VCAM-1

Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the VCAM1 gene.[5] VCAM-1 functions as a cell adhesion molecule.

VCAM1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesVCAM1, CD106, INCAM-100, vascular cell adhesion molecule 1
External IDsOMIM: 192225 MGI: 98926 HomoloGene: 838 GeneCards: VCAM1
Orthologs
SpeciesHumanMouse
Entrez

7412

22329

Ensembl

ENSG00000162692

ENSMUSG00000027962

UniProt

P19320

P29533

RefSeq (mRNA)

NM_080682
NM_001078
NM_001199834

NM_011693

RefSeq (protein)

NP_001069
NP_001186763
NP_542413

NP_035823

Location (UCSC)Chr 1: 100.72 – 100.74 MbChr 3: 115.9 – 115.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

VCAM-1 is a member of the immunoglobulin superfamily, the superfamily of proteins including antibodies and T-cell receptors. The VCAM-1 gene contains six or seven immunoglobulin domains, and is expressed on both large and small blood vessels only after the endothelial cells are stimulated by cytokines. It is alternatively spliced into two known RNA transcripts that encode different isoforms in humans.[6] The gene product is a cell surface sialoglycoprotein, a type I membrane protein that is a member of the Ig superfamily.

Function

The VCAM-1 protein mediates the adhesion of lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium. It also functions in leukocyte-endothelial cell signal transduction, and it may play a role in the development of atherosclerosis and rheumatoid arthritis.

Upregulation of VCAM-1 in endothelial cells by cytokines occurs as a result of increased gene transcription (e.g., in response to Tumor necrosis factor-alpha (TNF-α) and Interleukin-1 (IL-1)) and through stabilization of Messenger RNA (mRNA) (e.g., Interleukin-4 (IL-4)). The promoter region of the VCAM-1 gene contains functional tandem NF-κB (nuclear factor-kappa B) sites. The sustained expression of VCAM-1 lasts over 24 hours.

Primarily, the VCAM-1 protein is an endothelial ligand for VLA-4 (Very Late Antigen-4 or integrin α4β1) of the β1 subfamily of integrins. VCAM-1 expression has also been observed in other cell types (e.g., smooth muscle cells). It has also been shown to interact with EZR[7] and Moesin.[7]

VCAM-1 is also up regulate if vWF (Von Willebrand Factor) is given in Knock out ADMATS13 mice but not on mice withouth KO. [8]

CD106 also exists on the surface of some subpopulations of mesenchymal stem cells (MSC).[9]

Pharmacology

Certain melanoma cells can use VCAM-1 to adhere to the endothelium,[10] VCAM-1 may participate in monocyte recruitment to atherosclerotic sites, and it is highly overexpressed in the inflamed brain.[11] As a result, VCAM-1 is a potential drug target.

References
  1. GRCh38: Ensembl release 89: ENSG00000162692 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027962 - 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. Cybulsky M, Fries JW, Williams AJ, Sultan P, Eddy RL, Byers MG, Shows TB, Gimbrone MA Jr, Collins T (1991). "The human VCAM1 gene is assigned to chromosome 1p31-p32". Cytogenet. Cell Genet. 58 (3–4): 1850–1867. doi:10.1159/000133735.
  6. "Entrez Gene: VCAM1 vascular cell adhesion molecule 1".
  7. Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, Sanchez-Madrid F (Jun 2002). "Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes". J. Cell Biol. 157 (7): 1233–45. doi:10.1083/jcb.200112126. PMC 2173557. PMID 12082081.
  8. Lebesnerais et al. J Thromb Haemost 2016 14:1917 - 1930
  9. ZX Yang; et al. (2013). "CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties". PLOS One. 8 (3): e59354. Bibcode:2013PLoSO...859354Y. doi:10.1371/journal.pone.0059354. PMC 3595282. PMID 23555021.
  10. Eibl RH, Benoit M (2004). "Molecular resolution of cell adhesion forces". IEE Proceedings - Nanobiotechnology. 151 (3): 128–32. doi:10.1049/ip-nbt:20040707. PMID 16475855.
  11. Marcos-Contreras, Oscar A (2020). "Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood–brain barrier". Proceedings of the National Academy of Sciences of the United States of America. 117 (7): 3405–3414. doi:10.1073/pnas.1912012117. PMC 7035611. PMID 32005712.

Further reading
  • VCAM-1 at the US National Library of Medicine Medical Subject Headings (MeSH)
  • Overview of all the structural information available in the PDB for UniProt: P19320 (Vascular cell adhesion protein 1) at the PDBe-KB.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.