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 733918056 584 LLFEVTSASVVSERSSKYVLYTIYLIRSGHLDKAPAAISRRYSDFERLNRRLRGRFGCDMAGIAFPRKRLRRNFTAETIA 663
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 733918056 664 KRSRAFEQFLSHLHSIAEIRRSPEFLEFFFLQ 695
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 733918056 584 LLFEVTSASVVSERSSKYVLYTIYLIRSGHLDKAPAAISRRYSDFERLNRRLRGRFGCDMAGIAFPRKRLRRNFTAETIA 663
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 733918056 664 KRSRAFEQFLSHLHSIAEIRRSPEFLEFFFLQ 695
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 733918056   598 SSKYVLYTIYLIRSGHLDKApaAISRRYSDFERLNRRLRGRFGcDMAGIAFPRKRL---RRNFTAETIAKRSRAFEQFLS 674
Cdd:smart00312   9 DGKHYYYVIEIETKTGLEEW--TVSRRYSDFLELHSKLKKHFP-RSILPPLPGKKLfgrLNNFSEEFIEKRRRGLEKYLQ 85

                           90
                   ....*....|....*....
gi 733918056   675 HLHSIAE-IRRSPEFLEFF 692
Cdd:smart00312  86 SLLNHPElINHSEVVLEFL 104

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 733918056 584 LLFEVTSASVVSERSSKYVLYTIYLIRSGHLDKAPAAISRRYSDFERLNRRLRGRFGCDMAGIAFPRKRLRRNFTAETIA 663
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 733918056 664 KRSRAFEQFLSHLHSIAEIRRSPEFLEFFFLQ 695
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 733918056 584 LLFEVTSASVVSERSSKYVLYTIYLIRSGHLDKAPAAISRRYSDFERLNRRLRGRFGCDMAGIAFPRKRLRRNFTAETIA 663
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 733918056 664 KRSRAFEQFLSHLHSIAEIRRSPEFLEFFFLQDL 697
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 733918056  621 ISRRYSDFERLNRRLRGRFGcdMAGI-AFPRKRLRRNFTAETIAKRSRAFEQFLSHLHSIAEIRRSPEFLEFF 692
Cdd:pfam00787  11 VRRRYSDFVELHKKLLRKFP--SVIIpPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

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 733918056 594 VSERSSKYVLYTIYLirsghldKAPAA---ISRRYSDFERLNRRLrgrfgCDMAGIAFP------RKRLRRNFTAETIAK 664
Cdd:cd06897    8 TSVSPKPYTVYNIQV-------RLPLRsytVSRRYSEFVALHKQL-----ESEVGIEPPyplppkSWFLSTSSNPKLVEE 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 733918056 665 RSRAFEQFLSHL--HSIAEIRRSPEFLEFFFLQ 695
Cdd:cd06897   76 RRVGLEAFLRALlnDEDSRWRNSPAVKEFLNLP 108

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 733918056 587 EVTSASVVSERSSKYVLYTIYLIRSGHLDK-APAA---ISRRYSDFERLNRRLRGRFGcDMAGIAFPRKRL--RRNFTAE 660
Cdd:cd06876   21 RVSIQSYISDVEEEGKEFVVYLIEVQRLNNdDQSSgwvVARRYSEFLELHKYLKKRYP-GVLKLDFPQKRKisLKYSKTL 99

                         90       100       110
                 ....*....|....*....|....*....|.
gi 733918056 661 TIAKRSRAFEQFLSHLHSIAEIRRSPEFLEF 691
Cdd:cd06876  100 LVEERRKALEKYLQELLKIPEVCEDEEFRKF 130

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 733918056 582 QRLLFEVTSASVVSERSSKYVLYTIYLIR---SGHLDKApaAISRRYSDFERLNRRLRGRFGcDMAGIAFPRKRLRRNFT 658
Cdd:cd06873    3 FKLTAVIINTGIVKEHGKTYAVYAISVTRiypNGQEESW--HVYRRYSDFHDLHMRLKEKFP-NLSKLSFPGKKTFNNLD 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 733918056 659 AETIAKRSRAFEQFLSHLHSIAEIRRSP-------EFLE 690
Cdd:cd06873   80 RAFLEKRRKMLNQYLQSLLNPEVLDANPglqeivlDFLE 118

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 733918056 621 ISRRYSDFERLNRRLRGRFGcDMAGIAFPRKRLRRNFTAETIAKRSRAFEQFLSHL-HSIAEIRRSP 686
Cdd:cd06874   34 VFRRYSRFRELHKTMKLKYP-EVAALEFPPKKLFGNKSERVAKERRRQLETYLRNFfSVCLKLPACP 99

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 733918056 583 RLLFEVTSASVVSERSSKYVLYtiYLIRSGHLDKAPAA--ISRRYSDFERLNRRLRGRF-GCDMAgiAFPRK-RLRRnft 658
Cdd:cd06869   14 ETAGRLSSKKAYFVNRSKHHYE--FIIRVRREGEEYRTiyVARRYSDFKKLHHDLKKEFpGKKLP--KLPHKdKLPR--- 86

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 733918056 659 aetiaKRSR-AFEQFLSHLHSIAEIRRSPEFLEFFF 693
Cdd:cd06869   87 -----EKLRlSLRQYLRSLLKDPEVAHSSILQEFLT 117

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 733918056 604 YTIYLIR--SGHLDKAPAAISRRYSDFERLNRRLRgrfgcdMAGI--AFPRKRLRRNFTAETIAKRSRAFEQFL 673
Cdd:cd06871   21 HTEYIIRvqRGPSPENSWQVIRRYNDFDLLNASLQ------ISGIslPLPPKKLIGNMDREFIAERQQGLQNYL 88

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 733918056 604 YTIYLIRSGHLDkapAAISRRYSDFERLNRRLRGRFGCdmagIAFPR---KRLRRNFTAETIAKRSRAFEQFLSHL--HS 678
Cdd:cd06862   20 FIAYQITPTHTN---VTVSRRYKHFDWLYERLVEKYSC----IAIPPlpeKQVTGRFEEDFIEKRRERLELWMNRLarHP 92

                         90
                 ....*....|....*...
gi 733918056 679 IaeIRRSPEFLEFFFLQD 696
Cdd:cd06862   93 V--LSQSEVFRHFLTCTD 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 733918056 593 VVSERSSKYVLYTIYLIRSG--HLdkapaaISRRYSDFERLNRRLRGRfgCDMAGiaFPRKRLrRNFTAETIAKRSRAFE 670
Cdd:cd06880   11 EVDESEKPYTVFTIEVLVNGrrHT------VEKRYSEFHALHKKLKKS--IKTPD--FPPKRV-RNWNPKVLEQRRQGLE 79

                         90       100
                 ....*....|....*....|.
gi 733918056 671 QFLSHLHSIAEIRRspEFLEF 691
Cdd:cd06880   80 AYLQGLLKINELPK--QLLDF 98