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FLASH GENE
Symbol SORCS3 contributors: shn/npt - updated : 07-07-2020
HGNC name sortilin-related VPS10 domain containing receptor 3
HGNC id 16699
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal VPS10 domain
  • leucine rich repeat
  • transmembrane domain
  • intracellular domain
  • 9 BNR repeats
  • functional tyrosine-based motifs (Y10AQV/m13)
  • SORCS3 cytoplasmic domain targets receptors to the Golgi apparatus, vesicular structures, and the cell surface
    • HOMOLOGY
    interspecies ortholog to Sorcs3, Rattus norvegicus
    ortholog to Sorcs3, Mus musculus
    ortholog to SORCS3, pan troglodytes
    Homologene
    FAMILY
  • Vps10p-domain receptor family
    • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • single-pass type I membrane protein
  • is localized to vesicular structures
    • basic FUNCTION
  • functioning as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface
  • may also mediate transport from the endoplasmic reticulum to the Golgi
  • with SORCS2 and SORCS3, have diverse, but partly overlapping functions in the developing and mature central nervous system (Hermey 2004)
  • SORL1, SORCS1, SORCS2, and SORCS3 play pleiotropic functions in protein trafficking and intracellular and intercellular signaling in neuronal and non-neuronal cells
  • SORCS3 is likely a novel factor modulating aversive memory extinction
  • sortilin, SORL1, SORCS1, SORCS2, and SORCS3) modulate neurotrophic signaling pathways
  • role for SORCS3 in controlling proper positioning and mobility of glutamate receptors in the postsynaptic density
  • SORCS1 and SORCS3 control energy balance and orexigenic peptide production
  • important role of SORCS3 in the central nervous system
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    signaling
    a component
  • eight intrachain disulfide bonds
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ability of SORCS3 to functionally interact with PICK1, an adaptor that sorts glutamate receptors at the postsynapse
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    a neurological phenotype including infantile spasms, intellectual disability, global developmental delay, microcephaly, hypotonia, spastic quadriplegia, and delayed myelination
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Sorcs3-deficient mice suffer from deficits in behavioral activities associated with hippocampal long-term depression (LTD), particularly from an accelerated extinction of fear memory