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FLASH GENE
Symbol SORT1 contributors: shn/ - updated : 11-10-2017
HGNC name sortilin 1
HGNC id 11186
DNA
TYPE functioning gene
STRUCTURE 88.37 kb     20 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map pter - D1S2778 - D1S2792 - SORT1 - D1S2651 - D1S221 - cen
Physical map
FLJ30525 1p13.3 hypothetical protein FLJ30525 FLJ10330 1p13.3 hypothetical protein FLJ10330 FLJ35838 1p13.3 hypothetical protein FLJ35838 STXBP3 1p21-p13.3 syntaxin binding protein 3 MGC26989 1p13.3 hypothetical protein MGC26989 LGN MCLC 1p13.2 hypothetical protein MGC26989 KIAA0893 1p13.3 hypothetical protein MGC26989 NDUFB3P1 1 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa pseudogene 1 AD-020 1p13.3 protein x 013 LOC391065 1 similar to poly(rC) binding protein 1; heterogenous nuclear ribonucleoprotein X; poly(rC)-binding protein 1; alpha-CP1; nucleic acid binding protein sub 2.3; heterogenous nuclear ribonucleoprotein E1 LOC127003 1p13.3 similar to CG5435-PA KIAA1324 1p13.2 maba1 SARS 1p13 seryl-tRNA synthetase CELSR2 1p21.16p13.3 cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila) DDA3 1p13.2 differential display and activated by p53 LOC343263 1p13.2 similar to Myosin-binding protein H (MyBP-H) (H-protein) SORT1 1p21.3-p13.1 Sortilin 1 PSMA5 1p13 proteasome (prosome, macropain) subunit, alpha type, 5 LOC388660 1 similar to mitsugumin29 LOC284612 1p13.2 hypothetical protein LOC284612 MGC46534 1p13.2 hypothetical protein MGC46534 FLJ39035 1p13.2 hypothetical protein FLJ39035 KIAA1163 1p13.2 amphoterin-induced gene GPR61 1p13.1 G protein-coupled receptor 61 GNAI3 1p13 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 GNAT2 1p13 guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 2 AMPD2 1p21-p13 adenosine monophosphate deaminase 2 (isoform L) GSTM4 1p13.3 glutathione S-transferase M4 GSTM2 1p13.3 glutathione S-transferase M2 (muscle) GSTM1 1p13.3 glutathione S-transferase M1 GSTM5 1p13.3 glutathione S-transferase M5 GSTM3 1p13.3 glutathione S-transferase M3 (brain) EPS8L3 1p13.2-p11 EPS8-like 3
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
20 - 7018 95 831 Cerebral - cortex Pyramidal neurons and glia Hippocampus - Granule cells in the dentate gyrus and pyramidal neurons in CA1–CA3 Cerebellum - Purkinje cells Retina - Postmitotic retinal ganglion cells PNS - Sympathetic neurons and dorsal root ganglia 2009 19002190
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Endocrinepancreas   moderately
 thyroid   highly
Nervousbrain   highly
 spinal cord   highly
Reproductivefemale systemplacenta  highly
 male systemprostate  moderately
Respiratorylung   lowly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal furin cleavage site immediately preceding the N terminus luminal region determined in the purified protein
  • VPS10 domain
  • a transmembrane domain
  • C terminal intracellular domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Sort1, Rattus norvegicus
    ortholog to Sort1, Mus musculus
    ortholog to SORT1, Pan troglodytes
    ortholog to sort1l, Danio rerio
    Homologene
    FAMILY
  • Vps10p-domain receptor family
  • CATEGORY signaling hormone , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    text trans Golgi network
    basic FUNCTION
  • involved in endosomal protein sorting, acting as a receptor for neurotensin and as a clearance receptor on the cell surface
  • playing an essential role for NGFB-induced neuronal cell death
  • having distinct roles in pro-neurotrophin induced apoptotic signaling in pathological conditions, but also in specific stages of neuronal development and aging
  • having physiological role as a death-inducing pathway in the central and peripheral nervous system
  • functioning as an alternative sorting receptor to the M6PR for these soluble hydrolases
  • acts as a co-receptor and molecular switch governing the p75NTR-mediated pro-apoptotic signal induced by proNGF
  • essential, but also sufficient for biogenesis of GSVs and acquisition of insulin responsiveness in adipose cells
  • sortilin pathway has distinct roles in pro-neurotrophin-induced apoptotic signaling in pathological conditions, but also in specific stages of neuronal development and aging
  • involved in development of the insulin-responsive glucose transport system in myocytes and directly involved in muscle differentiation via modulation of proNGF-p75NTR
  • regulator of neuronal viability and function through the regulation of both protein transport and signal transduction
  • binds apolipoproteins and potentially modulates lipoprotein metabolism, which might also affect neuronal function
  • important regulator of GRN levels
  • facilitates the signaling of all helical type 1 cytokines, which engage the IL6ST/LIF receptor complex
  • new function for sortilin as a modulator of BACE1 retrograde trafficking and subsequent generation of Abeta
  • transports BACE1 from the endosome to the TGN
  • plays a unique role in regulating BACE1-mediated cleavage of APP through regulating the subcellular distribution of BACE1
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Golgi-localizing, gamma-adaptin ear homology domain, ARF-binding (GGA)
  • the VHS domain of the GGA2 sorting protein
  • Receptor-associated protein (RAP)
  • binds and mediates degradation of lipoprotein lipase (LPL)
  • pro-nerve growth factor (proNGF)
  • interacting with CNTF (CNTF, and related ligands targeting CNTFR{alpha}, binds to sortilin with high affinity
  • interacts with BACE1 and a sortilin construct lacking its cytoplasmic domain, which contains putative retromer sorting motifs, remains bound to BACE1
  • binds to the receptor DLK1, an inhibitor of adipocyte differentiation, and the overexpression of sortilin prevents DLK1 downregulation, leading to enhanced inhibition of adipogenesis
  • liver carboxylesterase 1 (CES1) is a novel SORT1-interacting protein
  • SORT1 may regulate CES1 lysosomal targeting and degradation and SORT1 deficiency resulted in higher liver CES1 protein abundance
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    age-down regulated in the frontal cortex
    Susceptibility
  • associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides
  • to myocardial infarction
  • Variant & Polymorphism other
  • strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction
  • common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1, increasing the risk of myocardial infarction
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    therapeutic inhibition of SORT1 may be beneficial in improving hepatic cholesterol homeostasis in metabolic and inflammatory liver diseases
    ANIMAL & CELL MODELS
  • SORT1-knockout mice have reduced levels of neuronal apoptosis in the developing retina, are protected against agedependent degeneration of sympathetic neurons and are
  • rescued from axotomy-induced death of corticospinal motor neurons
  • overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion