CCL13_HUMAN
ID CCL13_HUMAN Reviewed; 98 AA.
AC Q99616; O95689; Q6ICQ6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=C-C motif chemokine 13;
DE AltName: Full=CK-beta-10;
DE AltName: Full=Monocyte chemoattractant protein 4;
DE AltName: Full=Monocyte chemotactic protein 4;
DE Short=MCP-4;
DE AltName: Full=NCC-1;
DE AltName: Full=Small-inducible cytokine A13;
DE Contains:
DE RecName: Full=C-C motif chemokine 13, long chain;
DE Contains:
DE RecName: Full=C-C motif chemokine 13, medium chain;
DE Contains:
DE RecName: Full=C-C motif chemokine 13, short chain;
DE Flags: Precursor;
GN Name=CCL13; Synonyms=MCP4, NCC1, SCYA13;
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 [MRNA].
RC TISSUE=Lung;
RA Power C.A., Meyer A., Rison S.C.G., Guye-Coulin F., Wells T.N.C.;
RT "Cloning and characterization of MCP-4, a novel CC chemokine related to
RT MCP-1 and eotaxin.";
RL Eur. Cytokine Netw. 7:513-513(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8955214;
RA Garcia-Zepeda E.A., Combadiere C., Rothenberg M.E., Sarafi M.N.,
RA Lavigne F., Hamid Q., Murphy P.M., Luster A.D.;
RT "Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine
RT with activities on monocytes, eosinophils, and basophils induced in
RT allergic and nonallergic inflammation that signals through the CC chemokine
RT receptors (CCR)-2 and -3.";
RL J. Immunol. 157:5613-5626(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-98, PYROGLUTAMATE
RP FORMATION AT GLN-24, AND MASS SPECTROMETRY.
RC TISSUE=Fetus;
RX PubMed=8642349; DOI=10.1084/jem.183.5.2379;
RA Uguccioni M., Loetscher P., Forssmann U., Dewald B., Li H., Lima S.H.,
RA Li Y., Kreider B., Garotta G., Thelen M., Baggiolini M.;
RT "Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional
RT analogue of MCP-3 and eotaxin.";
RL J. Exp. Med. 183:2379-2384(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-33, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Fetus;
RX PubMed=9195948; DOI=10.1074/jbc.272.26.16404;
RA Berkhout T.A., Sarau H.M., Moores K., White J.R., Elshourbagy N.,
RA Appelbaum E., Reape T.J., Brawner M., Makwana J., Foley J.J., Schmidt D.B.,
RA Imburgia C., Macnulty D., Matthews J., O'Donnell K., O'Shannessy D.,
RA Scott M., Groot P.H.E., Macphee C.;
RT "Cloning, in vitro expression, and functional characterization of a novel
RT human CC chemokine of the monocyte chemotactic protein (MCP) family (MCP-4)
RT that binds and signals through the CC chemokine receptor 2B.";
RL J. Biol. Chem. 272:16404-16413(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9060459; DOI=10.1002/jlb.61.3.353;
RA Godiska R., Chantry D., Raport C.J., Schweickart V.L., Trong H.L.,
RA Gray P.W.;
RT "Monocyte chemotactic protein-4: tissue-specific expression and signaling
RT through CC chemokine receptor-2.";
RL J. Leukoc. Biol. 61:353-360(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin fibroblast;
RX PubMed=10049733; DOI=10.1006/bbrc.1999.0216;
RA Hein H., Schluter C., Kulke R., Christophers E., Schroeder J.-M.,
RA Bartels J.;
RT "Genomic organization, sequence analysis and transcriptional regulation of
RT the human MCP-4 chemokine gene (SCYA13) in dermal fibroblasts: a comparison
RT to other eosinophilic beta-chemokines.";
RL Biochem. Biophys. Res. Commun. 255:470-476(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-95.
RC TISSUE=Foreskin;
RA Bartels J.H., Schlueter C., Richter E., Noso N., Christophers E.,
RA Schroeder J.-M.;
RT "Expression of a MCP-4 like novel CC-chemokine in human dermal fibroblasts:
RT molecular cloning and RT-PCR analysis.";
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 24-98, AND DISULFIDE BONDS.
RX PubMed=18323622; DOI=10.1107/s0907444907066164;
RA Barinka C., Prahl A., Lubkowski J.;
RT "Structure of human monocyte chemoattractant protein 4 (MCP-4/CCL13).";
RL Acta Crystallogr. D 64:273-278(2008).
CC -!- FUNCTION: Chemotactic factor that attracts monocytes, lymphocytes,
CC basophils and eosinophils, but not neutrophils. Signals through CCR2B
CC and CCR3 receptors. Plays a role in the accumulation of leukocytes at
CC both sides of allergic and non-allergic inflammation. May be involved
CC in the recruitment of monocytes into the arterial wall during the
CC disease process of atherosclerosis. May play a role in the monocyte
CC attraction in tissues chronically exposed to exogenous pathogens.
CC -!- INTERACTION:
CC Q99616; O00585: CCL21; NbExp=2; IntAct=EBI-725342, EBI-953695;
CC Q99616; Q9Y258: CCL26; NbExp=2; IntAct=EBI-725342, EBI-7783416;
CC Q99616; P13501: CCL5; NbExp=3; IntAct=EBI-725342, EBI-2848366;
CC Q99616; P02778: CXCL10; NbExp=2; IntAct=EBI-725342, EBI-7815386;
CC Q99616; O14625: CXCL11; NbExp=2; IntAct=EBI-725342, EBI-2871971;
CC Q99616; P48061: CXCL12; NbExp=2; IntAct=EBI-725342, EBI-3913254;
CC Q99616; P02776: PF4; NbExp=2; IntAct=EBI-725342, EBI-2565740;
CC Q99616; P47992: XCL1; NbExp=2; IntAct=EBI-725342, EBI-10209901;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Widely expressed. Found in small intestine, thymus,
CC colon, lung, trachea, stomach and lymph node. Low levels seen in the
CC pulmonary artery smooth muscle cells.
CC -!- INDUCTION: By IL1/interleukin-1 and TNF.
CC -!- PTM: One major form (form long), and two minor forms (short chain and
CC medium chain) are produced by differential signal peptide cleavage. The
CC medium chain is about 30-fold less active than the long chain.
CC -!- MASS SPECTROMETRY: [C-C motif chemokine 13, long chain]: Mass=9314;
CC Mass_error=30; Method=MALDI; Evidence={ECO:0000269|PubMed:8642349};
CC -!- MASS SPECTROMETRY: [C-C motif chemokine 13, medium chain]: Mass=8760;
CC Mass_error=30; Method=MALDI; Evidence={ECO:0000269|PubMed:8642349};
CC -!- MASS SPECTROMETRY: [C-C motif chemokine 13, short chain]: Mass=8575;
CC Mass_error=30; Method=MALDI; Evidence={ECO:0000269|PubMed:8642349};
CC -!- MISCELLANEOUS: This protein can bind heparin.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL13 entry;
CC URL="https://en.wikipedia.org/wiki/CCL13";
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DR EMBL; U46767; AAB38703.1; -; mRNA.
DR EMBL; X98306; CAA66950.1; -; mRNA.
DR EMBL; U59808; AAD09362.1; -; mRNA.
DR EMBL; AJ001634; CAA04888.1; -; mRNA.
DR EMBL; BT007385; AAP36049.1; -; mRNA.
DR EMBL; AC002482; AAB67307.1; -; Genomic_DNA.
DR EMBL; CR450337; CAG29333.1; -; mRNA.
DR EMBL; CH471147; EAW80206.1; -; Genomic_DNA.
DR EMBL; BC008621; AAH08621.1; -; mRNA.
DR EMBL; Z77650; CAB01111.1; -; mRNA.
DR CCDS; CCDS11281.1; -.
DR RefSeq; NP_005399.1; NM_005408.2.
DR PDB; 2RA4; X-ray; 1.70 A; A/B=24-98.
DR PDBsum; 2RA4; -.
DR AlphaFoldDB; Q99616; -.
DR SMR; Q99616; -.
DR BioGRID; 112260; 21.
DR DIP; DIP-5874N; -.
DR IntAct; Q99616; 18.
DR STRING; 9606.ENSP00000225844; -.
DR PhosphoSitePlus; Q99616; -.
DR BioMuta; CCL13; -.
DR DMDM; 3024128; -.
DR MassIVE; Q99616; -.
DR PaxDb; Q99616; -.
DR PeptideAtlas; Q99616; -.
DR PRIDE; Q99616; -.
DR Antibodypedia; 15496; 408 antibodies from 27 providers.
DR DNASU; 6357; -.
DR Ensembl; ENST00000225844.7; ENSP00000225844.2; ENSG00000181374.8.
DR GeneID; 6357; -.
DR KEGG; hsa:6357; -.
DR MANE-Select; ENST00000225844.7; ENSP00000225844.2; NM_005408.3; NP_005399.1.
DR UCSC; uc002hic.3; human.
DR CTD; 6357; -.
DR DisGeNET; 6357; -.
DR GeneCards; CCL13; -.
DR HGNC; HGNC:10611; CCL13.
DR HPA; ENSG00000181374; Tissue enhanced (intestine, urinary bladder).
DR MIM; 601391; gene.
DR neXtProt; NX_Q99616; -.
DR OpenTargets; ENSG00000181374; -.
DR PharmGKB; PA35544; -.
DR VEuPathDB; HostDB:ENSG00000181374; -.
DR eggNOG; ENOG502S776; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_1_0_1; -.
DR InParanoid; Q99616; -.
DR OMA; STCCFIF; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; Q99616; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; Q99616; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; Q99616; -.
DR BioGRID-ORCS; 6357; 15 hits in 1055 CRISPR screens.
DR EvolutionaryTrace; Q99616; -.
DR GenomeRNAi; 6357; -.
DR Pharos; Q99616; Tbio.
DR PRO; PR:Q99616; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q99616; protein.
DR Bgee; ENSG00000181374; Expressed in mucosa of transverse colon and 122 other tissues.
DR ExpressionAtlas; Q99616; baseline and differential.
DR Genevisible; Q99616; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; TAS:ProtInc.
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:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0048245; P:eosinophil chemotaxis; 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: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:0008360; P:regulation of cell shape; IDA:UniProtKB.
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; Inflammatory response; Pyrrolidone carboxylic acid;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:8642349"
FT CHAIN 17..98
FT /note="C-C motif chemokine 13, long chain"
FT /id="PRO_0000005201"
FT CHAIN 22..98
FT /note="C-C motif chemokine 13, medium chain"
FT /id="PRO_0000005202"
FT CHAIN 24..98
FT /note="C-C motif chemokine 13, short chain"
FT /id="PRO_0000005203"
FT MOD_RES 24
FT /note="Pyrrolidone carboxylic acid; in short chain"
FT /evidence="ECO:0000269|PubMed:8642349"
FT DISULFID 34..58
FT /evidence="ECO:0000269|PubMed:18323622"
FT DISULFID 35..74
FT /evidence="ECO:0000269|PubMed:18323622"
FT VARIANT 5
FT /note="A -> S (in dbSNP:rs3136677)"
FT /id="VAR_024169"
FT VARIANT 29
FT /note="N -> S (in dbSNP:rs34566308)"
FT /id="VAR_048706"
FT CONFLICT 93..98
FT /note="AHTLKT -> LTP (in Ref. 12; CAB01111)"
FT /evidence="ECO:0000305"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:2RA4"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:2RA4"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:2RA4"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:2RA4"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2RA4"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:2RA4"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:2RA4"
SQ SEQUENCE 98 AA; 10986 MW; 612688DFCD308873 CRC64;
MKVSAVLLCL LLMTAAFNPQ GLAQPDALNV PSTCCFTFSS KKISLQRLKS YVITTSRCPQ
KAVIFRTKLG KEICADPKEK WVQNYMKHLG RKAHTLKT
