SEMA4A explained

Semaphorin-4A is a protein that in humans is encoded by the SEMA4A gene.^{[1] [2]}

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]

Clinical significance

A germline variant in SEMA4A (V78M) has been demonstrated to confer risk for colorectal cancer type X.^[3]

Recently it has been identified as a novel therapeutic target in Multiple myeloma.^[4]

References

Further reading

• Kikutani H, Kumanogoh A . Semaphorins in interactions between T cells and antigen-presenting cells . Nature Reviews. Immunology . 3 . 2 . 159–167 . February 2003 . 12563299 . 10.1038/nri1003 . 33203042 .
• Kumanogoh A, Kikutani H . Immune semaphorins: a new area of semaphorin research . Journal of Cell Science . 116 . Pt 17 . 3463–3470 . September 2003 . 12893810 . 10.1242/jcs.00674 . free .
• Elhabazi A, Marie-Cardine A, Chabbert-de Ponnat I, Bensussan A, Boumsell L . Structure and function of the immune semaphorin CD100/SEMA4D . Critical Reviews in Immunology . 23 . 1–2 . 65–81 . 2004 . 12906260 . 10.1615/CritRevImmunol.v23.i12.40 .
• Kumanogoh A, Marukawa S, Suzuki K, Takegahara N, Watanabe C, Ch'ng E, Ishida I, Fujimura H, Sakoda S, Yoshida K, Kikutani H . Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2 . Nature . 419 . 6907 . 629–633 . October 2002 . 12374982 . 10.1038/nature01037 . 4431066 . 2002Natur.419..629K .
• Abid A, Ismail M, Mehdi SQ, Khaliq S . Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases . Journal of Medical Genetics . 43 . 4 . 378–381 . April 2006 . 16199541 . 2563224 . 10.1136/jmg.2005.035055 .
• Nkyimbeng-Takwi E, Chapoval SP . Biology and function of neuroimmune semaphorins 4A and 4D . Immunologic Research . 50 . 1 . 10–21 . May 2011 . 21203905 . 3366695 . 10.1007/s12026-010-8201-y .
• Smith EP, Shanks K, Lipsky MM, DeTolla LJ, Keegan AD, Chapoval SP . 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 . May 2011 . 21595947 . 3118960 . 10.1186/1471-2172-12-30 . free .
• Nkyimbeng-Takwi EH, Shanks K, Smith E, Iyer A, Lipsky MM, Detolla LJ, Kikutani H, Keegan AD, Chapoval SP . Neuroimmune semaphorin 4A downregulates the severity of allergic response . Mucosal Immunology . 5 . 4 . 409–419 . July 2012 . 22472774 . 3378810 . 10.1038/mi.2012.18 .
• Mogie G, Shanks K, Nkyimbeng-Takwi EH, Smith E, Davila E, Lipsky MM, DeTolla LJ, Keegan AD, Chapoval SP . Neuroimmune semaphorin 4A as a drug and drug target for asthma . International Immunopharmacology . 17 . 3 . 568–575 . November 2013 . 23994348 . 3818409 . 10.1016/j.intimp.2013.08.005 .
• Chapoval SP . Semaphorin 4A as novel regulator and promising therapeutic target in rheumatoid arthritis . Arthritis Research & Therapy . 17 . 313 . November 2015 . 26542940 . 4635990 . 10.1186/s13075-015-0846-4 . 2024-04-12 . free .

Notes and References

1. Püschel AW, Adams RH, Betz H . Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension . Neuron . 14 . 5 . 941–948 . May 1995 . 7748561 . 10.1016/0896-6273(95)90332-1 . free .
2. Web site: Entrez Gene: SEMA4A sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4A.
3. Schulz E, Klampfl P, Holzapfel S, Janecke AR, Ulz P, Renner W, Kashofer K, Nojima S, Leitner A, Zebisch A, Wölfler A, Hofer S, Gerger A, Lax S, Beham-Schmid C, Steinke V, Heitzer E, Geigl JB, Windpassinger C, Hoefler G, Speicher MR, Boland CR, Kumanogoh A, Sill H . Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X . Nature Communications . 5 . 5191 . October 2014 . 25307848 . 4214414 . 10.1038/ncomms6191 . 2014NatCo...5.5191S .
4. Anderson GS, Ballester-Beltran J, Giotopoulos G, Guerrero JA, Surget S, Williamson JC, So T, Bloxham D, Aubareda A, Asby R, Walker I, Jenkinson L, Soilleux EJ, Roy JP, Teodósio A, Ficken C, Officer-Jones L, Nasser S, Skerget S, Keats JJ, Greaves P, Tai YT, Anderson KC, MacFarlane M, Thaventhiran JE, Huntly BJ, Lehner PJ, Chapman MA . Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma . Blood . 139 . 16 . 2471–2482 . April 2022 . 35134130. 10.1182/blood.2021015161 . free . 11022854 .