SEMA4A

Semaphorin-4A is a protein that in humans is encoded by the SEMA4A gene.^[5][6]

SEMA4A
Identifiers
Aliases	SEMA4A, CORD10, RP35, SEMAB, SEMB, semaphorin 4A
External IDs	OMIM: 607292; MGI: 107560; HomoloGene: 8425; GeneCards: SEMA4A; OMA:SEMA4A - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q22 Start 156,147,366 bp[1] End 156,177,752 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 F1 Start 88,343,266 bp[2] End 88,368,489 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte bone marrow cells blood amygdala nucleus accumbens skin of abdomen left lobe of thyroid gland retinal pigment epithelium cingulate gyrus Top expressed in granulocyte Paneth cell retinal pigment epithelium ventromedial nucleus jejunum paraventricular nucleus of hypothalamus arcuate nucleus prostate ileum duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding neuropilin binding semaphorin receptor binding chemorepellent activity Cellular component integral component of membrane nucleus cytosol intracellular membrane-bounded organelle plasma membrane extracellular space membrane integral component of plasma membrane Biological process cell differentiation adaptive immune response axonogenesis immune system process T-helper 1 cell differentiation nervous system development multicellular organism development angiogenesis regulation of endothelial cell migration regulation of cell shape negative regulation of angiogenesis T cell differentiation involved in immune response semaphorin-plexin signaling pathway negative chemotaxis neural crest cell migration positive regulation of cell migration negative regulation of axon extension involved in axon guidance positive regulation of excitatory synapse assembly positive regulation of inhibitory synapse assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 64218 20351 Ensembl ENSG00000196189 ENSMUSG00000028064 UniProt Q9H3S1 Q62178 RefSeq (mRNA) NM_001193300 NM_001193301 NM_001193302 NM_022367 NM_001370567 NM_001370568 NM_001370569 NM_001370571 NM_001163489 NM_001163490 NM_001163491 NM_013658 RefSeq (protein) NP_001180229 NP_001180230 NP_001180231 NP_071762 NP_001357496 NP_001357497 NP_001357498 NP_001357500 NP_001156961 NP_001156962 NP_001156963 NP_038686 Location (UCSC) Chr 1: 156.15 – 156.18 Mb Chr 3: 88.34 – 88.37 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

SEMA4A is a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in guidance of axonal migration during neuronal development and in immune responses.[supplied by OMIM]^[6]

Clinical significance

A germline variant in SEMA4A (V78M) has been demonstrated to confer risk for colorectal cancer type X.^[7]

Recently it has been identified as a novel therapeutic target in Multiple myeloma.^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000196189 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028064 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Püschel AW, Adams RH, Betz H (May 1995). "Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension". Neuron. 14 (5): 941–948. doi:10.1016/0896-6273(95)90332-1. PMID 7748561.
6. "Entrez Gene: SEMA4A sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4A".
7. Schulz E, Klampfl P, Holzapfel S, Janecke AR, Ulz P, Renner W, et al. (October 2014). "Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X". Nature Communications. 5: 5191. Bibcode:2014NatCo...5.5191S. doi:10.1038/ncomms6191. PMC 4214414. PMID 25307848.
8. Anderson GS, Ballester-Beltran J, Giotopoulos G, Guerrero JA, Surget S, Williamson JC, et al. (April 2022). "Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma". Blood. 139 (16): 2471–2482. doi:10.1182/blood.2021015161. PMC 11022854. PMID 35134130.

Further reading

• Kikutani H, Kumanogoh A (February 2003). "Semaphorins in interactions between T cells and antigen-presenting cells". Nature Reviews. Immunology. 3 (2): 159–167. doi:10.1038/nri1003. PMID 12563299. S2CID 33203042.
• Kumanogoh A, Kikutani H (September 2003). "Immune semaphorins: a new area of semaphorin research". Journal of Cell Science. 116 (Pt 17): 3463–3470. doi:10.1242/jcs.00674. PMID 12893810.
• Elhabazi A, Marie-Cardine A, Chabbert-de Ponnat I, Bensussan A, Boumsell L (2004). "Structure and function of the immune semaphorin CD100/SEMA4D". Critical Reviews in Immunology. 23 (1–2): 65–81. doi:10.1615/CritRevImmunol.v23.i12.40. PMID 12906260.
• Kumanogoh A, Marukawa S, Suzuki K, Takegahara N, Watanabe C, Ch'ng E, et al. (October 2002). "Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2". Nature. 419 (6907): 629–633. Bibcode:2002Natur.419..629K. doi:10.1038/nature01037. PMID 12374982. S2CID 4431066.
• Abid A, Ismail M, Mehdi SQ, Khaliq S (April 2006). "Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases". Journal of Medical Genetics. 43 (4): 378–381. doi:10.1136/jmg.2005.035055. PMC 2563224. PMID 16199541.
• Nkyimbeng-Takwi E, Chapoval SP (May 2011). "Biology and function of neuroimmune semaphorins 4A and 4D". Immunologic Research. 50 (1): 10–21. doi:10.1007/s12026-010-8201-y. PMC 3366695. PMID 21203905.
• Smith EP, Shanks K, Lipsky MM, DeTolla LJ, Keegan AD, Chapoval SP (May 2011). "Expression of neuroimmune semaphorins 4A and 4D and their receptors in the lung is enhanced by allergen and vascular endothelial growth factor". BMC Immunology. 12: 30. doi:10.1186/1471-2172-12-30. PMC 3118960. PMID 21595947.
• Nkyimbeng-Takwi EH, Shanks K, Smith E, Iyer A, Lipsky MM, Detolla LJ, et al. (July 2012). "Neuroimmune semaphorin 4A downregulates the severity of allergic response". Mucosal Immunology. 5 (4): 409–419. doi:10.1038/mi.2012.18. PMC 3378810. PMID 22472774.
• Mogie G, Shanks K, Nkyimbeng-Takwi EH, Smith E, Davila E, Lipsky MM, et al. (November 2013). "Neuroimmune semaphorin 4A as a drug and drug target for asthma". International Immunopharmacology. 17 (3): 568–575. doi:10.1016/j.intimp.2013.08.005. PMC 3818409. PMID 23994348.
• Chapoval SP (November 2015). "Semaphorin 4A as novel regulator and promising therapeutic target in rheumatoid arthritis". Arthritis Research & Therapy. 17: 313. doi:10.1186/s13075-015-0846-4 (inactive 1 November 2024). PMC 4635990. PMID 26542940.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)