdd:cd06888    20 VYIINVTwsDGSSN-VIYRRYSKFFDLQMQLLDKFPIEggqKDpsqriipFLPGKILFRRsHIRDVAVKRLKPIDEYCKA 98

                  ..
gi 1676318464  99 LL 100
Cdd:cd06888    99 LV 100

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1676318464 275 LEGPVTAVIPTWQALTTLDLSHNSVS-EIDESVKLIPKIEFLDLSHNGLL--VVDNLQHLYNLVHLDLSYNKLSSleGLH 351
Cdd:PLN00113  272 LSGPIPPSIFSLQKLISLDLSDNSLSgEIPELVIQLQNLEILHLFSNNFTgkIPVALTSLPRLQVLQLWSNKFSG--EIP 349