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 2217308154 273 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ 352
Cdd:cd07277     1 INVWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKR 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2217308154 353 LQNYLRSVMNKVIQMVPEFAASPKKETLIQLMPFFVDI 390
Cdd:cd07277    81 LQVYLRRVVNTLIQTSPELTACPSKETLIKLLPFFGDT 118

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 2217308154 273 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ 352
Cdd:cd07277     1 INVWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKR 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2217308154 353 LQNYLRSVMNKVIQMVPEFAASPKKETLIQLMPFFVDI 390
Cdd:cd07277    81 LQVYLRRVVNTLIQTSPELTACPSKETLIKLLPFFGDT 118

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217308154  288 NAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIG---NKDAKFVEERRKQLQNYLRSVMN 362
Cdd:smart00312  12 HYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89

leucine zipper domain found in the TSC22 domain family of leucine zipper transcription factors; The TGF-beta-stimulated clone-22 domain (TSC22D) family includes TSC22D1-4 and similar proteins. They have diverse physiological functions, including cell growth, development, homeostasis, and immune regulation. All family members contain a conserved leucine zipper (ZIP) domain located at the C-terminus. Its first helix is not basic and does not contain the consensus sequence, NXX(A)(A)XX(C/S)R, found in most basic region/leucine zipper (bZIP) proteins. In the bZIP family of transcription factors, the leucine zipper acts as a dimerization domain and the upstream basic region as a DNA-binding domain. However, DNA-binding capability of TSC22D family proteins is not obvious, due to the lack of the basic region found in the original bZIP DNA-binding domains. Similar to bZIP, ZIP forms homo- and heterodimers, resulting in many dimers that may have different effects on transcription.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2217308154 119 ALRQEVDTLKRKVAEQEERqgmkVQALARENEVLK 153
Cdd:cd21936    12 AVREEVDVLKEQIAELEER----ISQLERENSLLR 42

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 2217308154 273 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ 352
Cdd:cd07277     1 INVWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKR 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2217308154 353 LQNYLRSVMNKVIQMVPEFAASPKKETLIQLMPFFVDI 390
Cdd:cd07277    81 LQVYLRRVVNTLIQTSPELTACPSKETLIKLLPFFGDT 118

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 2217308154 274 NVWIPSVFLRGKAANAFHVYQVYIRIKD-DEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ 352
Cdd:cd06093     1 SVSIPDYEKVKDGGKKYVVYIIEVTTQGgEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERRKQ 80

                          90
                  ....*....|
gi 2217308154 353 LQNYLRSVMN 362
Cdd:cd06093    81 LEQYLQSLLN 90

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 2217308154 288 NAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYpQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVMNKVIQM 367
Cdd:cd06875    15 EGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEH-KVDKDLLPPKKLIGNKSPSFVEKRRKELEIYLQTLLSFFQKT 93

                  ...
gi 2217308154 368 VPE 370
Cdd:cd06875    94 MPR 96

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 2217308154 289 AFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVMNKViqmv 368
Cdd:cd06873    26 AISVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPE---- 101

                          90
                  ....*....|...
gi 2217308154 369 pEFAASPKKETLI 381
Cdd:cd06873   102 -VLDANPGLQEIV 113

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 2217308154 277 IPSVFLRGKAanaFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAI--GNKDAKFVEERRKQLQ 354
Cdd:cd06897     5 IPTTSVSPKP---YTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFlsTSSNPKLVEERRVGLE 81

                  ....*...
gi 2217308154 355 NYLRSVMN 362
Cdd:cd06897    82 AFLRALLN 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217308154 290 FHVYQVYIRIK-DDEWNIYRRYTEFRSLHHKLQNKYPQVRaYNFPPKKAIG-NKDAKFVEERRKQLQNYLRSVM 361
Cdd:cd07276    20 FTVYKIRVENKvGDSWFVFRRYTDFVRLNDKLKQMFPGFR-LSLPPKRWFKdNFDPDFLEERQLGLQAFVNNIM 92

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 2217308154 276 WIPSVFLRG-------KAANAFHVYQVYIRIKDDEW---NIYRRYTEFRSLHHKLQNKYPQVRAYNFP--PKKAIG---- 339
Cdd:cd07280     1 HATDVNVGDytivggdTGGGAYVVWKITIETKDLIGssiVAYKRYSEFVQLREALLDEFPRHKRNEIPqlPPKVPWydsr 80

                          90       100
                  ....*....|....*....|....*....
gi 2217308154 340 -NKDAKFVEERRKQLQNYLRSVM-NKVIQ 366
Cdd:cd07280    81 vNLNKAWLEKRRRGLQYFLNCVLlNPVFG 109

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 2217308154 290 FHVYQVYIRIKDDEWNI---------YRRYTEFRSLHHKLQNKYPQVRAYNFPPKKA--------IGNKDAKFVEERRKQ 352
Cdd:cd06864    23 YTVYLIETKIVEHESEEglskklsslWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAmfmwqklsSDTFDPDFVERRRAG 102

                  ....*...
gi 2217308154 353 LQNYLRSV 360
Cdd:cd06864   103 LENFLLRV 110

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217308154 290 FHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVrAYNFPPKKAIGNK-DAKFVEERRKQLQNYLRSVM 361
Cdd:cd06870    20 FTVYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQFPAS-NLKIPGKRLFGNNfDPDFIKQRRAGLDEFIQRLV 91

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 2217308154 304 WNIYRRYTEFRSLHHKLQNKYPQVRAYNFP--PKKAIGNKDAKFVEERRKQLQNYLRSVM 361
Cdd:cd06878    50 WVVTRKLSEFHDLHRKLKECSSWLKKVELPslSKKWFKSIDKKFLDKSKNQLQKYLQFIL 109

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308154 284 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQVrAYNFPP----------KKAIGNKDA---KF 345
Cdd:cd07282    12 GDGMNAYMAYRVTTKtslsmFSRSEFSVRRRFSDFLGLHSKLASKYLHV-GYIVPPapeksivgmtKVKVGKEDSsstEF 90

                          90       100
                  ....*....|....*....|....*.
gi 2217308154 346 VEERRKQLQNYL-RSVMNKVIQMVPE 370
Cdd:cd07282    91 VEKRRAALERYLqRTVKHPTLLQDPD 116

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 2217308154 293 YQVY-IRIKDDE---WNIYRRYTEFRSLHHKLQnKYPQVrAYNFPPKKAIGNK-DAKFVEERRKQLQNYLRSVMnkVIQM 367
Cdd:cd06872    18 FAVYsVAVTDNEnetWVVKRRFRNFETLHRRLK-EVPKY-NLELPPKRFLSSSlDGAFIEERCKLLDKYLKDLL--VIEK 93

                  ....*
gi 2217308154 368 VPEFA 372
Cdd:cd06872    94 VAESH 98

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 2217308154 274 NVWIPSVFLRGKAANAFHVYqVYI--------RIKDDE---WNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKD 342
Cdd:cd06877     4 RVSIPYVEMRRDPSNGERIY-VFCieverndrRAKGHEpqhWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRRIFGPKS 82

                          90       100
                  ....*....|....*....|.
gi 2217308154 343 AKFVEERRKQLQNYLRSVMNK 363
Cdd:cd06877    83 YEFLESKREIFEEFLQKLLQK 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; 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. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217308154 305 NIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGN-KDAKFVEERRKQLQNYLRSVM 361
Cdd:cd06898    38 CVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRfNNEGFIEERQQGLQDFLEKVL 95

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; 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. 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. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308154 306 IYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ-LQNYLRSVMnkviQMVPEFAAS 374
Cdd:cd06884    36 VFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQdIQQFLNSLF----KMAEEVSHS 101

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217308154 308 RRYTEFRSLHHKLQNKYpqvRAYNFPPKKaIGNKDAKFVEERRKQLQNYLRSVM--NKVIQMVPEF 371
Cdd:cd06880    37 KRYSEFHALHKKLKKSI---KTPDFPPKR-VRNWNPKVLEQRRQGLEAYLQGLLkiNELPKQLLDF 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308154 308 RRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNK-----DAKFVEERRKQLQNYLRSVM----------NKVIQMVPEFA 372
Cdd:COG5391   177 RRYSDFESLHSILIKLLPLCAIPPLPSKKSNSEYygdrfSDEFIEERRQSLQNFLRRVSthpllsnyknSKSWESHSTLL 256

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217308154 373 ASPKKETLIQLMPFFVDITPPGEPVNSRPK 402
Cdd:COG5391   257 SSFIENRKSVPTPLSLDLTSTTQELDMERK 286

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217308154 306 IYRRYTEFRSLHHKLQNKyPQVRAY-------NFPPKKAIGNKDAKFVEERRKQLQNYLRSVMNkviqmVPEFAASP 375
Cdd:cd06893    53 VNRRFREFLTLQTRLEEN-PKFRKImnvkgppKRLFDLPFGNMDKDKIEARRGLLETFLRQLCS-----IPEISNSE 123

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; 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. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308154 277 IPSVFLRGKAANAFHVYQVYI----RIKDDEWNIYRRYTEFRSLHHKLQNKY-PQVRAYNFPPKKAIGNKDAKFVEERRK 351
Cdd:cd07300     5 IPSARIIEQTISKHVVYQIIViqtgSFDCNKVVIERRYSDFLKLHQELLSDFsEELEDVVFPKKKLTGNFSEEIIAERRV 84

                  ....*..
gi 2217308154 352 QLQNYLR 358
Cdd:cd07300    85 ALRDYLT 91

The phosphoinositide binding Phox Homology domain of Sorting Nexin 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308154 306 IYRRYTEFRSLHHKLQNKYP-QVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVmnkviQMVPEFAASPkketliQLM 384
Cdd:cd07301    38 ISRRYSDFERLHRRLRRLFGgEMAGVSFPRKRLRKNFTAETIAKRSRAFEQFLCHL-----HSLPELRASP------AFL 106

                  ....
gi 2217308154 385 PFFV 388
Cdd:cd07301   107 EFFY 110

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; 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 SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2217308154 308 RRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYL 357
Cdd:cd06862    36 RRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDFIEKRRERLELWM 85

The phosphoinositide binding Phox Homology domain of uncharacterized 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 fungal proteins containing a 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308154 263 SDFEISNRALIN--VWIPSVFLRGKAANAFHVYQVYIRIKD---DEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKA 337
Cdd:cd06879    17 SDGKAINPKVGNmsVVYSEYQPLNNAVDKFYRVQVGVQSPEgitTMRGVLRRFNDFLKLHTDLKKLFPKKKLPAAPPKGL 96

                          90       100
                  ....*....|....*....|....*..
gi 2217308154 338 IGNKDAKFVEERRKQLQNYLRSVMNKV 364
Cdd:cd06879    97 LRMKNRALLEERRHSLEEWMGKLLSDI 123