CCL20_MOUSE
ID CCL20_MOUSE Reviewed; 97 AA.
AC O89093; Q9Z1X3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=C-C motif chemokine 20;
DE AltName: Full=Beta-chemokine exodus-1;
DE AltName: Full=CC chemokine LARC;
DE AltName: Full=CC chemokine ST38;
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 Flags: Precursor;
GN Name=Ccl20; Synonyms=Larc, Scya20;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND INDUCTION.
RX PubMed=9916893; DOI=10.1016/s0165-5728(98)00204-5;
RA Utans-Schneitz U., Lorez H., Klinkert W.E.F., da Silva J., Lesslauer W.;
RT "A novel rat CC chemokine, identified by targeted differential display, is
RT upregulated in brain inflammation.";
RL J. Neuroimmunol. 92:179-190(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM LONG).
RA Villares R.;
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM SHORT).
RC STRAIN=BALB/cJ;
RA McColl S.R., Carney T., Neote K.S.;
RT "Cloning and characterization of a murine homolog of macrophage
RT inflammatory protein 3 alpha.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=9862452; DOI=10.1016/s0014-5793(98)01450-1;
RA Varona R., Zaballos A., Gutierrez J., Martin P., Roncal F., Albar J.P.,
RA Ardavin C., Marquez G.;
RT "Molecular cloning, functional characterization and mRNA expression
RT analysis of the murine chemokine receptor CCR6 and its specific ligand MIP-
RT 3alpha.";
RL FEBS Lett. 440:188-194(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, PROTEIN SEQUENCE OF
RP N-TERMINUS, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10064080;
RX DOI=10.1002/(sici)1521-4141(199902)29:02<633::aid-immu633>3.0.co;2-i;
RA Tanaka Y., Imai T., Baba M., Ishikawa I., Uehira M., Nomiyama H.,
RA Yoshie O.;
RT "Selective expression of liver and activation-regulated chemokine (LARC) in
RT intestinal epithelium in mice and humans.";
RL Eur. J. Immunol. 29:633-642(1999).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19050256; DOI=10.4049/jimmunol.181.12.8391;
RA Yamazaki T., Yang X.O., Chung Y., Fukunaga A., Nurieva R., Pappu B.,
RA Martin-Orozco N., Kang H.S., Ma L., Panopoulos A.D., Craig S.,
RA Watowich S.S., Jetten A.M., Tian Q., Dong C.;
RT "CCR6 regulates the migration of inflammatory and regulatory T cells.";
RL J. Immunol. 181:8391-8401(2008).
RN [7]
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 [8]
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 [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24638065; DOI=10.1038/icb.2014.14;
RA Bunting M.D., Comerford I., Kara E.E., Korner H., McColl S.R.;
RT "CCR6 supports migration and differentiation of a subset of DN1 early
RT thymocyte progenitors but is not required for thymic nTreg development.";
RL Immunol. Cell Biol. 92:489-498(2014).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND BINDING TO CCR6.
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 [11]
RP STRUCTURE BY NMR OF 28-97, AND DISULFIDE BONDS.
RX PubMed=11373289; DOI=10.1074/jbc.m103121200;
RA Perez-Canadillas J.M., Zaballos A., Gutierrez J., Varona R., Roncal F.,
RA Albar J.P., Marquez G., Bruix M.;
RT "NMR solution structure of murine CCL20/MIP-3alpha, a chemokine that
RT specifically chemoattracts immature dendritic cells and lymphocytes through
RT its highly specific interaction with the beta-chemokine receptor CCR6.";
RL J. Biol. Chem. 276:28372-28379(2001).
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:9862452, PubMed:20068036). The ligand-receptor pair CCL20-CCR6
CC is responsible for the chemotaxis of dendritic cells (DC),
CC effector/memory T-cells and B-cells and plays an important role at skin
CC and mucosal surfaces under homeostatic and inflammatory conditions, as
CC well as in pathology, including cancer and autoimmune diseases
CC (PubMed:21376174). CCL20 acts as a chemotactic factor that attracts
CC lymphocytes and, slightly, neutrophils, but not monocytes (By
CC similarity). Involved in the recruitment of both the pro-inflammatory
CC IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg)
CC to sites of inflammation (PubMed:19050256). Required for optimal
CC migration of thymic natural regulatory T cells (nTregs) and DN1 early
CC thymocyte progenitor cells (PubMed:24638065). Positively regulates
CC sperm motility and chemotaxis via its binding to CCR6 which triggers
CC Ca2+ mobilization in the sperm which is important for its motility
CC (PubMed:25122636). May be involved in formation and function of the
CC mucosal lymphoid tissues by attracting lymphocytes and dendritic cells
CC towards epithelial cells (PubMed:10064080).
CC {ECO:0000250|UniProtKB:P78556, ECO:0000269|PubMed:10064080,
CC ECO:0000269|PubMed:19050256, ECO:0000269|PubMed:20068036,
CC ECO:0000269|PubMed:24638065, ECO:0000269|PubMed:25122636,
CC ECO:0000269|PubMed:9862452, ECO:0000303|PubMed:21376174}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P78556}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O89093-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O89093-2; Sequence=VSP_001062;
CC -!- TISSUE SPECIFICITY: Thymic medulla (at protein level). Prominently
CC expressed in the small intestine, colon and appendix. Also found in
CC thymus, spleen, lymph node and lung. The long form might be dominant in
CC intestinal, and the short form in lymphoid tissues. Expressed by IL17
CC producing helper T-cells (Th17). {ECO:0000269|PubMed:19050256,
CC ECO:0000269|PubMed:24638065}.
CC -!- INDUCTION: By lipopolysaccharide (LPS), TNF-alpha and interleukin-1.
CC IFN-gamma alone showed no effect, but potentiated the effect of TNF.
CC Induced synergistically by TGFB1 and IL6, which requires STAT3, RORC
CC and IL21. {ECO:0000269|PubMed:19050256, ECO:0000269|PubMed:9916893}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
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DR EMBL; AF053313; AAC78295.1; -; mRNA.
DR EMBL; AJ007862; CAA07714.1; -; Genomic_DNA.
DR EMBL; AF099052; AAC78680.1; -; mRNA.
DR EMBL; AJ222694; CAA10948.1; -; mRNA.
DR EMBL; AB015136; BAA76955.1; -; mRNA.
DR CCDS; CCDS35632.1; -. [O89093-1]
DR CCDS; CCDS78638.1; -. [O89093-2]
DR RefSeq; NP_001153210.1; NM_001159738.1. [O89093-2]
DR RefSeq; NP_058656.1; NM_016960.2. [O89093-1]
DR PDB; 1HA6; NMR; -; A=28-97.
DR PDBsum; 1HA6; -.
DR AlphaFoldDB; O89093; -.
DR BMRB; O89093; -.
DR SMR; O89093; -.
DR STRING; 10090.ENSMUSP00000109064; -.
DR PaxDb; O89093; -.
DR PRIDE; O89093; -.
DR ProteomicsDB; 283734; -. [O89093-1]
DR ProteomicsDB; 283735; -. [O89093-2]
DR Antibodypedia; 20171; 659 antibodies from 38 providers.
DR DNASU; 20297; -.
DR Ensembl; ENSMUST00000113437; ENSMUSP00000109064; ENSMUSG00000026166. [O89093-1]
DR Ensembl; ENSMUST00000186832; ENSMUSP00000139923; ENSMUSG00000026166. [O89093-2]
DR GeneID; 20297; -.
DR KEGG; mmu:20297; -.
DR UCSC; uc007bsk.2; mouse. [O89093-1]
DR CTD; 6364; -.
DR MGI; MGI:1329031; Ccl20.
DR VEuPathDB; HostDB:ENSMUSG00000026166; -.
DR eggNOG; ENOG502S776; Eukaryota.
DR GeneTree; ENSGT01050000244920; -.
DR HOGENOM; CLU_141716_3_3_1; -.
DR InParanoid; O89093; -.
DR OMA; FDCCLQY; -.
DR PhylomeDB; O89093; -.
DR TreeFam; TF334888; -.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 20297; 2 hits in 75 CRISPR screens.
DR EvolutionaryTrace; O89093; -.
DR PRO; PR:O89093; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O89093; protein.
DR Bgee; ENSMUSG00000026166; Expressed in duodenum and 18 other tissues.
DR ExpressionAtlas; O89093; baseline and differential.
DR Genevisible; O89093; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:MGI.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; ISS: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; 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; ISO:MGI.
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:0032730; P:positive regulation of interleukin-1 alpha production; ISO:MGI.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISO:MGI.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISO:MGI.
DR GO; GO:0072678; P:T cell migration; IDA:UniProtKB.
DR GO; GO:0072679; P:thymocyte migration; IDA: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; Chemotaxis; Cytokine;
KW Direct protein sequencing; Disulfide bond; Inflammatory response;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:10064080"
FT CHAIN 28..97
FT /note="C-C motif chemokine 20"
FT /id="PRO_0000005218"
FT DISULFID 33..59
FT /evidence="ECO:0000269|PubMed:11373289"
FT DISULFID 34..75
FT /evidence="ECO:0000269|PubMed:11373289"
FT VAR_SEQ 28
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_001062"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:1HA6"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:1HA6"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:1HA6"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:1HA6"
FT STRAND 63..76
FT /evidence="ECO:0007829|PDB:1HA6"
FT HELIX 81..93
FT /evidence="ECO:0007829|PDB:1HA6"
SQ SEQUENCE 97 AA; 10826 MW; 6E0C73C8AC80AB0A CRC64;
MACGGKRLLF LALAWVLLAH LCSQAEAASN YDCCLSYIQT PLPSRAIVGF TRQMADEACD
INAIIFHTKK RKSVCADPKQ NWVKRAVNLL SLRVKKM
