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 1720396596 121 LLFEVTSANVVKDPPSKYVawviseepqLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLR 200
Cdd:cd07301     1 LLFEVTDANVVQDAHSKYV---------LYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLR 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720396596 201 RNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 241
Cdd:cd07301    72 KNFTAETIAKRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 112

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 1720396596 121 LLFEVTSANVVKDPPSKYVawviseepqLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLR 200
Cdd:cd07301     1 LLFEVTDANVVQDAHSKYV---------LYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLR 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720396596 201 RNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 241
Cdd:cd07301    72 KNFTAETIAKRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 112

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 1720396596  166 QISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRL---RRNFTAETIARRSRAFEQFLGHLQAVPELRQA-PDLQDFF 238
Cdd:smart00312  29 TVSRRYSDFLELHSKLKKHF--PRSILpPLPGKKLfgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELINHsEVVLEFL 104

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720396596 243 LRRAQSLTCTGLYREALALWANAWQLQTQLGtpsGPDRPLL--TLAGLAVCHQELEDPGEARACSEKALQLL 312
Cdd:pfam13424   7 NNLAAVLRRLGRYDEALELLEKALEIARRLL---GPDHPLTatTLLNLGRLYLELGRYEEALELLERALALA 75

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 1720396596 121 LLFEVTSANVVKDPPSKYVawviseepqLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLR 200
Cdd:cd07301     1 LLFEVTDANVVQDAHSKYV---------LYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLR 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720396596 201 RNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 241
Cdd:cd07301    72 KNFTAETIAKRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 112

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 1720396596 121 LLFEVTSANVVKDPPSKYVawviseepqLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLR 200
Cdd:cd07300     1 LLFEIPSARIIEQTISKHV---------VYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLT 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1720396596 201 RNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLPEL 243
Cdd:cd07300    72 GNFSEEIIAERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396596 160 PDRQPAQISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFF 238
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKF--PSVIIpPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; 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. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. 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. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396596 149 LYTLAVMGP---GPPDRQPAQISRRYSDFERLHRNLQR-----QFRGPMSAisFPRKRLRRNFTAETIARRSRAFEQFLG 220
Cdd:cd06881    19 EYKITSKVFsrsVPEDVSEVVVWKRYSDFKKLHRELSRlhkqlYLSGSFPP--FPKGKYFGRFDAAVIEERRQAILELLD 96

                          90
                  ....*....|....*....
gi 1720396596 221 HLQAVPELRQAPDLQDFFV 239
Cdd:cd06881    97 FVGNHPALYQSSAFQQFFE 115

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 1720396596 169 RRYSDFERLHRNLQRQFrgPMSAISFPRKR-LRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVL 240
Cdd:cd07276    39 RRYTDFVRLNDKLKQMF--PGFRLSLPPKRwFKDNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFFCL 109

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396596 124 EVTSANVVKDPPSK-YVAWVISeepqlytlavmgpgppdRQPAQISRRYSDFERLHRNLQRQFrgPM----------SAI 192
Cdd:cd06867     3 QIVDAGKSSEGGSGsYIVYVIR-----------------LGGSEVKRRYSEFESLRKNLTRLY--PTliippipekhSLK 63

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1720396596 193 SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 237
Cdd:cd06867    64 DYAKKPSKAKNDAKIIERRKRMLQRFLNRCLQHPILRNDIVFQKF 108

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720396596 167 ISRRYSDFERLHRNLQRQFrGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAV 225
Cdd:cd06874    34 VFRRYSRFRELHKTMKLKY-PEVAALEFPPKKLFGNKSERVAKERRRQLETYLRNFFSV 91

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 1720396596 160 PDRQPAQISRRYSDFERLHRNLQRQ--FRGPMSAISfPRKRLRR----NFTAETIARRSRAFEQFLGHLQAVPELRQAPD 233
Cdd:cd06893    46 QPLATHTVNRRFREFLTLQTRLEENpkFRKIMNVKG-PPKRLFDlpfgNMDKDKIEARRGLLETFLRQLCSIPEISNSEE 124

                  ....*..
gi 1720396596 234 LQDFFVL 240
Cdd:cd06893   125 VQEFLAY 131

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720396596 167 ISRRYSDFERLHRNLQRQFrGPMSAISFPRKRL--RRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 237
Cdd:cd06876    59 VARRYSEFLELHKYLKKRY-PGVLKLDFPQKRKisLKYSKTLLVEERRKALEKYLQELLKIPEVCEDEEFRKF 130

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720396596 167 ISRRYSDFERLHRNLQRQFRGPMSAiSFPRKR--LRRNFTAETIARRSRAFEQFLGHL--QAVPELRQAPDLQDFFVLP 241
Cdd:cd06897    31 VSRRYSEFVALHKQLESEVGIEPPY-PLPPKSwfLSTSSNPKLVEERRVGLEAFLRALlnDEDSRWRNSPAVKEFLNLP 108

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 1720396596 158 GPPDRQPAQISRRYSDFERLHRNLqRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 237
Cdd:cd06877    37 KGHEPQHWSVLRRYNEFYVLESKL-TEFHGEFPDAPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDF 115

The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720396596 167 ISRRYSDFERLHRNLQRQFrgPMSAIS-FPRKRLRRnfTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 237
Cdd:cd06868    49 VSKKYSEFEELYKKLSEKY--PGTILPpLPRKALFV--SESDIRERRAAFNDFMRFISKDEKLANCPELLEF 116

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 1720396596 136 SKYVAW--VISEEPQLYTlavmgpgppdrqPAQISRRYSDFERLHRNLQRQFRG----------PMSAISFPRKRLRRNF 203
Cdd:cd07280    20 GAYVVWkiTIETKDLIGS------------SIVAYKRYSEFVQLREALLDEFPRhkrneipqlpPKVPWYDSRVNLNKAW 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1720396596 204 taetIARRSRAFEQFLGH------LQAVPELRQapdlqdfFVLP 241
Cdd:cd07280    88 ----LEKRRRGLQYFLNCvllnpvFGGSPVVKE-------FLLP 120

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396596 222 LQAVPELRQAPDLQDFFVLPELRRAQSLTCTGLYREALALWANAWQLQtqlgtpsgPDRPLlTLAGLAVCHQELEDPGEA 301
Cdd:COG3914    61 ALAAGEAAAAAAALLLLAALLELAALLLQALGRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEA 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720396596 302 RACSEKALQLLGDkrphpflapFLEAHVRLSWRLGLDKRQSEAqLQALQEA 352
Cdd:COG3914   132 LAALRRALALNPD---------FAEAYLNLGEALRRLGRLEEA-IAALRRA 172

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 1720396596 166 QISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 241
Cdd:cd06866    31 TVYRRYSDFVWLHEYLLKRY--PYRMVpALPPKRIGGSADREFLEARRRGLSRFLNLVARHPVLSEDELVRTFLTEP 105

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396596 166 QISRRYSDFERLHRNLQRQFRG----PMSAISFPRKRLRRnFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 237
Cdd:cd06860    38 SVRRRYQDFLWLRQKLEESHPThiipPLPEKHSVKGLLDR-FSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVF 112

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; 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. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720396596 168 SRRYSDFERLHRNLQRQFRGpmsaISFPRKRLRRNFT--AETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 237
Cdd:cd06886    35 SRRYREFANLHQNLKKEFPD----FQFPKLPGKWPFSlsEQQLDARRRGLEQYLEKVCSIRVIGESDIMQDF 102

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396596 148 QLYTLAVMGPGppdRQpAQISRRYSDFERLHRNLQRQFRGPmsaiSFPRKRLrRNFTAETIARRSRAFEQFLGHLQAVPE 227
Cdd:cd06880    20 TVFTIEVLVNG---RR-HTVEKRYSEFHALHKKLKKSIKTP----DFPPKRV-RNWNPKVLEQRRQGLEAYLQGLLKINE 90

                          90       100
                  ....*....|....*....|..
gi 1720396596 228 LRQapDLQDFFvlpELRRAQSL 249
Cdd:cd06880    91 LPK--QLLDFL---GVRHFPSL 107

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396596 157 PGPPDRQpaqISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQ 235
Cdd:cd06862    27 PTHTNVT---VSRRYKHFDWLYERLVEKY--SCIAIpPLPEKQVTGRFEEDFIEKRRERLELWMNRLARHPVLSQSEVFR 101

                          90
                  ....*....|....*..
gi 1720396596 236 DFfvlpelrraqsLTCT 252
Cdd:cd06862   102 HF-----------LTCT 107