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 10-JUN-2026, entry version 226. 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:16787399, CC PubMed:20015111). 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:14657016, PubMed:22431521). 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_001205228.2. [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 PDB; 8T8R; X-ray; 2.87 A; A=79-756. DR PDB; 8T8S; X-ray; 2.99 A; A/B=79-756. DR PDB; 9I0N; EM; 3.10 A; A=34-756. DR PDB; 9I0O; EM; 3.36 A; A=34-756. 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 PDBsum; 8T8R; -. DR PDBsum; 8T8S; -. DR PDBsum; 9I0N; -. DR PDBsum; 9I0O; -. DR AlphaFoldDB; Q99523; -. DR EMDB; EMD-52562; -. DR EMDB; EMD-52563; -. DR SMR; Q99523; -. DR BioGRID; 112180; 263. DR CORUM; Q99523; -. DR DIP; DIP-41798N; -. DR ELM; Q99523; -. DR FunCoup; Q99523; 887. DR IntAct; Q99523; 231. DR MINT; Q99523; -. DR NDEx; IQUERY-CP-SORT1; 6 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000256637; -. DR BindingDB; Q99523; -. DR ChEMBL; CHEMBL3091; -. DR GuidetoPHARMACOLOGY; 3300; -. DR TCDB; 9.A.63.1.3; the retromer-dependent vacuolar protein sorting (r-vps) family. DR GlyConnect; Q99523; 27 N-Linked glycans (4 sites). DR GlyCosmos; Q99523; 6 sites, 28 glycans. DR GlyGen; Q99523; 10 sites, 70 N-linked glycans (5 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q99523; -. DR PhosphoSitePlus; Q99523; -. DR SwissPalm; Q99523; -. DR BioMuta; SORT1; -. DR DMDM; 84028263; -. DR jPOST; Q99523; -. DR MassIVE; Q99523; -. DR PaxDb; 9606-ENSP00000256637; -. DR PeptideAtlas; Q99523; -. DR ProteomicsDB; 5342; -. DR ProteomicsDB; 78309; -. [Q99523-1] DR Pumba; Q99523; -. DR Antibodypedia; 1533; 338 antibodies from 34 providers. DR DNASU; 6272; -. DR Ensembl; ENST00000256637.8; ENSP00000256637.6; ENSG00000134243.13. [Q99523-1] DR Ensembl; ENST00000538502.5; ENSP00000438597.1; ENSG00000134243.13. [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 AGR; HGNC:11186; -. DR ClinPGx; PA36023; -. DR CTD; 6272; -. DR DisGeNET; 6272; -. DR GeneCards; SORT1; -. DR HGNC; HGNC:11186; SORT1. DR HPA; ENSG00000134243; Low tissue specificity. DR MalaCards; SORT1; -. DR MIM; 602458; gene. DR MIM; 613589; phenotype. DR NIAGADS; ENSG00000134243; -. DR OpenTargets; ENSG00000134243; -. 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; 443634at2759; -. DR PAN-GO; Q99523; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q99523; -. DR PathwayCommons; Q99523; -. DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis. DR SignaLink; Q99523; -. DR SIGNOR; Q99523; -. DR Agora; ENSG00000134243; -. DR BioGRID-ORCS; 6272; 18 hits in 1169 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 204 other cell types or tissues. DR ExpressionAtlas; Q99523; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0150053; C:cerebellar climbing fiber to Purkinje cell synapse; IEA:Ensembl. 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:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. 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:0098708; P:D-glucose import across plasma membrane; IMP:BHF-UCL. 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:0006895; P:Golgi to endosome transport; IDA:BHF-UCL. DR GO; GO:0090160; P:Golgi to lysosome transport; IDA:UniProtKB. DR GO; GO:0099558; P:maintenance of synapse structure; IEA:Ensembl. DR GO; GO:0014902; P:myotube differentiation; IMP: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:0015031; P:protein transport; IEA:UniProtKB-KW. 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 FunFam; 2.10.70.80:FF:000003; Sortilin; 1. DR FunFam; 2.130.10.10:FF:000802; Sortilin; 1. DR FunFam; 3.30.60.270:FF:000004; Sortilin; 1. DR Gene3D; 2.10.70.80; -; 1. DR Gene3D; 3.30.60.270; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR InterPro; IPR031777; Sortilin_C. DR InterPro; IPR031778; Sortilin_N. DR InterPro; IPR006581; VPS10. DR InterPro; IPR050310; VPS10-sortilin. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR PANTHER; PTHR12106:SF23; SORTILIN; 1. DR PANTHER; PTHR12106; SORTILIN RELATED; 1. DR Pfam; PF15902; Sortilin-Vps10; 1. DR Pfam; PF15901; Sortilin_C; 1. DR SMART; SM00602; VPS10; 1. DR SUPFAM; SSF110296; Oligoxyloglucan reducing end-specific cellobiohydrolase; 2. DR PROSITE; PS52072; VPS10P; 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; Protein transport; Proteomics identification; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix; KW 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 DOMAIN 98..742 FT /note="Vps10p" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" 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 98..604 FT /note="10-bladed beta-propeller" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" FT REGION 612..756 FT /note="Interactions with LRPAP1 and NGFB" FT REGION 612..666 FT /note="10CCa cysteine-knot" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" FT REGION 668..742 FT /note="10CCb cysteine-knot" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" 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 /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" FT DISULFID 634..666 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" FT DISULFID 668..723 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" FT DISULFID 675..688 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" FT DISULFID 702..740 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01417" 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 HELIX 187..189 FT /evidence="ECO:0007829|PDB:3F6K" 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 HELIX 446..448 FT /evidence="ECO:0007829|PDB:5MRI" 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 666..668 FT /evidence="ECO:0007829|PDB:4N7E" 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 HELIX 730..733 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" FT HELIX 745..748 FT /evidence="ECO:0007829|PDB:3F6K" FT HELIX 827..829 FT /evidence="ECO:0007829|PDB:3G2V" 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 //