Seroatlas · Human Serome Atlas

SEMA4A

Semaphorin-4A

Also known as: CORD10, FLJ12287, SEM4A_HUMAN, SEMAB, SemB

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

Protein identityUniProt · HPA

UniProt accession: Q9H3S1
Gene: SEMA4A
Ensembl: ENSG00000196189
Chromosome: 1
Canonical length: 761 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

Canonical amino-acid sequenceUniProt

761 residues, UniProt reviewed canonical sequence.

>Q9H3S1|SEMA4A
     1  MALPALGLDP WSLLGLFLFQ LLQLLLPTTT AGGGGQGPMP RVRYYAGDER RALSFFHQKG
    61  LQDFDTLLLS GDGNTLYVGA REAILALDIQ DPGVPRLKNM IPWPASDRKK SECAFKKKSN
   121  ETQCFNFIRV LVSYNVTHLY TCGTFAFSPA CTFIELQDSY LLPISEDKVM EGKGQSPFDP
   181  AHKHTAVLVD GMLYSGTMNN FLGSEPILMR TLGSQPVLKT DNFLRWLHHD ASFVAAIPST
   241  QVVYFFFEET ASEFDFFERL HTSRVARVCK NDVGGEKLLQ KKWTTFLKAQ LLCTQPGQLP
   301  FNVIRHAVLL PADSPTAPHI YAVFTSQWQV GGTRSSAVCA FSLLDIERVF KGKYKELNKE
   361  TSRWTTYRGP ETNPRPGSCS VGPSSDKALT FMKDHFLMDE QVVGTPLLVK SGVEYTRLAV
   421  ETAQGLDGHS HLVMYLGTTT GSLHKAVVSG DSSAHLVEEI QLFPDPEPVR NLQLAPTQGA
   481  VFVGFSGGVW RVPRANCSVY ESCVDCVLAR DPHCAWDPES RTCCLLSAPN LNSWKQDMER
   541  GNPEWACASG PMSRSLRPQS RPQIIKEVLA VPNSILELPC PHLSALASYY WSHGPAAVPE
   601  ASSTVYNGSL LLIVQDGVGG LYQCWATENG FSYPVISYWV DSQDQTLALD PELAGIPREH
   661  VKVPLTRVSG GAALAAQQSY WPHFVTVTVL FALVLSGALI ILVASPLRAL RARGKVQGCE
   721  TLRPGEKAPL SREQHLQSPK ECRTSASDVD ADNNCLGTEV A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SEMA4A 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): 0.32
Highest tissue expression: 48 nTPM

Expression across tissuesHPA

Tissue

epididymis: 48 nTPM
bone marrow: 35 nTPM
esophagus: 31 nTPM
tonsil: 31 nTPM
skin: 30 nTPM
lymph node: 29 nTPM

Single-cell type

salivary myoepithelial cells: 859 nCPM
salivary basal cells: 646 nCPM
alveolar cells type 2: 516 nCPM
mast cells: 392 nCPM
transitional alveolar cells: 309 nCPM
epicardial cells: 248 nCPM

Immune cell

neutrophil: 211 nTPM
myeloid DC: 183 nTPM
intermediate monocyte: 133 nTPM
classical monocyte: 124 nTPM
eosinophil: 121 nTPM
non-classical monocyte: 77 nTPM

Brain region

hypothalamus: 56 nTPM
cerebral cortex: 48 nTPM
amygdala: 43 nTPM
basal ganglia: 41 nTPM
midbrain: 29 nTPM
pons: 29 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SEMA4A.

Disease | AllUniProt

Conditions SEMA4A is implicated in, by any mechanism.

Retinitis pigmentosa 35 (RP35) MIM:610282
Cone-rod dystrophy 10 (CORD10) MIM:610283

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 687 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Cone-rod dystrophy 10
Retinitis pigmentosa 35
Retinitis pigmentosa
Helicoid peripapillary chorioretinal degeneration
Retinal dystrophy

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): 0.64
gnomAD pLI: 0
gnomAD missense Z: 0.22
DepMap mean gene effect: -0.11
DepMap dependency class: selective

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

Cellular components

plasma membrane

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SEMA4A 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 SEMA4A as an antibody target. Whether an autoantibody or antibody against SEMA4A could matter depends on whether native SEMA4A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SEMA4A is annotated at the cell surface, where native SEMA4A 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 SEMA4A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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