CCL20_HUMAN
ID CCL20_HUMAN Reviewed; 96 AA.
AC P78556; Q53S51; Q99664;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=C-C motif chemokine 20;
DE AltName: Full=Beta-chemokine exodus-1;
DE AltName: Full=CC chemokine LARC;
DE AltName: Full=Liver and activation-regulated chemokine;
DE AltName: Full=Macrophage inflammatory protein 3 alpha;
DE Short=MIP-3-alpha;
DE AltName: Full=Small-inducible cytokine A20;
DE Contains:
DE RecName: Full=CCL20(1-67);
DE Contains:
DE RecName: Full=CCL20(1-64);
DE Contains:
DE RecName: Full=CCL20(2-70);
DE Flags: Precursor;
GN Name=CCL20; Synonyms=LARC, MIP3A, SCYA20;
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] (ISOFORM 1), INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=9013939;
RA Rossi D.L., Vicari A.P., Franz-Bacon K., McClanahan T.K., Zlotnik A.;
RT "Identification through bioinformatics of two new macrophage
RT proinflammatory human chemokines: MIP-3alpha and MIP-3beta.";
RL J. Immunol. 158:1033-1036(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF N-TERMINUS,
RP TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=9038201; DOI=10.1074/jbc.272.9.5846;
RA Hieshima K., Imai T., Opdenakker G., van Damme J., Kusuda J., Tei H.,
RA Sakaki Y., Takatsuki K., Miura R., Yoshie O., Nomiyama H.;
RT "Molecular cloning of a novel human CC chemokine liver and activation-
RT regulated chemokine (LARC) expressed in liver. Chemotactic activity for
RT lymphocytes and gene localization on chromosome 2.";
RL J. Biol. Chem. 272:5846-5853(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION, FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Pancreas;
RX PubMed=9129037;
RA Hromas R.A., Gray P.W., Chantry D., Godiska R., Krathwohl M., Fife K.,
RA Bell G.I., Takeda J., Aronica S., Gordon M., Cooper S., Broxmeyer H.E.,
RA Klemsz M.J.;
RT "Cloning and characterization of Exodus, a novel beta-chemokine.";
RL Blood 89:3315-3322(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=11352563; DOI=10.1006/geno.2001.6482;
RA Nelson R.T., Boyd J., Gladue R.P., Paradis T., Thomas R., Cunningham A.C.,
RA Lira P., Brissette W.H., Hayes L., Hames L.M., Neote K.S., McColl S.R.;
RT "Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/
RT exodus/SCYA20, showing gene structure, splice variants, and chromosome
RT localization.";
RL Genomics 73:28-37(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
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 [7]
RP IDENTIFICATION OF CCL20(1-67); CCL20(1-64) AND CCL20(2-70), PROTEOLYTIC
RP PROCESSING OF C-TERMINAL, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=11035086; DOI=10.4049/jimmunol.165.8.4470;
RA Schutyser E., Struyf S., Menten P., Lenaerts J.-P., Conings R., Put W.,
RA Wuyts A., Proost P., Van Damme J.;
RT "Regulated production and molecular diversity of human liver and
RT activation-regulated chemokine/macrophage inflammatory protein-3 alpha from
RT normal and transformed cells.";
RL J. Immunol. 165:4470-4477(2000).
RN [8]
RP FUNCTION, AND BINDING TO CCR6.
RX PubMed=20068036; DOI=10.1074/jbc.m109.091090;
RA Roehrl J., Yang D., Oppenheim J.J., Hehlgans T.;
RT "Specific binding and chemotactic activity of mBD4 and its functional
RT orthologue hBD2 to CCR6-expressing cells.";
RL J. Biol. Chem. 285:7028-7034(2010).
RN [9]
RP REVIEW, AND FUNCTION.
RX PubMed=21376174; DOI=10.1016/j.yexcr.2010.12.018;
RA Ito T., Carson W.F. IV, Cavassani K.A., Connett J.M., Kunkel S.L.;
RT "CCR6 as a mediator of immunity in the lung and gut.";
RL Exp. Cell Res. 317:613-619(2011).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23765988; DOI=10.1002/jcp.24418;
RA Caballero-Campo P., Buffone M.G., Benencia F., Conejo-Garcia J.R.,
RA Rinaudo P.F., Gerton G.L.;
RT "A role for the chemokine receptor CCR6 in mammalian sperm motility and
RT chemotaxis.";
RL J. Cell. Physiol. 229:68-78(2014).
RN [11]
RP FUNCTION.
RX PubMed=25122636; DOI=10.1126/scitranslmed.3009071;
RA Diao R., Fok K.L., Chen H., Yu M.K., Duan Y., Chung C.M., Li Z., Wu H.,
RA Li Z., Zhang H., Ji Z., Zhen W., Ng C.F., Gui Y., Cai Z., Chan H.C.;
RT "Deficient human beta-defensin 1 underlies male infertility associated with
RT poor sperm motility and genital tract infection.";
RL Sci. Transl. Med. 6:249RA108-249RA108(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 27-96, AND FUNCTION AS AN
RP ANTIMICROBIAL PROTEIN.
RX PubMed=12149255; DOI=10.1074/jbc.m203907200;
RA Hoover D.M., Boulegue C., Yang D., Oppenheim J.J., Tucker K., Lu W.,
RA Lubkowski J.;
RT "The structure of human macrophage inflammatory protein-3alpha /CCL20.
RT Linking antimicrobial and CC chemokine receptor-6-binding activities with
RT human beta-defensins.";
RL J. Biol. Chem. 277:37647-37654(2002).
CC -!- FUNCTION: Acts as a ligand for C-C chemokine receptor CCR6. Signals
CC through binding and activation of CCR6 and induces a strong chemotactic
CC response and mobilization of intracellular calcium ions
CC (PubMed:11352563, PubMed:11035086, PubMed:20068036). The ligand-
CC receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic
CC cells (DC), effector/memory T-cells and B-cells and plays an important
CC role at skin and mucosal surfaces under homeostatic and inflammatory
CC conditions, as well as in pathology, including cancer and various
CC autoimmune diseases (PubMed:21376174). CCL20 acts as a chemotactic
CC factor that attracts lymphocytes and, slightly, neutrophils, but not
CC monocytes (PubMed:9038201, PubMed:11352563). Involved in the
CC recruitment of both the pro-inflammatory IL17 producing helper T-cells
CC (Th17) and the regulatory T-cells (Treg) to sites of inflammation.
CC Required for optimal migration of thymic natural regulatory T cells
CC (nTregs) and DN1 early thymocyte progenitor cells (By similarity). C-
CC terminal processed forms have been shown to be equally chemotactically
CC active for leukocytes (PubMed:11035086). Positively regulates sperm
CC motility and chemotaxis via its binding to CCR6 which triggers Ca2+
CC mobilization in the sperm which is important for its motility
CC (PubMed:23765988, PubMed:25122636). Inhibits proliferation of myeloid
CC progenitors in colony formation assays (PubMed:9129037). May be
CC involved in formation and function of the mucosal lymphoid tissues by
CC attracting lymphocytes and dendritic cells towards epithelial cells (By
CC similarity). Possesses antibacterial activity towards E.coli ATCC 25922
CC and S.aureus ATCC 29213 (PubMed:12149255).
CC {ECO:0000250|UniProtKB:O89093, ECO:0000269|PubMed:11035086,
CC ECO:0000269|PubMed:11352563, ECO:0000269|PubMed:12149255,
CC ECO:0000269|PubMed:20068036, ECO:0000269|PubMed:23765988,
CC ECO:0000269|PubMed:25122636, ECO:0000269|PubMed:9038201,
CC ECO:0000269|PubMed:9129037, ECO:0000303|PubMed:21376174}.
CC -!- INTERACTION:
CC P78556; P13501: CCL5; NbExp=2; IntAct=EBI-3913209, EBI-2848366;
CC P78556; P48061: CXCL12; NbExp=2; IntAct=EBI-3913209, EBI-3913254;
CC P78556; P02776: PF4; NbExp=2; IntAct=EBI-3913209, EBI-2565740;
CC P78556; Q15311: RALBP1; NbExp=2; IntAct=EBI-3913209, EBI-749285;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11035086}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P78556-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78556-2; Sequence=VSP_001061;
CC -!- TISSUE SPECIFICITY: Expressed in the seminal plasma, endometrial fluid
CC and follicular fluid (at protein level). Expressed predominantly in the
CC liver, lymph nodes, appendix, peripheral blood lymphocytes, and fetal
CC lung. Low levels seen in thymus, prostate, testis, small intestine and
CC colon. {ECO:0000269|PubMed:11352563, ECO:0000269|PubMed:23765988,
CC ECO:0000269|PubMed:9013939, ECO:0000269|PubMed:9038201,
CC ECO:0000269|PubMed:9129037}.
CC -!- INDUCTION: By bacterial lipopolysaccharides (LPS), TNF and IFNG/IFN-
CC gamma. Induced by phorbol myristate acetate (PMA) in U-937 cell line
CC and bowes melanoma. Repressed by IL10/interleukin-10.
CC {ECO:0000269|PubMed:9013939, ECO:0000269|PubMed:9038201,
CC ECO:0000269|PubMed:9129037}.
CC -!- PTM: C-terminal processed forms which lack 1, 3 or 6 amino acids are
CC produced by proteolytic cleavage after secretion from peripheral blood
CC monocytes. {ECO:0000269|PubMed:11035086}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL20 entry;
CC URL="https://en.wikipedia.org/wiki/CCL20";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U77035; AAC50943.1; -; mRNA.
DR EMBL; D86955; BAA13191.1; -; mRNA.
DR EMBL; U64197; AAB61534.1; -; mRNA.
DR EMBL; AC073065; AAX93214.1; -; Genomic_DNA.
DR EMBL; BC020698; AAH20698.1; -; mRNA.
DR CCDS; CCDS2469.1; -. [P78556-1]
DR CCDS; CCDS46536.1; -. [P78556-2]
DR RefSeq; NP_001123518.1; NM_001130046.1. [P78556-2]
DR RefSeq; NP_004582.1; NM_004591.2. [P78556-1]
DR PDB; 1M8A; X-ray; 1.70 A; A/B=27-96.
DR PDB; 2HCI; X-ray; 1.81 A; A/B=27-95.
DR PDB; 2JYO; NMR; -; A=27-96.
DR PDB; 5UR7; X-ray; 2.00 A; A/B=27-96.
DR PDB; 6WWZ; EM; 3.34 A; C=27-96.
DR PDBsum; 1M8A; -.
DR PDBsum; 2HCI; -.
DR PDBsum; 2JYO; -.
DR PDBsum; 5UR7; -.
DR PDBsum; 6WWZ; -.
DR AlphaFoldDB; P78556; -.
DR SMR; P78556; -.
DR BioGRID; 112267; 11.
DR DIP; DIP-5864N; -.
DR IntAct; P78556; 12.
DR MINT; P78556; -.
DR STRING; 9606.ENSP00000351671; -.
DR BioMuta; CCL20; -.
DR DMDM; 2829668; -.
DR EPD; P78556; -.
DR jPOST; P78556; -.
DR MassIVE; P78556; -.
DR PaxDb; P78556; -.
DR PeptideAtlas; P78556; -.
DR PRIDE; P78556; -.
DR ProteomicsDB; 57650; -. [P78556-1]
DR ProteomicsDB; 57651; -. [P78556-2]
DR ABCD; P78556; 11 sequenced antibodies.
DR Antibodypedia; 20171; 659 antibodies from 38 providers.
DR DNASU; 6364; -.
DR Ensembl; ENST00000358813.5; ENSP00000351671.4; ENSG00000115009.13. [P78556-1]
DR Ensembl; ENST00000409189.7; ENSP00000386273.3; ENSG00000115009.13. [P78556-2]
DR GeneID; 6364; -.
DR KEGG; hsa:6364; -.
DR MANE-Select; ENST00000358813.5; ENSP00000351671.4; NM_004591.3; NP_004582.1.
DR UCSC; uc002vpl.3; human. [P78556-1]
DR CTD; 6364; -.
DR DisGeNET; 6364; -.
DR GeneCards; CCL20; -.
DR HGNC; HGNC:10619; CCL20.
DR HPA; ENSG00000115009; Group enriched (gallbladder, lymphoid tissue, urinary bladder).
DR MIM; 601960; gene.
DR neXtProt; NX_P78556; -.
DR OpenTargets; ENSG00000115009; -.
DR PharmGKB; PA35551; -.
DR VEuPathDB; HostDB:ENSG00000115009; -.
DR eggNOG; ENOG502S776; Eukaryota.
DR GeneTree; ENSGT01050000244920; -.
DR HOGENOM; CLU_141716_3_3_1; -.
DR InParanoid; P78556; -.
DR OMA; FDCCLQY; -.
DR OrthoDB; 1528181at2759; -.
DR PhylomeDB; P78556; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; P78556; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR SignaLink; P78556; -.
DR SIGNOR; P78556; -.
DR BioGRID-ORCS; 6364; 9 hits in 1066 CRISPR screens.
DR ChiTaRS; CCL20; human.
DR EvolutionaryTrace; P78556; -.
DR GeneWiki; CCL20; -.
DR GenomeRNAi; 6364; -.
DR Pharos; P78556; Tbio.
DR PRO; PR:P78556; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P78556; protein.
DR Bgee; ENSG00000115009; Expressed in epithelium of nasopharynx and 124 other tissues.
DR ExpressionAtlas; P78556; baseline and differential.
DR Genevisible; P78556; 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:0031731; F:CCR6 chemokine receptor binding; IDA:UniProtKB.
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:0035584; P:calcium-mediated signaling using intracellular calcium source; IDA:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
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:2000406; P:positive regulation of T cell migration; IDA:MGI.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0072678; P:T cell migration; ISS:UniProtKB.
DR GO; GO:0072679; P:thymocyte migration; ISS:UniProtKB.
DR CDD; cd01119; Chemokine_CC_DCCL; 1.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR000827; Chemokine_CC_CS.
DR InterPro; IPR034133; Chemokine_CC_DCCL.
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; Alternative splicing; Antibiotic; Antimicrobial; Chemotaxis;
KW Cytokine; Direct protein sequencing; Disulfide bond; Inflammatory response;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:9038201"
FT CHAIN 27..96
FT /note="C-C motif chemokine 20"
FT /id="PRO_0000005217"
FT CHAIN 27..93
FT /note="CCL20(1-67)"
FT /id="PRO_0000041854"
FT CHAIN 27..90
FT /note="CCL20(1-64)"
FT /id="PRO_0000041855"
FT CHAIN 28..96
FT /note="CCL20(2-70)"
FT /id="PRO_0000041856"
FT DISULFID 32..58
FT DISULFID 33..74
FT VAR_SEQ 26
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11352563,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9129037"
FT /id="VSP_001061"
FT VARIANT 47
FT /note="V -> M (in dbSNP:rs1049617)"
FT /id="VAR_011915"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:1M8A"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:1M8A"
FT TURN 54..57
FT /evidence="ECO:0007829|PDB:1M8A"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1M8A"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:1M8A"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:6WWZ"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1M8A"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:1M8A"
SQ SEQUENCE 96 AA; 10762 MW; 1ED19EC2E1AC70AD CRC64;
MCCTKSLLLA ALMSVLLLHL CGESEAASNF DCCLGYTDRI LHPKFIVGFT RQLANEGCDI
NAIIFHTKKK LSVCANPKQT WVKYIVRLLS KKVKNM
