SORT_MOUSE
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 03-AUG-2022, entry version 162.
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, Spleen,
RC 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}.
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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.ENSMUSP00000099692; -.
DR BindingDB; Q6PHU5; -.
DR GlyConnect; 2734; 6 N-Linked glycans (3 sites).
DR GlyGen; Q6PHU5; 7 sites, 5 N-linked glycans (3 sites).
DR iPTMnet; Q6PHU5; -.
DR PhosphoSitePlus; Q6PHU5; -.
DR SwissPalm; Q6PHU5; -.
DR jPOST; Q6PHU5; -.
DR MaxQB; Q6PHU5; -.
DR PaxDb; Q6PHU5; -.
DR PeptideAtlas; Q6PHU5; -.
DR PRIDE; Q6PHU5; -.
DR ProteomicsDB; 261549; -. [Q6PHU5-1]
DR ProteomicsDB; 261550; -. [Q6PHU5-2]
DR Antibodypedia; 1533; 286 antibodies from 32 providers.
DR DNASU; 20661; -.
DR Ensembl; ENSMUST00000102632; ENSMUSP00000099692; ENSMUSG00000068747. [Q6PHU5-1]
DR Ensembl; ENSMUST00000135636; ENSMUSP00000123564; ENSMUSG00000068747. [Q6PHU5-2]
DR GeneID; 20661; -.
DR KEGG; mmu:20661; -.
DR UCSC; uc008qyr.2; mouse. [Q6PHU5-1]
DR UCSC; uc008qys.2; mouse. [Q6PHU5-2]
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; FAPFYSV; -.
DR OrthoDB; 1046610at2759; -.
DR PhylomeDB; Q6PHU5; -.
DR TreeFam; TF324918; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR BioGRID-ORCS; 20661; 0 hits in 71 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 247 other tissues.
DR Genevisible; Q6PHU5; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
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:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
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:0014902; P:myotube differentiation; IMP:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:MGI.
DR GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; ISO: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:0006892; P:post-Golgi vesicle-mediated transport; IBA:GO_Central.
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; 2.130.10.10; -; 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 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 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
