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 20140138 131 LLFEVTSANVVKDPPSKYVLYTLAVIGPGPPDCQPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIA 210
Cdd:cd07301   1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 20140138 211 RRSRAFEQFLGHLQAVPELRHAPDLQDFFVLP 242
Cdd:cd07301  81 KRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 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 20140138 131 LLFEVTSANVVKDPPSKYVLYTLAVIGPGPPDCQPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIA 210
Cdd:cd07301   1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 20140138 211 RRSRAFEQFLGHLQAVPELRHAPDLQDFFVLP 242
Cdd:cd07301  81 KRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138    142 KDPPSKYVLYTLAVIGPGPPdcQPAQISRRYSDFERLHRNLQRQFrgPMAAI-SFPRKRL---RRNFTAETIARRSRAFE 217
Cdd:smart00312   6 KIGDGKHYYYVIEIETKTGL--EEWTVSRRYSDFLELHSKLKKHF--PRSILpPLPGKKLfgrLNNFSEEFIEKRRRGLE 81

                           90       100
                   ....*....|....*....|...
gi 20140138    218 QFLGHLQAVPEL-RHAPDLQDFF 239
Cdd:smart00312  82 KYLQSLLNHPELiNHSEVVLEFL 104

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 164 QPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFFVLPE 243
Cdd:COG3914   5 ALLALAALAAAALLAAAAAAELALAAELEAAALAAALGLALLLLAALAEAAAAALLALAAGEAAAAAAALLLLAALLELA 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 244 LRRAQSLtctGLYREALALWANAWQLQaqlgtpsgPDRPLlTLAGLAVCHQELEDPGEARACCEKALQLLGDkslhplla 323
Cdd:COG3914  85 ALLLQAL---GRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEALAALRRALALNPD-------- 144

                       170       180       190
                ....*....|....*....|....*....|
gi 20140138 324 pFLEAHVRLSWRLGLDKRQSEArLQALQEA 353
Cdd:COG3914 145 -FAEAYLNLGEALRRLGRLEEA-IAALRRA 172

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 20140138 131 LLFEVTSANVVKDPPSKYVLYTLAVIGPGPPDCQPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIA 210
Cdd:cd07301   1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 20140138 211 RRSRAFEQFLGHLQAVPELRHAPDLQDFFVLP 242
Cdd:cd07301  81 KRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 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 20140138 131 LLFEVTSANVVKDPPSKYVLYTLAVIGPGPPDCQPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIA 210
Cdd:cd07300   1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 20140138 211 RRSRAFEQFLGHLQAVPELRHAPDLQDFFVLPEL 244
Cdd:cd07300  81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 20140138   167 QISRRYSDFERLHRNLQRQFrgPMAAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 239
Cdd:pfam00787  10 SVRRRYSDFVELHKKLLRKF--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 20140138 133 FEVTSAnvvKDPPSKYVLYTLAVIGP---GPPDCQPAQISRRYSDFERLHRNLQR-----QFRGPMAAisFPRKRLRRNF 204
Cdd:cd06881   5 FTVTDT---RRHKKGYTEYKITSKVFsrsVPEDVSEVVVWKRYSDFKKLHRELSRlhkqlYLSGSFPP--FPKGKYFGRF 79

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 20140138 205 TAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFFV 240
Cdd:cd06881  80 DAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115

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 20140138 134 EVTSANVVKDPPSK-YVLYTLAVigpgppdcQPAQISRRYSDFERLHRNLQRQFrgPMAAI----------SFPRKRLRR 202
Cdd:cd06867   3 QIVDAGKSSEGGSGsYIVYVIRL--------GGSEVKRRYSEFESLRKNLTRLY--PTLIIppipekhslkDYAKKPSKA 72

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 20140138 203 NFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDF 238
Cdd:cd06867  73 KNDAKIIERRKRMLQRFLNRCLQHPILRNDIVFQKF 108

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 20140138 141 VKDP---PSKYVLYTLA---VIGPGPPDCQPAQISRRYSDFERLH-------RNL-QRQFRGPmaaiSFPRKRLRRNFTA 206
Cdd:cd07288   7 VTDPrthPKGYTEYKVTaqfISKKQPEDVKEVVVWKRYSDLKKLHgelaythRNLfRRQEEFP----PFPRAQVFGRFEA 82

                        90       100       110
                ....*....|....*....|....*....|...
gi 20140138 207 ETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 239
Cdd:cd07288  83 AVIEERRNAAEAMLLFTVNIPALYNSPQLKEFF 115

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 20140138 145 PSKYVLYTLAVIGPGppdcQPAQISRRYSDFERLHRNLQRQFRGPMAAiSFPRKR--LRRNFTAETIARRSRAFEQFLGH 222
Cdd:cd06897  12 PKPYTVYNIQVRLPL----RSYTVSRRYSEFVALHKQLESEVGIEPPY-PLPPKSwfLSTSSNPKLVEERRVGLEAFLRA 86

                        90       100
                ....*....|....*....|..
gi 20140138 223 L--QAVPELRHAPDLQDFFVLP 242
Cdd:cd06897  87 LlnDEDSRWRNSPAVKEFLNLP 108

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 20140138 141 VKDPPSKYVLYTLAVIGPGPPDCQPA-QISRRYSDFERLHRNLQRQFRG----PMaaisfPRKRLRRNFTAETIARRSRA 215
Cdd:cd06861  11 VGDLTSAHTVYTVRTRTTSPNFEVSSfSVLRRYRDFRWLYRQLQNNHPGvivpPP-----PEKQSVGRFDDNFVEQRRAA 85

                        90       100
                ....*....|....*....|...
gi 20140138 216 FEQFLGHLQAVPELRHAPDLQDF 238
Cdd:cd06861  86 LEKMLRKIANHPVLQKDPDFRLF 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 168 ISRRYSDFERLHRNLQRQFrGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQD 237
Cdd:cd06873  43 VYRRYSDFHDLHMRLKEKF-PNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQE 111

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 20140138 167 QISRRYSDFERLHRNLQrqfrgpMAAIS--FPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 239
Cdd:cd06871  39 QVIRRYNDFDLLNASLQ------ISGISlpLPPKKLIGNMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

The phosphoinositide binding Phox Homology domain of RPK118-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 bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 141 VKDP---PSKYVLYTLA---VIGPGPPDCQPAQISRRYSDFERLHRNL----QRQFRGPMAAISFPRKRLRRNFTAETIA 210
Cdd:cd07287   7 VTDPrrhPKGYTVYKVTariVSRKNPEDVQEIVVWKRYSDFKKLHKDLwqihKNLCRQSELFPPFAKAKVFGRFDESVIE 86

                        90       100
                ....*....|....*....|....*....
gi 20140138 211 RRSRAFEQFLGHLQAVPELRHAPDLQDFF 239
Cdd:cd07287  87 ERRQCAEDLLQFSANIPALYNSSQLEDFF 115

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 145 PSKYVLYTLAVIGPGPPdcQPAQISRRYSDFERLHRNLQRQFrgPMAAI-SFP-RKRLRRNFTAETIARRSRAFEQFLGH 222
Cdd:cd06883  13 PEKYYIYVVKVTRENQT--EPSFVFRTFEEFQELHNKLSLLF--PSLKLpSFPaRVVLGRSHIKQVAERRKIELNSYLKS 88

                        90       100
                ....*....|....*....|.
gi 20140138 223 LQAVPELRHAPDLQDFFVLPE 243
Cdd:cd06883  89 LFNASPEVAESDLVYTFFHPL 109

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 164 QPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFFVLPE 243
Cdd:COG3914   5 ALLALAALAAAALLAAAAAAELALAAELEAAALAAALGLALLLLAALAEAAAAALLALAAGEAAAAAAALLLLAALLELA 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 244 LRRAQSLtctGLYREALALWANAWQLQaqlgtpsgPDRPLlTLAGLAVCHQELEDPGEARACCEKALQLLGDkslhplla 323
Cdd:COG3914  85 ALLLQAL---GRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEALAALRRALALNPD-------- 144

                       170       180       190
                ....*....|....*....|....*....|
gi 20140138 324 pFLEAHVRLSWRLGLDKRQSEArLQALQEA 353
Cdd:COG3914 145 -FAEAYLNLGEALRRLGRLEEA-IAALRRA 172

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 20140138 147 KYVLYTLAV----IGPGPPDCQPAQISRRYSDFERLHRNLqRQFRGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGH 222
Cdd:cd06877  21 RIYVFCIEVerndRRAKGHEPQHWSVLRRYNEFYVLESKL-TEFHGEFPDAPLPSRRIFGPKSYEFLESKREIFEEFLQK 99

                        90
                ....*....|....*.
gi 20140138 223 LQAVPELRHAPDLQDF 238
Cdd:cd06877 100 LLQKPELRGSELLYDF 115

The phosphoinositide binding Phox Homology domain of uncharacterized fungal 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 20140138 168 ISRRYSDFERLHRNLQRQFrgPMAAIS-FPRK-RLRRnftaetiaRRSR-AFEQFLGHLQAVPELRHAPDLQDFF 239
Cdd:cd06869  52 VARRYSDFKKLHHDLKKEF--PGKKLPkLPHKdKLPR--------EKLRlSLRQYLRSLLKDPEVAHSSILQEFL 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 176 ERLHRNLQRQFRGPMAAISFpRKRLRRN-------FTAETIARRSRAFEQFLGHLQAVpeLRHAPDlqdfFVLPELRRAQ 248
Cdd:COG3914  82 ELAALLLQALGRYEEALALY-RRALALNpdnaealFNLGNLLLALGRLEEALAALRRA--LALNPD----FAEAYLNLGE 154

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 20140138 249 SLTCTGLYREALALWANAWQLQaqlgtpsgPDRPLLtLAGLAVCHQELEDPGEARACCEKALQL 312
Cdd:COG3914 155 ALRRLGRLEEAIAALRRALELD--------PDNAEA-LNNLGNALQDLGRLEEAIAAYRRALEL 209

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 20140138 162 DCQPAQISRRYSDFERLHRNLQRQFRG----PMAAISFPRKRLRRnFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQD 237
Cdd:cd06860  33 DSSEYSVRRRYQDFLWLRQKLEESHPThiipPLPEKHSVKGLLDR-FSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKV 111

                .
gi 20140138 238 F 238
Cdd:cd06860 112 F 112

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 20140138 170 RRYSDFERLHRNLQRQFrgPMAAI-SFPRK-RLRR----NFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 239
Cdd:cd06863  42 RRYSDFVFLHECLSNDF--PACVVpPLPDKhRLEYitgdRFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 20140138   244 LRRAQSLTCTGLYREALALWANAWQLQAQLGtpsGPDRPLL--TLAGLAVCHQELEDPGEARACCEKALQLL 313
Cdd:pfam13424   7 NNLAAVLRRLGRYDEALELLEKALEIARRLL---GPDHPLTatTLLNLGRLYLELGRYEEALELLERALALA 75

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 133 FEVTSANVVKDppSK------YVLYTLAvigPGPPDcqpAQISRRYSDFERLHRNLQRQFrgPMAAI-SFPRKRLRRNFT 205
Cdd:cd06862   1 YHCTVTNPKKE--SKfkglksFIAYQIT---PTHTN---VTVSRRYKHFDWLYERLVEKY--SCIAIpPLPEKQVTGRFE 70

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 20140138 206 AETIARRSRAFEQFLGHLQAVPELRHAPDLQDFfvlpelrraqsLTCT 253
Cdd:cd06862  71 EDFIEKRRERLELWMNRLARHPVLSQSEVFRHF-----------LTCT 107

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140138 145 PSKYVLYTLAVIGPgppdcqpAQISRRYSDFERLHRNLQRQFrGPMAAISFPRKRLRRNFTAETIARRsrafEQFLGHLQ 224
Cdd:cd06885  15 GSTYVAYNIHINGV-------LHCSVRYSQLHGLNEQLKKEF-GNRKLPPFPPKKLLPLTPAQLEERR----LQLEKYLQ 82

                        90       100
                ....*....|....*....|....*..
gi 20140138 225 AV---PELRHAPDLQDFfvlpeLRRAQ 248
Cdd:cd06885  83 AVvqdPRIANSDIFNSF-----LLNAQ 104