DC-SIGN

Source: Wikipedia, the free encyclopedia.
CD209
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000090659

ENSMUSG00000040197

UniProt

Q9NNX6

Q91ZW7

RefSeq (mRNA)

NM_130905

RefSeq (protein)

NP_570975

Location (UCSC)Chr 19: 7.74 – 7.75 MbChr 8: 3.9 – 3.9 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 (Cluster of Differentiation 209) is a protein which in humans is encoded by the CD209 gene.[5]

DC-SIGN is a

dendritic cells. DC-SIGN on macrophages recognises and binds with high affinity to high-mannose type N-glycans, a class of PAMPs (pathogen associated molecular patterns) commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis.[6] On myeloid and pre-plasmacytoid dendritic cells DC-SIGN mediates dendritic cell rolling interactions with blood endothelium and activation of CD4+ T cells, as well as recognition of pathogen
haptens.

Function

DC-SIGN is a C-type lectin and has a high affinity for the ICAM3 molecule.[7] It binds various microorganisms by recognizing high-mannose-containing glycoproteins on their surface, and can function as a co-receptor for several viruses such as HIV and Hepatitis C.[8][9][10] Binding to DC-SIGN can promote HIV and Hepatitis C virus to infect target cells (T-cells and hepatocytes, respectively).[9][10]

Besides functioning as an adhesion molecule, recent studies have also shown that DC-SIGN can initiate innate immunity by modulating toll-like receptors,[11] though the detailed mechanism is not yet known. DC-SIGN together with other C-type lectins is involved in recognition of tumors by dendritic cells. DC-SIGN is also a potential engineering target for dendritic cell based cancer vaccine.[12]

Clinical significance

HIV infection

This

gp120 molecule causes co-internalization of the DC-SIGN molecule and HIV virus particle (virion). The dendritic cell then migrates to the cognate lymphoid organ, whereupon recycling of the DC-SIGN/HIV virion complex to the cell periphery facilitates HIV infection of CD4+ T cells by interaction between DC-SIGN and ICAM-3.[13]

Ebola infection

Different studies have demonstrated that the ebola virus infection process starts when the virus reaches the cellular DC-SIGN receptor to infect the dendritic cells (of the immune system). In 2015 European researchers designed a “giant” molecule formed by thirteen fullerenes covered by carbohydrates which, by blocking DC-SIGN receptor, are able to inhibit the cell infection by an artificial ebola virus model. These antiviral molecules decorated with specific carbohydrates (sugars) present affinity by the receptor used as an entry point to infect the cell and act blocking it, thus inhibiting the infection in a sub-nanomolar range.[14]

SARS-CoV-2

DC-sign and its counterpart L-SIGN (CD 209L) have also been identified as receptors facilitating the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells. Significant CD209L expression has been revealed in lung and kidney epithelia and endothelia and interactions with SARS-CoV-2 Spike protein (S protein) have been demonstrated in vitro.[15][16] CD209L also exhibits interaction with Angiotensin-converting enzyme-2 (ACE2), suggesting a potential role for CD209L-ACE2 heterodimerization in SARS-CoV-2 entry and infection in cell types expressing both proteins.[17] It is shown that DC/L-SIGN can enhance viral infection and dissemination by contributing to additional routes of infection mediated by the S protein in a process called trans-infection.[18] This process seems to be exclusive for DC/L-sign interaction. This complexity in the recognition patterns and functions of these receptors is similar to what has been observed in other viruses like HIV and ebola virus.

Gene family

DC-SIGN/CD209 is an animal "C-lectin", a large and diverse family of proteins found in both

innate immunity
.

A cluster of genes in both humans and mice contains three related members of the "DC Receptor" class, so named because of their homology to DC-SIGN. Of these,

B lymphocytes, and LSectin (CLEC4G) is expressed on the sinusoidal endothelium of the liver. The third gene group consists of multiple paralogues of CD209. Thus, both primates and mice have multiple paralogues of CD209 more closely related to each other within the species than to their orthologous counterparts in the other species. Higher primates have at least three DC-SIGN genes, DC-SIGN, DC-SIGNL1 (also known as DC-SIGNR or L-SIGN[19]) and DC-SIGNL2, although not all three are present in every species; DC-SIGNL2 has not been detected in humans. Eight paralogous of DC-SIGN have been reported in the laboratory mouse strain C57BL/6; these go by the names DC-SIGN, DC-SIGNR2...DC-SIGNR8. DC-SIGNR6 is a pseudogene. The genes labeled "DC-SIGN" in the human and mouse are thus not unique orthologues, although they resemble each other functionally and by being expressed on dendritic cells. Other members of the mouse CD209 gene group are differentially expressed on different cell types. For example, DC-SIGNR1 is expressed largely on macrophages in the marginal zones of the spleen and in the medulla of lymph nodes.[20]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000090659 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040197 – 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. PMID 1518869
    .
  6. PMID 15653305
    .
  7. PMID 18458800
    .
  8. PMID 17502670
    .
  9. ^
    PMID 15166245
    .
  10. ^
    S2CID 15041781
    .
  11. PMID 18998127
    .
  12. PMID 16303292
    .
  13. PMID 22975871
    .
  14. PMID 27055288
    .
  15. PMID 33375175
    .
  16. PMID 32766577
    .
  17. PMID 34341769
    .
  18. PMID 34015061
    .
  19. PMID 16415006
    .
  20. PMID 18528403
    .

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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