Sortilin 1

Sortilin 1

Rendering based on PDB 3F6K​.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SORT1 ; Gp95; LDLCQ6; NT3
External IDs OMIM: 602458 MGI: 1338015 HomoloGene: 136097 ChEMBL: 3091 GeneCards: SORT1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 6272 20661
Ensembl ENSG00000134243 ENSMUSG00000068747
UniProt Q99523 Q6PHU5
RefSeq (mRNA) NM_001205228 NM_001271599
RefSeq (protein) NP_001192157 NP_001258528
Location (UCSC) Chr 1:
109.31 – 109.4 Mb		 Chr 3:
108.28 – 108.36 Mb
PubMed search

Sortilin (Sort1) is a protein that in humans is encoded by the SORT1 gene.[1] The SORT1 locus shows the strongest association with serum lipoproteins of any genetic locus in the genome.[2] In hepatocytes, sortilin participates in the presecretory degradation of nascent VLDL particles.[3]

Function

This gene encodes a protein that is a multi-ligand type-1 receptor with similarity to the yeast carboxypeptidase Y sorting receptor Vps10 protein. The encoded protein, a trans-Golgi network (TGN) transmembrane protein, binds a number of unrelated ligands that participate in a wide range of cellular processes; however, it lacks the typical features of a signalling receptor. In the TGN, furin mediates the activation of the mature binding form. The encoded protein consists of a large luminal domain, a single transmembrane segment and short C-terminal cytoplasmic tail. The luminal domain contains a cysteine-rich region similar to two corresponding segments in the yeast Vps10p; the cytoplasmic tail is similar to the corresponding segment of the cation-independent mannose 6-phosphate receptor and the tail also interacts with the VHS domains of GGA (Golgi-associated, gamma-adaptin homologous, ARF-interacting) proteins.[1]

In melanocytic cells SORT1 gene expression may be regulated by MITF.[4]

Interactions

Sortilin 1 has been shown to interact with GGA1[5] and GGA2.[5][6]

See also

References

  1. 1 2 "Entrez Gene: SORT1 sortilin 1".
  2. ↑ Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O'Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PK, Lucas G, Luben R, Loos RJ, Lokki ML, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, König IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR, Janssens AC, Ingelsson E, Igl W, Kees Hovingh G, Hottenga JJ, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Döring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor HA, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S (Aug 2010). "Biological, clinical and population relevance of 95 loci for blood lipids". Nature 466 (7307): 707–13. doi:10.1038/nature09270. PMC 3039276. PMID 20686565.
  3. ↑ Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JP, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S, Rader DJ (Aug 2010). "From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus". Nature 466 (7307): 714–9. doi:10.1038/nature09266. PMC 3062476. PMID 20686566.
  4. ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
  5. 1 2 Jacobsen L, Madsen P, Nielsen MS, Geraerts WP, Gliemann J, Smit AB, Petersen CM (Jan 2002). "The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding". FEBS Letters 511 (1-3): 155–8. doi:10.1016/S0014-5793(01)03299-9. PMID 11821067.
  6. ↑ Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM (May 2001). "The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein". The EMBO Journal 20 (9): 2180–90. doi:10.1093/emboj/20.9.2180. PMC 125444. PMID 11331584.

Further reading

  • Vincent JP, Mazella J, Kitabgi P (Jul 1999). "Neurotensin and neurotensin receptors". Trends in Pharmacological Sciences 20 (7): 302–9. doi:10.1016/S0165-6147(99)01357-7. PMID 10390649. 
  • Mazella J (Jan 2001). "Sortilin/neurotensin receptor-3: a new tool to investigate neurotensin signaling and cellular trafficking?". Cellular Signalling 13 (1): 1–6. doi:10.1016/S0898-6568(00)00130-3. PMID 11257441. 
  • Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, Roigaard H, Gliemann J, Madsen P, Moestrup SK (Feb 1997). "Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography". The Journal of Biological Chemistry 272 (6): 3599–605. doi:10.1074/jbc.272.6.3599. PMID 9013611. 
  • Lin BZ, Pilch PF, Kandror KV (Sep 1997). "Sortilin is a major protein component of Glut4-containing vesicles". The Journal of Biological Chemistry 272 (39): 24145–7. doi:10.1074/jbc.272.39.24145. PMID 9305862. 
  • Tauris J, Ellgaard L, Jacobsen C, Nielsen MS, Madsen P, Thøgersen HC, Gliemann J, Petersen CM, Moestrup SK (Jun 1998). "The carboxy-terminal domain of the receptor-associated protein binds to the Vps10p domain of sortilin". FEBS Letters 429 (1): 27–30. doi:10.1016/S0014-5793(98)00559-6. PMID 9657377. 
  • Mazella J, Zsürger N, Navarro V, Chabry J, Kaghad M, Caput D, Ferrara P, Vita N, Gully D, Maffrand JP, Vincent JP (Oct 1998). "The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor". The Journal of Biological Chemistry 273 (41): 26273–6. doi:10.1074/jbc.273.41.26273. PMID 9756851. 
  • Munck Petersen C, Nielsen MS, Jacobsen C, Tauris J, Jacobsen L, Gliemann J, Moestrup SK, Madsen P (Feb 1999). "Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding". The EMBO Journal 18 (3): 595–604. doi:10.1093/emboj/18.3.595. PMC 1171152. PMID 9927419. 
  • Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM (Mar 1999). "Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase". The Journal of Biological Chemistry 274 (13): 8832–6. doi:10.1074/jbc.274.13.8832. PMID 10085125. 
  • Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM (May 2001). "The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein". The EMBO Journal 20 (9): 2180–90. doi:10.1093/emboj/20.9.2180. PMC 125444. PMID 11331584. 
  • Takatsu H, Katoh Y, Shiba Y, Nakayama K (Jul 2001). "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". The Journal of Biological Chemistry 276 (30): 28541–5. doi:10.1074/jbc.C100218200. PMID 11390366. 
  • Hampe W, Rezgaoui M, Hermans-Borgmeyer I, Schaller HC (Jun 2001). "The genes for the human VPS10 domain-containing receptors are large and contain many small exons". Human Genetics 108 (6): 529–36. doi:10.1007/s004390100504. PMID 11499680. 
  • Shiba T, Takatsu H, Nogi T, Matsugaki N, Kawasaki M, Igarashi N, Suzuki M, Kato R, Earnest T, Nakayama K, Wakatsuki S (Feb 2002). "Structural basis for recognition of acidic-cluster dileucine sequence by GGA1". Nature 415 (6874): 937–41. doi:10.1038/415937a. PMID 11859376. 
  • Maeda S, Nobukuni T, Shimo-Onoda K, Hayashi K, Yone K, Komiya S, Inoue I (Oct 2002). "Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization". Journal of Cellular Physiology 193 (1): 73–9. doi:10.1002/jcp.10151. PMID 12209882. 
  • Martin S, Navarro V, Vincent JP, Mazella J (Oct 2002). "Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line". Gastroenterology 123 (4): 1135–43. doi:10.1053/gast.2002.36000. PMID 12360476. 
  • Navarro V, Vincent JP, Mazella J (Nov 2002). "Shedding of the luminal domain of the neurotensin receptor-3/sortilin in the HT29 cell line". Biochemical and Biophysical Research Communications 298 (5): 760–4. doi:10.1016/S0006-291X(02)02564-0. PMID 12419319. 
  • Martin S, Vincent JP, Mazella J (Feb 2003). "Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia". The Journal of Neuroscience 23 (4): 1198–205. PMID 12598608. 
  • Lefrancois S, Zeng J, Hassan AJ, Canuel M, Morales CR (Dec 2003). "The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin". The EMBO Journal 22 (24): 6430–7. doi:10.1093/emboj/cdg629. PMC 291824. PMID 14657016. 
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