SEMA3A

Protein identityUniProt · HPA

UniProt accession

Q14563

Gene

SEMA3A

Ensembl

ENSG00000075213

Chromosome

7

Canonical length

771 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

771 residues, UniProt reviewed canonical sequence.

>Q14563|SEMA3A
     1  MGWLTRIVCL FWGVLLTARA NYQNGKNNVP RLKLSYKEML ESNNVITFNG LANSSSYHTF
    61  LLDEERSRLY VGAKDHIFSF DLVNIKDFQK IVWPVSYTRR DECKWAGKDI LKECANFIKV
   121  LKAYNQTHLY ACGTGAFHPI CTYIEIGHHP EDNIFKLENS HFENGRGKSP YDPKLLTASL
   181  LIDGELYSGT AADFMGRDFA IFRTLGHHHP IRTEQHDSRW LNDPKFISAH LISESDNPED
   241  DKVYFFFREN AIDGEHSGKA THARIGQICK NDFGGHRSLV NKWTTFLKAR LICSVPGPNG
   301  IDTHFDELQD VFLMNFKDPK NPVVYGVFTT SSNIFKGSAV CMYSMSDVRR VFLGPYAHRD
   361  GPNYQWVPYQ GRVPYPRPGT CPSKTFGGFD STKDLPDDVI TFARSHPAMY NPVFPMNNRP
   421  IVIKTDVNYQ FTQIVVDRVD AEDGQYDVMF IGTDVGTVLK VVSIPKETWY DLEEVLLEEM
   481  TVFREPTAIS AMELSTKQQQ LYIGSTAGVA QLPLHRCDIY GKACAECCLA RDPYCAWDGS
   541  ACSRYFPTAK RRTRRQDIRN GDPLTHCSDL HHDNHHGHSP EERIIYGVEN SSTFLECSPK
   601  SQRALVYWQF QRRNEERKEE IRVDDHIIRT DQGLLLRSLQ QKDSGNYLCH AVEHGFIQTL
   661  LKVTLEVIDT EHLEELLHKD DDGDGSKTKE MSNSMTPSQK VWYRDFMQLI NHPNLNTMDE
   721  FCEQVWKRDR KQRRQRPGHT PGNSNKWKHL QENKKGRNRR THEFERAPRS V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SEMA3A 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

21 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SEMA3A.

Disease | AllUniProt

Conditions SEMA3A is implicated in, by any mechanism.

• Hypogonadotropic hypogonadism 16 with or without anosmia (HH16) MIM:614897

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 390 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• SEMA3A-related disorder
• Hypogonadotropic hypogonadism 16 with or without anosmia

ReferencesPubMed · IEDB

Publications for SEMA3A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.31

gnomAD pLI

0.98

gnomAD missense Z

1.75

DepMap mean gene effect

0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon extension involved in axon guidance
• axon guidance
• axonogenesis involved in innervation
• basal dendrite arborization
• branchiomotor neuron axon guidance
• facial nerve structural organization
• motor neuron axon guidance
• negative chemotaxis
• negative regulation of neuron projection development
• nerve development
• neural crest cell migration
• neural crest cell migration involved in autonomic nervous system development
• neuron migration
• olfactory bulb development
• positive regulation of cell migration
• positive regulation of JNK cascade
• regulation of axon extension involved in axon guidance
• semaphorin-plexin signaling pathway
• sensory system development
• sympathetic ganglion development
• sympathetic nervous system development
• sympathetic neuron projection extension
• sympathetic neuron projection guidance
• trigeminal nerve structural organization

Molecular functions

• chemorepellent activity
• neuropilin binding
• semaphorin receptor binding

Cellular components

• axon
• extracellular region
• extracellular space
• glutamatergic synapse
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Sema domain
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin-like fold
• WD40/YVTN repeat-like-containing domain superfamily
• PSI domain
• Semaphorin
• Immunoglobulin-like domain superfamily
• Sema domain superfamily
• IL-1Ra-like, immunoglobulin domain
• Sema domain
• Immunoglobulin domain
• Semaphorin-3A, sema domain

KeywordsUniProt

• Developmental protein
• Differentiation
• Disulfide bond
• Glycoprotein
• Hypogonadotropic hypogonadism
• Immunoglobulin domain
• Kallmann syndrome
• Neurogenesis
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of SEMA3A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PLXND1