semaphorin 4D (CD100) | CD molecules | IUPHAR/BPS Guide to PHARMACOLOGY

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semaphorin 4D (CD100)

target has curated data in GtoImmuPdb

Target id: 2883

Nomenclature: semaphorin 4D (CD100)

Family: CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 862 9q22.2 SEMA4D semaphorin 4D
Mouse 1 861 13 B1 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
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

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Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
VX15/2503 Hs Binding 9.4 pKd 1
pKd 9.4 (Kd 4.5x10-10 M) [1]
Description: Measuring binding to native SEMA4D expressed on human peripheral blood T lymphocytes.
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
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0070486 leukocyte aggregation IMP
Clinically-Relevant Mutations and Pathophysiology
Disease:  Bullous pemphigoid
Description: Bullous pemphigoid is a potentially fatal, autoimmune subepidermal blistering skin disease.
Orphanet: ORPHA703
References:  5


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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. U.S.A., 104 (5): 1621-6. [PMID:17244710]

How to cite this page

CD molecules: semaphorin 4D (CD100). Last modified on 25/10/2017. Accessed on 03/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY,