CCL15_HUMAN
ID CCL15_HUMAN Reviewed; 113 AA.
AC Q16663; B2RU34; E1P651; Q9UM74;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=C-C motif chemokine 15;
DE AltName: Full=Chemokine CC-2;
DE Short=HCC-2;
DE AltName: Full=Leukotactin-1;
DE Short=LKN-1;
DE AltName: Full=MIP-1 delta;
DE AltName: Full=Macrophage inflammatory protein 5;
DE Short=MIP-5;
DE AltName: Full=Mrp-2b;
DE AltName: Full=NCC-3;
DE AltName: Full=Small-inducible cytokine A15;
DE Contains:
DE RecName: Full=CCL15(22-92);
DE Contains:
DE RecName: Full=CCL15(25-92);
DE Contains:
DE RecName: Full=CCL15(29-92);
DE Flags: Precursor;
GN Name=CCL15; Synonyms=MIP5, NCC3, SCYA15;
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=9548457;
RA Youn B.-S., Zhang S.M., Lee E.K., Park D.H., Broxmeyer H.E., Murphy P.M.,
RA Locati M., Pease J.E., Kim K.K., Antol K., Kwon B.S.;
RT "Molecular cloning of leukotactin-1: a novel human beta-chemokine, a
RT chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent
RT agonist at CC chemokine receptors 1 and 3.";
RL J. Immunol. 159:5201-5205(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-24.
RC TISSUE=Spleen;
RX PubMed=9624581; DOI=10.1023/a:1020535106684;
RA Wang W., Bacon K.B., Oldham E.R., Schall T.J.;
RT "Molecular cloning and functional characterization of human MIP-1 delta, a
RT new C-C chemokine related to mouse CCF-18 and C10.";
RL J. Clin. Immunol. 18:214-222(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=9600961; DOI=10.1073/pnas.95.11.6308;
RA Pardigol A., Forssmann U., Zucht H.-D., Loetscher P., Schulz-Knappe P.,
RA Baggiolini M., Forssmann W.-G., Maegert H.-J.;
RT "HCC-2, a human chemokine: gene structure, expression pattern, and
RT biological activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6308-6313(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10213461; DOI=10.1089/107999099314153;
RA Nomiyama H., Fukuda S., Iio M., Tanase S., Miura R., Yoshie O.;
RT "Organization of the chemokine gene cluster on human chromosome 17q11.2
RT containing the genes for CC chemokine MPIF-1, HCC-2, LEC, and RANTES.";
RL J. Interferon Cytokine Res. 19:227-234(1999).
RN [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-113.
RA Coulin F., Power C.A., Alouani S., Peitsch M.C., Schroeder J.-M.,
RA Moshizuki M., Clark-Lewis I., Wells T.N.C.;
RL Submitted (JAN-1997) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 22-36.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [9]
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 [10]
RP TISSUE SPECIFICITY.
RX PubMed=9558365;
RA Youn B.-S., Zhang S.M., Broxmeyer H.E., Cooper S., Antol K., Fraser M. Jr.,
RA Kwon B.S.;
RT "Characterization of CKbeta8 and CKbeta8-1: two alternatively spliced forms
RT of human beta-chemokine, chemoattractants for neutrophils, monocytes, and
RT lymphocytes, and potent agonists at CC chemokine receptor 1.";
RL Blood 91:3118-3126(1998).
RN [11]
RP IDENTIFICATION OF CCL15(22-92); CCL15(25-92) AND CCL15(29-92), PROTEOLYTIC
RP PROCESSING OF N-TERMINUS, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=15905581; DOI=10.4049/jimmunol.174.11.7341;
RA Berahovich R.D., Miao Z., Wang Y., Premack B., Howard M.C., Schall T.J.;
RT "Proteolytic activation of alternative CCR1 ligands in inflammation.";
RL J. Immunol. 174:7341-7351(2005).
RN [12]
RP STRUCTURE BY NMR OF 48-113, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=10320325; DOI=10.1021/bi990065i;
RA Sticht H., Escher S.E., Schweimer K., Forssmann W.G., Rosch P.,
RA Adermann K.;
RT "Solution structure of the human CC chemokine 2: A monomeric representative
RT of the CC chemokine subtype.";
RL Biochemistry 38:5995-6002(1999).
CC -!- FUNCTION: Chemotactic factor that attracts T-cells and monocytes, but
CC not neutrophils, eosinophils, or B-cells. Acts mainly via CC chemokine
CC receptor CCR1. Also binds to CCR3. CCL15(22-92), CCL15(25-92) and
CC CCL15(29-92) are more potent chemoattractants than the small-inducible
CC cytokine A15. {ECO:0000269|PubMed:15905581}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10320325}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Most abundant in heart, skeletal muscle and adrenal
CC gland. Lower levels in placenta, liver, pancreas and bone marrow.
CC CCL15(22-92), CCL15(25-92) and CCL15(29-92) are found in high levels in
CC synovial fluids from rheumatoid patients. {ECO:0000269|PubMed:15905581,
CC ECO:0000269|PubMed:9558365}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL15 entry;
CC URL="https://en.wikipedia.org/wiki/CCL15";
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; U58914; AAD10847.1; -; mRNA.
DR EMBL; AF031587; AAB94617.1; -; mRNA.
DR EMBL; Z70293; CAA94308.1; -; mRNA.
DR EMBL; Z70292; CAA94306.1; -; mRNA.
DR EMBL; AF088219; AAC63328.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80110.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80111.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80112.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80113.1; -; Genomic_DNA.
DR EMBL; BC140941; AAI40942.1; -; mRNA.
DR CCDS; CCDS11304.1; -.
DR RefSeq; NP_116741.2; NM_032965.5.
DR PDB; 2HCC; NMR; -; A=48-113.
DR PDB; 7VL9; EM; 2.60 A; L=47-113.
DR PDB; 7VLA; EM; 2.70 A; L=48-113.
DR PDBsum; 2HCC; -.
DR PDBsum; 7VL9; -.
DR PDBsum; 7VLA; -.
DR AlphaFoldDB; Q16663; -.
DR BMRB; Q16663; -.
DR SMR; Q16663; -.
DR BioGRID; 112262; 6.
DR DIP; DIP-6218N; -.
DR IntAct; Q16663; 1.
DR STRING; 9606.ENSP00000484078; -.
DR BioMuta; CCL15; -.
DR DMDM; 3915594; -.
DR MassIVE; Q16663; -.
DR PaxDb; Q16663; -.
DR PeptideAtlas; Q16663; -.
DR PRIDE; Q16663; -.
DR ProteomicsDB; 61020; -.
DR Antibodypedia; 73667; 417 antibodies from 25 providers.
DR DNASU; 6359; -.
DR Ensembl; ENST00000614050.1; ENSP00000477788.1; ENSG00000275528.2.
DR Ensembl; ENST00000617897.2; ENSP00000484078.1; ENSG00000275718.2.
DR GeneID; 6359; -.
DR KEGG; hsa:6359; -.
DR MANE-Select; ENST00000617897.2; ENSP00000484078.1; NM_032965.6; NP_116741.2.
DR UCSC; uc032gbw.1; human.
DR CTD; 6359; -.
DR DisGeNET; 6359; -.
DR GeneCards; CCL15; -.
DR HGNC; HGNC:10613; CCL15.
DR HPA; ENSG00000275718; Group enriched (intestine, liver).
DR MIM; 601393; gene.
DR neXtProt; NX_Q16663; -.
DR OpenTargets; ENSG00000275718; -.
DR PharmGKB; PA35546; -.
DR VEuPathDB; HostDB:ENSG00000275718; -.
DR eggNOG; ENOG502TJX7; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_4_1_1; -.
DR InParanoid; Q16663; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; Q16663; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; Q16663; -.
DR SignaLink; Q16663; -.
DR BioGRID-ORCS; 6359; 6 hits in 1020 CRISPR screens.
DR EvolutionaryTrace; Q16663; -.
DR GenomeRNAi; 6359; -.
DR Pharos; Q16663; Tbio.
DR PRO; PR:Q16663; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q16663; protein.
DR Bgee; ENSG00000275718; Expressed in mucosa of transverse colon and 70 other tissues.
DR ExpressionAtlas; Q16663; baseline and differential.
DR Genevisible; Q16663; 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:0042056; F:chemoattractant activity; IDA:UniProtKB.
DR GO; GO:0008009; F:chemokine activity; IBA:GO_Central.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
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:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
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; Heparin-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 22..113
FT /note="C-C motif chemokine 15"
FT /id="PRO_0000005208"
FT CHAIN 43..113
FT /note="CCL15(22-92)"
FT /id="PRO_0000041868"
FT CHAIN 46..113
FT /note="CCL15(25-92)"
FT /id="PRO_0000041869"
FT CHAIN 50..113
FT /note="CCL15(29-92)"
FT /id="PRO_0000041870"
FT DISULFID 53..77
FT /evidence="ECO:0000269|PubMed:10320325"
FT DISULFID 54..93
FT /evidence="ECO:0000269|PubMed:10320325"
FT DISULFID 64..104
FT /evidence="ECO:0000269|PubMed:10320325"
FT VARIANT 24
FT /note="T -> I (in dbSNP:rs854625)"
FT /evidence="ECO:0000269|PubMed:9624581"
FT /id="VAR_011640"
FT CONFLICT 14
FT /note="V -> I (in Ref. 1; AAD10847)"
FT /evidence="ECO:0000305"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2HCC"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:2HCC"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:2HCC"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:2HCC"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:2HCC"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:2HCC"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:2HCC"
FT HELIX 101..107
FT /evidence="ECO:0007829|PDB:2HCC"
SQ SEQUENCE 113 AA; 12236 MW; 0BBC31FB696E16C9 CRC64;
MKVSVAALSC LMLVAVLGSQ AQFTNDAETE LMMSKLPLEN PVVLNSFHFA ADCCTSYISQ
SIPCSLMKSY FETSSECSKP GVIFLTKKGR QVCAKPSGPG VQDCMKKLKP YSI
