Sortilin 1

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Sortilin 1
Protein SORT1 PDB 3F6K.png
Rendering based on PDB 3F6K.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SORT1 ; Gp95; LDLCQ6; NT3
External IDs OMIM602458 MGI1338015 HomoloGene136097 ChEMBL: 3091 GeneCards: SORT1 Gene
RNA expression pattern
PBB GE SORT1 212797 at tn.png
PBB GE SORT1 212807 s at tn.png
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:
109.85 – 109.94 Mb
Chr 3:
108.28 – 108.36 Mb
PubMed search [1] [2]

Sortilin (SorL1) 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]

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[edit]

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

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: SORT1 sortilin 1". 
  2. ^ Teslovich TM, Musunuru K, Smith AV, et al. (August 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, et al. (August 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, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  5. ^ a b Jacobsen, Linda; Madsen Peder; Nielsen Morten S; Geraerts Wijnand P M; Gliemann Jørgen; Smit August B; Petersen Claus M (January 2002). "The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding". FEBS Lett. (Netherlands) 511 (1-3): 155–8. doi:10.1016/S0014-5793(01)03299-9. ISSN 0014-5793. PMID 11821067. 
  6. ^ Nielsen, M S; Madsen P; Christensen E I; Nykjaer A; Gliemann J; Kasper D; Pohlmann R; Petersen C M (May 2001). "The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein". EMBO J. (England) 20 (9): 2180–90. doi:10.1093/emboj/20.9.2180. ISSN 0261-4189. PMC 125444. PMID 11331584. 

Further reading[edit]