CCL3L1
Identifiers
AliasesCCL3L1, 464.2, D17S1718, G0S19-2, LD78, LD78-beta(1-70), LD78BETA, MIP1AP, SCYA3L, SCYA3L1, C-C motif chemokine ligand 3 like 1
External IDsOMIM: 601395 GeneCards: CCL3L1
Orthologs
SpeciesHumanMouse
Entrez

6349

n/a

Ensembl

n/a

n/a

UniProt

P16619

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RefSeq (mRNA)

NM_021006

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RefSeq (protein)

NP_001001437
NP_066286

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Location (UCSC)n/an/a
PubMed search[1]n/a
Wikidata
View/Edit Human

Chemokine (C-C motif) ligand 3-like 1, also known as CCL3L1, is a protein which in humans is encoded by the CCL3L1 gene.[2][3][4]

Function

This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. Specifically, chemokines attract lymphocytes to sites of infection or damage. This protein binds to several chemokine receptors including chemokine binding protein 2 (CCBP2 or D6) and chemokine (C-C motif) receptor 5 (CCR5).

CCR5 is a co-receptor for HIV, and binding of CCL3L1 to CCR5 inhibits HIV entry. Furthermore, the binding causes the receptor to be taken inside the cell by endocytosis, to eventually be reprocessed and re-expressed.[2]

Gene organization

The human genome reference assembly contains two full copies of the gene (CCL3L1 and CCL3L3) and an additional partial duplication, which is thought to result in a pseudogene, designated CCL3L2. This record represents the more telomeric full-length gene.[2]

Clinical significance

The copy number of this gene varies among individuals. This is hypothesized to be due to segmental duplication of the region containing CCL3. Most individuals have 1-6 copies in the diploid genome, although rare individuals have zero or more than six copies. With increased copy number, there is more CCL3L1 expressed, and so competition for the CCR5 binding site is increased. This leads to slower advancement of disease in HIV-infected individuals, giving those with greater copy number more resistance.[2]

Interactions

CCL3L1 has been shown to interact with CCR5.[5][6]

References

  1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. 1 2 3 4 "Entrez Gene: CCL3L1 chemokine (C-C motif) ligand 3-like 1".
  3. Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (June 1990). "Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q". Nucleic Acids Research. 18 (11): 3261–70. doi:10.1093/nar/18.11.3261. PMC 330932. PMID 1972563.
  4. Hirashima M, Ono T, Nakao M, Nishi H, Kimura A, Nomiyama H, Hamada F, Yoshida MC, Shimada K (1992). "Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17". DNA Sequence. 3 (4): 203–12. doi:10.3109/10425179209034019. PMID 1296815.
  5. Miyakawa T, Obaru K, Maeda K, Harada S, Mitsuya H (Feb 2002). "Identification of amino acid residues critical for LD78beta, a variant of human macrophage inflammatory protein-1alpha, binding to CCR5 and inhibition of R5 human immunodeficiency virus type 1 replication". The Journal of Biological Chemistry. 277 (7): 4649–55. doi:10.1074/jbc.M109198200. PMID 11734558.
  6. Struyf S, Menten P, Lenaerts JP, Put W, D'Haese A, De Clercq E, Schols D, Proost P, Van Damme J (Jul 2001). "Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils". European Journal of Immunology. 31 (7): 2170–8. doi:10.1002/1521-4141(200107)31:7<2170::AID-IMMU2170>3.0.CO;2-D. PMID 11449371.

Further reading

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