SEMA4A semaphorin 4A [Homo sapiens (human)] - Gene

Summary

Official Symbol: SEMA4Aprovided by HGNC
Official Full Name: semaphorin 4Aprovided by HGNC
Primary source: HGNC:HGNC:10729
See related: Ensembl:ENSG00000196189 MIM:607292; AllianceGenome:HGNC:10729
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RP35; SEMB; SEMAB; CORD10
Summary: 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]
Expression: Broad expression in skin (RPKM 12.9), lymph node (RPKM 12.8) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q22

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (156147373..156177744)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (155285786..155316193)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (156119735..156147535)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Semaphorin4A promotes lung cancer by activation of NF-kappaB pathway mediated by PlexinB1.
Title: Semaphorin4A promotes lung cancer by activation of NF-κB pathway mediated by PlexinB1.
Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8[+] T cell cytotoxicity and proliferation.
Title: Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8(+) T cell cytotoxicity and proliferation.
The possible involvement of sema3A and sema4A in the pathogenesis of multiple sclerosis.
Title: The possible involvement of sema3A and sema4A in the pathogenesis of multiple sclerosis.
Identifying Function Determining Residues in Neuroimmune Semaphorin 4A.
Title: Identifying Function Determining Residues in Neuroimmune Semaphorin 4A.
Semaphorin 4A restricts tumor progression by inhibiting angiogenesis of oral squamous cell carcinoma cells.
Title: Semaphorin 4A restricts tumor progression by inhibiting angiogenesis of oral squamous cell carcinoma cells.
Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner.
Title: Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner.
T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis.
Title: T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis.
Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase.
Title: Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase.
Sema4D and 4A seem to play a critical role in the pathogenesis of some autoimmune diseases, such as multiple sclerosis.
Title: Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer.
Sema4A plays direct and dual roles in promoting inflammation and fibrosis in systemic sclerosis.
Title: Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cone-rod dystrophy 10 MedGen: C1846529 OMIM: 610283 GeneReviews: Not available	Compare labs
Retinitis pigmentosa 35 MedGen: C1853214 OMIM: 610282 GeneReviews: Nonsyndromic Retinitis Pigmentosa Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of SEMA4A	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chemorepellent activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables semaphorin receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in T-helper 1 cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in neural crest cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of excitatory synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of inhibitory synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell shape	IEA Inferred from Electronic Annotation more info
involved_in regulation of endothelial cell migration	IEA Inferred from Electronic Annotation more info
involved_in semaphorin-plexin signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: semaphorin-4A

Names: sema B; sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4A; semaphorin-B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027683.1 RefSeqGene

Range

8642..32801

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193300.2 → NP_001180229.1 semaphorin-4A isoform 1 precursor

See identical proteins and their annotated locations for NP_001180229.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, as compared to variant 1. Variants 1-3 encode the same isoform (1).

Source sequence(s)

AL135927

Consensus CDS

CCDS1132.1

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5

Conserved Domains (3) summary

cd11256
Location:55 → 495

Sema_4A; The Sema domain, a protein interacting module, of semaphorin 4A (Sema4A)

smart00423
Location:496 → 541

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:566 → 638

Ig; Immunoglobulin domain
NM_001193301.2 → NP_001180230.1 semaphorin-4A isoform 1 precursor

See identical proteins and their annotated locations for NP_001180230.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate 5' UTR, as compared to variant 1. Variants 1-3 encode the same isoform (1).

Source sequence(s)

AY358531

Consensus CDS

CCDS1132.1

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5

Related

ENSP00000347117.2, ENST00000355014.6

Conserved Domains (3) summary

cd11256
Location:55 → 495

Sema_4A; The Sema domain, a protein interacting module, of semaphorin 4A (Sema4A)

smart00423
Location:496 → 541

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:566 → 638

Ig; Immunoglobulin domain
NM_001193302.2 → NP_001180231.1 semaphorin-4A isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two internal exons in 5' different regions respectively, resulting in a downstream AUG start codon, as compared to variant 1. The resulting isoform (2) is shorter at the N-terminus and lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AK091127, AY358531

Consensus CDS

CCDS53378.1

UniProtKB/TrEMBL

Q5TCJ5

Related

ENSP00000357267.1, ENST00000368284.5

Conserved Domains (3) summary

pfam01437
Location:364 → 408

PSI; Plexin repeat

cl11960
Location:434 → 506

Ig; Immunoglobulin domain

cl15693
Location:1 → 363

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
NM_001370567.1 → NP_001357496.1 semaphorin-4A isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AL135927

Consensus CDS

CCDS1132.1

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5

Related

ENSP00000357265.1, ENST00000368282.1

Conserved Domains (3) summary

cd11256
Location:55 → 495

Sema_4A; The Sema domain, a protein interacting module, of semaphorin 4A (Sema4A)

smart00423
Location:496 → 541

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:566 → 638

Ig; Immunoglobulin domain
NM_001370568.1 → NP_001357497.1 semaphorin-4A isoform 3

Status: REVIEWED

Source sequence(s)

AL135927

UniProtKB/TrEMBL

B4DKS5, Q5TCJ5

Conserved Domains (3) summary

smart00423
Location:397 → 442

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:467 → 539

Ig; Immunoglobulin domain

cl15693
Location:1 → 396

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
NM_001370569.1 → NP_001357498.1 semaphorin-4A isoform 4

Status: REVIEWED

Source sequence(s)

AL135927

UniProtKB/TrEMBL

Q5TCJ5

Conserved Domains (3) summary

smart00423
Location:327 → 372

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:397 → 469

Ig; Immunoglobulin domain

cl15693
Location:1 → 326

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
NM_001370571.1 → NP_001357500.1 semaphorin-4A isoform 4

Status: REVIEWED

Source sequence(s)

AL135927

UniProtKB/TrEMBL

Q5TCJ5

Conserved Domains (3) summary

smart00423
Location:327 → 372

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:397 → 469

Ig; Immunoglobulin domain

cl15693
Location:1 → 326

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
NM_022367.4 → NP_071762.2 semaphorin-4A isoform 1 precursor

See identical proteins and their annotated locations for NP_071762.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longest transcript. Variants 1-3 encode the same isoform (1).

Source sequence(s)

AY358531, BC020974, DA409501

Consensus CDS

CCDS1132.1

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5

Related

ENSP00000357268.3, ENST00000368285.8

Conserved Domains (3) summary

cd11256
Location:55 → 495

Sema_4A; The Sema domain, a protein interacting module, of semaphorin 4A (Sema4A)

smart00423
Location:496 → 541

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:566 → 638

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

156147373..156177744

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047427664.1 → XP_047283620.1 semaphorin-4A isoform X2

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5
XM_047427677.1 → XP_047283633.1 semaphorin-4A isoform X3

UniProtKB/TrEMBL

B4DKS5, Q5TCJ5
XM_011509878.3 → XP_011508180.1 semaphorin-4A isoform X3

See identical proteins and their annotated locations for XP_011508180.1

UniProtKB/TrEMBL

B4DKS5, Q5TCJ5

Conserved Domains (3) summary

smart00423
Location:397 → 442

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:467 → 539

Ig; Immunoglobulin domain

cl15693
Location:1 → 396

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
XM_011509871.4 → XP_011508173.1 semaphorin-4A isoform X1

UniProtKB/TrEMBL

Q5TCJ5

Conserved Domains (3) summary

cd11256
Location:17 → 457

Sema_4A; The Sema domain, a protein interacting module, of semaphorin 4A (Sema4A)

pfam01437
Location:458 → 502

PSI; Plexin repeat

cl11960
Location:528 → 600

Ig; Immunoglobulin domain
XM_047427678.1 → XP_047283634.1 semaphorin-4A isoform X4

Related

ENST00000487358.5
XM_047427670.1 → XP_047283626.1 semaphorin-4A isoform X2

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5
XM_047427671.1 → XP_047283627.1 semaphorin-4A isoform X2

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5
XM_011509872.3 → XP_011508174.1 semaphorin-4A isoform X2

See identical proteins and their annotated locations for XP_011508174.1

UniProtKB/Swiss-Prot

B2RDH8, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9, Q9H3S1

UniProtKB/TrEMBL

Q5TCJ5

Conserved Domains (3) summary

cd11256
Location:55 → 495

Sema_4A; The Sema domain, a protein interacting module, of semaphorin 4A (Sema4A)

smart00423
Location:496 → 541

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:566 → 638

Ig; Immunoglobulin domain
XM_011509874.3 → XP_011508176.1 semaphorin-4A isoform X3

See identical proteins and their annotated locations for XP_011508176.1

UniProtKB/TrEMBL

B4DKS5, Q5TCJ5

Conserved Domains (3) summary

smart00423
Location:397 → 442

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:467 → 539

Ig; Immunoglobulin domain

cl15693
Location:1 → 396

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
XM_011509875.4 → XP_011508177.1 semaphorin-4A isoform X3

See identical proteins and their annotated locations for XP_011508177.1

UniProtKB/TrEMBL

B4DKS5, Q5TCJ5

Conserved Domains (3) summary

smart00423
Location:397 → 442

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:467 → 539

Ig; Immunoglobulin domain

cl15693
Location:1 → 396

Sema; The Sema domain, a protein interacting module, of semaphorins and plexins