ID SORT_MOUSE Reviewed; 825 AA. AC Q6PHU5; A2AEE8; Q3UHE2; Q8K043; Q9QXW6; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 171. DE RecName: Full=Sortilin {ECO:0000305}; DE AltName: Full=Neurotensin receptor 3; DE Short=NTR3; DE Short=mNTR3; DE Flags: Precursor; GN Name=Sort1 {ECO:0000312|MGI:MGI:1338015}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION AS A NEUROTENSIN RP RECEPTOR, SUBCELLULAR LOCATION, AND GLYCOSYLATION. RC STRAIN=BALB/cJ; TISSUE=Brain; RX PubMed=11322955; DOI=10.1016/s0014-5793(01)02367-5; RA Navarro V., Martin S., Sarret P., Nielsen M.S., Petersen C.M., RA Vincent J.-P., Mazella J.; RT "Pharmacological properties of the mouse neurotensin receptor 3. RT Maintenance of cell surface receptor during internalization of RT neurotensin."; RL FEBS Lett. 495:100-105(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Brain, and Salivary gland; 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 [5] RP SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=9452485; DOI=10.1074/jbc.273.6.3582; RA Morris N.J., Ross S.A., Lane W.S., Moestrup S.K., Petersen C.M., RA Keller S.R., Lienhard G.E.; RT "Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes."; RL J. Biol. Chem. 273:3582-3587(1998). RN [6] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=10064893; DOI=10.1016/s0169-328x(99)00022-4; RA Hermans-Borgmeyer I., Hermey G., Nykjaer A., Schaller C.; RT "Expression of the 100-kDa neurotensin receptor sortilin during mouse RT embryonal development."; RL Brain Res. Mol. Brain Res. 65:216-219(1999). RN [7] RP INTERACTION WITH LPL. 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 [8] RP FUNCTION. RX PubMed=10594043; DOI=10.1128/mcb.20.1.416-427.2000; RA Hashiramoto M., James D.E.; RT "Characterization of insulin-responsive GLUT4 storage vesicles isolated RT from 3T3-L1 adipocytes."; RL Mol. Cell. Biol. 20:416-427(2000). RN [9] RP FUNCTION, INTERACTION WITH PSAP, AND SUBCELLULAR LOCATION. RX PubMed=15236332; DOI=10.1002/mrd.20097; RA Zeng J., Hassan A.J., Morales C.R.; RT "Study of the mouse sortilin gene: effects of its transient silencing by RT RNA interference in TM4 Sertoli cells."; RL Mol. Reprod. Dev. 68:469-475(2004). RN [10] RP FUNCTION. RX PubMed=15236333; DOI=10.1002/mrd.20096; RA Hassan A.J., Zeng J., Ni X., Morales C.R.; RT "The trafficking of prosaposin (SGP-1) and GM2AP to the lysosomes of TM4 RT Sertoli cells is mediated by sortilin and monomeric adaptor proteins."; RL Mol. Reprod. Dev. 68:476-483(2004). RN [11] RP FUNCTION. RX PubMed=15372498; DOI=10.1002/jnr.20231; RA Dicou E., Vincent J.-P., Mazella J.; RT "Neurotensin receptor-3/sortilin mediates neurotensin-induced RT cytokine/chemokine expression in a murine microglial cell line."; RL J. Neurosci. Res. 78:92-99(2004). RN [12] RP FUNCTION, INTERACTION WITH SLC2A4, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=15992544; DOI=10.1016/j.devcel.2005.04.004; RA Shi J., Kandror K.V.; RT "Sortilin is essential and sufficient for the formation of Glut4 storage RT vesicles in 3T3-L1 adipocytes."; RL Dev. Cell 9:99-108(2005). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-819, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NGFR AND NRADD. RX PubMed=19407813; DOI=10.1038/emboj.2009.118; RA Kim T., Hempstead B.L.; RT "NRH2 is a trafficking switch to regulate sortilin localization and permit RT proneurotrophin-induced cell death."; RL EMBO J. 28:1612-1623(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-819, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP FUNCTION IN NTRK1 SIGNALING. 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). 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. The receptor is then recycled back to the Golgi for CC another round of trafficking through its binding to the retromer. Also CC required for protein transport from the Golgi apparatus to the CC endosomes. Promotes neuronal apoptosis by mediating endocytosis of the CC proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also CC acts as a receptor for neurotensin. May promote mineralization of the CC extracellular matrix during osteogenic differentiation by scavenging CC extracellular LPL. Probably required in adipocytes for the formation of CC specialized storage vesicles containing the glucose transporter CC SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide CC a stable pool of SLC2A4 and confer increased responsiveness to insulin. CC May also mediate transport from the endoplasmic reticulum to the Golgi. CC {ECO:0000269|PubMed:10594043, ECO:0000269|PubMed:15236332, CC ECO:0000269|PubMed:15236333, ECO:0000269|PubMed:15372498, CC ECO:0000269|PubMed:15992544, ECO:0000269|PubMed:19407813, CC ECO:0000269|PubMed:21102451}. CC -!- SUBUNIT: Interacts with the cytosolic adapter proteins GGA1 and GGA2. CC Interacts with numerous ligands including the receptor-associated CC protein LRPAP1/RAP, NTS and GM2A. Forms a complex with NGFR which binds CC specifically to the precursor forms of NGFB (proNGFB) and BDNF CC (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may CC regulate their anterograde axonal transport and signaling (By CC similarity). Interacts with LPL (PubMed:10085125). Interacts with PSAP CC (PubMed:15236332). Interacts with SLC2A4 (PubMed:15992544). Interacts CC with NRADD and NGFR (PubMed:19407813). Interaction with NRADD protects CC against degradation in the lysosome. Interacts with CLN5 (By CC similarity). Interacts with GRN; this interaction mediates endocytosis CC and lysosome delivery of progranulin; interaction occurs at the CC neuronal cell surface in a stressed nervous system (By similarity). CC Interacts with the heterotrimeric retromer cargo-selective complex CC (CSC), also described as vacuolar protein sorting subcomplex (VPS), CC formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved CC in retrograde trafficking of the receptor from endosomes to the Golgi CC apparatus (By similarity). Interacts with SMPD1; the interaction is CC required for SMPD1 targeting to lysosomes (By similarity). CC {ECO:0000250|UniProtKB:Q99523, ECO:0000269|PubMed:10085125, CC ECO:0000269|PubMed:15236332, ECO:0000269|PubMed:15992544, CC ECO:0000269|PubMed:19407813}. CC -!- INTERACTION: CC Q6PHU5; P12023: App; NbExp=3; IntAct=EBI-6985663, EBI-78814; CC Q6PHU5; P97438: Kcnk2; NbExp=4; IntAct=EBI-6985663, EBI-7091062; CC Q6PHU5; Q8CJ26: Nradd; NbExp=5; IntAct=EBI-6985663, EBI-6985725; CC Q6PHU5; P15209: Ntrk2; NbExp=3; IntAct=EBI-6985663, EBI-309647; CC Q6PHU5; Q9EQH3: Vps35; NbExp=3; IntAct=EBI-6985663, EBI-775825; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane CC {ECO:0000250|UniProtKB:Q99523}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q99523}. Endosome membrane CC {ECO:0000250|UniProtKB:Q99523}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q99523}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q99523}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q99523}. Nucleus membrane CC {ECO:0000250|UniProtKB:Q99523}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q99523}. Cell membrane CC {ECO:0000250|UniProtKB:Q99523}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q99523}; Extracellular side CC {ECO:0000250|UniProtKB:Q99523}. Lysosome membrane CC {ECO:0000250|UniProtKB:Q99523}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q99523}. Note=Localized to membranes of the CC endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A CC small fraction of the protein is also localized to the plasma membrane. CC May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in CC adipocytes. Localization to the plasma membrane in adipocytes may be CC enhanced by insulin. {ECO:0000250|UniProtKB:Q99523}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q6PHU5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6PHU5-2; Sequence=VSP_016650; CC -!- TISSUE SPECIFICITY: Expressed in the brain, particularly the piriform CC cortex, the cerebral cortex and the hippocampus. CC {ECO:0000269|PubMed:10064893}. CC -!- DEVELOPMENTAL STAGE: Expressed in the ectoderm at 7.5 dpc and within CC the germ cell layers at 8.5 dpc. Expressed within the neural epithelium CC and the neural tube at 9.5 dpc and subsequently expressed in the CC nervous system throughout development. Expression in the proliferative CC zones of the central nervous system declines between 14.5 dpc and 16.5 CC dpc, while expression remains high in the cerebral cortex and the CC neural retina. Expressed in the pituitary and the sensory epithelia CC throughout development. {ECO:0000269|PubMed:10064893}. CC -!- INDUCTION: During adipocyte differentiation. CC {ECO:0000269|PubMed:15992544, ECO:0000269|PubMed:9452485}. 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 (By similarity). {ECO:0000250}. CC -!- DOMAIN: The extracellular domain may be shed following protease CC cleavage in some cell types. {ECO:0000250}. CC -!- PTM: The N-terminal propeptide is cleaved by furin and possibly other CC homologous proteases. {ECO:0000250|UniProtKB:Q99523}. CC -!- PTM: Phosphorylation at Ser-819 facilitates the interaction with GGA1. CC {ECO:0000250|UniProtKB:Q99523}. CC -!- PTM: Palmitoylated. Undergoes cysteine S-palmitoylation which promotes CC the partitioning of the receptor into an endosomal membrane subdomain CC where it can interact with the retromer cargo-selective complex which CC mediates its retrograde trafficking to the Golgi apparatus. CC {ECO:0000250|UniProtKB:Q99523}. 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; AF175279; AAF22639.1; -; mRNA. DR EMBL; AK147442; BAE27915.1; -; mRNA. DR EMBL; AL671899; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034129; AAH34129.1; -; mRNA. DR EMBL; BC056343; AAH56343.1; -; mRNA. DR CCDS; CCDS17756.1; -. [Q6PHU5-1] DR CCDS; CCDS80003.1; -. [Q6PHU5-2] DR RefSeq; NP_001258528.1; NM_001271599.1. [Q6PHU5-2] DR RefSeq; NP_064356.2; NM_019972.3. [Q6PHU5-1] DR PDB; 5NMR; X-ray; 2.10 A; A=32-753. DR PDB; 5NMT; X-ray; 2.30 A; A/B=32-753. DR PDB; 5NNI; X-ray; 3.21 A; A/B=31-753. DR PDB; 5NNJ; X-ray; 4.00 A; A/B/C/D=31-753. DR PDB; 5ZNN; X-ray; 2.45 A; A/B=76-744. DR PDBsum; 5NMR; -. DR PDBsum; 5NMT; -. DR PDBsum; 5NNI; -. DR PDBsum; 5NNJ; -. DR PDBsum; 5ZNN; -. DR AlphaFoldDB; Q6PHU5; -. DR SASBDB; Q6PHU5; -. DR SMR; Q6PHU5; -. DR BioGRID; 203393; 12. DR DIP; DIP-46095N; -. DR IntAct; Q6PHU5; 12. DR MINT; Q6PHU5; -. DR STRING; 10090.ENSMUSP00000123564; -. DR BindingDB; Q6PHU5; -. DR GlyConnect; 2734; 6 N-Linked glycans (3 sites). DR GlyCosmos; Q6PHU5; 6 sites, 5 glycans. DR GlyGen; Q6PHU5; 7 sites, 6 N-linked glycans (3 sites). DR iPTMnet; Q6PHU5; -. DR PhosphoSitePlus; Q6PHU5; -. DR SwissPalm; Q6PHU5; -. DR jPOST; Q6PHU5; -. DR MaxQB; Q6PHU5; -. DR PaxDb; 10090-ENSMUSP00000099692; -. DR PeptideAtlas; Q6PHU5; -. DR ProteomicsDB; 261549; -. [Q6PHU5-1] DR ProteomicsDB; 261550; -. [Q6PHU5-2] DR Antibodypedia; 1533; 363 antibodies from 32 providers. DR DNASU; 20661; -. DR Ensembl; ENSMUST00000102632.7; ENSMUSP00000099692.5; ENSMUSG00000068747.15. [Q6PHU5-1] DR Ensembl; ENSMUST00000135636.6; ENSMUSP00000123564.3; ENSMUSG00000068747.15. [Q6PHU5-2] DR GeneID; 20661; -. DR KEGG; mmu:20661; -. DR UCSC; uc008qyr.2; mouse. [Q6PHU5-1] DR UCSC; uc008qys.2; mouse. [Q6PHU5-2] DR AGR; MGI:1338015; -. DR CTD; 6272; -. DR MGI; MGI:1338015; Sort1. DR VEuPathDB; HostDB:ENSMUSG00000068747; -. DR eggNOG; KOG3511; Eukaryota. DR GeneTree; ENSGT01030000234563; -. DR HOGENOM; CLU_013596_0_0_1; -. DR InParanoid; Q6PHU5; -. DR OMA; GGHWSYL; -. DR OrthoDB; 5840at2759; -. DR PhylomeDB; Q6PHU5; -. DR TreeFam; TF324918; -. DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis. DR BioGRID-ORCS; 20661; 1 hit in 76 CRISPR screens. DR ChiTaRS; Sort1; mouse. DR PRO; PR:Q6PHU5; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; Q6PHU5; Protein. DR Bgee; ENSMUSG00000068747; Expressed in dentate gyrus of hippocampal formation granule cell and 249 other cell types or tissues. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0150053; C:cerebellar climbing fiber to Purkinje cell synapse; IDA:SynGO. DR GO; GO:0005905; C:clathrin-coated pit; ISO:MGI. DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0005769; C:early endosome; ISO:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0010008; C:endosome membrane; ISO:MGI. DR GO; GO:0005794; C:Golgi apparatus; ISS: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; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISO:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IDA:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0048406; F:nerve growth factor binding; ISO:MGI. DR GO; GO:0010465; F:nerve growth factor receptor activity; ISO:MGI. DR GO; GO:0030379; F:neurotensin receptor activity, non-G protein-coupled; ISO:MGI. DR GO; GO:1905394; F:retromer complex binding; ISO:MGI. DR GO; GO:0006897; P:endocytosis; IMP:MGI. DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI. DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; ISO:MGI. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI. DR GO; GO:0046323; P:glucose import; IMP:BHF-UCL. DR GO; GO:0006895; P:Golgi to endosome transport; ISO:MGI. DR GO; GO:0090160; P:Golgi to lysosome transport; ISS:UniProtKB. DR GO; GO:0099558; P:maintenance of synapse structure; IDA:SynGO. DR GO; GO:0014902; P:myotube differentiation; IMP:BHF-UCL. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:MGI. DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:MGI. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISO:MGI. DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW. DR GO; GO:0048227; P:plasma membrane to endosome transport; ISO:MGI. DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; ISO:MGI. DR GO; GO:0006622; P:protein targeting to lysosome; IMP:MGI. DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI. DR GO; GO:0032868; P:response to insulin; IMP:BHF-UCL. DR GO; GO:0016050; P:vesicle organization; IMP:BHF-UCL. 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; 1. DR InterPro; IPR031777; Sortilin_C. DR InterPro; IPR031778; Sortilin_N. DR InterPro; IPR006581; VPS10. 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 Genevisible; Q6PHU5; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; KW Cleavage on pair of basic residues; Developmental protein; Differentiation; KW Disulfide bond; Endocytosis; Endoplasmic reticulum; Endosome; Glycoprotein; KW Golgi apparatus; Lipoprotein; Lysosome; Membrane; Nucleus; Osteogenesis; KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1..31 FT /evidence="ECO:0000250|UniProtKB:O54861" FT PROPEP 32..73 FT /note="Removed in mature form" FT /evidence="ECO:0000250|UniProtKB:O54861" FT /id="PRO_0000045155" FT CHAIN 74..825 FT /note="Sortilin" FT /id="PRO_0000436377" FT TOPO_DOM 74..754 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 755..775 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 776..825 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 143..154 FT /note="BNR 1" FT REPEAT 196..207 FT /note="BNR 2" FT REPEAT 238..249 FT /note="BNR 3" FT REPEAT 285..296 FT /note="BNR 4" FT REPEAT 326..337 FT /note="BNR 5" FT REPEAT 375..386 FT /note="BNR 6" FT REPEAT 426..437 FT /note="BNR 7" FT REPEAT 504..515 FT /note="BNR 8" FT REPEAT 546..557 FT /note="BNR 9" FT REGION 48..59 FT /note="Intrachain binding of the propeptide and the FT extracellular domain" FT /evidence="ECO:0000250" FT REGION 610..754 FT /note="Interactions with LRPAP1 and NGFB" FT /evidence="ECO:0000250" FT REGION 777..825 FT /note="Golgi to endosome transport and interactions with FT GGA1 and GGA2" FT /evidence="ECO:0000250" FT REGION 804..825 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 785..790 FT /note="Endocytosis signal" FT /evidence="ECO:0000255" FT MOTIF 820..824 FT /note="DXXLL motif involved in the interaction with GGA1" FT /evidence="ECO:0000250|UniProtKB:Q99523" FT COMPBIAS 810..825 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 809 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99523" FT MOD_RES 813 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99523" FT MOD_RES 819 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT LIPID 781 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q99523" FT CARBOHYD 96 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 404 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 580 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 682 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 84..554 FT /evidence="ECO:0000250" FT DISULFID 255..275 FT /evidence="ECO:0000250" FT DISULFID 446..456 FT /evidence="ECO:0000250" FT DISULFID 610..649 FT /evidence="ECO:0000250" FT DISULFID 632..664 FT /evidence="ECO:0000250" FT DISULFID 666..721 FT /evidence="ECO:0000250" FT DISULFID 673..686 FT /evidence="ECO:0000250" FT DISULFID 700..738 FT /evidence="ECO:0000250" FT VAR_SEQ 748 FT /note="Q -> QDSRPQGHSLSQNPAPPPLGYTENTHFLSPTQKQ (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_016650" FT CONFLICT 315 FT /note="V -> E (in Ref. 1; AAF22639)" FT /evidence="ECO:0000305" FT HELIX 92..95 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 98..103 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 108..119 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 121..128 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:5NNI" FT STRAND 139..147 FT /evidence="ECO:0007829|PDB:5NMR" FT HELIX 156..159 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 162..165 FT /evidence="ECO:0007829|PDB:5NMT" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 170..172 FT /evidence="ECO:0007829|PDB:5NMR" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:5NMT" FT STRAND 180..184 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 194..200 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 206..209 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 214..216 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 219..221 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 224..232 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 237..242 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 248..259 FT /evidence="ECO:0007829|PDB:5NMR" FT HELIX 261..263 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 265..269 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:5NMR" FT TURN 275..280 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 281..289 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 295..307 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 310..316 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 318..321 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 323..330 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 349..354 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 359..364 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 366..377 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 384..393 FT /evidence="ECO:0007829|PDB:5NMR" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:5NMT" FT STRAND 412..417 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 423..430 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 436..438 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 457..460 FT /evidence="ECO:0007829|PDB:5NMR" FT HELIX 463..467 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 480..482 FT /evidence="ECO:0007829|PDB:5NNI" FT STRAND 486..495 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 502..512 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 514..519 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 521..526 FT /evidence="ECO:0007829|PDB:5NMR" FT HELIX 527..529 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 531..536 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 538..540 FT /evidence="ECO:0007829|PDB:5NMT" FT STRAND 544..550 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 556..559 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 565..571 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 579..588 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 589..592 FT /evidence="ECO:0007829|PDB:5ZNN" FT STRAND 593..601 FT /evidence="ECO:0007829|PDB:5NMR" FT TURN 603..605 FT /evidence="ECO:0007829|PDB:5NMR" FT HELIX 612..614 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 615..619 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 623..626 FT /evidence="ECO:0007829|PDB:5NMT" FT TURN 628..631 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 636..643 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 659..663 FT /evidence="ECO:0007829|PDB:5NMR" FT HELIX 668..670 FT /evidence="ECO:0007829|PDB:5NMR" FT STRAND 671..673 FT /evidence="ECO:0007829|PDB:5NMT" FT HELIX 690..692 FT /evidence="ECO:0007829|PDB:5NMT" FT STRAND 693..695 FT /evidence="ECO:0007829|PDB:5ZNN" FT STRAND 697..701 FT /evidence="ECO:0007829|PDB:5NMT" FT STRAND 704..715 FT /evidence="ECO:0007829|PDB:5NMT" FT STRAND 729..737 FT /evidence="ECO:0007829|PDB:5NMT" SQ SEQUENCE 825 AA; 91200 MW; 9A7A73C6FE1C8201 CRC64; MERPRGAADG LLRWPLGLLL LLQLLPPAAV GQDRLDAPPP PAPPLLRWAG PVGVSWGLRA AAPGGPVPRA GRWRRGAPAE DQDCGRLPDF IAKLTNNTHQ HVFDDLSGSV SLSWVGDSTG VILVLTTFQV PLVIVSFGQS KLYRSEDYGK NFKDITNLIN NTFIRTEFGM AIGPENSGKV ILTAEVSGGS RGGRVFRSSD FAKNFVQTDL PFHPLTQMMY SPQNSDYLLA LSTENGLWVS KNFGEKWEEI HKAVCLAKWG PNNIIFFTTH VNGSCKADLG ALELWRTSDL GKTFKTIGVK IYSFGLGGRF LFASVMADKD TTRRIHVSTD QGDTWSMAQL PSVGQEQFYS ILAANEDMVF MHVDEPGDTG FGTIFTSDDR GIVYSKSLDR HLYTTTGGET DFTNVTSLRG VYITSTLSED NSIQSMITFD QGGRWEHLRK PENSKCDATA KNKNECSLHI HASYSISQKL NVPMAPLSEP NAVGIVIAHG SVGDAISVMV PDVYISDDGG YSWAKMLEGP HYYTILDSGG IIVAIEHSNR PINVIKFSTD EGQCWQSYVF TQEPIYFTGL ASEPGARSMN ISIWGFTESF ITRQWVSYTV DFKDILERNC EEDDYTTWLA HSTDPGDYKD GCILGYKEQF LRLRKSSVCQ NGRDYVVAKQ PSVCPCSLED FLCDFGYFRP ENASECVEQP ELKGHELEFC LYGKEEHLTT NGYRKIPGDK CQGGMNPARE VKDLKKKCTS NFLNPTKQNS KSNSVPIILA IVGLMLVTVV AGVLIVKKYV CGGRFLVHRY SVLQQHAEAD GVEALDSTSH AKSGYHDDSD EDLLE //