CCL3L1

Chemokine (C-C motif) ligand 3-like 1
PDB rendering based on 1b50.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1b50​, 1b53​
Identifiers
Symbols	CCL3L1 ; 464.2; D17S1718; G0S19-2; LD78; LD78-beta(1-70); LD78BETA; MIP1AP; SCYA3L; SCYA3L1
External IDs	OMIM: 601395 MGI: 98260 HomoloGene: 2242 GeneCards: CCL3L1 Gene
Gene ontology Molecular function • chemokine activity • CCR chemokine receptor binding Cellular component • extracellular region • extracellular space Biological process • monocyte chemotaxis • inflammatory response • G-protein coupled receptor signaling pathway • negative regulation of cell proliferation • neutrophil chemotaxis • positive regulation of GTPase activity • eosinophil chemotaxis • lymphocyte chemotaxis • positive regulation of inflammatory response • chemokine-mediated signaling pathway • positive regulation of ERK1 and ERK2 cascade • cellular response to interferon-gamma • cellular response to interleukin-1 • cellular response to tumor necrosis factor Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6349	20302
Ensembl	ENSG00000276085	ENSMUSG00000000982
UniProt	P16619	P10855
RefSeq (mRNA)	NM_021006	NM_011337
RefSeq (protein)	NP_066286	NP_035467
Location (UCSC)	Chr 17: 36.19 – 36.2 Mb	Chr 11: 83.65 – 83.65 Mb
PubMed search

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

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.^[1]

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.^[1]

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.^[1]

Interactions

CCL3L1 has been shown to interact with CCR5.^[4][5]

References

1. "Entrez Gene: CCL3L1 chemokine (C-C motif) ligand 3-like 1".
2. Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (Jun 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.
3. 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 : The Journal of DNA Sequencing and Mapping 3 (4): 203–12. doi:10.3109/10425179209034019. PMID 1296815.
4. 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.
5. 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

• Hirashima M, Ono T, Nakao M, Nishi H, Kimura A, Nomiyama H, Hamada F, Yoshida MC, Shimada K (1993). "Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17". DNA Sequence : The Journal of DNA Sequencing and Mapping 3 (4): 203–12. doi:10.3109/10425179209034019. PMID 1296815.
• Nakao M, Nomiyama H, Shimada K (Jul 1990). "Structures of human genes coding for cytokine LD78 and their expression". Molecular and Cellular Biology 10 (7): 3646–58. PMC 360801. PMID 1694014.
• Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (Jun 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.
• Blum S, Forsdyke RE, Forsdyke DR (Oct 1990). "Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation". DNA and Cell Biology 9 (8): 589–602. doi:10.1089/dna.1990.9.589. PMID 2271120. Check date values in: |year= / |date= mismatch (help)
• Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (Sep 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature 377 (6547 Suppl): 3–174. PMID 7566098.
• Naruse K, Ueno M, Satoh T, Nomiyama H, Tei H, Takeda M, Ledbetter DH, Coillie EV, Opdenakker G, Gunge N, Sakaki Y, Iio M, Miura R (Jun 1996). "A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2". Genomics 34 (2): 236–40. doi:10.1006/geno.1996.0274. PMID 8661057. Check date values in: |year= / |date= mismatch (help)
• Nibbs RJ, Yang J, Landau NR, Mao JH, Graham GJ (Jun 1999). "LD78beta, a non-allelic variant of human MIP-1alpha (LD78alpha), has enhanced receptor interactions and potent HIV suppressive activity". The Journal of Biological Chemistry 274 (25): 17478–83. doi:10.1074/jbc.274.25.17478. PMID 10364178.
• Xin X, Shioda T, Kato A, Liu H, Sakai Y, Nagai Y (Aug 1999). "Enhanced anti-HIV-1 activity of CC-chemokine LD78beta, a non-allelic variant of MIP-1alpha/LD78alpha". FEBS Letters 457 (2): 219–22. doi:10.1016/S0014-5793(99)01035-2. PMID 10471782.
• Proost P, Menten P, Struyf S, Schutyser E, De Meester I, Van Damme J (Sep 2000). "Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a most efficient monocyte attractant and CCR1 agonist". Blood 96 (5): 1674–80. PMID 10961862.
• Lambeir AM, Proost P, Durinx C, Bal G, Senten K, Augustyns K, Scharpé S, Van Damme J, De Meester I (Aug 2001). "Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family". The Journal of Biological Chemistry 276 (32): 29839–45. doi:10.1074/jbc.M103106200. PMID 11390394.
• 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.
• 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.
• Townson JR, Barcellos LF, Nibbs RJ (Oct 2002). "Gene copy number regulates the production of the human chemokine CCL3-L1". European Journal of Immunology 32 (10): 3016–26. doi:10.1002/1521-4141(2002010)32:10<3016::AID-IMMU3016>3.0.CO;2-D. PMID 12355456.
• Modi WS (Apr 2004). "CCL3L1 and CCL4L1 chemokine genes are located in a segmental duplication at chromosome 17q12". Genomics 83 (4): 735–8. doi:10.1016/j.ygeno.2003.09.019. PMID 15028295.
• Zhang Z, Henzel WJ (Oct 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science : A Publication of the Protein Society 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161. Check date values in: |year= / |date= mismatch (help)
• Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, Nibbs RJ, Freedman BI, Quinones MP, Bamshad MJ, Murthy KK, Rovin BH, Bradley W, Clark RA, Anderson SA, O'connell RJ, Agan BK, Ahuja SS, Bologna R, Sen L, Dolan MJ, Ahuja SK (Mar 2005). "The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility". Science 307 (5714): 1434–40. doi:10.1126/science.1101160. PMID 15637236.
• Ryu OH, Choi SJ, Firatli E, Choi SW, Hart PS, Shen RF, Wang G, Wu WW, Hart TC (Apr 2005). "Proteolysis of macrophage inflammatory protein-1alpha isoforms LD78beta and LD78alpha by neutrophil-derived serine proteases". The Journal of Biological Chemistry 280 (17): 17415–21. doi:10.1074/jbc.M500340200. PMID 15728180.
• Burns JC, Shimizu C, Gonzalez E, Kulkarni H, Patel S, Shike H, Sundel RS, Newburger JW, Ahuja SK (Jul 2005). "Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease". The Journal of Infectious Diseases 192 (2): 344–9. doi:10.1086/430953. PMC 2894631. PMID 15962231.