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   24-JAN-2024, entry version 191.
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 CCL15.
CC       {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   -!- PTM: The N-terminal is proteolytically cleaved by proteases associated
CC       with inflammatory responses. The processed forms CCL15(22-92),
CC       CCL15(25-92) and CCL15(29-92) exhibit increase in CCR1-mediated
CC       signaling and chemotaxis assays in vitro.
CC       {ECO:0000269|PubMed:15905581}.
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";
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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   EMDB; EMD-32021; -.
DR   EMDB; EMD-32022; -.
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; 9606-ENSP00000484078; -.
DR   PeptideAtlas; Q16663; -.
DR   ProteomicsDB; 61020; -.
DR   Antibodypedia; 73667; 471 antibodies from 26 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   AGR; HGNC:10613; -.
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; ENSGT01100000263482; -.
DR   HOGENOM; CLU_141716_4_1_1; -.
DR   InParanoid; Q16663; -.
DR   OMA; FHHPSDC; -.
DR   OrthoDB; 4265193at2759; -.
DR   PhylomeDB; Q16663; -.
DR   TreeFam; TF334888; -.
DR   PathwayCommons; Q16663; -.
DR   SignaLink; Q16663; -.
DR   BioGRID-ORCS; 6359; 6 hits in 1093 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 71 other cell types or tissues.
DR   ExpressionAtlas; Q16663; baseline and differential.
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: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:0071346; P:cellular response to type II interferon; 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:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
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:0006874; P:intracellular calcium ion homeostasis; TAS:ProtInc.
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:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd00272; Chemokine_CC; 1.
DR   Gene3D; 2.40.50.40; -; 1.
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:SF77; C-C MOTIF CHEMOKINE 15; 1.
DR   PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1.
DR   Pfam; PF00048; IL8; 1.
DR   SMART; SM00199; SCY; 1.
DR   SUPFAM; SSF54117; Interleukin 8-like chemokines; 1.
DR   PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
DR   Genevisible; Q16663; HS.
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                   /evidence="ECO:0000269|PubMed:15905581"
FT                   /id="PRO_0000041868"
FT   CHAIN           46..113
FT                   /note="CCL15(25-92)"
FT                   /evidence="ECO:0000269|PubMed:15905581"
FT                   /id="PRO_0000041869"
FT   CHAIN           50..113
FT                   /note="CCL15(29-92)"
FT                   /evidence="ECO:0000269|PubMed:15905581"
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:7VL9"
FT   STRAND          67..72
FT                   /evidence="ECO:0007829|PDB:7VL9"
FT   STRAND          77..79
FT                   /evidence="ECO:0007829|PDB:7VL9"
FT   STRAND          82..88
FT                   /evidence="ECO:0007829|PDB:7VL9"
FT   STRAND          92..94
FT                   /evidence="ECO:0007829|PDB:7VL9"
FT   HELIX           99..107
FT                   /evidence="ECO:0007829|PDB:7VL9"
SQ   SEQUENCE   113 AA;  12236 MW;  0BBC31FB696E16C9 CRC64;
     MKVSVAALSC LMLVAVLGSQ AQFTNDAETE LMMSKLPLEN PVVLNSFHFA ADCCTSYISQ
     SIPCSLMKSY FETSSECSKP GVIFLTKKGR QVCAKPSGPG VQDCMKKLKP YSI
//