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Identification
HMDB Protein ID HMDBP10753
Secondary Accession Numbers
  • 17020
Name Sortilin
Synonyms
  1. 100 kDa NT receptor
  2. Glycoprotein 95
  3. Gp95
  4. NT3
  5. NTR3
  6. Neurotensin receptor 3
Gene Name SORT1
Protein Type Unknown
Biological Properties
General Function Involved in enzyme binding
Specific Function Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Cellular Location
  1. Cell membrane
  2. Endosome membrane
  3. Membrane
  4. Endoplasmic reticulum membrane
  5. Golgi apparatus
  6. Golgi stack membrane
  7. Single-pass type I membrane protein
  8. Single-pass type I membrane protein
  9. Lysosome membrane
  10. Lysosome membrane
  11. Extracellular side
  12. Single-pass type I membrane protein (Potential)
  13. Single-pass type I membrane protein (Potential)
  14. Single-pass type I membrane protein (Potential)
  15. Single-pass type I membrane protein (Potential)
  16. Single-pass type I membrane protein (Potential)
  17. Single-pass type I membrane protein (Potential)
  18. Nucleus membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 1p13.3|1p21.3-p13.1
SNPs SORT1
Gene Sequence
>2496 bp
ATGGAGCGGCCCTGGGGAGCTGCGGACGGCCTCTCGCGCTGGCCCCATGGCCTCGGCCTC
CTCCTCCTCCTGCAGCTGCTGCCGCCGTCGACCCTCAGCCAGGACCGGCTGGACGCGCCG
CCGCCGCCCGCTGCGCCGCTGCCGCGCTGGTCTGGCCCCATCGGGGTGAGCTGGGGGCTG
CGGGCGGCCGCAGCCGGGGGCGCGTTTCCCCGCGGCGGCCGTTGGCGTCGCAGCGCGCCG
GGCGAGGACGAGGAGTGCGGCCGGGTCCGGGACTTCGTCGCCAAGCTGGCCAACAACACG
CACCAGCATGTGTTTGATGATCTCAGAGGCTCAGTATCCTTGTCCTGGGTTGGAGATAGC
ACTGGGGTCATTCTAGTCTTGACTACCTTCCATGTACCACTGGTAATTATGACTTTTGGA
CAGTCCAAGCTATATCGAAGTGAGGATTATGGGAAGAACTTTAAGGATATTACAGATCTC
ATCAATAACACCTTTATTCGGACTGAATTTGGCATGGCTATTGGTCCTGAGAACTCTGGA
AAGGTGGTGTTAACAGCAGAGGTGTCTGGAGGAAGTCGTGGAGGAAGAATCTTTAGATCA
TCAGATTTTGCGAAGAATTTTGTGCAAACAGATCTCCCTTTTCATCCTCTCACTCAGATG
ATGTATAGCCCTCAGAATTCTGATTATCTTTTAGCTCTCAGCACTGAAAATGGCCTGTGG
GTGTCCAAGAATTTTGGGGGAAAATGGGAAGAAATCCACAAAGCAGTATGTTTGGCCAAA
TGGGGATCAGACAACACCATCTTCTTTACAACCTATGCAAATGGCTCCTGCAAAGCTGAC
CTTGGGGCTCTGGAATTATGGAGAACTTCAGACTTGGGAAAAAGCTTCAAAACTATTGGT
GTGAAAATCTACTCATTTGGTCTTGGGGGACGTTTCCTTTTTGCCTCTGTGATGGCTGAT
AAGGATACAACAAGAAGGATCCACGTTTCAACAGATCAAGGGGACACATGGAGCATGGCC
CAGCTCCCCTCCGTGGGACAGGAACAGTTCTATTCTATTCTGGCAGCAAATGATGACATG
GTATTCATGCATGTAGATGAACCTGGAGACACTGGGTTTGGCACAATCTTTACCTCAGAT
GATCGAGGCATTGTCTATTCCAAGTCTTTGGACCGACATCTCTACACTACCACAGGCGGA
GAGACGGACTTTACCAACGTGACCTCCCTCCGCGGCGTCTACATAACAAGCGTGCTCTCC
GAAGATAATTCTATCCAGACCATGATCACTTTTGACCAAGGAGGAAGGTGGACGCACCTG
AGGAAGCCTGAAAACAGTGAATGTGATGCTACAGCAAAAAACAAGAATGAGTGCAGCCTT
CATATTCATGCTTCCTACAGCATCTCCCAGAAACTGAATGTTCCAATGGCCCCACTCTCA
GAGCCGAATGCCGTAGGCATTGTCATTGCTCATGGTAGCGTGGGGGATGCCATCTCAGTG
ATGGTTCCAGATGTGTACATCTCAGATGATGGGGGTTACTCCTGGACAAAGATGCTGGAA
GGACCCCACTATTACACCATCCTGGATTCTGGAGGCATCATTGTGGCCATTGAGCACAGC
AGCCGTCCTATCAATGTGATTAAGTTCTCCACAGACGAAGGTCAATGCTGGCAAACCTAC
ACGTTCACCAGGGACCCCATCTATTTCACTGGCCTAGCTTCAGAACCTGGAGCTAGGTCC
ATGAATATCAGCATTTGGGGCTTCACAGAATCTTTCCTGACCAGCCAGTGGGTCTCCTAC
ACCATTGATTTTAAAGATATCCTTGAAAGGAACTGTGAAGAGAAGGACTATACCATATGG
CTGGCACACTCCACAGACCCTGAAGATTATGAAGATGGCTGCATTTTGGGCTACAAAGAA
CAGTTTCTGCGGCTACGCAAGTCATCCGTGTGTCAGAATGGTCGAGACTATGTTGTGACC
AAGCAGCCCTCCATCTGCCTCTGTTCCCTGGAGGACTTTCTCTGTGATTTTGGCTACTAC
CGTCCAGAAAATGACTCCAAGTGTGTGGAACAGCCAGAACTGAAGGGCCACGACCTGGAG
TTTTGTCTGTACGGAAGAGAAGAACACCTAACAACAAATGGGTACCGGAAAATTCCAGGG
GACAAATGCCAGGGTGGGGTAAATCCAGTTCGAGAAGTAAAAGACTTGAAAAAGAAATGC
ACAAGCAACTTTTTGAGTCCGGAAAAACAGAATTCCAAGTCAAATTCTGTTCCAATTATC
CTGGCCATCGTGGGATTGATGCTGGTCACAGTCGTAGCAGGAGTGCTCATTGTGAAGAAA
TATGTCTGTGGGGGAAGGTTCCTGGTGCATCGATACTCTGTGCTGCAGCAGCATGCAGAG
GCCAATGGTGTGGATGGTGTGGATGCTTTGGACACAGCCTCCCACACTAATAAAAGTGGT
TATCATGATGACTCAGATGAGGACCTCTTGGAATAG
Protein Properties
Number of Residues 831
Molecular Weight 92066.9
Theoretical pI 5.51
Pfam Domain Function
Signals
  • 1-33
Transmembrane Regions
  • 756-778
Protein Sequence
>Sortilin
MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGL
RAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDS
TGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSG
KVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLW
VSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIG
VKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDM
VFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLS
EDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLS
EPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHS
SRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSY
TIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVT
KQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPG
DKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKK
YVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE
GenBank ID Protein 55959339
UniProtKB/Swiss-Prot ID Q99523
UniProtKB/Swiss-Prot Entry Name SORT_HUMAN
PDB IDs Not Available
GenBank Gene ID AL390252
GeneCard ID SORT1
GenAtlas ID SORT1
HGNC ID HGNC:11186
References
General References
  1. Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, Aebersold R, Watts JD: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009 Apr;27(4):378-86. doi: 10.1038/nbt.1532. Epub 2009 Apr 6. [PubMed:19349973 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414 ]
  4. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  5. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087 ]
  6. Lewandrowski U, Moebius J, Walter U, Sickmann A: Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. Mol Cell Proteomics. 2006 Feb;5(2):226-33. Epub 2005 Oct 31. [PubMed:16263699 ]
  7. Takatsu H, Katoh Y, Shiba Y, Nakayama K: Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains. J Biol Chem. 2001 Jul 27;276(30):28541-5. Epub 2001 Jun 4. [PubMed:11390366 ]
  8. Shiba T, Takatsu H, Nogi T, Matsugaki N, Kawasaki M, Igarashi N, Suzuki M, Kato R, Earnest T, Nakayama K, Wakatsuki S: Structural basis for recognition of acidic-cluster dileucine sequence by GGA1. Nature. 2002 Feb 21;415(6874):937-41. [PubMed:11859376 ]
  9. Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM: The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J. 2001 May 1;20(9):2180-90. [PubMed:11331584 ]
  10. Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, Roigaard H, Gliemann J, Madsen P, Moestrup SK: Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem. 1997 Feb 7;272(6):3599-605. [PubMed:9013611 ]
  11. Mazella J, Zsurger N, Navarro V, Chabry J, Kaghad M, Caput D, Ferrara P, Vita N, Gully D, Maffrand JP, Vincent JP: The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. J Biol Chem. 1998 Oct 9;273(41):26273-6. [PubMed:9756851 ]
  12. Munck Petersen C, Nielsen MS, Jacobsen C, Tauris J, Jacobsen L, Gliemann J, Moestrup SK, Madsen P: Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding. EMBO J. 1999 Feb 1;18(3):595-604. [PubMed:9927419 ]
  13. Tauris J, Ellgaard L, Jacobsen C, Nielsen MS, Madsen P, Thogersen HC, Gliemann J, Petersen CM, Moestrup SK: The carboxy-terminal domain of the receptor-associated protein binds to the Vps10p domain of sortilin. FEBS Lett. 1998 Jun 5;429(1):27-30. [PubMed:9657377 ]
  14. Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM: Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J Biol Chem. 1999 Mar 26;274(13):8832-6. [PubMed:10085125 ]
  15. Navarro V, Vincent JP, Mazella J: Shedding of the luminal domain of the neurotensin receptor-3/sortilin in the HT29 cell line. Biochem Biophys Res Commun. 2002 Nov 15;298(5):760-4. [PubMed:12419319 ]
  16. Maeda S, Nobukuni T, Shimo-Onoda K, Hayashi K, Yone K, Komiya S, Inoue I: Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization. J Cell Physiol. 2002 Oct;193(1):73-9. [PubMed:12209882 ]
  17. Lefrancois S, Zeng J, Hassan AJ, Canuel M, Morales CR: The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin. EMBO J. 2003 Dec 15;22(24):6430-7. [PubMed:14657016 ]
  18. Martin S, Vincent JP, Mazella J: Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia. J Neurosci. 2003 Feb 15;23(4):1198-205. [PubMed:12598608 ]
  19. Morinville A, Martin S, Lavallee M, Vincent JP, Beaudet A, Mazella J: Internalization and trafficking of neurotensin via NTS3 receptors in HT29 cells. Int J Biochem Cell Biol. 2004 Nov;36(11):2153-68. [PubMed:15313463 ]
  20. Westergaard UB, Sorensen ES, Hermey G, Nielsen MS, Nykjaer A, Kirkegaard K, Jacobsen C, Gliemann J, Madsen P, Petersen CM: Functional organization of the sortilin Vps10p domain. J Biol Chem. 2004 Nov 26;279(48):50221-9. Epub 2004 Sep 10. [PubMed:15364913 ]
  21. Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM: Sortilin is essential for proNGF-induced neuronal cell death. Nature. 2004 Feb 26;427(6977):843-8. [PubMed:14985763 ]
  22. Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, Kraemer RT, Nykjaer A, Hempstead BL: ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci. 2005 Jun 1;25(22):5455-63. [PubMed:15930396 ]
  23. Chen ZY, Ieraci A, Teng H, Dall H, Meng CX, Herrera DG, Nykjaer A, Hempstead BL, Lee FS: Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J Neurosci. 2005 Jun 29;25(26):6156-66. [PubMed:15987945 ]
  24. Quistgaard EM, Madsen P, Groftehauge MK, Nissen P, Petersen CM, Thirup SS: Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain. Nat Struct Mol Biol. 2009 Jan;16(1):96-8. doi: 10.1038/nsmb.1543. Epub 2009 Jan 4. [PubMed:19122660 ]