SNX3_HUMAN
ID SNX3_HUMAN Reviewed; 162 AA.
AC O60493; A8K0B1; E1P5E4; E1P5E5; O60718; Q4TT29; Q4TT31; Q5JXJ7; Q5JXJ8;
AC Q96AP9; Q9C0J5; Q9NU45;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Sorting nexin-3;
DE AltName: Full=Protein SDP3;
GN Name=SNX3 {ECO:0000303|PubMed:30213940, ECO:0000312|HGNC:HGNC:11174};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9819414; DOI=10.1128/mcb.18.12.7278;
RA Haft C.R., de la Luz Sierra M., Barr V.A., Haft D.H., Taylor S.I.;
RT "Identification of a family of sorting nexin molecules and characterization
RT of their association with receptors.";
RL Mol. Cell. Biol. 18:7278-7287(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP PHOSPHOINOSITIDE-BINDING, DOMAIN PX, AND MUTAGENESIS OF 69-ARG--TYR-71 AND
RP TYR-71.
RX PubMed=11433298; DOI=10.1038/35083051;
RA Xu Y., Hortsman H., Seet L., Wong S.H., Hong W.;
RT "SNX3 regulates endosomal function through its PX-domain-mediated
RT interaction with PtdIns(3)P.";
RL Nat. Cell Biol. 3:658-666(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Hayama A., Uchida S., Sasaki S., Marumo F.;
RT "Homo sapiens sorting nexin 3A (SNX 3A) mRNA.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, Colon, Pancreas, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT ALA-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [11]
RP CHROMOSOMAL TRANSLOCATION.
RX PubMed=12471201; DOI=10.1136/jmg.39.12.893;
RA Vervoort V.S., Viljoen D., Smart R., Suthers G., DuPont B.R., Abbott A.,
RA Schwartz C.E.;
RT "Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation
RT t(6;13)(q21;q12) and microcephaly, microphthalmia, ectrodactyly,
RT prognathism (MMEP) phenotype.";
RL J. Med. Genet. 39:893-899(2002).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH PTPRU.
RX PubMed=17622474; DOI=10.1111/j.1745-7270.2007.00303.x;
RA Dong H., Yuan H., Jin W., Shen Y., Xu X., Wang H.-Y.;
RT "Involvement of beta3A subunit of adaptor protein-3 in intracellular
RT trafficking of receptor-like protein tyrosine phosphatase PCP-2.";
RL Acta Biochim. Biophys. Sin. 39:540-546(2007).
RN [14]
RP FUNCTION.
RX PubMed=18767904; DOI=10.1371/journal.pbio.0060214;
RA Pons V., Luyet P.P., Morel E., Abrami L., van der Goot F.G., Parton R.G.,
RA Gruenberg J.;
RT "Hrs and SNX3 functions in sorting and membrane invagination within
RT multivesicular bodies.";
RL PLoS Biol. 6:E214-E214(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20482551; DOI=10.1111/j.1462-5822.2010.01476.x;
RA Braun V., Wong A., Landekic M., Hong W.J., Grinstein S., Brumell J.H.;
RT "Sorting nexin 3 (SNX3) is a component of a tubular endosomal network
RT induced by Salmonella and involved in maturation of the Salmonella-
RT containing vacuole.";
RL Cell. Microbiol. 12:1352-1367(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP FUNCTION, INTERACTION WITH VPS26 AND VPS35, FUNCTION OF THE SNX3-RETROMER,
RP AND SUBCELLULAR LOCATION.
RX PubMed=21725319; DOI=10.1038/ncb2281;
RA Harterink M., Port F., Lorenowicz M.J., McGough I.J., Silhankova M.,
RA Betist M.C., van Weering J.R., van Heesbeen R.G., Middelkoop T.C.,
RA Basler K., Cullen P.J., Korswagen H.C.;
RT "A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt
RT sorting receptor Wntless and is required for Wnt secretion.";
RL Nat. Cell Biol. 13:914-923(2011).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23237080; DOI=10.1111/imm.12051;
RA Chua R.Y., Wong S.H.;
RT "SNX3 recruits to phagosomes and negatively regulates phagocytosis in
RT dendritic cells.";
RL Immunology 139:30-47(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP INTERACTION WITH SNX8.
RX PubMed=24866125; DOI=10.1074/mcp.m113.037275;
RA Sierecki E., Stevers L.M., Giles N., Polinkovsky M.E., Moustaqil M.,
RA Mureev S., Johnston W.A., Dahmer-Heath M., Skalamera D., Gonda T.J.,
RA Gabrielli B., Collins B.M., Alexandrov K., Gambin Y.;
RT "Rapid mapping of interactions between Human SNX-BAR proteins measured in
RT vitro by AlphaScreen and single-molecule spectroscopy.";
RL Mol. Cell. Proteomics 13:2233-2245(2014).
RN [25]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-43, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [26]
RP FUNCTION, INTERACTION WITH VPS26A:VPS35:VPS29 COMPLEX, AND MUTAGENESIS OF
RP PHE-28; GLU-30 AND ASP-32.
RX PubMed=24344282; DOI=10.1073/pnas.1316482111;
RA Harrison M.S., Hung C.S., Liu T.T., Christiano R., Walther T.C., Burd C.G.;
RT "A mechanism for retromer endosomal coat complex assembly with cargo.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:267-272(2014).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-95, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [29]
RP FUNCTION, INTERACTION WITH VPS26A:VPS35:VPS29 COMPLEX, INTERACTION WITH
RP MON2 AND DOP1B, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF 9-ARG-ARG-10; TYR-22; 22-TYR--PHE-28; 30-GLU--ASP-32;
RP GLU-50; GLU-75; 84-GLU--LYS-86; 99-ARG--PHE-110; TYR-154; PRO-156 AND
RP ARG-160.
RX PubMed=30213940; DOI=10.1038/s41467-018-06114-3;
RA McGough I.J., de Groot R.E.A., Jellett A.P., Betist M.C., Varandas K.C.,
RA Danson C.M., Heesom K.J., Korswagen H.C., Cullen P.J.;
RT "SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex
RT to mediate Wntless sorting and Wnt secretion.";
RL Nat. Commun. 9:3737-3737(2018).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 24-155.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the PX domain of human sorting nexin 3.";
RL Submitted (MAR-2013) to the PDB data bank.
CC -!- FUNCTION: Phosphoinositide-binding protein required for multivesicular
CC body formation. Specifically binds phosphatidylinositol 3-phosphate
CC (PtdIns(P3)). Can also bind phosphatidylinositol 4-phosphate
CC (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and
CC phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (By similarity).
CC Plays a role in protein transport between cellular compartments.
CC Together with RAB7A facilitates endosome membrane association of the
CC retromer cargo-selective subcomplex (CSC/VPS). May in part act as
CC component of the SNX3-retromer complex which mediates the retrograde
CC endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer
CC pathway (PubMed:21725319, PubMed:24344282, PubMed:30213940). Promotes
CC stability and cell surface expression of epithelial sodium channel
CC (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR
CC degradation. Involved in the regulation of phagocytosis in dendritic
CC cells possibly by regulating EEA1 recruitment to the nascent phagosomes
CC (PubMed:23237080). Involved in iron homeostasis through regulation of
CC endocytic recycling of the transferrin receptor TFRC presumably by
CC delivering the transferrin:transferrin receptor complex to recycling
CC endosomes; the function may involve the CSC retromer subcomplex (By
CC similarity). In the case of Salmonella enterica infection plays arole
CC in maturation of the Salmonella-containing vacuole (SCV) and promotes
CC recruitment of LAMP1 to SCVs (PubMed:20482551).
CC {ECO:0000250|UniProtKB:O70492, ECO:0000269|PubMed:11433298,
CC ECO:0000269|PubMed:18767904, ECO:0000269|PubMed:21725319,
CC ECO:0000269|PubMed:23237080, ECO:0000269|PubMed:24344282,
CC ECO:0000305|PubMed:21725319}.
CC -!- SUBUNIT: Interacts with VPS26A, VPS29 and VPS35; the interaction with
CC VPS35 is direct. The association with the retromer CSC subcomplex
CC subunits is proposed to represent a functional distinct retromer
CC variant described as SNX3-retromer complex (PubMed:21725319,
CC PubMed:24344282, PubMed:30213940). Interacts with USP10 and SCNN1A (By
CC similarity). Interacts with TRFC (By similarity). Interacts with SNX8;
CC 2 molecules of SNX8 seems to associate with one molecule of SNX3
CC (PubMed:24866125). Interacts with PTPRU (PubMed:17622474). Interacts
CC with MON2 and DOP1B. {ECO:0000250|UniProtKB:O70492,
CC ECO:0000269|PubMed:17622474, ECO:0000269|PubMed:21725319,
CC ECO:0000269|PubMed:24344282, ECO:0000269|PubMed:24866125,
CC ECO:0000269|PubMed:30213940, ECO:0000305|PubMed:21725319}.
CC -!- INTERACTION:
CC O60493; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-727209, EBI-714543;
CC O60493; P46108: CRK; NbExp=2; IntAct=EBI-727209, EBI-886;
CC O60493; Q9NS64: RPRM; NbExp=3; IntAct=EBI-727209, EBI-1052363;
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:11433298,
CC ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:30213940}. Cytoplasmic
CC vesicle, phagosome {ECO:0000269|PubMed:23237080}. Note=Colocalizes to
CC clathrin-coated endosomal vesicles morphologically distinct from
CC retromer-decorated non-branched endosomal tubule structures
CC (PubMed:21725319) Colocalizes with EEA1 on nascent phagosomes in
CC dendritic cells but competes with EEA1 for binding to phagosomal
CC membrane (PubMed:23237080). In the case of Salmonella enterica
CC infection localizes to Salmonella-containing vacuoles (SCVs) from which
CC SNX3-containing tubules form 30-60 min after infection
CC (PubMed:20482551). {ECO:0000269|PubMed:20482551,
CC ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:23237080}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O60493-1; Sequence=Displayed;
CC Name=2; Synonyms=SNX 3A;
CC IsoId=O60493-2; Sequence=VSP_006190;
CC Name=3;
CC IsoId=O60493-3; Sequence=VSP_012928;
CC Name=4;
CC IsoId=O60493-4; Sequence=VSP_014694;
CC -!- DOMAIN: The PX domain mediates specific binding to phosphatidylinositol
CC 3-phosphate (PtdIns(P3)). {ECO:0000269|PubMed:11433298}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC Deubiquitinated by USP10 (By similarity).
CC {ECO:0000250|UniProtKB:O70492}.
CC -!- DISEASE: Note=A chromosomal aberration involving SNX3 has been found in
CC patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).
CC {ECO:0000269|PubMed:12471201}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; AF034546; AAC16040.1; -; mRNA.
DR EMBL; AF062483; AAC16018.1; -; mRNA.
DR EMBL; AB047360; BAB32649.1; -; mRNA.
DR EMBL; AK289476; BAF82165.1; -; mRNA.
DR EMBL; BT007114; AAP35778.1; -; mRNA.
DR EMBL; CR456898; CAG33179.1; -; mRNA.
DR EMBL; AL078596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z98742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48378.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48379.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48381.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48382.1; -; Genomic_DNA.
DR EMBL; BC008444; AAH08444.1; -; mRNA.
DR EMBL; BC014580; AAH14580.1; -; mRNA.
DR EMBL; BC015179; AAH15179.1; -; mRNA.
DR EMBL; BC016863; AAH16863.1; -; mRNA.
DR CCDS; CCDS5064.1; -. [O60493-1]
DR CCDS; CCDS5065.1; -. [O60493-2]
DR CCDS; CCDS75501.1; -. [O60493-4]
DR RefSeq; NP_001287858.1; NM_001300929.1. [O60493-4]
DR RefSeq; NP_003786.1; NM_003795.5. [O60493-1]
DR RefSeq; NP_690040.1; NM_152827.3. [O60493-2]
DR PDB; 2MXC; NMR; -; A=2-162.
DR PDB; 2YPS; X-ray; 2.60 A; A/B/C/D=24-155.
DR PDB; 5F0J; X-ray; 2.70 A; C=1-162.
DR PDB; 5F0L; X-ray; 3.20 A; C=1-162.
DR PDB; 5F0M; X-ray; 3.10 A; C=1-162.
DR PDB; 5F0P; X-ray; 2.78 A; C=1-162.
DR PDB; 7BLO; EM; 9.50 A; G/L=4-158.
DR PDBsum; 2MXC; -.
DR PDBsum; 2YPS; -.
DR PDBsum; 5F0J; -.
DR PDBsum; 5F0L; -.
DR PDBsum; 5F0M; -.
DR PDBsum; 5F0P; -.
DR PDBsum; 7BLO; -.
DR AlphaFoldDB; O60493; -.
DR SMR; O60493; -.
DR BioGRID; 114263; 180.
DR IntAct; O60493; 53.
DR MINT; O60493; -.
DR STRING; 9606.ENSP00000230085; -.
DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine.
DR TCDB; 9.A.3.1.1; the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family.
DR iPTMnet; O60493; -.
DR PhosphoSitePlus; O60493; -.
DR BioMuta; SNX3; -.
DR REPRODUCTION-2DPAGE; IPI00815770; -.
DR UCD-2DPAGE; O60493; -.
DR EPD; O60493; -.
DR jPOST; O60493; -.
DR MassIVE; O60493; -.
DR MaxQB; O60493; -.
DR PaxDb; O60493; -.
DR PeptideAtlas; O60493; -.
DR PRIDE; O60493; -.
DR ProteomicsDB; 49428; -. [O60493-1]
DR ProteomicsDB; 49429; -. [O60493-2]
DR ProteomicsDB; 49430; -. [O60493-3]
DR ProteomicsDB; 49431; -. [O60493-4]
DR TopDownProteomics; O60493-1; -. [O60493-1]
DR TopDownProteomics; O60493-2; -. [O60493-2]
DR TopDownProteomics; O60493-4; -. [O60493-4]
DR Antibodypedia; 32208; 351 antibodies from 30 providers.
DR DNASU; 8724; -.
DR Ensembl; ENST00000230085.13; ENSP00000230085.8; ENSG00000112335.15. [O60493-1]
DR Ensembl; ENST00000349379.5; ENSP00000296991.7; ENSG00000112335.15. [O60493-4]
DR Ensembl; ENST00000368979.6; ENSP00000357975.2; ENSG00000112335.15. [O60493-3]
DR Ensembl; ENST00000426155.6; ENSP00000401779.2; ENSG00000112335.15. [O60493-2]
DR GeneID; 8724; -.
DR KEGG; hsa:8724; -.
DR MANE-Select; ENST00000230085.13; ENSP00000230085.8; NM_003795.6; NP_003786.1.
DR UCSC; uc003psh.4; human. [O60493-1]
DR CTD; 8724; -.
DR DisGeNET; 8724; -.
DR GeneCards; SNX3; -.
DR HGNC; HGNC:11174; SNX3.
DR HPA; ENSG00000112335; Low tissue specificity.
DR MalaCards; SNX3; -.
DR MIM; 605930; gene.
DR neXtProt; NX_O60493; -.
DR OpenTargets; ENSG00000112335; -.
DR PharmGKB; PA36013; -.
DR VEuPathDB; HostDB:ENSG00000112335; -.
DR eggNOG; KOG2527; Eukaryota.
DR GeneTree; ENSGT00940000153609; -.
DR HOGENOM; CLU_2183109_0_0_1; -.
DR InParanoid; O60493; -.
DR OMA; MFLQDEF; -.
DR OrthoDB; 1407986at2759; -.
DR PhylomeDB; O60493; -.
DR TreeFam; TF314980; -.
DR PathwayCommons; O60493; -.
DR Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; O60493; -.
DR BioGRID-ORCS; 8724; 13 hits in 1083 CRISPR screens.
DR ChiTaRS; SNX3; human.
DR GeneWiki; SNX3; -.
DR GenomeRNAi; 8724; -.
DR Pharos; O60493; Tbio.
DR PRO; PR:O60493; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O60493; protein.
DR Bgee; ENSG00000112335; Expressed in trabecular bone tissue and 208 other tissues.
DR Genevisible; O60493; HS.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030904; C:retromer complex; IBA:GO_Central.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:1905394; F:retromer complex binding; IDA:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0070676; P:intralumenal vesicle formation; IMP:UniProtKB.
DR GO; GO:0034499; P:late endosome to Golgi transport; IBA:GO_Central.
DR GO; GO:0010324; P:membrane invagination; IDA:UniProtKB.
DR GO; GO:2000642; P:negative regulation of early endosome to late endosome transport; IDA:UniProtKB.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB.
DR GO; GO:0051224; P:negative regulation of protein transport; IDA:UniProtKB.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0022615; P:protein to membrane docking; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IDA:UniProtKB.
DR CDD; cd07293; PX_SNX3; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR042137; PX_SNX3_Vert.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosomal rearrangement;
KW Cytoplasmic vesicle; Direct protein sequencing; Endosome; Isopeptide bond;
KW Lipid-binding; Methylation; Microphthalmia; Phosphoprotein;
KW Protein transport; Reference proteome; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:25944712"
FT CHAIN 2..162
FT /note="Sorting nexin-3"
FT /id="PRO_0000213840"
FT DOMAIN 27..151
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT REGION 147..162
FT /note="Binds predominantly to PtdIns(P5) and weaker to
FT PtdIns(P3) abd PtdIns(P4); involved in neurite outgrowth
FT regulation"
FT /evidence="ECO:0000250|UniProtKB:O70492"
FT BINDING 70
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250"
FT BINDING 95
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250"
FT BINDING 118
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:25944712"
FT MOD_RES 43
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT CROSSLNK 95
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 33..54
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_014694"
FT VAR_SEQ 55..86
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_006190"
FT VAR_SEQ 87..162
FT /note="VVVPPLPGKAFLRQLPFRGDDGIFDDNFIEERKQGLEQFINKVAGHPLAQNE
FT RCLHMFLQDEIIDKSYTPSKIRHA -> PCLRMTSEARSHGRTWCAQNDEKLFCD (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012928"
FT MUTAGEN 9..10
FT /note="RR->AA: Loss of VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 22..28
FT /note="Missing: Loss of VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 22
FT /note="Y->A: Loss of VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 28
FT /note="F->A: Abolishes interaction with retromer cargo-
FT selective subcomplex VPS26A:VPS29:VPS35; when associated
FT with A-30 and A-32."
FT /evidence="ECO:0000269|PubMed:24344282"
FT MUTAGEN 30..32
FT /note="EID->TIR: Loss of VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 30
FT /note="E->A: Abolishes interaction with retromer cargo-
FT selective subcomplex VPS26A:VPS29:VPS35; when associated
FT with A-28 and A-32."
FT /evidence="ECO:0000269|PubMed:24344282"
FT MUTAGEN 32
FT /note="D->A: Abolishes interaction with retromer cargo-
FT selective subcomplex VPS26A:VPS29:VPS35; when associated
FT with A-28 and A-30."
FT /evidence="ECO:0000269|PubMed:24344282"
FT MUTAGEN 50
FT /note="E->K: Loss of VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 69..71
FT /note="RRY->AAA: Abolishes binding to phosphatidylinositol
FT 3-phosphate."
FT /evidence="ECO:0000269|PubMed:11433298"
FT MUTAGEN 71
FT /note="Y->A: Abolishes binding to phosphatidylinositol 3-
FT phosphate."
FT /evidence="ECO:0000269|PubMed:11433298"
FT MUTAGEN 75
FT /note="E->A: Increases VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 84..86
FT /note="ESK->NAG: Decreases VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 99..110
FT /note="Missing: Increases VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 154
FT /note="Y->A: Decreases VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 156
FT /note="P->A: Decreases VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT MUTAGEN 160
FT /note="R->A: Loss of VPS35 binding."
FT /evidence="ECO:0000269|PubMed:30213940"
FT CONFLICT 100..101
FT /note="QL -> HF (in Ref. 2; AAC16018)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="D -> V (in Ref. 4; BAF82165)"
FT /evidence="ECO:0000305"
FT HELIX 18..22
FT /evidence="ECO:0007829|PDB:5F0J"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:2YPS"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:2YPS"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:2YPS"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:2YPS"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:2YPS"
FT HELIX 97..100
FT /evidence="ECO:0007829|PDB:5F0J"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 114..131
FT /evidence="ECO:0007829|PDB:2YPS"
FT HELIX 133..136
FT /evidence="ECO:0007829|PDB:2YPS"
FT HELIX 139..146
FT /evidence="ECO:0007829|PDB:2YPS"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:5F0J"
SQ SEQUENCE 162 AA; 18762 MW; 983D422FCA6E07BC CRC64;
MAETVADTRR LITKPQNLND AYGPPSNFLE IDVSNPQTVG VGRGRFTTYE IRVKTNLPIF
KLKESTVRRR YSDFEWLRSE LERESKVVVP PLPGKAFLRQ LPFRGDDGIF DDNFIEERKQ
GLEQFINKVA GHPLAQNERC LHMFLQDEII DKSYTPSKIR HA
