CCL19_HUMAN
ID CCL19_HUMAN Reviewed; 98 AA.
AC Q99731; O00697; O00736;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=C-C motif chemokine 19;
DE AltName: Full=Beta-chemokine exodus-3;
DE AltName: Full=CK beta-11;
DE AltName: Full=Epstein-Barr virus-induced molecule 1 ligand chemokine;
DE Short=EBI1 ligand chemokine;
DE Short=ELC;
DE AltName: Full=Macrophage inflammatory protein 3 beta;
DE Short=MIP-3-beta;
DE AltName: Full=Small-inducible cytokine A19;
DE Flags: Precursor;
GN Name=CCL19; Synonyms=ELC, MIP3B, SCYA19;
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].
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], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Fetal lung;
RX PubMed=9153236; DOI=10.1074/jbc.272.21.13803;
RA Yoshida R., Imai T., Hieshima K., Kusuda J., Baba M., Kitaura M.,
RA Nishimura M., Kakizaki M., Nomiyama H., Yoshie O.;
RT "Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that
RT is a specific functional ligand for EBI1, CCR7.";
RL J. Biol. Chem. 272:13803-13809(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hromas R.A., Gray P., Klemsz M., Fife K., Broxmeyer H.;
RT "DCCL chemokines represent a novel beta chemokine subfamily.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Reiterer P., Bernhardt G., Lipp M.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas, and Spleen;
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 [6]
RP FUNCTION.
RX PubMed=9498785;
RA Kim C.H., Pelus L.M., White J.R., Applebaum E., Johanson K.,
RA Broxmeyer H.E.;
RT "CK beta-11/macrophage inflammatory protein-3 beta/EBI1-ligand chemokine is
RT an efficacious chemoattractant for T and B cells.";
RL J. Immunol. 160:2418-2424(1998).
RN [7]
RP RECEPTOR INTERACTION.
RX PubMed=23341447; DOI=10.1074/jbc.m112.406108;
RA Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M.,
RA van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J.,
RA Vischer H.F.;
RT "Beta-arrestin recruitment and G protein signaling by the atypical human
RT chemokine decoy receptor CCX-CKR.";
RL J. Biol. Chem. 288:7169-7181(2013).
RN [8]
RP INTERACTION WITH TNFAIP6.
RX PubMed=27044744; DOI=10.1074/jbc.m116.720953;
RA Dyer D.P., Salanga C.L., Johns S.C., Valdambrini E., Fuster M.M.,
RA Milner C.M., Day A.J., Handel T.M.;
RT "The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by
RT Inhibiting Chemokine/Glycosaminoglycan Interactions.";
RL J. Biol. Chem. 291:12627-12640(2016).
CC -!- FUNCTION: May play a role not only in inflammatory and immunological
CC responses but also in normal lymphocyte recirculation and homing. May
CC play an important role in trafficking of T-cells in thymus, and T-cell
CC and B-cell migration to secondary lymphoid organs. Binds to chemokine
CC receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for
CC T-cells and B-cells but not for granulocytes and monocytes. Binds to
CC atypical chemokine receptor ACKR4 and mediates the recruitment of beta-
CC arrestin (ARRB1/2) to ACKR4. {ECO:0000269|PubMed:9498785}.
CC -!- SUBUNIT: Interacts with TNFAIP6 (via Link domain).
CC {ECO:0000269|PubMed:27044744}.
CC -!- INTERACTION:
CC Q99731; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11711434, EBI-16439278;
CC PRO_0000005214; P98066: TNFAIP6; NbExp=2; IntAct=EBI-11711510, EBI-11700693;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the lymph nodes, thymus
CC and appendix. Intermediate levels seen in colon and trachea, while low
CC levels found in spleen, small intestine, lung, kidney and stomach.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL19 entry;
CC URL="https://en.wikipedia.org/wiki/CCL19";
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DR EMBL; U77180; AAC50944.1; -; mRNA.
DR EMBL; AB000887; BAA20383.1; -; mRNA.
DR EMBL; U88321; AAC23905.1; -; mRNA.
DR EMBL; AJ223410; CAA11307.1; -; Genomic_DNA.
DR EMBL; BC027968; AAH27968.1; -; mRNA.
DR CCDS; CCDS6570.1; -.
DR RefSeq; NP_006265.1; NM_006274.2.
DR PDB; 2MP1; NMR; -; A=22-98.
DR PDB; 7STA; X-ray; 2.50 A; A/B/C/D=28-91.
DR PDBsum; 2MP1; -.
DR PDBsum; 7STA; -.
DR AlphaFoldDB; Q99731; -.
DR BMRB; Q99731; -.
DR SMR; Q99731; -.
DR BioGRID; 112266; 23.
DR DIP; DIP-5857N; -.
DR IntAct; Q99731; 3.
DR STRING; 9606.ENSP00000308815; -.
DR PhosphoSitePlus; Q99731; -.
DR BioMuta; CCL19; -.
DR DMDM; 2842763; -.
DR MassIVE; Q99731; -.
DR PaxDb; Q99731; -.
DR PeptideAtlas; Q99731; -.
DR PRIDE; Q99731; -.
DR ProteomicsDB; 78447; -.
DR Antibodypedia; 11384; 498 antibodies from 33 providers.
DR DNASU; 6363; -.
DR Ensembl; ENST00000311925.7; ENSP00000308815.2; ENSG00000172724.12.
DR GeneID; 6363; -.
DR KEGG; hsa:6363; -.
DR MANE-Select; ENST00000311925.7; ENSP00000308815.2; NM_006274.3; NP_006265.1.
DR UCSC; uc003zvn.4; human.
DR CTD; 6363; -.
DR DisGeNET; 6363; -.
DR GeneCards; CCL19; -.
DR HGNC; HGNC:10617; CCL19.
DR HPA; ENSG00000172724; Tissue enriched (lymphoid).
DR MIM; 602227; gene.
DR neXtProt; NX_Q99731; -.
DR OpenTargets; ENSG00000172724; -.
DR PharmGKB; PA35550; -.
DR VEuPathDB; HostDB:ENSG00000172724; -.
DR eggNOG; ENOG502SENW; Eukaryota.
DR GeneTree; ENSGT01050000244920; -.
DR HOGENOM; CLU_141716_3_1_1; -.
DR InParanoid; Q99731; -.
DR OMA; PDQPWVG; -.
DR OrthoDB; 1542802at2759; -.
DR PhylomeDB; Q99731; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; Q99731; -.
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; Q99731; -.
DR SIGNOR; Q99731; -.
DR BioGRID-ORCS; 6363; 7 hits in 1065 CRISPR screens.
DR GeneWiki; CCL19; -.
DR GenomeRNAi; 6363; -.
DR Pharos; Q99731; Tbio.
DR PRO; PR:Q99731; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q99731; protein.
DR Bgee; ENSG00000172724; Expressed in vermiform appendix and 137 other tissues.
DR ExpressionAtlas; Q99731; baseline and differential.
DR Genevisible; Q99731; 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; IPI:UniProtKB.
DR GO; GO:0031735; F:CCR10 chemokine receptor binding; IDA:BHF-UCL.
DR GO; GO:0031732; F:CCR7 chemokine receptor binding; ISS:BHF-UCL.
DR GO; GO:0008009; F:chemokine activity; IDA:BHF-UCL.
DR GO; GO:0042379; F:chemokine receptor binding; IDA:UniProtKB.
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:0048469; P:cell maturation; ISS:BHF-UCL.
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:0098586; P:cellular response to virus; IMP:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0002407; P:dendritic cell chemotaxis; IDA:BHF-UCL.
DR GO; GO:0001768; P:establishment of T cell polarity; IDA:BHF-UCL.
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:0001771; P:immunological synapse formation; ISS:BHF-UCL.
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:0097029; P:mature conventional dendritic cell differentiation; ISS:BHF-UCL.
DR GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0002408; P:myeloid dendritic cell chemotaxis; IDA:BHF-UCL.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:2000147; P:positive regulation of cell motility; IDA:BHF-UCL.
DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:BHF-UCL.
DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; ISS:BHF-UCL.
DR GO; GO:2000549; P:positive regulation of dendritic cell dendrite assembly; ISS:BHF-UCL.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISS:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:0010560; P:positive regulation of glycoprotein biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:BHF-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:BHF-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:BHF-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:BHF-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IDA:BHF-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:BHF-UCL.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:BHF-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISS:BHF-UCL.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:BHF-UCL.
DR GO; GO:0045627; P:positive regulation of T-helper 1 cell differentiation; ISS:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0060491; P:regulation of cell projection assembly; ISS:BHF-UCL.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:BHF-UCL.
DR GO; GO:0071731; P:response to nitric oxide; IDA:BHF-UCL.
DR GO; GO:0034695; P:response to prostaglandin E; IDA:BHF-UCL.
DR GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR GO; GO:0031295; P:T cell costimulation; ISS:BHF-UCL.
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; Chemotaxis; Cytokine; Direct protein sequencing;
KW Disulfide bond; Inflammatory response; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..21
FT CHAIN 22..98
FT /note="C-C motif chemokine 19"
FT /id="PRO_0000005214"
FT DISULFID 29..55
FT /evidence="ECO:0000250"
FT DISULFID 30..71
FT /evidence="ECO:0000250"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:2MP1"
FT STRAND 42..49
FT /evidence="ECO:0007829|PDB:2MP1"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:2MP1"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:2MP1"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:2MP1"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2MP1"
FT HELIX 77..90
FT /evidence="ECO:0007829|PDB:2MP1"
SQ SEQUENCE 98 AA; 10993 MW; 0D2516DB2EB1C81B CRC64;
MALLLALSLL VLWTSPAPTL SGTNDAEDCC LSVTQKPIPG YIVRNFHYLL IKDGCRVPAV
VFTTLRGRQL CAPPDQPWVE RIIQRLQRTS AKMKRRSS
