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CD31

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(Redirected from PECAM) Mammalian protein found in humans
PECAM1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2KY5, 5C14

Identifiers
AliasesPECAM1, CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM, platelet and endothelial cell adhesion molecule 1, PCAM-1
External IDsOMIM: 173445; MGI: 97537; HomoloGene: 47925; GeneCards: PECAM1; OMA:PECAM1 - orthologs
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)
Chromosome 17 (human)Genomic location for PECAM1Genomic location for PECAM1
Band17q23.3Start64,319,415 bp
End64,413,776 bp
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)
Chromosome 11 (mouse)Genomic location for PECAM1Genomic location for PECAM1
Band11|11 E1Start106,545,043 bp
End106,641,454 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • tendon of biceps brachii

  • visceral pleura

  • lower lobe of lung

  • pericardium

  • right lung

  • parietal pleura

  • monocyte

  • upper lobe of lung

  • epithelium of colon

  • upper lobe of left lung
Top expressed in
  • right lung lobe

  • left lung

  • left lung lobe

  • vasculature of trunk

  • mesenteric lymph nodes

  • muscle of thigh

  • ascending aorta

  • aortic valve

  • glomerular capillary

  • digastric muscle
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5175

18613

Ensembl

ENSG00000261371

ENSMUSG00000020717

UniProt

P16284

Q08481

RefSeq (mRNA)

NM_000442

NM_001032378
NM_008816
NM_001305157
NM_001305158

RefSeq (protein)

NP_000433

NP_001027550
NP_001292086
NP_001292087
NP_032842

Location (UCSC)Chr 17: 64.32 – 64.41 MbChr 11: 106.55 – 106.64 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the PECAM1 gene found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrophils from the body.

Structure

PECAM-1 is a highly glycosylated protein with a mass of approximately 130 kDa. The structure of this protein was determined by molecular cloning in 1990, when it was found out that PECAM-1 has an N-terminal domain with 574 amino acids, a transmembrane domain with 19 amino acids and a C-terminal cytoplasmic domain with 118 amino acids. The N-terminal domain consists of six extracellular Ig-like domains.

Interactions

PECAM-1 is a cell-cell adhesion protein which interacts with other PECAM-1 molecules through homophilic interactions or with non-PECAM-1 molecules through heterophilic interactions. Homophilic interactions between PECAM-1 molecules are mediated by antiparallel interactions between extracellular Ig-like domain 1 and Ig-like domain 2. These interactions are regulated by the level of PECAM-1 expression. Homophilic interactions occur, only when the surface expression of PECAM-1 is high. Otherwise, when expression is low, heterophilic interactions occur.

Tissue distribution

CD31 is normally found on endothelial cells, platelets, macrophages and Kupffer cells, granulocytes, lymphocytes (T cells, B cells, and NK cells), megakaryocytes, and osteoclasts.

Immunohistochemistry

Micrograph of an angiosarcoma stained with a CD31 immunostain (dark brown).

In immunohistochemistry, CD31 is used primarily to demonstrate the presence of endothelial cells in histological tissue sections. This can help to evaluate the degree of tumor angiogenesis, which can imply a rapidly growing tumor. Malignant endothelial cells also commonly retain the antigen, so that CD31 immunohistochemistry can also be used to demonstrate both angiomas and angiosarcomas. It can also be demonstrated in small lymphocytic and lymphoblastic lymphomas, although more specific markers are available for these conditions.

Function

PECAM-1 is found on the surface of platelets, monocytes, neutrophils, and some types of T-cells, and makes up a large portion of endothelial cell intercellular junctions. The encoded protein is a member of the immunoglobulin superfamily and is likely involved in leukocyte transmigration, angiogenesis, and integrin activation. CD31 on endothelial cells binds to the CD38 receptor on natural killer cells for those cells to attach to the endothelium.

Role in signaling

PECAM-1 plays a role in cell signaling. In the cytoplasmic domain of PECAM-1 are serine and tyrosine residues which are suitable for phosphorylation. After the tyrosine is phosphorylated, PECAM-1 recruits Src homology 2 (SH2) domain–containing signaling proteins. These proteins can then initiate signaling pathways. Of all these proteins, the protein most widely reported as interacting with the PECAM-1 cytoplasmic domain is SH2 domain–containing protein-tyrosine phosphatase SHP-2. Signaling through PECAM-1 leads to the activation of neutrophils, monocytes and leukocytes.

Leukocyte transmigration

PECAM-1 is involved in migration of monocytes and neutrophils, natural killer cells, Vδ1+ γδ T lymphocytes and CD34+ hematopoietic progenitor cells through the endothelial cells. Moreover, PECAM-1 is involved in transendothelial migration of recent thymic emigrants to the secondary lymphoid organs. Mechanism of leukocyte transmigration can be explained by creating a homophilic interaction. In this interaction migrating leukocytes express PECAM-1 on the surface and then they react with PECAM-1 on the surface of endothelial cell.

Angiogenesis

PECAM-1 is also important for angiogenesis because it enables the formation of new blood vessels through the cell-cell adhesion.

Role of CD31 in diseases

Cancer

PECAM-1 is expressed by many solid tumor cell lines such as hemangioma, angiosarcoma, Kaposi’s sarcoma, breast carcinoma, glioblastoma, colon carcinoma, skin carcinoma and other tumor cell lines. On the surface of these tumor cells PECAM-1 mediates the adhesion to endothelial cells. PECAM-1 modulates tumor growth by the formation of new endothelial cell tubes. In mice, this process can be inhibited using an anti-PECAM-1 antibody.

Recently, it was found out that elderly patients with gastric cancer have high concentration of PECAM-1 in the serum. That suggests that the use of a serum PECAM-1 level can be a good prognostic marker.

Atherosclerosis

Inhibition of PECAM-1 leads to a reduction of atherosclerotic lesions in mice. That means that PECAM-1 is involved in atherosclerosis. The exact mechanism, how PECAM-1 contributes to atherosclerosis is not known, but there are some theories. PECAM-1 can act as a mechanoresponsive molecule. Or the pathogenesis can be caused by the infiltration of leukocytes mediated by PECAM-1. Finally, polymorphisms in the PECAM-1 gene can lead to the progression of atherosclerosis.

Disseminated intravascular coagulation

Extensive microvascular thrombosis and increased microvascular permeability are main characteristics of disseminated intravascular coagulation, a fatal complication of sepsis. Patients with this devastating condition have high levels of PECAM-1 in the serum indicating PECAM-1 as a good diagnostic marker. Moreover, PECAM-1 can protect from the development of disseminated intravascular coagulation by inhibiting macrophage pyroptosis.

Neuroinflammation

PECAM-1 contributes to at least two of the nervous system diseases, multiple sclerosis and cerebral ischaemia. First signs of multiple sclerosis are defects in the blood brain barrier and leukocyte migration mediated by adhesion molecules such as PECAM-1. Moreover, monocytes in patients with multiple sclerosis express high level of PECAM-1. Cerebral ischaemia is caused by the accumulation of leukocytes, which then infiltrate brain parenchyma and release toxic compounds such as oxygen radicals. Interactions between leukocyte and endothelium are mediated by PECAM-1. High levels of soluble PECAM-1 can be used to diagnose both diseases. Increased PECAM-1 levels indicate damage in the blood brain barrier in patients with multiple sclerosis and high PECAM-1 levels can be used as a short-term prediction of a stroke in patients with cerebral ischaemia.

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000261371Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000020717Ensembl, 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.
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Further reading

External links

Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50
51–100
101–150
151–200
201–250
251–300
301–350
Membrane proteins: cell adhesion molecules
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Integrins
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