Seroatlas · Human Serome Atlas

SORCS3

VPS10 domain-containing receptor SorCS3

Also known as: KIAA1059, SORC3_HUMAN, SORCS

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9UPU3
Gene: SORCS3
Ensembl: ENSG00000156395
Chromosome: 10
Canonical length: 1222 aa
Protein class: Predicted intracellular proteins, Predicted membrane proteins, Transporters
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

1222 residues, UniProt reviewed canonical sequence.

>Q9UPU3|SORCS3
     1  MEAARTERPA GRPGAPLVRT GLLLLSTWVL AGAEITWDAT GGPGRPAAPA SRPPALSPLS
    61  PRAVASQWPE ELASARRAAV LGRRAGPELL PQQGGGRGGE MQVEAGGTSP AGERRGRGIP
   121  APAKLGGARR SRRAQPPITQ ERGDAWATAP ADGSRGSRPL AKGSREEVKA PRAGGSAAED
   181  LRLPSTSFAL TGDSAHNQAM VHWSGHNSSV ILILTKLYDF NLGSVTESSL WRSTDYGTTY
   241  EKLNDKVGLK TVLSYLYVNP TNKRKIMLLS DPEMESSILI SSDEGATYQK YRLTFYIQSL
   301  LFHPKQEDWV LAYSLDQKLY SSMDFGRRWQ LMHERITPNR FYWSVAGLDK EADLVHMEVR
   361  TTDGYAHYLT CRIQECAETT RSGPFARSID ISSLVVQDEY IFIQVTTSGR ASYYVSYRRE
   421  AFAQIKLPKY SLPKDMHIIS TDENQVFAAV QEWNQNDTYN LYISDTRGIY FTLAMENIKS
   481  SRGLMGNIII ELYEVAGIKG IFLANKKVDD QVKTYITYNK GRDWRLLQAP DVDLRGSPVH
   541  CLLPFCSLHL HLQLSENPYS SGRISSKETA PGLVVATGNI GPELSYTDIG VFISSDGGNT
   601  WRQIFDEEYN VWFLDWGGAL VAMKHTPLPV RHLWVSFDEG HSWDKYGFTS VPLFVDGALV
   661  EAGMETHIMT VFGHFSLRSE WQLVKVDYKS IFSRHCTKED YQTWHLLNQG EPCVMGERKI
   721  FKKRKPGAQC ALGRDHSGSV VSEPCVCANW DFECDYGYER HGESQCVPAF WYNPASPSKD
   781  CSLGQSYLNS TGYRRIVSNN CTDGLREKYT AKAQMCPGKA PRGLHVVTTD GRLVAEQGHN
   841  ATFIILMEEG DLQRTNIQLD FGDGIAVSYA NFSPIEDGIK HVYKSAGIFQ VTAYAENNLG
   901  SDTAVLFLHV VCPVEHVHLR VPFVAIRNKE VNISAVVWPS QLGTLTYFWW FGNSTKPLIT
   961  LDSSISFTFL AEGTDTITVQ VAAGNALIQD TKEIAVHEYF QSQLLSFSPN LDYHNPDIPE
  1021  WRKDIGNVIK RALVKVTSVP EDQILIAVFP GLPTSAELFI LPPKNLTERR KGNEGDLEQI
  1081  VETLFNALNQ NLVQFELKPG VQVIVYVTQL TLAPLVDSSA GHSSSAMLML LSVVFVGLAV
  1141  FLIYKFKRKI PWINIYAQVQ HDKEQEMIGS VSQSENAPKI TLSDFTEPEE LLDKELDTRV
  1201  IGGIATIANS ESTKEIPNCT SV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SORCS3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.37
Highest tissue expression: 7.5 nTPM

Expression across tissuesHPA

Tissue

basal ganglia: 7.5 nTPM
cerebral cortex: 6.8 nTPM
hypothalamus: 5.8 nTPM
hippocampal formation: 3.3 nTPM
amygdala: 3.2 nTPM
pituitary gland: 2.3 nTPM

Single-cell type

oligodendrocyte progenitor cells: 593 nCPM
brain inhibitory neurons: 384 nCPM
adrenal medulla cells: 223 nCPM
somatotrophs: 196 nCPM
brain excitatory neurons: 191 nCPM
thyrotrophs: 181 nCPM

Immune cell

naive CD4 T-cell: 0.5 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM

Brain region

hypothalamus: 30 nTPM
cerebral cortex: 21 nTPM
basal ganglia: 19 nTPM
hippocampal formation: 16 nTPM
white matter: 15 nTPM
midbrain: 14 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.47
gnomAD pLI: 0
gnomAD missense Z: 1.52
DepMap mean gene effect: -0.02
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

neuropeptide receptor activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SORCS3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SORCS3 as an antibody target. Whether an autoantibody or antibody against SORCS3 could matter depends on whether native SORCS3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SORCS3 is annotated at the cell surface, where native SORCS3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SORCS3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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