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CCL16_HUMAN
ID   CCL16_HUMAN             Reviewed;         120 AA.
AC   O15467; Q4KKU0;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 172.
DE   RecName: Full=C-C motif chemokine 16;
DE   AltName: Full=Chemokine CC-4;
DE            Short=HCC-4;
DE   AltName: Full=Chemokine LEC;
DE   AltName: Full=IL-10-inducible chemokine;
DE   AltName: Full=LCC-1;
DE   AltName: Full=Liver-expressed chemokine;
DE   AltName: Full=Lymphocyte and monocyte chemoattractant;
DE            Short=LMC;
DE   AltName: Full=Monotactin-1;
DE            Short=MTN-1;
DE   AltName: Full=NCC-4;
DE   AltName: Full=Small-inducible cytokine A16;
DE   Flags: Precursor;
GN   Name=CCL16; Synonyms=ILINCK, NCC4, SCYA16;
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], AND PROTEIN SEQUENCE OF N-TERMINUS.
RC   TISSUE=Liver;
RX   PubMed=9596672;
RA   Hedrick J.A., Helms A., Vicari A., Zlotnik A.;
RT   "Characterization of a novel CC chemokine, HCC-4, whose expression is
RT   increased by interleukin-10.";
RL   Blood 91:4242-4247(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RX   PubMed=9545580; DOI=10.1016/s0167-4781(97)00235-2;
RA   Shoudai K., Hieshima K., Fukuda S., Iio M., Miura R., Imai T., Yoshie O.,
RA   Nomiyama H.;
RT   "Isolation of cDNA encoding a novel human CC chemokine NCC-4/LEC.";
RL   Biochim. Biophys. Acta 1396:273-277(1998).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9642106; DOI=10.1006/bbrc.1998.8762;
RA   Youn B.-S., Zhang S., Broxmeyer H.E., Antol K., Fraser M.J. Jr., Hangoc G.,
RA   Kwon B.S.;
RT   "Isolation and characterization of LMC, a novel lymphocyte and monocyte
RT   chemoattractant human CC chemokine, with myelosuppressive activity.";
RL   Biochem. Biophys. Res. Commun. 247:217-222(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Liver;
RX   PubMed=10235110; DOI=10.1089/104454999315330;
RA   Fukuda S., Hanano Y., Iio M., Miura R., Yoshie O., Nomiyama H.;
RT   "Genomic organization of the genes for human and mouse CC chemokine LEC.";
RL   DNA Cell Biol. 18:275-283(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   TISSUE=Liver;
RX   PubMed=10671294; DOI=10.1006/cyto.1999.0548;
RA   Yang J.-Y., Spanaus K.S., Widmer U.;
RT   "Cloning, characterization and genomic organization of LCC-1 (scya16), a
RT   novel human CC chemokine expressed in liver.";
RL   Cytokine 12:101-109(2000).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
CC   -!- FUNCTION: Shows chemotactic activity for lymphocytes and monocytes but
CC       not neutrophils. Also shows potent myelosuppressive activity,
CC       suppresses proliferation of myeloid progenitor cells. Recombinant
CC       SCYA16 shows chemotactic activity for monocytes and THP-1 monocytes,
CC       but not for resting lymphocytes and neutrophils. Induces a calcium flux
CC       in THP-1 cells that were desensitized by prior expression to RANTES.
CC   -!- INTERACTION:
CC       O15467; P13501: CCL5; NbExp=2; IntAct=EBI-12204739, EBI-2848366;
CC       O15467; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12204739, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Mainly expressed in liver, also found in spleen and
CC       thymus. Highly expressed in LPS- and IFN-gamma-activated monocytes,
CC       weakly in some lymphocytes, including natural killer cells, gamma-delta
CC       T-cells, and some T-cell clones.
CC   -!- INDUCTION: By IL10/interleukin-10.
CC   -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=CCL16 entry;
CC       URL="https://en.wikipedia.org/wiki/CCL16";
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DR   EMBL; U91746; AAC05587.1; -; mRNA.
DR   EMBL; AB007454; BAA24057.1; -; mRNA.
DR   EMBL; AF088219; AAC63330.1; -; Genomic_DNA.
DR   EMBL; AF055467; AAC28844.1; -; mRNA.
DR   EMBL; AB018249; BAA35138.1; -; Genomic_DNA.
DR   EMBL; AF039954; AAC97450.1; -; Genomic_DNA.
DR   EMBL; AF039955; AAC97451.1; -; mRNA.
DR   EMBL; BC099662; AAH99662.1; -; mRNA.
DR   CCDS; CCDS11303.1; -.
DR   PIR; JE0177; JE0177.
DR   RefSeq; NP_004581.1; NM_004590.3.
DR   RefSeq; XP_005258077.1; XM_005258020.4.
DR   PDB; 5LTL; X-ray; 1.45 A; A/B=24-120.
DR   PDBsum; 5LTL; -.
DR   AlphaFoldDB; O15467; -.
DR   SMR; O15467; -.
DR   BioGRID; 112263; 8.
DR   DIP; DIP-5831N; -.
DR   IntAct; O15467; 2.
DR   STRING; 9606.ENSP00000478024; -.
DR   BioMuta; CCL16; -.
DR   MassIVE; O15467; -.
DR   PaxDb; O15467; -.
DR   PeptideAtlas; O15467; -.
DR   PRIDE; O15467; -.
DR   ProteomicsDB; 48683; -.
DR   TopDownProteomics; O15467; -.
DR   Antibodypedia; 73562; 502 antibodies from 28 providers.
DR   DNASU; 6360; -.
DR   Ensembl; ENST00000611905.2; ENSP00000478024.1; ENSG00000275152.5.
DR   Ensembl; ENST00000621559.2; ENSP00000482168.1; ENSG00000275095.2.
DR   GeneID; 6360; -.
DR   KEGG; hsa:6360; -.
DR   MANE-Select; ENST00000611905.2; ENSP00000478024.1; NM_004590.4; NP_004581.1.
DR   UCSC; uc002hkl.4; human.
DR   CTD; 6360; -.
DR   DisGeNET; 6360; -.
DR   GeneCards; CCL16; -.
DR   HGNC; HGNC:10614; CCL16.
DR   HPA; ENSG00000275152; Tissue enriched (liver).
DR   MIM; 601394; gene.
DR   neXtProt; NX_O15467; -.
DR   OpenTargets; ENSG00000275152; -.
DR   PharmGKB; PA35547; -.
DR   VEuPathDB; HostDB:ENSG00000275152; -.
DR   eggNOG; ENOG502TDPW; Eukaryota.
DR   GeneTree; ENSGT01050000244920; -.
DR   InParanoid; O15467; -.
DR   OMA; CCLKFYE; -.
DR   OrthoDB; 1575018at2759; -.
DR   PhylomeDB; O15467; -.
DR   TreeFam; TF334888; -.
DR   PathwayCommons; O15467; -.
DR   Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; O15467; -.
DR   BioGRID-ORCS; 6360; 13 hits in 1024 CRISPR screens.
DR   GenomeRNAi; 6360; -.
DR   Pharos; O15467; Tbio.
DR   PRO; PR:O15467; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; O15467; protein.
DR   Bgee; ENSG00000275152; Expressed in liver and 71 other tissues.
DR   ExpressionAtlas; O15467; baseline and differential.
DR   Genevisible; O15467; 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:0042056; F:chemoattractant activity; IDA:UniProtKB.
DR   GO; GO:0008009; F:chemokine activity; IBA:GO_Central.
DR   GO; GO:0007154; P:cell communication; TAS:ProtInc.
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; 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   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; Inflammatory response; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:9596672"
FT   CHAIN           24..120
FT                   /note="C-C motif chemokine 16"
FT                   /id="PRO_0000005209"
FT   DISULFID        37..60
FT                   /evidence="ECO:0000250"
FT   DISULFID        38..76
FT                   /evidence="ECO:0000250"
FT   STRAND          35..37
FT                   /evidence="ECO:0007829|PDB:5LTL"
FT   HELIX           48..50
FT                   /evidence="ECO:0007829|PDB:5LTL"
FT   STRAND          51..57
FT                   /evidence="ECO:0007829|PDB:5LTL"
FT   STRAND          59..62
FT                   /evidence="ECO:0007829|PDB:5LTL"
FT   STRAND          64..69
FT                   /evidence="ECO:0007829|PDB:5LTL"
FT   STRAND          74..77
FT                   /evidence="ECO:0007829|PDB:5LTL"
FT   HELIX           82..89
FT                   /evidence="ECO:0007829|PDB:5LTL"
SQ   SEQUENCE   120 AA;  13600 MW;  373D73016134D894 CRC64;
     MKVSEAALSL LVLILIITSA SRSQPKVPEW VNTPSTCCLK YYEKVLPRRL VVGYRKALNC
     HLPAIIFVTK RNREVCTNPN DDWVQEYIKD PNLPLLPTRN LSTVKIITAK NGQPQLLNSQ
 
 
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