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melanoma cell adhesion molecule

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2988

Nomenclature: melanoma cell adhesion molecule

Systematic Nomenclature: CD146

Family: Immunoglobulin C2-set domain-containing proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 646 11q23.3 MCAM melanoma cell adhesion molecule 4-5
Mouse 1 648 9 A5.1 Mcam melanoma cell adhesion molecule
Rat 1 648 8q22 Mcam melanoma cell adhesion molecule
Gene and Protein Information Comments
Shorter isoforms from the rat and mouse genes (both 606 aa) have been identified.
Previous and Unofficial Names Click here for help
CD146 | Gicerin | MUC18
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
imaprelimab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 8.1 pKd 3
pKd 8.1 (Kd 8.7x10-9 M) [3]
Immunopharmacology Comments
In addition to its tumourigenic activity, MCAM is implicated in the development of human autoimmune diseases. A subset of peripheral effector memory phenotype T cells expressing MCAM have been identified in elevated numbers in patients with autoimmune diseases, where they appear to be the major producers of IL-17, a key mediator in autoimmune diseases [2]. MCAM on the surface of Th17 cells facilitates their interaction with the vasculature. MCAM is the target of the investigational monoclonal antibody imaprelimab (PRX-003) that was developed as an anti-psoriasis therapy.
General Comments
MCAM is a cell adhesion molecule that has been implicated in tumour growth and metastasis [1,6-7].
In addition to its immunoglobulin (Ig) C2-set domain the MCAM protein contains an Ig-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590.

References

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1. Colomb F, Wang W, Simpson D, Zafar M, Beynon R, Rhodes JM, Yu LG. (2017) Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells. J Biol Chem, 292 (20): 8381-8389. [PMID:28364041]

2. Dagur PK, McCoy Jr JP. (2015) Endothelial-binding, proinflammatory T cells identified by MCAM (CD146) expression: Characterization and role in human autoimmune diseases. Autoimmun Rev, 14 (5): 415-22. [PMID:25595133]

3. Flanagan K, Baker J, Yednock TA. (2014) Anti-mcam antibodies and associated methods of use. Patent number: WO2014039975. Assignee: Neotope Biosciences Limited. Priority date: 10/09/2012. Publication date: 13/03/2012.

4. Kuske MD, Johnson JP. (1999) Assignment of the human melanoma cell adhesion molecule gene (MCAM) to chromosome 11 band q23.3 by radiation hybrid mapping. Cytogenet Cell Genet, 87 (3-4): 258. [PMID:10702685]

5. Lehmann JM, Riethmüller G, Johnson JP. (1989) MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci USA, 86 (24): 9891-5. [PMID:2602381]

6. Sechler M, Parrish JK, Birks DK, Jedlicka P. (2017) The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis. Oncogene, 36 (29): 4150-4160. [PMID:28319067]

7. Wang J, Tang X, Weng W, Qiao Y, Lin J, Liu W, Liu R, Ma L, Yu W, Yu Y et al.. (2015) The membrane protein melanoma cell adhesion molecule (MCAM) is a novel tumor marker that stimulates tumorigenesis in hepatocellular carcinoma. Oncogene, 34 (47): 5781-95. [PMID:25728681]

How to cite this page

Immunoglobulin C2-set domain-containing proteins: melanoma cell adhesion molecule. Last modified on 07/08/2019. Accessed on 18/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2988.