SORT_HUMAN
ID SORT_HUMAN Reviewed; 831 AA.
AC Q99523; B4DWI3; C0JYZ0; Q8IZ49;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 3.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Sortilin {ECO:0000305};
DE AltName: Full=100 kDa NT receptor;
DE AltName: Full=Glycoprotein 95;
DE Short=Gp95;
DE AltName: Full=Neurotensin receptor 3;
DE Short=NT3;
DE Short=NTR3;
DE Flags: Precursor;
GN Name=SORT1 {ECO:0000312|HGNC:HGNC:11186};
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), PARTIAL PROTEIN SEQUENCE,
RP INTERACTION WITH LRPAP1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
RC TISSUE=T-cell;
RX PubMed=9013611; DOI=10.1074/jbc.272.6.3599;
RA Petersen C.M., Nielsen M.S., Nykjaer A., Jacobsen L., Tommerup N.,
RA Rasmussen H.H., Roeigaard H., Gliemann J., Madsen P., Moestrup S.K.;
RT "Molecular identification of a novel candidate sorting receptor purified
RT from human brain by receptor-associated protein affinity chromatography.";
RL J. Biol. Chem. 272:3599-3605(1997).
RN [2]
RP SEQUENCE REVISION.
RA Madsen P.;
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary gland;
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 PROTEIN SEQUENCE OF 78-100, AND IDENTIFICATION AS A NEUROTENSIN RECEPTOR.
RC TISSUE=Brain;
RX PubMed=9756851; DOI=10.1074/jbc.273.41.26273;
RA Mazella J., Zsurger N., Navarro V., Chabry J., Kaghad M., Caput D.,
RA Ferrara P., Vita M., Gully D., Maffrand J.-P., Vincent J.-P.;
RT "The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled
RT receptor.";
RL J. Biol. Chem. 273:26273-26276(1998).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, INTERACTION WITH LRPAP1, MUTAGENESIS OF
RP 74-ARG--ARG-77 AND 76-ARG-ARG-77, CLEAVAGE BY FURIN, AND GLYCOSYLATION.
RX PubMed=9927419; DOI=10.1093/emboj/18.3.595;
RA Petersen C.M., Nielsen M.S., Jacobsen C., Tauris J., Jacobsen L.,
RA Gliemann J., Moestrup S.K., Madsen P.;
RT "Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand
RT binding.";
RL EMBO J. 18:595-604(1999).
RN [9]
RP INTERACTION WITH LRPAP1.
RX PubMed=9657377; DOI=10.1016/s0014-5793(98)00559-6;
RA Tauris J., Ellgaard L., Jacobsen C., Nielsen M.S., Madsen P.,
RA Thoegersen H.C., Gliemann J., Petersen C.M., Moestrup S.K.;
RT "The carboxy-terminal domain of the receptor-associated protein binds to
RT the Vps10p domain of sortilin.";
RL FEBS Lett. 429:27-30(1998).
RN [10]
RP FUNCTION.
RX PubMed=10085125; DOI=10.1074/jbc.274.13.8832;
RA Nielsen M.S., Jacobsen C., Olivecrona G., Gliemann J., Petersen C.M.;
RT "Sortilin/neurotensin receptor-3 binds and mediates degradation of
RT lipoprotein lipase.";
RL J. Biol. Chem. 274:8832-8836(1999).
RN [11]
RP FUNCTION, INTERACTION WITH GGA2, AND MUTAGENESIS OF TYR-792; LEU-795 AND
RP 829-LEU-LEU-830.
RX PubMed=11331584; DOI=10.1093/emboj/20.9.2180;
RA Nielsen M.S., Madsen P., Christensen E.I., Nykjaer A., Gliemann J.,
RA Kasper D., Pohlmann R., Petersen C.M.;
RT "The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds
RT the VHS domain of the GGA2 sorting protein.";
RL EMBO J. 20:2180-2190(2001).
RN [12]
RP FUNCTION, INTERACTION WITH GGA1 AND GGA2, AND MUTAGENESIS OF
RP 823-ASP-ASP-824; SER-825; 826-ASP--ASP-828 AND 829-LEU-LEU-830.
RX PubMed=11390366; DOI=10.1074/jbc.c100218200;
RA Takatsu H., Katoh Y., Shiba Y., Nakayama K.;
RT "Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation
RT factor-binding (GGA) proteins interact with acidic dileucine sequences
RT within the cytoplasmic domains of sorting receptors through their
RT Vps27p/Hrs/STAM (VHS) domains.";
RL J. Biol. Chem. 276:28541-28545(2001).
RN [13]
RP CLEAVAGE OF THE EXTRACELLULAR DOMAIN.
RX PubMed=12419319; DOI=10.1016/s0006-291x(02)02564-0;
RA Navarro V., Vincent J.-P., Mazella J.;
RT "Shedding of the luminal domain of the neurotensin receptor-3/sortilin in
RT the HT29 cell line.";
RL Biochem. Biophys. Res. Commun. 298:760-764(2002).
RN [14]
RP FUNCTION, AND INDUCTION.
RX PubMed=12209882; DOI=10.1002/jcp.10151;
RA Maeda S., Nobukuni T., Shimo-Onoda K., Hayashi K., Yone K., Komiya S.,
RA Inoue I.;
RT "Sortilin is upregulated during osteoblastic differentiation of mesenchymal
RT stem cells and promotes extracellular matrix mineralization.";
RL J. Cell. Physiol. 193:73-79(2002).
RN [15]
RP INTERACTION WITH GGA1.
RX PubMed=11859376; DOI=10.1038/415937a;
RA Shiba T., Takatsu H., Nogi T., Matsugaki N., Kawasaki M., Igarashi N.,
RA Suzuki M., Kato R., Earnest T., Nakayama K., Wakatsuki S.;
RT "Structural basis for recognition of acidic-cluster dileucine sequence by
RT GGA1.";
RL Nature 415:937-941(2002).
RN [16]
RP FUNCTION, INTERACTION WITH GM2A AND PSAP, AND SUBCELLULAR LOCATION.
RX PubMed=14657016; DOI=10.1093/emboj/cdg629;
RA Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R.;
RT "The lysosomal trafficking of sphingolipid activator proteins (SAPs) is
RT mediated by sortilin.";
RL EMBO J. 22:6430-6437(2003).
RN [17]
RP ERRATUM OF PUBMED:14657016.
RA Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R.;
RL EMBO J. 23:1680-1680(2004).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12598608; DOI=10.1523/jneurosci.23-04-01198.2003;
RA Martin S., Vincent J.-P., Mazella J.;
RT "Involvement of the neurotensin receptor-3 in the neurotensin-induced
RT migration of human microglia.";
RL J. Neurosci. 23:1198-1205(2003).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15313463; DOI=10.1016/j.biocel.2004.04.013;
RA Morinville A., Martin S., Lavallee M., Vincent J.-P., Beaudet A.,
RA Mazella J.;
RT "Internalization and trafficking of neurotensin via NTS3 receptors in HT29
RT cells.";
RL Int. J. Biochem. Cell Biol. 36:2153-2168(2004).
RN [20]
RP INTERACTION WITH LRPAP1 AND NGFB, SUBCELLULAR LOCATION, DISULFIDE BONDS,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15364913; DOI=10.1074/jbc.m408873200;
RA Westergaard U.B., Soerensen E.S., Hermey G., Nielsen M.S., Nykjaer A.,
RA Kirkegaard K., Jacobsen C., Gliemann J., Madsen P., Petersen C.M.;
RT "Functional organization of the sortilin Vps10p domain.";
RL J. Biol. Chem. 279:50221-50229(2004).
RN [21]
RP FUNCTION, AND INTERACTION WITH NGFB AND NGFR.
RX PubMed=14985763; DOI=10.1038/nature02319;
RA Nykjaer A., Lee R., Teng K.K., Jansen P., Madsen P., Nielsen M.S.,
RA Jacobsen C., Kliemannel M., Schwarz E., Willnow T.E., Hempstead B.L.,
RA Petersen C.M.;
RT "Sortilin is essential for proNGF-induced neuronal cell death.";
RL Nature 427:843-848(2004).
RN [22]
RP FUNCTION.
RX PubMed=15930396; DOI=10.1523/jneurosci.5123-04.2005;
RA Teng H.K., Teng K.K., Lee R., Wright S., Tevar S., Almeida R.D.,
RA Kermani P., Torkin R., Chen Z.-Y., Lee F.S., Kraemer R.T., Nykjaer A.,
RA Hempstead B.L.;
RT "ProBDNF induces neuronal apoptosis via activation of a receptor complex of
RT p75NTR and sortilin.";
RL J. Neurosci. 25:5455-5463(2005).
RN [23]
RP FUNCTION, AND INTERACTION WITH BDNF.
RX PubMed=15987945; DOI=10.1523/jneurosci.1017-05.2005;
RA Chen Z.-Y., Ieraci A., Teng H., Dall H., Meng C.-X., Herrera D.G.,
RA Nykjaer A., Hempstead B.L., Lee F.S.;
RT "Sortilin controls intracellular sorting of brain-derived neurotrophic
RT factor to the regulated secretory pathway.";
RL J. Neurosci. 25:6156-6166(2005).
RN [24]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GGA AND SMPD1.
RX PubMed=16787399; DOI=10.1111/j.1600-0854.2006.00429.x;
RA Ni X., Morales C.R.;
RT "The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin
RT and mannose 6-phosphate receptor.";
RL Traffic 7:889-902(2006).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [27]
RP IDENTIFICATION BY 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 [28]
RP FUNCTION, INTERACTION WITH THE RETROMER COMPLEX, SUBCELLULAR LOCATION,
RP PALMITOYLATION AT CYS-783, AND MUTAGENESIS OF CYS-783.
RX PubMed=18817523; DOI=10.1111/j.1600-0854.2008.00814.x;
RA McCormick P.J., Dumaresq-Doiron K., Pluviose A.S., Pichette V., Tosato G.,
RA Lefrancois S.;
RT "Palmitoylation controls recycling in lysosomal sorting and trafficking.";
RL Traffic 9:1984-1997(2008).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [30]
RP TISSUE SPECIFICITY.
RX PubMed=20048080; DOI=10.1158/0008-5472.can-09-1252;
RA Swift S.L., Burns J.E., Maitland N.J.;
RT "Altered expression of neurotensin receptors is associated with the
RT differentiation state of prostate cancer.";
RL Cancer Res. 70:347-356(2010).
RN [31]
RP INVOLVEMENT IN LDLCQ6.
RX PubMed=20686565; DOI=10.1038/nature09270;
RA Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M.,
RA Koseki M., Pirruccello J.P., Ripatti S., Chasman D.I., Willer C.J.,
RA Johansen C.T., Fouchier S.W., Isaacs A., Peloso G.M., Barbalic M.,
RA Ricketts S.L., Bis J.C., Aulchenko Y.S., Thorleifsson G., Feitosa M.F.,
RA Chambers J., Orho-Melander M., Melander O., Johnson T., Li X., Guo X.,
RA Li M., Shin Cho Y., Jin Go M., Jin Kim Y., Lee J.Y., Park T., Kim K.,
RA Sim X., Twee-Hee Ong R., Croteau-Chonka D.C., Lange L.A., Smith J.D.,
RA Song K., Hua Zhao J., Yuan X., Luan J., Lamina C., Ziegler A., Zhang W.,
RA Zee R.Y., Wright A.F., Witteman J.C., Wilson J.F., Willemsen G.,
RA Wichmann H.E., Whitfield J.B., Waterworth D.M., Wareham N.J., Waeber G.,
RA Vollenweider P., Voight B.F., Vitart V., Uitterlinden A.G., Uda M.,
RA Tuomilehto J., Thompson J.R., Tanaka T., Surakka I., Stringham H.M.,
RA Spector T.D., Soranzo N., Smit J.H., Sinisalo J., Silander K.,
RA Sijbrands E.J., Scuteri A., Scott J., Schlessinger D., Sanna S.,
RA Salomaa V., Saharinen J., Sabatti C., Ruokonen A., Rudan I., Rose L.M.,
RA Roberts R., Rieder M., Psaty B.M., Pramstaller P.P., Pichler I., Perola M.,
RA Penninx B.W., Pedersen N.L., Pattaro C., Parker A.N., Pare G., Oostra B.A.,
RA O'Donnell C.J., Nieminen M.S., Nickerson D.A., Montgomery G.W.,
RA Meitinger T., McPherson R., McCarthy M.I., McArdle W., Masson D.,
RA Martin N.G., Marroni F., Mangino M., Magnusson P.K., Lucas G., Luben R.,
RA Loos R.J., Lokki M.L., Lettre G., Langenberg C., Launer L.J., Lakatta E.G.,
RA Laaksonen R., Kyvik K.O., Kronenberg F., Konig I.R., Khaw K.T., Kaprio J.,
RA Kaplan L.M., Johansson A., Jarvelin M.R., Janssens A.C., Ingelsson E.,
RA Igl W., Kees Hovingh G., Hottenga J.J., Hofman A., Hicks A.A.,
RA Hengstenberg C., Heid I.M., Hayward C., Havulinna A.S., Hastie N.D.,
RA Harris T.B., Haritunians T., Hall A.S., Gyllensten U., Guiducci C.,
RA Groop L.C., Gonzalez E., Gieger C., Freimer N.B., Ferrucci L., Erdmann J.,
RA Elliott P., Ejebe K.G., Doring A., Dominiczak A.F., Demissie S.,
RA Deloukas P., de Geus E.J., de Faire U., Crawford G., Collins F.S.,
RA Chen Y.D., Caulfield M.J., Campbell H., Burtt N.P., Bonnycastle L.L.,
RA Boomsma D.I., Boekholdt S.M., Bergman R.N., Barroso I., Bandinelli S.,
RA Ballantyne C.M., Assimes T.L., Quertermous T., Altshuler D., Seielstad M.,
RA Wong T.Y., Tai E.S., Feranil A.B., Kuzawa C.W., Adair L.S.,
RA Taylor H.A. Jr., Borecki I.B., Gabriel S.B., Wilson J.G., Holm H.,
RA Thorsteinsdottir U., Gudnason V., Krauss R.M., Mohlke K.L., Ordovas J.M.,
RA Munroe P.B., Kooner J.S., Tall A.R., Hegele R.A., Kastelein J.J.,
RA Schadt E.E., Rotter J.I., Boerwinkle E., Strachan D.P., Mooser V.,
RA Stefansson K., Reilly M.P., Samani N.J., Schunkert H., Cupples L.A.,
RA Sandhu M.S., Ridker P.M., Rader D.J., van Duijn C.M., Peltonen L.,
RA Abecasis G.R., Boehnke M., Kathiresan S.;
RT "Biological, clinical and population relevance of 95 loci for blood
RT lipids.";
RL Nature 466:707-713(2010).
RN [32]
RP INVOLVEMENT IN SUSCEPTIBILITY TO MYOCARDIAL INFARCTION.
RX PubMed=20686566; DOI=10.1038/nature09266;
RA Musunuru K., Strong A., Frank-Kamenetsky M., Lee N.E., Ahfeldt T.,
RA Sachs K.V., Li X., Li H., Kuperwasser N., Ruda V.M., Pirruccello J.P.,
RA Muchmore B., Prokunina-Olsson L., Hall J.L., Schadt E.E., Morales C.R.,
RA Lund-Katz S., Phillips M.C., Wong J., Cantley W., Racie T., Ejebe K.G.,
RA Orho-Melander M., Melander O., Koteliansky V., Fitzgerald K., Krauss R.M.,
RA Cowan C.A., Kathiresan S., Rader D.J.;
RT "From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol
RT locus.";
RL Nature 466:714-719(2010).
RN [33]
RP INTERACTION WITH GRN.
RX PubMed=21092856; DOI=10.1016/j.neuron.2010.09.034;
RA Hu F., Padukkavidana T., Vaegter C.B., Brady O.A., Zheng Y.,
RA Mackenzie I.R., Feldman H.H., Nykjaer A., Strittmatter S.M.;
RT "Sortilin-mediated endocytosis determines levels of the frontotemporal
RT dementia protein, progranulin.";
RL Neuron 68:654-667(2010).
RN [34]
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 [35]
RP INTERACTION WITH NTRK1.
RX PubMed=21102451; DOI=10.1038/nn.2689;
RA Vaegter C.B., Jansen P., Fjorback A.W., Glerup S., Skeldal S., Kjolby M.,
RA Richner M., Erdmann B., Nyengaard J.R., Tessarollo L., Lewin G.R.,
RA Willnow T.E., Chao M.V., Nykjaer A.;
RT "Sortilin associates with Trk receptors to enhance anterograde transport
RT and neurotrophin signaling.";
RL Nat. Neurosci. 14:54-61(2011).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-819 AND SER-825, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [37]
RP INTERACTION WITH CLN5 AND PSAP.
RX PubMed=22431521; DOI=10.1128/mcb.06726-11;
RA Mamo A., Jules F., Dumaresq-Doiron K., Costantino S., Lefrancois S.;
RT "The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal
RT sorting.";
RL Mol. Cell. Biol. 32:1855-1866(2012).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-814 AND SER-825, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [39]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 78-756 IN COMPLEX WITH NTS,
RP SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-406 AND ASN-582.
RX PubMed=19122660; DOI=10.1038/nsmb.1543;
RA Quistgaard E.M., Madsen P., Groftehauge M.K., Nissen P., Petersen C.M.,
RA Thirup S.S.;
RT "Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller
RT domain.";
RL Nat. Struct. Mol. Biol. 16:96-98(2009).
RN [40] {ECO:0007744|PDB:3G2U, ECO:0007744|PDB:3G2V}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 819-831 IN COMPLEX WITH GGA1, AND
RP INTERACTION WITH GGA1.
RX PubMed=20015111; DOI=10.1111/j.1600-0854.2009.01017.x;
RA Cramer J.F., Gustafsen C., Behrens M.A., Oliveira C.L., Pedersen J.S.,
RA Madsen P., Petersen C.M., Thirup S.S.;
RT "GGA autoinhibition revisited.";
RL Traffic 11:259-273(2010).
CC -!- FUNCTION: Functions as a sorting receptor in the Golgi compartment and
CC as a clearance receptor on the cell surface. Required for protein
CC transport from the Golgi apparatus to the lysosomes by a pathway that
CC is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal
CC proteins bind specifically to the receptor in the Golgi apparatus and
CC the resulting receptor-ligand complex is transported to an acidic
CC prelysosomal compartment where the low pH mediates the dissociation of
CC the complex (PubMed:16787399). The receptor is then recycled back to
CC the Golgi for another round of trafficking through its binding to the
CC retromer. Also required for protein transport from the Golgi apparatus
CC to the endosomes. Promotes neuronal apoptosis by mediating endocytosis
CC of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB
CC (proNGFB). Also acts as a receptor for neurotensin. May promote
CC mineralization of the extracellular matrix during osteogenic
CC differentiation by scavenging extracellular LPL. Probably required in
CC adipocytes for the formation of specialized storage vesicles containing
CC the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs).
CC These vesicles provide a stable pool of SLC2A4 and confer increased
CC responsiveness to insulin. May also mediate transport from the
CC endoplasmic reticulum to the Golgi. {ECO:0000269|PubMed:10085125,
CC ECO:0000269|PubMed:11331584, ECO:0000269|PubMed:11390366,
CC ECO:0000269|PubMed:12209882, ECO:0000269|PubMed:12598608,
CC ECO:0000269|PubMed:14657016, ECO:0000269|PubMed:14985763,
CC ECO:0000269|PubMed:15313463, ECO:0000269|PubMed:15930396,
CC ECO:0000269|PubMed:15987945, ECO:0000269|PubMed:16787399,
CC ECO:0000269|PubMed:18817523}.
CC -!- SUBUNIT: Interacts with LPL and SLC2A4 (By similarity). Interacts with
CC the cytosolic adapter proteins GGA1 and GGA2 (PubMed:20015111,
CC PubMed:16787399). Interacts with numerous ligands including the
CC receptor-associated protein LRPAP1/RAP, GM2A and NTS. Forms a complex
CC with NGFR which binds specifically to the precursor forms of NGFB
CC (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1,
CC NTRK2 and NTRK3; may regulate their anterograde axonal transport and
CC signaling. Interacts with CLN5 (PubMed:22431521). Interacts with PSAP
CC (PubMed:22431521, PubMed:14657016). Interacts with GRN; this
CC interaction mediates endocytosis and lysosome delivery of progranulin;
CC interaction occurs at the neuronal cell surface in a stressed nervous
CC system (PubMed:21092856). Interacts with the heterotrimeric retromer
CC cargo-selective complex (CSC), also described as vacuolar protein
CC sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and
CC VPS35; which is involved in retrograde trafficking of the receptor from
CC endosomes to the Golgi apparatus (PubMed:18817523). Interacts with
CC SMPD1; the interaction is required for SMPD1 targeting to lysosomes
CC (PubMed:16787399). {ECO:0000250|UniProtKB:Q6PHU5,
CC ECO:0000269|PubMed:11331584, ECO:0000269|PubMed:11390366,
CC ECO:0000269|PubMed:11859376, ECO:0000269|PubMed:14657016,
CC ECO:0000269|PubMed:14985763, ECO:0000269|PubMed:15364913,
CC ECO:0000269|PubMed:15987945, ECO:0000269|PubMed:16787399,
CC ECO:0000269|PubMed:18817523, ECO:0000269|PubMed:19122660,
CC ECO:0000269|PubMed:20015111, ECO:0000269|PubMed:21092856,
CC ECO:0000269|PubMed:21102451, ECO:0000269|PubMed:22431521,
CC ECO:0000269|PubMed:9013611, ECO:0000269|PubMed:9657377,
CC ECO:0000269|PubMed:9927419}.
CC -!- INTERACTION:
CC Q99523; Q96K78: ADGRG7; NbExp=3; IntAct=EBI-1057058, EBI-10290200;
CC Q99523; P23560-2: BDNF; NbExp=3; IntAct=EBI-1057058, EBI-12275524;
CC Q99523; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-1057058, EBI-12244618;
CC Q99523; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-1057058, EBI-12208021;
CC Q99523; P26441: CNTF; NbExp=6; IntAct=EBI-1057058, EBI-1050897;
CC Q99523; Q92520: FAM3C; NbExp=3; IntAct=EBI-1057058, EBI-2876774;
CC Q99523; Q9UJY5: GGA1; NbExp=2; IntAct=EBI-1057058, EBI-447141;
CC Q99523; P06280: GLA; NbExp=3; IntAct=EBI-1057058, EBI-2513305;
CC Q99523; P28799: GRN; NbExp=3; IntAct=EBI-1057058, EBI-747754;
CC Q99523; P05231: IL6; NbExp=4; IntAct=EBI-1057058, EBI-720533;
CC Q99523; P42702: LIFR; NbExp=3; IntAct=EBI-1057058, EBI-7702162;
CC Q99523; P30533: LRPAP1; NbExp=5; IntAct=EBI-1057058, EBI-715927;
CC Q99523; P01138: NGF; NbExp=5; IntAct=EBI-1057058, EBI-1028250;
CC Q99523; PRO_0000019599 [P01138]: NGF; NbExp=2; IntAct=EBI-1057058, EBI-9345310;
CC Q99523; P04629: NTRK1; NbExp=3; IntAct=EBI-1057058, EBI-1028226;
CC Q99523; Q16288: NTRK3; NbExp=2; IntAct=EBI-1057058, EBI-3936704;
CC Q99523; Q8WY21: SORCS1; NbExp=4; IntAct=EBI-1057058, EBI-21198627;
CC Q99523; PRO_0000033162 [Q99523]: SORT1; NbExp=4; IntAct=EBI-1057058, EBI-21474780;
CC Q99523; P02787: TF; NbExp=3; IntAct=EBI-1057058, EBI-714319;
CC Q99523; P01266: TG; NbExp=3; IntAct=EBI-1057058, EBI-2800425;
CC Q99523; O95183: VAMP5; NbExp=3; IntAct=EBI-1057058, EBI-10191195;
CC Q99523; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-1057058, EBI-11141397;
CC Q99523; P83714: Ctf2; Xeno; NbExp=2; IntAct=EBI-1057058, EBI-25298303;
CC Q99523; P11151: LPL; Xeno; NbExp=6; IntAct=EBI-1057058, EBI-8794090;
CC Q99523; Q9JLC4: Sorcs1; Xeno; NbExp=2; IntAct=EBI-1057058, EBI-25300487;
CC Q99523; P06882: Tg; Xeno; NbExp=4; IntAct=EBI-1057058, EBI-1549657;
CC PRO_0000033163; P05067-4: APP; NbExp=4; IntAct=EBI-21467118, EBI-302641;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:16787399, ECO:0000269|PubMed:18817523}; Single-pass
CC type I membrane protein {ECO:0000305}. Endosome membrane
CC {ECO:0000269|PubMed:18817523}; Single-pass type I membrane protein
CC {ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}. Nucleus membrane
CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Cell
CC membrane; Single-pass type I membrane protein; Extracellular side.
CC Lysosome membrane {ECO:0000305}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=Localized to membranes of the endoplasmic
CC reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small
CC fraction of the protein is also localized to the plasma membrane. May
CC also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes.
CC Localization to the plasma membrane in adipocytes may be enhanced by
CC insulin.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99523-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99523-2; Sequence=VSP_046239, VSP_046240;
CC -!- TISSUE SPECIFICITY: Expressed in brain and prostate (at protein level).
CC Expressed at high levels in brain, spinal cord, heart, skeletal muscle,
CC thyroid, placenta and testis. Expressed at lower levels in lymphoid
CC organs, kidney, colon and liver. {ECO:0000269|PubMed:20048080,
CC ECO:0000269|PubMed:9013611}.
CC -!- INDUCTION: During osteoblast differentiation.
CC {ECO:0000269|PubMed:12209882}.
CC -!- DOMAIN: The N-terminal propeptide may facilitate precursor transport
CC within the Golgi stack. Intrachain binding of the N-terminal propeptide
CC and the extracellular domain may also inhibit premature ligand binding.
CC -!- DOMAIN: The extracellular domain may be shed following protease
CC cleavage in some cell types.
CC -!- PTM: The N-terminal propeptide is cleaved by furin and possibly other
CC homologous proteases. {ECO:0000269|PubMed:12419319,
CC ECO:0000269|PubMed:9927419}.
CC -!- PTM: Palmitoylated (PubMed:18817523). Undergoes cysteine S-
CC palmitoylation which promotes the partitioning of the receptor into an
CC endosomal membrane subdomain where it can interact with the retromer
CC cargo-selective complex which mediates its retrograde trafficking to
CC the Golgi apparatus (PubMed:18817523). {ECO:0000269|PubMed:18817523}.
CC -!- PTM: Phosphorylation at Ser-825 facilitates the interaction with GGA1.
CC {ECO:0000269|PubMed:20015111}.
CC -!- POLYMORPHISM: Genetic variations in SORT1 influence low density
CC lipoprotein cholesterol (LDL-C) variability and contribute to the low
CC density lipoprotein cholesterol level quantitative trait locus 6
CC (LDLCQ6) [MIM:613589]. {ECO:0000269|PubMed:20686565}.
CC -!- DISEASE: Note=A common polymorphism located in a non-coding region
CC between CELSR2 and PSRC1 alters a CEBP transcription factor binding
CC site and is responsible for changes in hepatic expression of SORT1.
CC Altered SORT1 expression in liver affects low density lipoprotein
CC cholesterol levels in plasma and is associated with susceptibility to
CC myocardial infarction. {ECO:0000269|PubMed:20686566}.
CC -!- SIMILARITY: Belongs to the VPS10-related sortilin family. SORT1
CC subfamily. {ECO:0000305}.
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; X98248; CAA66904.2; -; mRNA.
DR EMBL; FJ525881; ACN81319.1; -; Genomic_DNA.
DR EMBL; AK301548; BAG63045.1; -; mRNA.
DR EMBL; AL390252; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023542; AAH23542.1; -; mRNA.
DR CCDS; CCDS55618.1; -. [Q99523-2]
DR CCDS; CCDS798.1; -. [Q99523-1]
DR RefSeq; NP_001192157.1; NM_001205228.1. [Q99523-2]
DR RefSeq; NP_002950.3; NM_002959.6. [Q99523-1]
DR PDB; 3F6K; X-ray; 2.00 A; A=78-756.
DR PDB; 3G2U; X-ray; 2.30 A; C/D=819-831.
DR PDB; 3G2V; X-ray; 2.10 A; C/D=819-831.
DR PDB; 4MSL; X-ray; 2.70 A; A=78-756.
DR PDB; 4N7E; X-ray; 2.70 A; A=78-756.
DR PDB; 4PO7; X-ray; 2.66 A; A=78-756.
DR PDB; 5MRH; X-ray; 2.50 A; A=78-756.
DR PDB; 5MRI; X-ray; 2.00 A; A=78-756.
DR PDB; 6EHO; X-ray; 3.50 A; A=34-756.
DR PDB; 6X3L; X-ray; 2.70 A; A=1-756.
DR PDB; 6X48; X-ray; 2.90 A; A=86-748.
DR PDB; 6X4H; X-ray; 2.90 A; A=86-748.
DR PDBsum; 3F6K; -.
DR PDBsum; 3G2U; -.
DR PDBsum; 3G2V; -.
DR PDBsum; 4MSL; -.
DR PDBsum; 4N7E; -.
DR PDBsum; 4PO7; -.
DR PDBsum; 5MRH; -.
DR PDBsum; 5MRI; -.
DR PDBsum; 6EHO; -.
DR PDBsum; 6X3L; -.
DR PDBsum; 6X48; -.
DR PDBsum; 6X4H; -.
DR AlphaFoldDB; Q99523; -.
DR SMR; Q99523; -.
DR BioGRID; 112180; 223.
DR CORUM; Q99523; -.
DR DIP; DIP-41798N; -.
DR ELM; Q99523; -.
DR IntAct; Q99523; 171.
DR MINT; Q99523; -.
DR STRING; 9606.ENSP00000256637; -.
DR BindingDB; Q99523; -.
DR ChEMBL; CHEMBL3091; -.
DR TCDB; 9.A.63.1.3; the retromer-dependent vacuolar protein sorting (r-vps) family.
DR GlyConnect; 1765; 26 N-Linked glycans (4 sites).
DR GlyGen; Q99523; 9 sites, 27 N-linked glycans (4 sites).
DR iPTMnet; Q99523; -.
DR PhosphoSitePlus; Q99523; -.
DR SwissPalm; Q99523; -.
DR BioMuta; SORT1; -.
DR DMDM; 84028263; -.
DR EPD; Q99523; -.
DR jPOST; Q99523; -.
DR MassIVE; Q99523; -.
DR MaxQB; Q99523; -.
DR PaxDb; Q99523; -.
DR PeptideAtlas; Q99523; -.
DR PRIDE; Q99523; -.
DR ProteomicsDB; 5342; -.
DR ProteomicsDB; 78309; -. [Q99523-1]
DR Antibodypedia; 1533; 286 antibodies from 32 providers.
DR DNASU; 6272; -.
DR Ensembl; ENST00000256637.8; ENSP00000256637.6; ENSG00000134243.12. [Q99523-1]
DR Ensembl; ENST00000538502.5; ENSP00000438597.1; ENSG00000134243.12. [Q99523-2]
DR GeneID; 6272; -.
DR KEGG; hsa:6272; -.
DR MANE-Select; ENST00000256637.8; ENSP00000256637.6; NM_002959.7; NP_002950.3.
DR UCSC; uc001dxm.3; human. [Q99523-1]
DR CTD; 6272; -.
DR DisGeNET; 6272; -.
DR GeneCards; SORT1; -.
DR HGNC; HGNC:11186; SORT1.
DR HPA; ENSG00000134243; Tissue enhanced (brain).
DR MalaCards; SORT1; -.
DR MIM; 602458; gene.
DR MIM; 613589; phenotype.
DR neXtProt; NX_Q99523; -.
DR OpenTargets; ENSG00000134243; -.
DR PharmGKB; PA36023; -.
DR VEuPathDB; HostDB:ENSG00000134243; -.
DR eggNOG; KOG3511; Eukaryota.
DR GeneTree; ENSGT01030000234563; -.
DR HOGENOM; CLU_013596_0_0_1; -.
DR InParanoid; Q99523; -.
DR OMA; FAPFYSV; -.
DR OrthoDB; 1046610at2759; -.
DR PhylomeDB; Q99523; -.
DR TreeFam; TF324918; -.
DR PathwayCommons; Q99523; -.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR SignaLink; Q99523; -.
DR BioGRID-ORCS; 6272; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; SORT1; human.
DR EvolutionaryTrace; Q99523; -.
DR GeneWiki; Sortilin_1; -.
DR GenomeRNAi; 6272; -.
DR Pharos; Q99523; Tchem.
DR PRO; PR:Q99523; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q99523; protein.
DR Bgee; ENSG00000134243; Expressed in inferior vagus X ganglion and 202 other tissues.
DR ExpressionAtlas; Q99523; baseline and differential.
DR Genevisible; Q99523; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:BHF-UCL.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:BHF-UCL.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IDA:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0048406; F:nerve growth factor binding; IPI:BHF-UCL.
DR GO; GO:0010465; F:nerve growth factor receptor activity; IDA:BHF-UCL.
DR GO; GO:0030379; F:neurotensin receptor activity, non-G protein-coupled; IDA:BHF-UCL.
DR GO; GO:1905394; F:retromer complex binding; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IDA:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; IDA:BHF-UCL.
DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; IDA:BHF-UCL.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0046323; P:glucose import; IMP:BHF-UCL.
DR GO; GO:0006895; P:Golgi to endosome transport; IDA:BHF-UCL.
DR GO; GO:0090160; P:Golgi to lysosome transport; IDA:UniProtKB.
DR GO; GO:0014902; P:myotube differentiation; IMP:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; IDA:BHF-UCL.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0048227; P:plasma membrane to endosome transport; IDA:BHF-UCL.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0006622; P:protein targeting to lysosome; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0032868; P:response to insulin; IMP:BHF-UCL.
DR GO; GO:0016050; P:vesicle organization; IDA:BHF-UCL.
DR DisProt; DP01551; -.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR031777; Sortilin_C.
DR InterPro; IPR031778; Sortilin_N.
DR InterPro; IPR006581; VPS10.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF15902; Sortilin-Vps10; 1.
DR Pfam; PF15901; Sortilin_C; 1.
DR SMART; SM00602; VPS10; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Cleavage on pair of basic residues; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; Endocytosis;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus;
KW Lipoprotein; Lysosome; Membrane; Nucleus; Osteogenesis; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..33
FT /evidence="ECO:0000250|UniProtKB:O54861"
FT PROPEP 34..77
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:9756851"
FT /id="PRO_0000033162"
FT CHAIN 78..831
FT /note="Sortilin"
FT /id="PRO_0000033163"
FT TOPO_DOM 78..755
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 756..778
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 779..831
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 145..156
FT /note="BNR 1"
FT REPEAT 198..209
FT /note="BNR 2"
FT REPEAT 240..251
FT /note="BNR 3"
FT REPEAT 287..298
FT /note="BNR 4"
FT REPEAT 328..339
FT /note="BNR 5"
FT REPEAT 377..388
FT /note="BNR 6"
FT REPEAT 428..439
FT /note="BNR 7"
FT REPEAT 506..517
FT /note="BNR 8"
FT REPEAT 548..559
FT /note="BNR 9"
FT REGION 50..61
FT /note="Intrachain binding of the propeptide and the
FT extracellular domain"
FT REGION 612..756
FT /note="Interactions with LRPAP1 and NGFB"
FT REGION 779..831
FT /note="Golgi to endosome transport and interactions with
FT GGA1 and GGA2"
FT /evidence="ECO:0000269|PubMed:16787399"
FT MOTIF 787..792
FT /note="Endocytosis signal"
FT /evidence="ECO:0000305"
FT MOTIF 826..830
FT /note="DXXLL motif involved in the interaction with GGA1"
FT /evidence="ECO:0000269|PubMed:20015111"
FT MOD_RES 814
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 819
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 825
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT LIPID 783
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:18817523"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16263699,
FT ECO:0000269|PubMed:19349973"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19122660"
FT CARBOHYD 582
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19122660"
FT CARBOHYD 684
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 86..556
FT DISULFID 257..277
FT DISULFID 448..458
FT DISULFID 612..651
FT DISULFID 634..666
FT DISULFID 668..723
FT DISULFID 675..688
FT DISULFID 702..740
FT VAR_SEQ 1..136
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046239"
FT VAR_SEQ 278..279
FT /note="KA -> T (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046240"
FT VARIANT 358
FT /note="D -> Y (in dbSNP:rs2228605)"
FT /id="VAR_053681"
FT MUTAGEN 74..77
FT /note="RWRR->GWRA: Abrogates propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:9927419"
FT MUTAGEN 76..77
FT /note="RR->GG: Abrogates propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:9927419"
FT MUTAGEN 783
FT /note="C->S: Loss of palmitoylation. Decreased recycling
FT from endosomes to the Golgi apparatus. Increased lysosomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:18817523"
FT MUTAGEN 792
FT /note="Y->A: Reduces endocytosis and Golgi to endosome
FT sorting; when associated with A-795."
FT /evidence="ECO:0000269|PubMed:11331584"
FT MUTAGEN 795
FT /note="L->A: Reduces endocytosis and Golgi to endosome
FT sorting; when associated with A-792."
FT /evidence="ECO:0000269|PubMed:11331584"
FT MUTAGEN 823..824
FT /note="DD->NN: Reduces interaction with GGA1."
FT /evidence="ECO:0000269|PubMed:11390366"
FT MUTAGEN 825
FT /note="S->A: Reduces interaction with GGA1."
FT /evidence="ECO:0000269|PubMed:11390366"
FT MUTAGEN 826..828
FT /note="DED->NQN: Abrogates interaction with GGA1 and
FT impairs localization to the Golgi."
FT /evidence="ECO:0000269|PubMed:11390366"
FT MUTAGEN 829..830
FT /note="LL->AA: Abrogates interaction with GGA1 and impairs
FT localization to the Golgi."
FT /evidence="ECO:0000269|PubMed:11331584,
FT ECO:0000269|PubMed:11390366"
FT MUTAGEN 829..830
FT /note="Missing: Abrogates interaction with GGA2. Reduces
FT endocytosis and Golgi to endosome sorting; when associated
FT with A-792 and A-795."
FT /evidence="ECO:0000269|PubMed:11331584,
FT ECO:0000269|PubMed:11390366"
FT CONFLICT 650
FT /note="V -> M (in Ref. 1; CAA66904)"
FT /evidence="ECO:0000305"
FT HELIX 92..97
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:5MRI"
FT STRAND 141..149
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:6X3L"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:6EHO"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:3F6K"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:5MRH"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:6EHO"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 247..261
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:5MRH"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:3F6K"
FT TURN 277..282
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 297..309
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 312..318
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 320..323
FT /evidence="ECO:0007829|PDB:5MRH"
FT STRAND 325..332
FT /evidence="ECO:0007829|PDB:3F6K"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:6X48"
FT STRAND 351..356
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 361..366
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:5MRI"
FT STRAND 372..379
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:6EHO"
FT STRAND 385..395
FT /evidence="ECO:0007829|PDB:3F6K"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 405..410
FT /evidence="ECO:0007829|PDB:6EHO"
FT STRAND 414..419
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:4N7E"
FT STRAND 425..432
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:6EHO"
FT TURN 449..451
FT /evidence="ECO:0007829|PDB:6EHO"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:5MRI"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 465..469
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:5MRH"
FT STRAND 488..497
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 504..510
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 516..521
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 523..528
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 529..531
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 533..538
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:6EHO"
FT STRAND 546..552
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 558..561
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 567..573
FT /evidence="ECO:0007829|PDB:3F6K"
FT TURN 576..578
FT /evidence="ECO:0007829|PDB:6X48"
FT STRAND 581..590
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:5MRI"
FT STRAND 595..603
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 604..606
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 614..616
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 617..621
FT /evidence="ECO:0007829|PDB:3F6K"
FT TURN 630..633
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 638..645
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 661..665
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 670..672
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 673..675
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 683..685
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 696..704
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 707..710
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 714..717
FT /evidence="ECO:0007829|PDB:3F6K"
FT STRAND 724..726
FT /evidence="ECO:0007829|PDB:5MRH"
FT STRAND 734..736
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 737..740
FT /evidence="ECO:0007829|PDB:3F6K"
FT HELIX 741..743
FT /evidence="ECO:0007829|PDB:3F6K"
SQ SEQUENCE 831 AA; 92068 MW; 91F96A3035A4B43A CRC64;
MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW SGPIGVSWGL
RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT HQHVFDDLRG SVSLSWVGDS
TGVILVLTTF HVPLVIMTFG QSKLYRSEDY GKNFKDITDL INNTFIRTEF GMAIGPENSG
KVVLTAEVSG GSRGGRIFRS SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW
VSKNFGGKWE EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG
VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF YSILAANDDM
VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG ETDFTNVTSL RGVYITSVLS
EDNSIQTMIT FDQGGRWTHL RKPENSECDA TAKNKNECSL HIHASYSISQ KLNVPMAPLS
EPNAVGIVIA HGSVGDAISV MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS
SRPINVIKFS TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY
TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV CQNGRDYVVT
KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE FCLYGREEHL TTNGYRKIPG
DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ NSKSNSVPII LAIVGLMLVT VVAGVLIVKK
YVCGGRFLVH RYSVLQQHAE ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E
