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.

"CD106" redirects here. For the radio station formerly known as "CD106 the Wolf", see WNCD.

VCAM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IJ9, 1VCA, 1VSC
Identifiers
Aliases	VCAM1, CD106, INCAM-100, vascular cell adhesion molecule 1
External IDs	OMIM: 192225 MGI: 98926 HomoloGene: 838 GeneCards: VCAM1
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p21.2 Start 100,719,742 bp[1] End 100,739,045 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 G1|3 50.17 cM Start 116,109,949 bp[2] End 116,129,688 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • primary amine oxidase activity • integrin binding • cell adhesion molecule binding Cellular component • integral component of membrane • Golgi apparatus • alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex • membrane • filopodium • cell membrane • apical part of cell • microvilli • cell surface • early endosome • endoplasmic reticulum • podosome • sarcolemma • extracellular exosome • external side of plasma membrane • extracellular • integral component of plasma membrane Biological process • leukocyte cell-cell adhesion • response to ionizing radiation • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules • response to hypoxia • response to nutrient • interferon-gamma-mediated signaling pathway • cellular response to tumor necrosis factor • response to nicotine • aging • response to zinc ion • extracellular matrix organization • amine metabolic process • response to lipopolysaccharide • cell adhesion • acute inflammatory response • positive regulation of T cell proliferation • membrane to membrane docking • regulation of immune response • leukocyte tethering or rolling • cell chemotaxis • B cell differentiation • cellular response to vascular endothelial growth factor stimulus • cell-matrix adhesion • GO:0022415 viral process • response to ethanol • calcium-mediated signaling using intracellular calcium source • chronic inflammation • oxidation-reduction process • cell-cell adhesion • cytokine-mediated signaling pathway • heterotypic cell-cell adhesion • innervation • cardiac neuron differentiation • cell-cell adhesion in response to extracellular stimulus • cellular response to amyloid-beta Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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 Mb	Chr 3: 116.11 – 116.13 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

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]

CD106 also exists on the surface of some subpopulations of mesenchymal stem cells(MSC).[8]

Pharmacology

Certain melanoma cells can use VCAM-1 to adhere to the endothelium,[9], VCAM-1 may participate in monocyte recruitment to atherosclerotic sites, and it is highly overexpressed in the inflamed brain.[10] 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. 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.
9. 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.
10. 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

• Yonekawa K, Harlan JM (2005). "Targeting leukocyte integrins in human diseases". J. Leukoc. Biol. 77 (2): 129–40. doi:10.1189/jlb.0804460. PMID 15548573.
• Wu TC (2007). "The role of vascular cell adhesion molecule-1 in tumor immune evasion". Cancer Res. 67 (13): 6003–6. doi:10.1158/0008-5472.CAN-07-1543. PMC 3179385. PMID 17616653.

External links

• 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.