CCL8_HUMAN
ID CCL8_HUMAN Reviewed; 99 AA.
AC P80075; A0AV77; P78388;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=C-C motif chemokine 8;
DE AltName: Full=HC14;
DE AltName: Full=Monocyte chemoattractant protein 2;
DE AltName: Full=Monocyte chemotactic protein 2;
DE Short=MCP-2;
DE AltName: Full=Small-inducible cytokine A8;
DE Contains:
DE RecName: Full=MCP-2(6-76);
DE Flags: Precursor;
GN Name=CCL8; Synonyms=MCP2, SCYA10, SCYA8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-69.
RX PubMed=9119400; DOI=10.1006/geno.1996.4594;
RA van Coillie E., Fiten P., Nomiyama H., Sakaki Y., Miura R., Yoshie O.,
RA van Damme J., Opdenakker G.;
RT "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue
RT expression, and assignment to the CC chemokine gene contig on chromosome
RT 17q11.2.";
RL Genomics 40:323-331(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-69.
RC TISSUE=Bone marrow;
RX PubMed=9070881; DOI=10.1006/bbrc.1997.6177;
RA van Coillie E., Froyen F., Nomiyama H., Miura R., Fiten P., van Aelst I.,
RA van Damme J., Opdenakker G.;
RT "Human monocyte chemotactic protein-2: cDNA cloning and regulated
RT expression of mRNA in mesenchymal cells.";
RL Biochem. Biophys. Res. Commun. 231:726-730(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-69.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-99.
RX PubMed=2518726; DOI=10.1093/intimm/1.4.388;
RA Chang H.C., Hsu F., Freeman G.J., Griffin J.D., Reinherz E.L.;
RT "Cloning and expression of a gamma-interferon-inducible gene in monocytes:
RT a new member of a cytokine gene family.";
RL Int. Immunol. 1:388-397(1989).
RN [5]
RP PROTEIN SEQUENCE OF 26-99.
RC TISSUE=Osteosarcoma;
RX PubMed=1613466; DOI=10.1084/jem.176.1.59;
RA van Damme J., Proost P., Lenaerts J.-P., Opdenakker G.;
RT "Structural and functional identification of two human, tumor-derived
RT monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine
RT family.";
RL J. Exp. Med. 176:59-65(1992).
RN [6]
RP SUBUNIT.
RX PubMed=8898111; DOI=10.1016/0014-5793(96)01024-1;
RA Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.;
RT "Structural characterization of a monomeric chemokine: monocyte
RT chemoattractant protein-3.";
RL FEBS Lett. 395:277-282(1996).
RN [7]
RP IDENTIFICATION OF MCP-2(6-76), IDENTIFICATION BY MASS SPECTROMETRY,
RP PROTEOLYTIC PROCESSING OF N-TERMINAL, AND FUNCTION.
RX PubMed=9558113;
RA Proost P., Struyf S., Couvreur M., Lenaerts J.-P., Conings R., Menten P.,
RA Verhaert P., Wuyts A., Van Damme J.;
RT "Posttranslational modifications affect the activity of the human monocyte
RT chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a
RT natural chemokine inhibitor.";
RL J. Immunol. 160:4034-4041(1998).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-99, PYROGLUTAMATE FORMATION AT
RP GLN-24, AND DISULFIDE BONDS.
RX PubMed=11087354; DOI=10.1021/bi0009340;
RA Blaszczyk J., Coillie E.V., Proost P., Damme J.V., Opdenakker G.,
RA Bujacz G.D., Wang J.M., Ji X.;
RT "Complete crystal structure of monocyte chemotactic protein-2, a CC
RT chemokine that interacts with multiple receptors.";
RL Biochemistry 39:14075-14081(2000).
CC -!- FUNCTION: Chemotactic factor that attracts monocytes, lymphocytes,
CC basophils and eosinophils. May play a role in neoplasia and
CC inflammatory host responses. This protein can bind heparin. The
CC processed form MCP-2(6-76) does not show monocyte chemotactic activity,
CC but inhibits the chemotactic effect most predominantly of CCL7, and
CC also of CCL2 and CCL5 and CCL8. {ECO:0000269|PubMed:9558113}.
CC -!- SUBUNIT: Monomer or homodimer; in equilibrium.
CC {ECO:0000269|PubMed:8898111}.
CC -!- INTERACTION:
CC P80075; P13500: CCL2; NbExp=2; IntAct=EBI-16803830, EBI-1034732;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highest expression found in the small intestine and
CC peripheral blood cells. Intermediate levels seen in the heart,
CC placenta, lung, skeletal muscle, thymus, colon, ovary, spinal cord and
CC pancreas. Low levels seen in the brain, liver, spleen and prostate.
CC -!- INDUCTION: By IFNG/IFN-gamma, mitogens and IL1/interleukin-1.
CC -!- PTM: N-terminal processed form MCP-2(6-76) is produced by proteolytic
CC cleavage after secretion from peripheral blood monocytes.
CC {ECO:0000269|PubMed:9558113}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA68168.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL8 entry;
CC URL="https://en.wikipedia.org/wiki/CCL8";
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DR EMBL; X99886; CAA68168.1; ALT_INIT; Genomic_DNA.
DR EMBL; Y10802; CAA71760.1; -; mRNA.
DR EMBL; Y16645; CAA76341.1; -; mRNA.
DR EMBL; BC126242; AAI26243.1; -; mRNA.
DR CCDS; CCDS11280.1; -.
DR PIR; JC5295; JC5295.
DR RefSeq; NP_005614.2; NM_005623.2.
DR PDB; 1ESR; X-ray; 2.00 A; A=24-99.
DR PDB; 7S59; X-ray; 2.39 A; 2/4=24-40.
DR PDB; 7S5A; X-ray; 1.37 A; A/B=24-99.
DR PDBsum; 1ESR; -.
DR PDBsum; 7S59; -.
DR PDBsum; 7S5A; -.
DR AlphaFoldDB; P80075; -.
DR SMR; P80075; -.
DR BioGRID; 112258; 14.
DR DIP; DIP-5871N; -.
DR IntAct; P80075; 12.
DR STRING; 9606.ENSP00000378118; -.
DR DrugBank; DB03088; Pidolic acid.
DR PhosphoSitePlus; P80075; -.
DR BioMuta; CCL8; -.
DR DMDM; 2506280; -.
DR MassIVE; P80075; -.
DR PaxDb; P80075; -.
DR PeptideAtlas; P80075; -.
DR PRIDE; P80075; -.
DR Antibodypedia; 15489; 484 antibodies from 30 providers.
DR DNASU; 6355; -.
DR Ensembl; ENST00000394620.2; ENSP00000378118.1; ENSG00000108700.5.
DR GeneID; 6355; -.
DR KEGG; hsa:6355; -.
DR MANE-Select; ENST00000394620.2; ENSP00000378118.1; NM_005623.3; NP_005614.2.
DR UCSC; uc002hib.4; human.
DR CTD; 6355; -.
DR DisGeNET; 6355; -.
DR GeneCards; CCL8; -.
DR HGNC; HGNC:10635; CCL8.
DR HPA; ENSG00000108700; Low tissue specificity.
DR MIM; 602283; gene.
DR neXtProt; NX_P80075; -.
DR OpenTargets; ENSG00000108700; -.
DR PharmGKB; PA35567; -.
DR VEuPathDB; HostDB:ENSG00000108700; -.
DR eggNOG; ENOG502S8M4; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_1_0_1; -.
DR InParanoid; P80075; -.
DR OMA; SIPVTCC; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P80075; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; P80075; -.
DR SignaLink; P80075; -.
DR BioGRID-ORCS; 6355; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; CCL8; human.
DR EvolutionaryTrace; P80075; -.
DR GeneWiki; CCL8; -.
DR GenomeRNAi; 6355; -.
DR Pharos; P80075; Tbio.
DR PRO; PR:P80075; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P80075; protein.
DR Bgee; ENSG00000108700; Expressed in buccal mucosa cell and 148 other tissues.
DR Genevisible; P80075; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0008009; F:chemokine activity; IBA:GO_Central.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0016004; F:phospholipase activator activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
DR GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
DR GO; GO:0006887; P:exocytosis; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:ARUK-UCL.
DR GO; GO:0070664; P:negative regulation of leukocyte proliferation; IEA:Ensembl.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR000827; Chemokine_CC_CS.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015; PTHR12015; 1.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
DR PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chemotaxis; Cytokine; Direct protein sequencing;
KW Disulfide bond; Heparin-binding; Inflammatory response;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000305|PubMed:11087354,
FT ECO:0000305|PubMed:9558113"
FT CHAIN 24..99
FT /note="C-C motif chemokine 8"
FT /id="PRO_0000005188"
FT CHAIN 29..99
FT /note="MCP-2(6-76)"
FT /id="PRO_0000005189"
FT MOD_RES 24
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:11087354"
FT DISULFID 34..59
FT /evidence="ECO:0000269|PubMed:11087354"
FT DISULFID 35..75
FT /evidence="ECO:0000269|PubMed:11087354"
FT VARIANT 14
FT /note="A -> V (in dbSNP:rs35401229)"
FT /id="VAR_048704"
FT VARIANT 69
FT /note="K -> Q (in dbSNP:rs1133763)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9070881, ECO:0000269|PubMed:9119400"
FT /id="VAR_001633"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:7S5A"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:7S5A"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:7S5A"
FT STRAND 48..54
FT /evidence="ECO:0007829|PDB:7S5A"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:7S5A"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:7S5A"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:7S5A"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:7S5A"
SQ SEQUENCE 99 AA; 11246 MW; 9D67976BB9422F2A CRC64;
MKVSAALLCL LLMAATFSPQ GLAQPDSVSI PITCCFNVIN RKIPIQRLES YTRITNIQCP
KEAVIFKTKR GKEVCADPKE RWVRDSMKHL DQIFQNLKP
