Sortilin 1

Sortilin 1

Rendering based on PDB 3F6K.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsSORT1 ; Gp95; LDLCQ6; NT3
External IDsOMIM: 602458 MGI: 1338015 HomoloGene: 136097 ChEMBL: 3091 GeneCards: SORT1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez627220661
EnsemblENSG00000134243ENSMUSG00000068747
UniProtQ99523Q6PHU5
RefSeq (mRNA)NM_001205228NM_001271599
RefSeq (protein)NP_001192157NP_001258528
Location (UCSC)Chr 1:
109.85 – 109.94 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. ↑ 1.0 1.1 "Entrez Gene: SORT1 sortilin 1".
  2. ↑ Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M et al. (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 et al. (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 et al. (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. ↑ 5.0 5.1 Jacobsen L, Madsen P, Nielsen MS, Geraerts WP, Gliemann J, Smit AB et al. (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 et al. (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 et al. (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 et al. (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. Vancouver style error (help)
  • Mazella J, Zsürger N, Navarro V, Chabry J, Kaghad M, Caput D et al. (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. Vancouver style error (help)
  • Munck Petersen C, Nielsen MS, Jacobsen C, Tauris J, Jacobsen L, Gliemann J et al. (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 et al. (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 et al. (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 et al. (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.