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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	10q25.1      Physical location : 106.400.858 - 107.024.993
Synonym name	VPS10 domain receptor protein SORCS3
Synonym symbol(s)	KIAA1059, SORCS, RP11-107L7.1

DNA

TYPE	functioning gene
SPECIAL FEATURE	overlapping, gene in gene
STRUCTURE	624.14 kb     27 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D10S1268 - D10S540 - SORCS3 - D10S530 - D10S254 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_014978 27 - 5757 NP_055793 - 1222 Cerebral cortex - Neurons in layers 5 and 6 Hippocampus - Pyramidal neurons in CA1 Cerebellum - Basket cells and stellate cells Olfactory bulbs - mitral cell layer Amygdala 2018 30586538

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain diencephalon hypothalamus   highly Homo sapiens   brain limbic system hippocampus   highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central     highly

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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