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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 1 | 862 | 9q22.2 | SEMA4D | semaphorin 4D | |
| Mouse | 1 | 861 | 13 A5 | Sema4d | sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D | |
| Rat | - | 862 | 17p14 | Sema4d | semaphorin 4D | |
| Gene and Protein Information Comments | ||||||
| A second shorter isoform of human semaphorin-4D with 738 amino acids is reported. | ||||||
| Previous and Unofficial Names |
| SEMAJ | M-sema-G | sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D | sema domain |
| Database Links |
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| Alphafold | Q92854 (Hs), O09126 (Mm) |
| CATH/Gene3D | 2.130.10.10, 2.60.40.10 |
| ChEMBL Target | CHEMBL4630887 (Hs) |
| Ensembl Gene | ENSG00000187764 (Hs), ENSMUSG00000021451 (Mm), ENSRNOG00000013679 (Rn) |
| Entrez Gene | 10507 (Hs), 20354 (Mm), 306790 (Rn), ENSRNOG00000013679 (Rn) |
| Human Protein Atlas | ENSG00000187764 (Hs) |
| KEGG Gene | hsa:10507 (Hs), mmu:20354 (Mm), rno:306790 (Rn), rno:ENSRNOG00000013679 (Rn) |
| OMIM | 601866 (Hs) |
| Pharos | Q92854 (Hs) |
| RefSeq Nucleotide | NM_001142287 (Hs), NM_006378 (Hs), NM_001281880 (Hs), NM_001170563 (Rn) |
| RefSeq Protein | NP_006369 (Hs), NP_001135759 (Hs), NP_001268809 (Mm), NP_001164034 (Rn) |
| UniProtKB | Q92854 (Hs), O09126 (Mm) |
| Wikipedia | SEMA4D (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Immunopharmacology Comments |
| Semaphorin 4D (Sema4D) is an important mediator of the movement and differentiation of multiple cell types, including immune cells [6-7], vascular cells [9], and cells of the nervous system [4]. For example, in the immune system, Sema4D activates B cells and dendritic cells through interaction with CD72 (HGNC ID 1696; P21854) [2-3], and is reported to regulate γδ T cells by binding plexin B2 (PLXNB2; O15031) which contributes to skin wound healing [8]. Experimental evidence using patient-derived cells has identified soluble Sema4D, shed from CD15+ granulocytes, as a causal factor in the promotion of autoreactive antibody secretion by B cells that leads to the development of the autoimmune skin condition bullous pemphigoid [5]. |
| Immuno Process Associations | ||
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| Clinically-Relevant Mutations and Pathophysiology
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1. Fisher TL, Reilly CA, Winter LA, Pandina T, Jonason A, Scrivens M, Balch L, Bussler H, Torno S, Seils J et al.. (2016) Generation and preclinical characterization of an antibody specific for SEMA4D. MAbs, 8 (1): 150-62. [PMID:26431358]
2. Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H. (2003) Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses. Int Immunol, 15 (8): 1027-34. [PMID:12882840]
3. Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T et al.. (2000) Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity, 13 (5): 621-31. [PMID:11114375]
4. Nkyimbeng-Takwi E, Chapoval SP. (2011) Biology and function of neuroimmune semaphorins 4A and 4D. Immunol Res, 50 (1): 10-21. [PMID:21203905]
5. Shen S, Ke Y, Dang E, Fang H, Chang Y, Zhang J, Zhu Z, Shao S, Qiao P, Zhang T et al.. (2018) Semaphorin 4D from CD15+ Granulocytes via ADAM10-Induced Cleavage Contributes to Antibody Production in Bullous Pemphigoid. J Invest Dermatol, 138 (3): 588-597. [PMID:29054606]
6. Suzuki K, Kumanogoh A, Kikutani H. (2008) Semaphorins and their receptors in immune cell interactions. Nat Immunol, 9 (1): 17-23. [PMID:18087252]
7. Takamatsu H, Okuno T, Kumanogoh A. (2010) Regulation of immune cell responses by semaphorins and their receptors. Cell Mol Immunol, 7 (2): 83-8. [PMID:20118971]
8. Witherden DA, Watanabe M, Garijo O, Rieder SE, Sarkisyan G, Cronin SJ, Verdino P, Wilson IA, Kumanogoh A, Kikutani H et al.. (2012) The CD100 receptor interacts with its plexin B2 ligand to regulate epidermal γδ T cell function. Immunity, 37 (2): 314-25. [PMID:22902232]
9. Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M, Fan R, Boumsell L, Kumanogoh A, Kikutani H et al.. (2007) Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci USA, 104 (5): 1621-6. [PMID:17244710]
CD molecules: semaphorin 4D (CD100). Last modified on 25/10/2017. Accessed on 24/03/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2883.
target has curated data in GtoImmuPdb
