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 755562522   9 FLRHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDIKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEFPAFPRAQVFGRF 88
Cdd:cd07288    1 YYRFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRF 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 755562522  89 EASVIEERRKGAEDLLRFTVPIPALNNSPQLKEFFRGG 126
Cdd:cd07288   81 EAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522   9 FLRHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDIKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEFPAFPRAQVFGRF 88
Cdd:cd07288    1 YYRFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRF 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 755562522  89 EASVIEERRKGAEDLLRFTVPIPALNNSPQLKEFFRGG 126
Cdd:cd07288   81 EAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755562522   47 VVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGRFEASVIEERRKGAEDLLRFTVPIPALNNSPQLKEFF 123
Cdd:pfam00787  10 SVRRRYSDFVELHKKLLRKFPSVI-----IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522   9 FLRHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDIKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEFPAFPRAQVFGRF 88
Cdd:cd07288    1 YYRFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRF 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 755562522  89 EASVIEERRKGAEDLLRFTVPIPALNNSPQLKEFFRGG 126
Cdd:cd07288   81 EAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

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 755562522  11 RHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDIKEVVVWKRYSDFRKLHGDLAYTHRNLFRRlEEFPAFPRAQVFGRFEA 90
Cdd:cd06881    3 RSFTVTDTRRHKKGYTEYKITSKVFSRSVPEDVSEVVVWKRYSDFKKLHRELSRLHKQLYLS-GSFPPFPKGKYFGRFDA 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 755562522  91 SVIEERRKGAEDLLRFTVPIPALNNSPQLKEFFRGG 126
Cdd:cd06881   82 AVIEERRQAILELLDFVGNHPALYQSSAFQQFFEEA 117

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522    15 VSDPRTHpkGYTEYKVTAQFISKKDPEdiKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGR---FEAS 91
Cdd:smart00312   1 VVEPEKI--GDGKHYYYVIEIETKTGL--EEWTVSRRYSDFLELHSKLKKHFPRSI-----LPPLPGKKLFGRlnnFSEE 71

                           90       100       110
                   ....*....|....*....|....*....|...
gi 755562522    92 VIEERRKGAEDLLRFTVPIPAL-NNSPQLKEFF 123
Cdd:smart00312  72 FIEKRRRGLEKYLQSLLNHPELiNHSEVVLEFL 104

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 755562522  14 TVSDPRTHPKG---YTEYKVTaqfiSKKDPEDIK--EVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGRF 88
Cdd:cd06859    4 SVTDPVKVGDGmsaYVVYRVT----TKTNLPDFKksEFSVLRRYSDFLWLYERLVEKYPGRI-----VPPPPEKQAVGRF 74

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 755562522  89 EASV--IEERRKGAEDLLRFTVPIPALNNSPQLKEF 122
Cdd:cd06859   75 KVKFefIEKRRAALERFLRRIAAHPVLRKDPDFRLF 110

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; 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. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522  14 TVSDPRT---HPKGYTEYKVTAQfISKKDPEdIKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGRFEA 90
Cdd:cd06861    4 TVGDPHKvgdLTSAHTVYTVRTR-TTSPNFE-VSSFSVLRRYRDFRWLYRQLQNNHPGVI-----VPPPPEKQSVGRFDD 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 755562522  91 SVIEERRKGAEDLLRFTVPIPALNNSPQLKEF 122
Cdd:cd06861   77 NFVEQRRAALEKMLRKIANHPVLQKDPDFRLF 108

The phosphoinositide binding Phox Homology domain of SNX-like proteins; 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 is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522  14 TVSDPRTHP---------KGYTEYKVTAQfiSKKDPEDIKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFP---- 80
Cdd:cd06865    3 TVSDPKKEQepsrvplggPPYISYKVTTR--TNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAF-----VPPRPdksv 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 755562522  81 -RAQVFGRFEasVIEERRKGAEDLLRFTVPIPALNNSPQLKEFFR 124
Cdd:cd06865   76 vESQVMQSAE--FIEQRRVALEKYLNRLAAHPVIGLSDELRVFLT 118

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 755562522  15 VSDPRTHPKG---YTEYKVTAQfiSKKDPEDIKEVVVWKRYSDFRKLHGDLA--YTHRNLFrrleeFPAFPRAQVFGRFE 89
Cdd:cd07282    5 VSDPEKVGDGmnaYMAYRVTTK--TSLSMFSRSEFSVRRRFSDFLGLHSKLAskYLHVGYI-----VPPAPEKSIVGMTK 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 755562522  90 ASV----------IEERRKGAEDLLRFTVPIPALNNSPQLKEFF 123
Cdd:cd07282   78 VKVgkedssstefVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 121

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 755562522  40 PEDIKEVVVWKRYSDFRKLHGDLaythRNLFRRLEEFPAFPRAQVFGRFEASVIEERRKGAEDLLRFTVPIPALNNSPQL 119
Cdd:cd07301   30 QYDPSPAYISRRYSDFERLHRRL----RRLFGGEMAGVSFPRKRLRKNFTAETIAKRSRAFEQFLCHLHSLPELRASPAF 105

                 ....
gi 755562522 120 KEFF 123
Cdd:cd07301  106 LEFF 109

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 755562522  20 THPkgYTEYKVTAQFISKKDPE---------DIKEVVVWKRYSDFRKLHGDLayTHRNLFRRL-------EEFPAFPraq 83
Cdd:cd06893   18 THP--YTLYTVQYETILDVQSEqnpnaaseqPLATHTVNRRFREFLTLQTRL--EENPKFRKImnvkgppKRLFDLP--- 90

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 755562522  84 vFGRFEASVIEERRKGAEDLLRFTVPIPALNNSPQLKEF 122
Cdd:cd06893   91 -FGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEF 128

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 755562522  14 TVSDPRTHPKGYTEYKVTAQFIskkdpedIKEVVVWKRYSDFRKLHGDLAY-THRNlfrRLEEFPafPRAQVFGRF-EAS 91
Cdd:cd06897    4 SIPTTSVSPKPYTVYNIQVRLP-------LRSYTVSRRYSEFVALHKQLESeVGIE---PPYPLP--PKSWFLSTSsNPK 71

                         90       100       110
                 ....*....|....*....|....*....|...
gi 755562522  92 VIEERRKGAEDLLRFTV--PIPALNNSPQLKEF 122
Cdd:cd06897   72 LVEERRVGLEAFLRALLndEDSRWRNSPAVKEF 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 755562522  48 VWKRYSDFRKLHGDLaythRNLFRRLEEFpAFPRAQVFGRFEASVIEERRKGAEDLLR 105
Cdd:cd07277   34 VYRRYSEFYELHKKL----KKKFPVVRSF-DFPPKKAIGNKDAKFVEERRKRLQVYLR 86

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX 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. 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 755562522  14 TVSDPR----THPKGYTEYKVTAQfISKKDPEDiKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVF---- 85
Cdd:cd06863    4 LVSDPQkeldGSSDTYISYLITTK-TNLPSFSR-KEFKVRRRYSDFVFLHECLSNDFPACV-----VPPLPDKHRLeyit 76

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 755562522  86 -GRFEASVIEERRKGAEDLLRFTVPIPALNNSPQLKEFF 123
Cdd:cd06863   77 gDRFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522   8 DFLRHYTVSDPRTH------PKGYTEYKV--TAQFISKKDPEDIkEVVVWKRYSDFRKLHGDLAytHRNLFRRLEEFPA- 78
Cdd:COG5391  128 DYFISSTVSNPQSLtllvdsRDKHTSYEIitVTNLPSFQLRESR-PLVVRRRYSDFESLHSILI--KLLPLCAIPPLPSk 204

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 755562522  79 -FPRAQVFGRFEASVIEERRKGAEDLLRFTVPIPALNNSP 117
Cdd:COG5391  205 kSNSEYYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYK 244

The phosphoinositide binding Phox Homology domain of fungal Grd19; 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. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522  15 VSDPRTHPKG---YTEYKVtaqfISKKDPEDIKevvvwKRYSDFRKLHGDLAYTHRNLFRRLEE--FPAFPRAQVFGRFE 89
Cdd:cd07295    6 VRNPKTHGIGrgmFTDYEI----VCRTNIPAFK-----LRVSSVRRRYSDFEYFRDILERESPRvmIPPLPGKIFTNRFS 76

                         90       100
                 ....*....|....*....|....
gi 755562522  90 ASVIEERRKGAEDLLRFTVPIPAL 113
Cdd:cd07295   77 DEVIEERRQGLETFLQSVAGHPLL 100

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755562522  14 TVSDPRTH---PKGYTEYKVTAQfiSKKDPEDIKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVF----G 86
Cdd:cd06860    4 TVDNPEKHvttLETYITYRVTTK--TTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHI-----IPPLPEKHSVkgllD 76

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 755562522  87 RFEASVIEERRKGAEDLLRFTVPIPALNNSPQLKEF 122
Cdd:cd06860   77 RFSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVF 112

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.

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gi 755562522  47 VVWKRYSDFRKLHGDLaythRNLFRRLEEfpAFPRAQVFG-RFEASVIEERRKGAEDLLRFTVPIPALNNSPQLKEFF 123
Cdd:cd07276   36 FVFRRYTDFVRLNDKL----KQMFPGFRL--SLPPKRWFKdNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFF 107