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C-C motif chemokine 8 (HC14) (Monocyte chemoattractant protein 2) (Monocyte chemotactic protein 2) (MCP-2) (Small-inducible cytokine A8) [Cleaved into: MCP-2(6-76)]

 CCL8_HUMAN              Reviewed;          99 AA.
P80075; A0AV77; P78388;
01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
01-NOV-1997, sequence version 2.
10-APR-2019, entry version 179.
RecName: Full=C-C motif chemokine 8;
AltName: Full=HC14;
AltName: Full=Monocyte chemoattractant protein 2;
AltName: Full=Monocyte chemotactic protein 2;
Short=MCP-2;
AltName: Full=Small-inducible cytokine A8;
Contains:
RecName: Full=MCP-2(6-76);
Flags: Precursor;
Name=CCL8; Synonyms=MCP2, SCYA10, SCYA8;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-69.
PubMed=9119400; DOI=10.1006/geno.1996.4594;
van Coillie E., Fiten P., Nomiyama H., Sakaki Y., Miura R., Yoshie O.,
van Damme J., Opdenakker G.;
"The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue
expression, and assignment to the CC chemokine gene contig on
chromosome 17q11.2.";
Genomics 40:323-331(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-69.
TISSUE=Bone marrow;
PubMed=9070881; DOI=10.1006/bbrc.1997.6177;
van Coillie E., Froyen F., Nomiyama H., Miura R., Fiten P.,
van Aelst I., van Damme J., Opdenakker G.;
"Human monocyte chemotactic protein-2: cDNA cloning and regulated
expression of mRNA in mesenchymal cells.";
Biochem. Biophys. Res. Commun. 231:726-730(1997).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-69.
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 23-99.
PubMed=2518726; DOI=10.1093/intimm/1.4.388;
Chang H.C., Hsu F., Freeman G.J., Griffin J.D., Reinherz E.L.;
"Cloning and expression of a gamma-interferon-inducible gene in
monocytes: a new member of a cytokine gene family.";
Int. Immunol. 1:388-397(1989).
[5]
PROTEIN SEQUENCE OF 26-99.
TISSUE=Osteosarcoma;
PubMed=1613466; DOI=10.1084/jem.176.1.59;
van Damme J., Proost P., Lenaerts J.-P., Opdenakker G.;
"Structural and functional identification of two human, tumor-derived
monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the
chemokine family.";
J. Exp. Med. 176:59-65(1992).
[6]
SUBUNIT.
PubMed=8898111; DOI=10.1016/0014-5793(96)01024-1;
Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.;
"Structural characterization of a monomeric chemokine: monocyte
chemoattractant protein-3.";
FEBS Lett. 395:277-282(1996).
[7]
IDENTIFICATION OF MCP-2(6-76), IDENTIFICATION BY MASS SPECTROMETRY,
PROTEOLYTIC PROCESSING OF N-TERMINAL, AND FUNCTION.
PubMed=9558113;
Proost P., Struyf S., Couvreur M., Lenaerts J.-P., Conings R.,
Menten P., Verhaert P., Wuyts A., Van Damme J.;
"Posttranslational modifications affect the activity of the human
monocyte chemotactic proteins MCP-1 and MCP-2: identification of MCP-
2(6-76) as a natural chemokine inhibitor.";
J. Immunol. 160:4034-4041(1998).
[8]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-99, PYROGLUTAMATE
FORMATION AT GLN-24, AND DISULFIDE BONDS.
PubMed=11087354; DOI=10.1021/bi0009340;
Blaszczyk J., Coillie E.V., Proost P., Damme J.V., Opdenakker G.,
Bujacz G.D., Wang J.M., Ji X.;
"Complete crystal structure of monocyte chemotactic protein-2, a CC
chemokine that interacts with multiple receptors.";
Biochemistry 39:14075-14081(2000).
-!- FUNCTION: Chemotactic factor that attracts monocytes, lymphocytes,
basophils and eosinophils. May play a role in neoplasia and
inflammatory host responses. This protein can bind heparin. The
processed form MCP-2(6-76) does not show monocyte chemotactic
activity, but inhibits the chemotactic effect most predominantly
of CCL7, and also of CCL2 and CCL5 and CCL8.
{ECO:0000269|PubMed:9558113}.
-!- SUBUNIT: Monomer or homodimer; in equilibrium.
{ECO:0000269|PubMed:8898111}.
-!- INTERACTION:
P13500:CCL2; NbExp=2; IntAct=EBI-16803830, EBI-1034732;
-!- SUBCELLULAR LOCATION: Secreted.
-!- TISSUE SPECIFICITY: Highest expression found in the small
intestine and peripheral blood cells. Intermediate levels seen in
the heart, placenta, lung, skeletal muscle, thymus, colon, ovary,
spinal cord and pancreas. Low levels seen in the brain, liver,
spleen and prostate.
-!- INDUCTION: By IFNG/IFN-gamma, mitogens and IL1/interleukin-1.
-!- PTM: N-terminal processed form MCP-2(6-76) is produced by
proteolytic cleavage after secretion from peripheral blood
monocytes. {ECO:0000269|PubMed:9558113}.
-!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=CAA68168.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
-!- WEB RESOURCE: Name=Wikipedia; Note=CCL8 entry;
URL="https://en.wikipedia.org/wiki/CCL8";
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; X99886; CAA68168.1; ALT_INIT; Genomic_DNA.
EMBL; Y10802; CAA71760.1; -; mRNA.
EMBL; Y16645; CAA76341.1; -; mRNA.
EMBL; BC126242; AAI26243.1; -; mRNA.
CCDS; CCDS11280.1; -.
PIR; JC5295; JC5295.
RefSeq; NP_005614.2; NM_005623.2.
UniGene; Hs.271387; -.
PDB; 1ESR; X-ray; 2.00 A; A=24-99.
PDBsum; 1ESR; -.
ProteinModelPortal; P80075; -.
SMR; P80075; -.
BioGrid; 112258; 2.
DIP; DIP-5871N; -.
IntAct; P80075; 12.
STRING; 9606.ENSP00000378118; -.
DrugBank; DB03088; Pyroglutamic Acid.
PhosphoSitePlus; P80075; -.
BioMuta; CCL8; -.
DMDM; 2506280; -.
PaxDb; P80075; -.
PeptideAtlas; P80075; -.
PRIDE; P80075; -.
ProteomicsDB; 57664; -.
DNASU; 6355; -.
Ensembl; ENST00000394620; ENSP00000378118; ENSG00000108700.
GeneID; 6355; -.
KEGG; hsa:6355; -.
UCSC; uc002hib.4; human.
CTD; 6355; -.
DisGeNET; 6355; -.
EuPathDB; HostDB:ENSG00000108700.4; -.
GeneCards; CCL8; -.
HGNC; HGNC:10635; CCL8.
MIM; 602283; gene.
neXtProt; NX_P80075; -.
OpenTargets; ENSG00000108700; -.
PharmGKB; PA35567; -.
eggNOG; ENOG410J1ST; Eukaryota.
eggNOG; ENOG410YXJU; LUCA.
GeneTree; ENSGT00950000182671; -.
HOGENOM; HOG000036686; -.
HOVERGEN; HBG017871; -.
InParanoid; P80075; -.
KO; K16596; -.
OMA; VIFKTKW; -.
OrthoDB; 1575018at2759; -.
PhylomeDB; P80075; -.
TreeFam; TF334888; -.
ChiTaRS; CCL8; human.
EvolutionaryTrace; P80075; -.
GeneWiki; CCL8; -.
GenomeRNAi; 6355; -.
PMAP-CutDB; P80075; -.
PRO; PR:P80075; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000108700; Expressed in 168 organ(s), highest expression level in decidua.
Genevisible; P80075; HS.
GO; GO:0005623; C:cell; IEA:GOC.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
GO; GO:0008009; F:chemokine activity; IBA:GO_Central.
GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
GO; GO:0016004; F:phospholipase activator activity; IDA:UniProtKB.
GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
GO; GO:0007267; P:cell-cell signaling; IDA:UniProtKB.
GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
GO; GO:0006887; P:exocytosis; IDA:UniProtKB.
GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
GO; GO:0031640; P:killing of cells of other organism; IDA:UniProtKB.
GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:ARUK-UCL.
GO; GO:0070664; P:negative regulation of leukocyte proliferation; IEA:Ensembl.
GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
GO; GO:0002687; P:positive regulation of leukocyte migration; IEA:Ensembl.
GO; GO:0009615; P:response to virus; TAS:ProtInc.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
InterPro; IPR039809; Chemokine_b/g/d.
InterPro; IPR000827; Chemokine_CC_CS.
InterPro; IPR001811; Chemokine_IL8-like_dom.
InterPro; IPR036048; Interleukin_8-like_sf.
PANTHER; PTHR12015; PTHR12015; 1.
Pfam; PF00048; IL8; 1.
SMART; SM00199; SCY; 1.
SUPFAM; SSF54117; SSF54117; 1.
PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
1: Evidence at protein level;
3D-structure; Chemotaxis; Complete proteome; Cytokine;
Direct protein sequencing; Disulfide bond; Heparin-binding;
Inflammatory response; Polymorphism; Pyrrolidone carboxylic acid;
Reference proteome; Secreted; Signal.
SIGNAL 1 23 {ECO:0000305|PubMed:11087354,
ECO:0000305|PubMed:9558113}.
CHAIN 24 99 C-C motif chemokine 8.
/FTId=PRO_0000005188.
CHAIN 29 99 MCP-2(6-76).
/FTId=PRO_0000005189.
MOD_RES 24 24 Pyrrolidone carboxylic acid.
{ECO:0000269|PubMed:11087354}.
DISULFID 34 59 {ECO:0000269|PubMed:11087354}.
DISULFID 35 75 {ECO:0000269|PubMed:11087354}.
VARIANT 14 14 A -> V (in dbSNP:rs35401229).
/FTId=VAR_048704.
VARIANT 69 69 K -> Q (in dbSNP:rs1133763).
{ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:9070881,
ECO:0000269|PubMed:9119400}.
/FTId=VAR_001633.
TURN 26 29 {ECO:0000244|PDB:1ESR}.
HELIX 45 47 {ECO:0000244|PDB:1ESR}.
STRAND 48 53 {ECO:0000244|PDB:1ESR}.
STRAND 59 61 {ECO:0000244|PDB:1ESR}.
STRAND 64 68 {ECO:0000244|PDB:1ESR}.
STRAND 73 76 {ECO:0000244|PDB:1ESR}.
HELIX 81 96 {ECO:0000244|PDB:1ESR}.
SEQUENCE 99 AA; 11246 MW; 9D67976BB9422F2A CRC64;
MKVSAALLCL LLMAATFSPQ GLAQPDSVSI PITCCFNVIN RKIPIQRLES YTRITNIQCP
KEAVIFKTKR GKEVCADPKE RWVRDSMKHL DQIFQNLKP


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Pathways :
WP2292: Chemokine signaling pathway
WP1049: G Protein Signaling Pathways
WP1165: G Protein Signaling Pathways
WP1371: G Protein Signaling Pathways
WP1438: Influenza A virus infection
WP1493: Carbon assimilation C4 pathway
WP1502: Mitochondrial biogenesis
WP1531: Vitamin D synthesis
WP1566: Citrate cycle (TCA cycle)
WP1613: 1,4-Dichlorobenzene degradation
WP1616: ABC transporters
WP1624: Bacterial secretion system
WP1625: Base excision repair
WP1644: DNA replication
WP1650: Fluorobenzoate degradation
WP1654: gamma-Hexachlorocyclohexane degradation
WP1657: Glycerolipid metabolism
WP1659: Glycine, serine and threonine metabolism
WP1661: Glyoxylate and dicarboxylate metabolism
WP1663: Homologous recombination
WP1665: Limonene and pinene degradation
WP1672: Mismatch repair
WP1673: Naphthalene and anthracene degradation
WP1675: Nitrogen metabolism
WP1676: Non-homologous end-joining

Related Genes :
[CCL8 MCP2 SCYA10 SCYA8] C-C motif chemokine 8 (HC14) (Monocyte chemoattractant protein 2) (Monocyte chemotactic protein 2) (MCP-2) (Small-inducible cytokine A8) [Cleaved into: MCP-2(6-76)]
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (HC11) (Monocyte chemoattractant protein 1) (Monocyte chemotactic and activating factor) (MCAF) (Monocyte chemotactic protein 1) (MCP-1) (Monocyte secretory protein JE) (Small-inducible cytokine A2)
[Ccl2 Je Mcp1 Scya2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Platelet-derived growth factor-inducible protein JE) (Small-inducible cytokine A2)
[CCL8 MCP2 SCYA8] C-C motif chemokine 8 (Monocyte chemoattractant protein 2) (Monocyte chemotactic protein 2) (MCP-2) (Small-inducible cytokine A8)
[Ccl2 Je Mcp1 Scya2] C-C motif chemokine 2 (Immediate-early serum-responsive protein JE) (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)
[CCL2 SCYA2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)
[Ccl8 Mcp2 Scya8] C-C motif chemokine 8 (Monocyte chemoattractant protein 2) (Monocyte chemotactic protein 2) (MCP-2) (Small-inducible cytokine A8)
[CCL8 MCP2] C-C motif chemokine 8 (Monocyte chemoattractant protein 2) (Monocyte chemotactic protein 2) (MCP-2) (Small-inducible cytokine A8)
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)
[CCL2 SCYA2] C-C motif chemokine 2 (Acidic seminal fluid protein) (Monocyte chemotactic protein 1A) (MCP-1) (MCP-1A) (Small-inducible cytokine A2)
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)
[CCL8 MCP2 SCYA8] C-C motif chemokine 8 (Monocyte chemoattractant protein 2) (Monocyte chemotactic protein 2) (MCP-2) (Small-inducible cytokine A8)
[CCR2 CMKBR2] C-C chemokine receptor type 2 (C-C CKR-2) (CC-CKR-2) (CCR-2) (CCR2) (Monocyte chemoattractant protein 1 receptor) (MCP-1-R) (CD antigen CD192)
[Zc3h12a Mcpip Mcpip1] Endoribonuclease ZC3H12A (EC 3.1.-.-) (Monocyte chemotactic protein-induced protein 1) (MCP-induced protein 1) (MCPIP-1) (Regnase-1) (Reg1) (Zinc finger CCCH domain-containing protein 12A)
[Ccl11 Scya11] Eotaxin (C-C motif chemokine 11) (Eosinophil chemotactic protein) (Small-inducible cytokine A11)
[Ccl1 Scya1 Tca3] C-C motif chemokine 1 (P500) (SIS-epsilon) (Small-inducible cytokine A1) (T-cell activation protein 3) (TCA-3) (TCA3)
[Ccl21a Scya21 Scya21a] C-C motif chemokine 21a (6Ckine) (Beta-chemokine exodus-2) (Small-inducible cytokine A21a) (Thymus-derived chemotactic agent 4) (TCA4)
[Cxcl10 Crg2 Ifi10 Inp10 Scyb10] C-X-C motif chemokine 10 (10 kDa interferon gamma-induced protein) (Gamma-IP10) (IP-10) (C7) (Interferon-gamma induced protein CRG-2) (Small-inducible cytokine B10)
[ZC3H12A MCPIP MCPIP1] Endoribonuclease ZC3H12A (EC 3.1.-.-) (Monocyte chemotactic protein-induced protein 1) (MCP-induced protein 1) (MCPIP-1) (Regnase-1) (Reg1) (Zinc finger CCCH domain-containing protein 12A)
[Ccl21b Scya21 Scya21b] C-C motif chemokine 21b (6Ckine) (Beta-chemokine exodus-2) (Small-inducible cytokine A21b) (Thymus-derived chemotactic agent 4) (TCA4)
[CCL15 MIP5 NCC3 SCYA15] C-C motif chemokine 15 (Chemokine CC-2) (HCC-2) (Leukotactin-1) (LKN-1) (MIP-1 delta) (Macrophage inflammatory protein 5) (MIP-5) (Mrp-2b) (NCC-3) (Small-inducible cytokine A15) [Cleaved into: CCL15(22-92); CCL15(25-92); CCL15(29-92)]
[Ccl24 Scya24] C-C motif chemokine 24 (Eosinophil chemotactic protein 2) (Eotaxin-2) (Small-inducible cytokine A24)
[S100a8 Caga Mrp8] Protein S100-A8 (Calgranulin-A) (Chemotactic cytokine CP-10) (Leukocyte L1 complex light chain) (Migration inhibitory factor-related protein 8) (MRP-8) (p8) (Pro-inflammatory S100 cytokine) (S100 calcium-binding protein A8)
[Ccr2 Cmkbr2] C-C chemokine receptor type 2 (C-C CKR-2) (CC-CKR-2) (CCR-2) (CCR2) (JE/FIC receptor) (MCP-1 receptor) (CD antigen CD192)
[env] Envelope glycoprotein gp160 (Env polyprotein) [Cleaved into: Surface protein gp120 (SU) (Glycoprotein 120) (gp120); Transmembrane protein gp41 (TM) (Glycoprotein 41) (gp41)]
[CCL4L1 CCL4L LAG1 SCYA4L1; CCL4L2 CCL4L SCYA4L2] C-C motif chemokine 4-like (Lymphocyte activation gene 1 protein) (LAG-1) (Macrophage inflammatory protein 1-beta) (MIP-1-beta) (Monocyte adherence-induced protein 5-alpha) (Small-inducible cytokine A4-like)
[CXCL11 ITAC SCYB11 SCYB9B] C-X-C motif chemokine 11 (Beta-R1) (H174) (Interferon gamma-inducible protein 9) (IP-9) (Interferon-inducible T-cell alpha chemoattractant) (I-TAC) (Small-inducible cytokine B11)
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (Monocyte chemoattractant protein 1) (Monocyte chemotactic protein 1) (MCP-1) (Small-inducible cytokine A2)

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