SNX5_HUMAN
ID SNX5_HUMAN Reviewed; 404 AA.
AC Q9Y5X3; B7ZKN3; D3DW26; Q52LC4; Q7KZN0; Q9BWP0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Sorting nexin-5;
GN Name=SNX5;
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), AND SUBCELLULAR LOCATION.
RX PubMed=11485546; DOI=10.1042/0264-6021:3580007;
RA Teasdale R.D., Loci D., Houghton F., Karlsson L., Gleeson P.A.;
RT "A large family of endosome-localized proteins related to sorting nexin
RT 1.";
RL Biochem. J. 358:7-16(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ovarian carcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Placenta;
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 [7]
RP SUBCELLULAR LOCATION, AND PHOSPHATIDYLINOSITOL 3,4-BISPHOSPHATE BINDING.
RX PubMed=15561769; DOI=10.1242/jcs.01561;
RA Merino-Trigo A., Kerr M.C., Houghton F., Lindberg A., Mitchell C.,
RA Teasdale R.D., Gleeson P.A.;
RT "Sorting nexin 5 is localized to a subdomain of the early endosomes and is
RT recruited to the plasma membrane following EGF stimulation.";
RL J. Cell Sci. 117:6413-6424(2004).
RN [8]
RP INTERACTION WITH MIB1.
RX PubMed=16857196; DOI=10.1016/j.febslet.2006.07.009;
RA Yoo K.W., Kim E.H., Jung S.H., Rhee M., Koo B.K., Yoon K.J., Kong Y.Y.,
RA Kim C.H.;
RT "Snx5, as a Mind bomb-binding protein, is expressed in hematopoietic and
RT endothelial precursor cells in zebrafish.";
RL FEBS Lett. 580:4409-4416(2006).
RN [9]
RP INTERACTION WITH SNX1, AND SUBCELLULAR LOCATION.
RX PubMed=16968745; DOI=10.1242/jcs.03167;
RA Kerr M.C., Lindsay M.R., Luetterforst R., Hamilton N., Simpson F.,
RA Parton R.G., Gleeson P.A., Teasdale R.D.;
RT "Visualisation of macropinosome maturation by the recruitment of sorting
RT nexins.";
RL J. Cell Sci. 119:3967-3980(2006).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17148574; DOI=10.1242/jcs.03302;
RA Wassmer T., Attar N., Bujny M.V., Oakley J., Traer C.J., Cullen P.J.;
RT "A loss-of-function screen reveals SNX5 and SNX6 as potential components of
RT the mammalian retromer.";
RL J. Cell Sci. 120:45-54(2007).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18854019; DOI=10.1186/1471-2121-9-58;
RA Lim J.P., Wang J.T., Kerr M.C., Teasdale R.D., Gleeson P.A.;
RT "A role for SNX5 in the regulation of macropinocytosis.";
RL BMC Cell Biol. 9:58-58(2008).
RN [12]
RP FUNCTION, AND INTERACTION WITH DOCK1.
RX PubMed=18596235; DOI=10.1091/mbc.e08-03-0314;
RA Hara S., Kiyokawa E., Iemura S., Natsume T., Wassmer T., Cullen P.J.,
RA Hiai H., Matsuda M.;
RT "The DHR1 domain of DOCK180 binds to SNX5 and regulates cation-independent
RT mannose 6-phosphate receptor transport.";
RL Mol. Biol. Cell 19:3823-3835(2008).
RN [13]
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 [14]
RP INTERACTION WITH SNX1; SNX2; VPS26A; VPS29; VPS35 AND DCTN1.
RX PubMed=19619496; DOI=10.1016/j.devcel.2009.04.016;
RA Wassmer T., Attar N., Harterink M., van Weering J.R., Traer C.J.,
RA Oakley J., Goud B., Stephens D.J., Verkade P., Korswagen H.C., Cullen P.J.;
RT "The retromer coat complex coordinates endosomal sorting and dynein-
RT mediated transport, with carrier recognition by the trans-Golgi network.";
RL Dev. Cell 17:110-122(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-275, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21048941; DOI=10.1371/journal.pone.0013763;
RA Wang J.T., Kerr M.C., Karunaratne S., Jeanes A., Yap A.S., Teasdale R.D.;
RT "The SNX-PX-BAR family in macropinocytosis: the regulation of macropinosome
RT formation by SNX-PX-BAR proteins.";
RL PLoS ONE 5:E13763-E13763(2010).
RN [18]
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 [19]
RP FUNCTION, INTERACTION WITH SNX1 AND SNX2, DOMAIN, AND MUTAGENESIS OF
RP 186-PHE-PHE-187; GLU-280 AND GLU-383.
RX PubMed=23085988; DOI=10.1038/emboj.2012.283;
RA van Weering J.R., Sessions R.B., Traer C.J., Kloer D.P., Bhatia V.K.,
RA Stamou D., Carlsson S.R., Hurley J.H., Cullen P.J.;
RT "Molecular basis for SNX-BAR-mediated assembly of distinct endosomal
RT sorting tubules.";
RL EMBO J. 31:4466-4480(2012).
RN [20]
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=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [21]
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=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP FUNCTION, AND INTERACTION WITH PIP5K1C.
RX PubMed=23602387; DOI=10.1016/j.devcel.2013.03.010;
RA Sun Y., Hedman A.C., Tan X., Schill N.J., Anderson R.A.;
RT "Endosomal type Igamma PIP 5-kinase controls EGF receptor lysosomal
RT sorting.";
RL Dev. Cell 25:144-155(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
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 [24]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHOINOSITIDE BINDING, INTERACTION WITH
RP PIP5K1C AND HGS, AND MUTAGENESIS OF LYS-224; ARG-235; LYS-324; LYS-328 AND
RP ARG-330.
RX PubMed=24610942; DOI=10.1242/jcs.132423;
RA Schill N.J., Hedman A.C., Choi S., Anderson R.A.;
RT "Isoform 5 of PIPKIgamma regulates the endosomal trafficking and
RT degradation of E-cadherin.";
RL J. Cell Sci. 127:2189-2203(2014).
RN [25]
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 [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [27]
RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEINS UL35 AND UL35A (MICROBIAL
RP INFECTION).
RX PubMed=29444945; DOI=10.1128/jvi.00013-18;
RA Maschkowitz G., Gaertner S., Hofmann-Winkler H., Fickenscher H.,
RA Winkler M.;
RT "Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A
RT with Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization.";
RL J. Virol. 92:0-0(2018).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 257-265 IN COMPLEX WITH HLA CLASS
RP I HISTOCOMPATIBILITY COMPLEX.
RX PubMed=15226359; DOI=10.1084/jem.20031680;
RA Zernich D., Purcell A.W., Macdonald W.A., Kjer-Nielsen L., Ely L.K.,
RA Laham N., Crockford T., Mifsud N.A., Bharadwaj M., Chang L., Tait B.D.,
RA Holdsworth R., Brooks A.G., Bottomley S.P., Beddoe T., Peh C.A.,
RA Rossjohn J., McCluskey J.;
RT "Natural HLA class I polymorphism controls the pathway of antigen
RT presentation and susceptibility to viral evasion.";
RL J. Exp. Med. 200:13-24(2004).
CC -!- FUNCTION: Involved in several stages of intracellular trafficking.
CC Interacts with membranes containing phosphatidylinositol 3-phosphate
CC (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2)
CC (PubMed:15561769). Acts in part as component of the retromer membrane-
CC deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde
CC transport of cargo proteins from endosomes to the trans-Golgi network
CC (TGN) and is involved in endosome-to-plasma membrane transport for
CC cargo protein recycling. The SNX-BAR subcomplex functions to deform the
CC donor membrane into a tubular profile called endosome-to-TGN transport
CC carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane
CC remodeling activity (PubMed:23085988). Involved in retrograde transport
CC of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235).
CC May function as link between endosomal transport vesicles and dynactin
CC (Probable). Plays a role in the internalization of EGFR after EGF
CC stimulation (Probable). Involved in EGFR endosomal sorting and
CC degradation; the function involves PIP5K1C isoform 3 and is retromer-
CC independent (PubMed:23602387). Together with PIP5K1C isoform 3
CC facilitates HGS interaction with ubiquitinated EGFR, which initiates
CC EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body
CC for subsequent lysosomal degradation (Probable). Involved in E-cadherin
CC sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin
CC degradation (PubMed:24610942). Plays a role in macropinocytosis
CC (PubMed:18854019, PubMed:21048941). {ECO:0000269|PubMed:18854019,
CC ECO:0000269|PubMed:21048941, ECO:0000269|PubMed:24610942,
CC ECO:0000303|PubMed:15561769, ECO:0000303|PubMed:19619496,
CC ECO:0000303|PubMed:23085988}.
CC -!- SUBUNIT: Forms heterodimers with BAR domain-containing sorting nexins
CC SNX1 and SNX2; does not homodimerize (PubMed:23085988). The
CC heterodimers are proposed to self-assemble into helical arrays on the
CC membrane to stabilize and expand local membrane curvature underlying
CC endosomal tubule formation. Thought to be a component of the originally
CC described retromer complex (also called SNX-BAR retromer) which is a
CC pentamer containing the heterotrimeric retromer cargo-selective complex
CC (CSC), also described as vacuolar protein sorting subcomplex (VPS), and
CC a heterodimeric membrane-deforming subcomplex formed between SNX1 or
CC SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective
CC CSC and SNX-BAR subcomplexes associate with low affinity (Probable).
CC Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1,
CC PIP5K1C isoform 3. Interacts with HGS; increased by PIP5K1C isoform 3
CC kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2
CC (PubMed:16857196, PubMed:16968745, PubMed:19619496, PubMed:23085988,
CC PubMed:18596235, PubMed:23602387, PubMed:24610942).
CC {ECO:0000269|PubMed:15226359, ECO:0000269|PubMed:16857196,
CC ECO:0000269|PubMed:16968745, ECO:0000269|PubMed:18596235,
CC ECO:0000269|PubMed:19619496, ECO:0000269|PubMed:23602387,
CC ECO:0000269|PubMed:24610942, ECO:0000303|PubMed:19619496,
CC ECO:0000303|PubMed:23085988}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC proteins UL35 and UL35A; these interactions inhibit the ability of USP7
CC to form nuclear bodies. {ECO:0000269|PubMed:29444945}.
CC -!- INTERACTION:
CC Q9Y5X3; Q92624: APPBP2; NbExp=3; IntAct=EBI-715760, EBI-743771;
CC Q9Y5X3; Q13596: SNX1; NbExp=2; IntAct=EBI-715760, EBI-2822329;
CC Q9Y5X3-2; Q92624: APPBP2; NbExp=3; IntAct=EBI-12229025, EBI-743771;
CC Q9Y5X3-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-12229025, EBI-11524452;
CC Q9Y5X3-2; P28062-2: PSMB8; NbExp=3; IntAct=EBI-12229025, EBI-372312;
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000269|PubMed:11485546}. Early
CC endosome {ECO:0000269|PubMed:17148574, ECO:0000269|PubMed:24610942}.
CC Early endosome membrane {ECO:0000269|PubMed:15561769}; Peripheral
CC membrane protein; Cytoplasmic side. Cell membrane
CC {ECO:0000269|PubMed:15561769}; Peripheral membrane protein; Cytoplasmic
CC side {ECO:0000269|PubMed:18854019}. Cytoplasmic vesicle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Cell
CC projection, phagocytic cup. Cell projection, ruffle. Note=Recruited to
CC the plasma membrane after EGF stimulation, which leads to increased
CC levels of phosphatidylinositol 3,4-bisphosphate (PdtIns(3,4)P2)
CC (PubMed:15561769). Detected on macropinosomes (PubMed:16968745,
CC PubMed:21048941). Targeted to membrane ruffles in response to EGFR
CC stimulation. {ECO:0000269|PubMed:15561769, ECO:0000269|PubMed:16968745,
CC ECO:0000269|PubMed:21048941}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y5X3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5X3-2; Sequence=VSP_056386, VSP_056387;
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-
CC bisphosphate. {ECO:0000250}.
CC -!- DOMAIN: The BAR domain is able to sense membrane curvature upon
CC dimerization. Membrane remodeling seems to implicate insertion of an
CC amphipathic helix (AH) in the membrane (Probable).
CC {ECO:0000303|PubMed:23085988}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
CC -!- CAUTION: The selectivity for particular phosphatidylinositol lipids is
CC under debate. According to one report (PubMed:19553671), the rat
CC protein binds exclusively to phosphatidylinositol 4,5-bisphosphate,
CC while the human protein has been reported (PubMed:15561769) to bind to
CC phosphatidylinositol 3,4-bisphosphate and also to phosphatidylinositol
CC 3-phosphate. {ECO:0000305|PubMed:15561769}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF121855; AAD27828.1; -; mRNA.
DR EMBL; BT007191; AAP35855.1; -; mRNA.
DR EMBL; AK001793; BAA91914.1; -; mRNA.
DR EMBL; AK123903; BAG53980.1; -; mRNA.
DR EMBL; AL121585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000100; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471133; EAX10264.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10265.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10266.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10268.1; -; Genomic_DNA.
DR EMBL; BC093623; AAH93623.1; -; mRNA.
DR EMBL; BC093980; AAH93980.1; -; mRNA.
DR EMBL; BC143274; AAI43275.1; -; mRNA.
DR CCDS; CCDS13130.1; -. [Q9Y5X3-1]
DR RefSeq; NP_055241.1; NM_014426.3. [Q9Y5X3-1]
DR RefSeq; NP_689413.1; NM_152227.2. [Q9Y5X3-1]
DR PDB; 1SYS; X-ray; 2.40 A; C=257-265.
DR PDB; 5TGH; X-ray; 2.80 A; A/C/E/G=22-170.
DR PDB; 5TGI; X-ray; 1.98 A; A/B=22-170.
DR PDB; 5TGJ; X-ray; 2.60 A; A/C=22-170.
DR PDB; 5WY2; X-ray; 1.90 A; A/C=20-180.
DR PDB; 6N5X; X-ray; 2.05 A; A=22-170.
DR PDB; 6N5Y; X-ray; 2.26 A; A=22-170.
DR PDB; 6N5Z; X-ray; 2.45 A; A/B=22-170.
DR PDBsum; 1SYS; -.
DR PDBsum; 5TGH; -.
DR PDBsum; 5TGI; -.
DR PDBsum; 5TGJ; -.
DR PDBsum; 5WY2; -.
DR PDBsum; 6N5X; -.
DR PDBsum; 6N5Y; -.
DR PDBsum; 6N5Z; -.
DR AlphaFoldDB; Q9Y5X3; -.
DR SMR; Q9Y5X3; -.
DR BioGRID; 118022; 113.
DR IntAct; Q9Y5X3; 43.
DR MINT; Q9Y5X3; -.
DR STRING; 9606.ENSP00000366998; -.
DR GlyGen; Q9Y5X3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y5X3; -.
DR MetOSite; Q9Y5X3; -.
DR PhosphoSitePlus; Q9Y5X3; -.
DR BioMuta; SNX5; -.
DR DMDM; 10720289; -.
DR EPD; Q9Y5X3; -.
DR jPOST; Q9Y5X3; -.
DR MassIVE; Q9Y5X3; -.
DR MaxQB; Q9Y5X3; -.
DR PaxDb; Q9Y5X3; -.
DR PeptideAtlas; Q9Y5X3; -.
DR PRIDE; Q9Y5X3; -.
DR ProteomicsDB; 86528; -. [Q9Y5X3-1]
DR Antibodypedia; 24488; 227 antibodies from 33 providers.
DR DNASU; 27131; -.
DR Ensembl; ENST00000377759.9; ENSP00000366988.3; ENSG00000089006.17. [Q9Y5X3-1]
DR Ensembl; ENST00000377768.7; ENSP00000366998.3; ENSG00000089006.17. [Q9Y5X3-1]
DR Ensembl; ENST00000606557.1; ENSP00000475510.1; ENSG00000089006.17. [Q9Y5X3-2]
DR GeneID; 27131; -.
DR KEGG; hsa:27131; -.
DR MANE-Select; ENST00000377759.9; ENSP00000366988.3; NM_014426.4; NP_055241.1.
DR UCSC; uc002wqc.5; human. [Q9Y5X3-1]
DR CTD; 27131; -.
DR DisGeNET; 27131; -.
DR GeneCards; SNX5; -.
DR HGNC; HGNC:14969; SNX5.
DR HPA; ENSG00000089006; Low tissue specificity.
DR MIM; 605937; gene.
DR neXtProt; NX_Q9Y5X3; -.
DR OpenTargets; ENSG00000089006; -.
DR PharmGKB; PA37945; -.
DR VEuPathDB; HostDB:ENSG00000089006; -.
DR eggNOG; KOG1660; Eukaryota.
DR GeneTree; ENSGT00940000154632; -.
DR HOGENOM; CLU_040966_0_0_1; -.
DR InParanoid; Q9Y5X3; -.
DR OMA; CAEDSTP; -.
DR OrthoDB; 1009572at2759; -.
DR PhylomeDB; Q9Y5X3; -.
DR TreeFam; TF313698; -.
DR PathwayCommons; Q9Y5X3; -.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR SignaLink; Q9Y5X3; -.
DR BioGRID-ORCS; 27131; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; SNX5; human.
DR EvolutionaryTrace; Q9Y5X3; -.
DR GeneWiki; SNX5; -.
DR GenomeRNAi; 27131; -.
DR Pharos; Q9Y5X3; Tbio.
DR PRO; PR:Q9Y5X3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y5X3; protein.
DR Bgee; ENSG00000089006; Expressed in left lobe of thyroid gland and 199 other tissues.
DR ExpressionAtlas; Q9Y5X3; baseline and differential.
DR Genevisible; Q9Y5X3; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0031313; C:extrinsic component of endosome membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0070685; C:macropinocytic cup; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:CACAO.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0030904; C:retromer complex; IDA:UniProtKB.
DR GO; GO:0030905; C:retromer, tubulation complex; NAS:ParkinsonsUK-UCL.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0097422; C:tubular endosome; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0034452; F:dynactin binding; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0006907; P:pinocytosis; IDA:UniProtKB.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:CACAO.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:CACAO.
DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR CDD; cd07291; PX_SNX5; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR042135; PX_SNX5.
DR InterPro; IPR028654; SNX5.
DR InterPro; IPR014637; SNX5/SNX6/SNX32.
DR InterPro; IPR015404; Vps5_C.
DR PANTHER; PTHR45850:SF5; PTHR45850:SF5; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF09325; Vps5; 1.
DR PIRSF; PIRSF036924; Snx5_Snx6; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Endocytosis; Endosome;
KW Host-virus interaction; Lipid-binding; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..404
FT /note="Sorting nexin-5"
FT /id="PRO_0000213844"
FT DOMAIN 25..172
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 202..404
FT /note="BAR"
FT REGION 169..261
FT /note="Interaction with DOCK1"
FT /evidence="ECO:0000269|PubMed:18596235"
FT REGION 183..200
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000303|PubMed:23085988"
FT BINDING 40..46
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 99..105
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 113..116
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 275
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 18..126
FT /note="LRSVSVDLNVDPSLQIDIPDALSERDKVKFTVHTKTTLPTFQSPEFSVTRQH
FT EDFVWLHDTLIETTDYAGLIIPPAPTKPDFDGPREKMQKLGEGEGSMTKEEFAKMKQ
FT -> VRSSQPQTPGRAALRAPGSLHSFPCASIGRGCSPPSPAREAPVRPGRPLSLVFTEG
FT CPGESLWMSRILLGQNQRRGTLAPAQAPVPSGLGEMISGDPGMFFLKLSSASW (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT /id="VSP_056386"
FT VAR_SEQ 127..404
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT /id="VSP_056387"
FT MUTAGEN 186..187
FT /note="FF->EE: No effect on dimerization."
FT /evidence="ECO:0000269|PubMed:23085988"
FT MUTAGEN 224
FT /note="K->E: Decreaes phosphoinositide binding, including
FT PtdIns(3,4)P2 and PtdIns(3P); when associated with E-235,
FT E-324, E-328 and E-330."
FT /evidence="ECO:0000269|PubMed:23602387"
FT MUTAGEN 235
FT /note="R->E: Decreaes phosphoinositide binding, including
FT PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224,
FT E-324, E-328 and E-330."
FT /evidence="ECO:0000269|PubMed:23602387"
FT MUTAGEN 280
FT /note="E->A: Enables homodimerization; when associated with
FT A-383."
FT /evidence="ECO:0000269|PubMed:23085988"
FT MUTAGEN 324
FT /note="K->E: Decreaes phosphoinositide binding, including
FT PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224,
FT E-235, E-328 and E-330."
FT /evidence="ECO:0000269|PubMed:23602387"
FT MUTAGEN 328
FT /note="K->E: Decreaes phosphoinositide binding, including
FT PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224,
FT E-235, E-324 and E-330."
FT /evidence="ECO:0000269|PubMed:23602387"
FT MUTAGEN 330
FT /note="R->E: Decreaes phosphoinositide binding, including
FT PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224,
FT E-235, E-324 and E-328."
FT /evidence="ECO:0000269|PubMed:23602387"
FT MUTAGEN 383
FT /note="E->A: Enables homodimerization; when associated with
FT A-280."
FT CONFLICT 279
FT /note="V -> L (in Ref. 3)"
FT /evidence="ECO:0000305"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:5WY2"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:5WY2"
FT STRAND 44..53
FT /evidence="ECO:0007829|PDB:5WY2"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:5TGH"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 100..108
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 122..152
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:5WY2"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:5WY2"
SQ SEQUENCE 404 AA; 46816 MW; 87A85620AF827EC6 CRC64;
MAAVPELLQQ QEEDRSKLRS VSVDLNVDPS LQIDIPDALS ERDKVKFTVH TKTTLPTFQS
PEFSVTRQHE DFVWLHDTLI ETTDYAGLII PPAPTKPDFD GPREKMQKLG EGEGSMTKEE
FAKMKQELEA EYLAVFKKTV SSHEVFLQRL SSHPVLSKDR NFHVFLEYDQ DLSVRRKNTK
EMFGGFFKSV VKSADEVLFT GVKEVDDFFE QEKNFLINYY NRIKDSCVKA DKMTRSHKNV
ADDYIHTAAC LHSLALEEPT VIKKYLLKVA ELFEKLRKVE GRVSSDEDLK LTELLRYYML
NIEAAKDLLY RRTKALIDYE NSNKALDKAR LKSKDVKLAE AHQQECCQKF EQLSESAKEE
LINFKRKRVA AFRKNLIEMS ELEIKHARNN VSLLQSCIDL FKNN
