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FLASH GENE
Symbol SORT1 contributors: shn/ - updated : 11-10-2017
HGNC name sortilin 1
HGNC id 11186
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