CCL18_HUMAN
ID CCL18_HUMAN Reviewed; 89 AA.
AC P55774; B5BUM2; Q53X71;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=C-C motif chemokine 18;
DE AltName: Full=Alternative macrophage activation-associated CC chemokine 1;
DE Short=AMAC-1;
DE AltName: Full=CC chemokine PARC;
DE AltName: Full=Dendritic cell chemokine 1;
DE Short=DC-CK1;
DE AltName: Full=Macrophage inflammatory protein 4;
DE Short=MIP-4;
DE AltName: Full=Pulmonary and activation-regulated chemokine;
DE AltName: Full=Small-inducible cytokine A18;
DE Contains:
DE RecName: Full=CCL18(1-68);
DE Contains:
DE RecName: Full=CCL18(3-69);
DE Contains:
DE RecName: Full=CCL18(4-69);
DE Flags: Precursor;
GN Name=CCL18; Synonyms=AMAC1, DCCK1, MIP4, PARC, SCYA18;
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].
RA Li H., Ruben S.;
RT "Macrophage inflammatory protein-3 and -4.";
RL Patent number US5504003, 02-APR-1996.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Aorta, and Lung;
RX PubMed=9233607;
RA Hieshima K., Imai T., Baba M., Shoudai K., Ishizuka K., Nakagawa T.,
RA Tsuruta J., Takeya M., Sakaki Y., Takatsuki K., Miura R., Opdenakker G.,
RA van Damme J., Yoshie O., Nomiyama H.;
RT "A novel human CC chemokine PARC that is most homologous to macrophage-
RT inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes,
RT but not for monocytes.";
RL J. Immunol. 159:1140-1149(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9570561;
RA Kodelja V., Mueller C., Politz O., Hakij N., Orfanos C.E., Goerdt S.;
RT "Alternative macrophage activation-associated CC-chemokine-1, a novel
RT structural homologue of macrophage inflammatory protein-1 alpha with a Th2-
RT associated expression pattern.";
RL J. Immunol. 160:1411-1418(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF N-TERMINUS.
RC TISSUE=Dendritic cell;
RX PubMed=9192897; DOI=10.1038/42716;
RA Adema G.J., Hartgers F., Verstraten R., de Vries E., Marland G., Menon S.,
RA Foster J., Xu Y., Nooyen P., McClanahan T., Bacon K.B., Figdor C.G.;
RT "A dendritic-cell-derived C-C chemokine that preferentially attracts naive
RT T cells.";
RL Nature 387:713-717(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10049593; DOI=10.1006/geno.1998.5670;
RA Tasaki Y., Fukuda S., Iio M., Miura R., Imai T., Sugano S., Yoshie O.,
RA Hughes A.L., Nomiyama H.;
RT "Chemokine PARC gene (SCYA18) generated by fusion of two MIP-
RT 1alpha/LD78alpha-like genes.";
RL Genomics 55:353-357(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RX PubMed=10087196; DOI=10.1006/geno.1998.5635;
RA Guan P., Burghes A.H.M., Cunningham A., Lira P., Brissette W.H., Neote K.,
RA McColl S.R.;
RT "Genomic organization and biological characterization of the novel human CC
RT chemokine DC-CK-1/PARC/MIP-4/SCYA18.";
RL Genomics 56:296-302(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Politz O., Kodelja V., Guillot P., Orfanos C.E., Goerdt S.;
RT "The genomic locus for the AMAC-1 gene contains possible pseudo-exons
RT within the first intron sequence.";
RL Submitted (DEC-1998) 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].
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 DISCUSSION OF SEQUENCE.
RX PubMed=9129202; DOI=10.1002/jlb.61.5.545;
RA Wells T.N.C., Peitsch M.C.;
RT "The chemokine information source: identification and characterization of
RT novel chemokines using the WorldWideWeb and expressed sequence tag
RT databases.";
RL J. Leukoc. Biol. 61:545-550(1997).
RN [13]
RP IDENTIFICATION OF CCL18(3-69) AND CCL18(4-69), PROTEOLYTIC PROCESSING OF
RP N-TERMINAL, FUNCTION, MASS SPECTROMETRY, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11745396;
RX DOI=10.1002/1521-4141(200112)31:12<3755::aid-immu3755>3.0.co;2-o;
RA Schutyser E., Struyf S., Wuyts A., Put W., Geboes K., Grillet B.,
RA Opdenakker G., Van Damme J.;
RT "Selective induction of CCL18/PARC by staphylococcal enterotoxins in
RT mononuclear cells and enhanced levels in septic and rheumatoid arthritis.";
RL Eur. J. Immunol. 31:3755-3762(2001).
RN [14]
RP IDENTIFICATION OF CCL18(1-68), PROTEOLYTIC PROCESSING OF C-TERMINAL, AND
RP FUNCTION.
RX PubMed=11978786; DOI=10.1074/jbc.m112275200;
RA Schutyser E., Struyf S., Proost P., Opdenakker G., Laureys G.,
RA Verhasselt B., Peperstraete L., Van de Putte I., Saccani A., Allavena P.,
RA Mantovani A., Van Damme J.;
RT "Identification of biologically active chemokine isoforms from ascitic
RT fluid and elevated levels of CCL18/pulmonary and activation-regulated
RT chemokine in ovarian carcinoma.";
RL J. Biol. Chem. 277:24584-24593(2002).
RN [15]
RP DISULFIDE BONDS.
RX PubMed=23742785; DOI=10.1016/j.cyto.2013.04.028;
RA Legendre B., Tokarski C., Chang Y., De Freitas Caires N., Lortat-Jacob H.,
RA Nadai P.D., Rolando C., Duez C., Tsicopoulos A., Lassalle P.;
RT "The disulfide bond between cysteine 10 and cysteine 34 is required for
RT CCL18 activity.";
RL Cytokine 64:463-470(2013).
CC -!- FUNCTION: Chemotactic factor that attracts lymphocytes but not
CC monocytes or granulocytes. May be involved in B-cell migration into B-
CC cell follicles in lymph nodes. Attracts naive T-lymphocytes toward
CC dendritic cells and activated macrophages in lymph nodes, has
CC chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus
CC may play a role in both humoral and cell-mediated immunity responses.
CC {ECO:0000269|PubMed:11745396, ECO:0000269|PubMed:11978786}.
CC -!- INTERACTION:
CC P55774; Q9BZ71: PITPNM3; NbExp=4; IntAct=EBI-711240, EBI-2815766;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in lung, lymph nodes,
CC placenta, bone marrow, dendritic cells present in germinal centers and
CC T-cell areas of secondary lymphoid organs and macrophages derived from
CC peripheral blood monocytes. Not expressed by peripheral blood monocytes
CC and a monocyte-to-macrophage differentiation is a prerequisite for
CC expression. Expressed in synovial fluids from patients with rheumatoid
CC and septic arthritis and in ovarian carcinoma ascitic fluid.
CC {ECO:0000269|PubMed:11745396}.
CC -!- INDUCTION: Specifically induced in macrophages by IL4/interleukin-4,
CC IL13/interleukin-13, and IL10/interleukin-10. Expression is inhibited
CC by IFNG/IFN-gamma while glucocorticoids exert a slightly positive
CC synergistic effect in combination with IL4/interleukin-4. Strongly
CC induced in several human cell lines, including monocytic U-937 cells,
CC by phorbol myristate acetate (PMA). Induced in PBMC by staphylococcal
CC enterotoxins SEA and SEB. {ECO:0000269|PubMed:11745396}.
CC -!- PTM: The Cys-30/Cys-54 disulfide bond is required for activity.
CC -!- MASS SPECTROMETRY: [C-C motif chemokine 18]: Mass=7849.4;
CC Method=Electrospray; Evidence={ECO:0000269|PubMed:11745396};
CC -!- MASS SPECTROMETRY: [CCL18(3-69)]: Mass=7652.1; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11745396};
CC -!- MASS SPECTROMETRY: [CCL18(4-69)]: Mass=7552.0; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11745396};
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL18 entry;
CC URL="https://en.wikipedia.org/wiki/CCL18";
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DR EMBL; AB000221; BAA21670.1; -; mRNA.
DR EMBL; Y13710; CAA74039.1; -; mRNA.
DR EMBL; AB012113; BAA34368.1; -; Genomic_DNA.
DR EMBL; AF082214; AAC32287.1; -; Genomic_DNA.
DR EMBL; AF082212; AAC32287.1; JOINED; Genomic_DNA.
DR EMBL; AF082213; AAC32287.1; JOINED; Genomic_DNA.
DR EMBL; AF111198; AAD30390.1; -; Genomic_DNA.
DR EMBL; CR407660; CAG28588.1; -; mRNA.
DR EMBL; AB451458; BAG70272.1; -; mRNA.
DR EMBL; CH471147; EAW80102.1; -; Genomic_DNA.
DR EMBL; BC069700; AAH69700.1; -; mRNA.
DR EMBL; BC096124; AAH96124.1; -; mRNA.
DR EMBL; BC096125; AAH96125.1; -; mRNA.
DR EMBL; BC096126; AAH96126.1; -; mRNA.
DR EMBL; BC096127; AAH96127.1; -; mRNA.
DR CCDS; CCDS11306.1; -.
DR RefSeq; NP_002979.1; NM_002988.3.
DR PDB; 4MHE; X-ray; 2.10 A; A/B/C/D=21-89.
DR PDBsum; 4MHE; -.
DR AlphaFoldDB; P55774; -.
DR SMR; P55774; -.
DR BioGRID; 112265; 47.
DR IntAct; P55774; 9.
DR STRING; 9606.ENSP00000479955; -.
DR BioMuta; CCL18; -.
DR DMDM; 2493666; -.
DR MassIVE; P55774; -.
DR PaxDb; P55774; -.
DR PeptideAtlas; P55774; -.
DR PRIDE; P55774; -.
DR ProteomicsDB; 56863; -.
DR Antibodypedia; 72699; 293 antibodies from 28 providers.
DR DNASU; 6362; -.
DR Ensembl; ENST00000614828.2; ENSP00000483144.1; ENSG00000278167.2.
DR Ensembl; ENST00000615723.2; ENSP00000483347.1; ENSG00000278006.2.
DR Ensembl; ENST00000616054.2; ENSP00000479955.1; ENSG00000275385.2.
DR GeneID; 6362; -.
DR KEGG; hsa:6362; -.
DR MANE-Select; ENST00000616054.2; ENSP00000479955.1; NM_002988.4; NP_002979.1.
DR UCSC; uc002hku.4; human.
DR CTD; 6362; -.
DR DisGeNET; 6362; -.
DR GeneCards; CCL18; -.
DR HGNC; HGNC:10616; CCL18.
DR HPA; ENSG00000275385; Tissue enriched (lung).
DR MIM; 603757; gene.
DR neXtProt; NX_P55774; -.
DR OpenTargets; ENSG00000275385; -.
DR PharmGKB; PA35549; -.
DR VEuPathDB; HostDB:ENSG00000275385; -.
DR eggNOG; ENOG502S8M4; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_4_2_1; -.
DR InParanoid; P55774; -.
DR OMA; TNKEFCC; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P55774; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; P55774; -.
DR SignaLink; P55774; -.
DR BioGRID-ORCS; 6362; 11 hits in 1061 CRISPR screens.
DR GenomeRNAi; 6362; -.
DR Pharos; P55774; Tbio.
DR PRO; PR:P55774; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P55774; protein.
DR Bgee; ENSG00000275385; Expressed in lymph node and 88 other tissues.
DR Genevisible; P55774; 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:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0007154; P:cell communication; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; 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:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
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: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; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:9192897"
FT CHAIN 21..89
FT /note="C-C motif chemokine 18"
FT /id="PRO_0000005212"
FT CHAIN 21..88
FT /note="CCL18(1-68)"
FT /id="PRO_0000041851"
FT CHAIN 23..89
FT /note="CCL18(3-69)"
FT /id="PRO_0000041852"
FT CHAIN 24..89
FT /note="CCL18(4-69)"
FT /id="PRO_0000041853"
FT DISULFID 30..54
FT /evidence="ECO:0000269|PubMed:23742785"
FT DISULFID 31..70
FT /evidence="ECO:0000269|PubMed:23742785"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:4MHE"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:4MHE"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:4MHE"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:4MHE"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:4MHE"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:4MHE"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:4MHE"
SQ SEQUENCE 89 AA; 9849 MW; C287B94B9C0518E4 CRC64;
MKGLAAALLV LVCTMALCSC AQVGTNKELC CLVYTSWQIP QKFIVDYSET SPQCPKPGVI
LLTKRGRQIC ADPNKKWVQK YISDLKLNA
