CCL14_HUMAN
ID CCL14_HUMAN Reviewed; 93 AA.
AC Q16627; E1P649; E1P650; Q13954;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=C-C motif chemokine 14;
DE AltName: Full=Chemokine CC-1/CC-3;
DE Short=HCC-1/HCC-3;
DE AltName: Full=HCC-1(1-74);
DE AltName: Full=NCC-2;
DE AltName: Full=Small-inducible cytokine A14;
DE Contains:
DE RecName: Full=HCC-1(3-74);
DE Contains:
DE RecName: Full=HCC-1(4-74);
DE Contains:
DE RecName: Full=HCC-1(9-74);
DE Flags: Precursor;
GN Name=CCL14; Synonyms=NCC2, SCYA14;
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] (ISOFORM HCC-1), AND PROTEIN SEQUENCE OF 20-93.
RC TISSUE=Bone marrow;
RX PubMed=8551235; DOI=10.1084/jem.183.1.295;
RA Schulz-Knappe P., Maegert H.-J., Dewald B., Meyer M., Cetin Y., Kubbies M.,
RA Tomeczkowski J., Kirchhoff K., Raida M., Adermann K., Kist A., Reinecke M.,
RA Sillard R., Pardigol A., Uguccioni M., Baggiolini M., Forssmann W.-G.;
RT "HCC-1, a novel chemokine from human plasma.";
RL J. Exp. Med. 183:295-299(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HCC-1 AND HCC-3), AND TISSUE
RP SPECIFICITY.
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 [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 [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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HCC-1).
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 PROTEIN SEQUENCE OF 20-32, IDENTIFICATION OF HCC-1(3-74) AND HCC-1(4-74),
RP IDENTIFICATION BY MASS SPECTROMETRY, AND GLYCOSYLATION AT SER-26.
RX PubMed=10978165; DOI=10.1021/bi992488q;
RA Richter R., Schulz-Knappe P., John H., Forssmann W.-G.;
RT "Posttranslationally processed forms of the human chemokine HCC-1.";
RL Biochemistry 39:10799-10805(2000).
RN [7]
RP PROTEIN SEQUENCE OF 20-48, IDENTIFICATION OF HCC-1(9-74), IDENTIFICATION BY
RP MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=11085751; DOI=10.1084/jem.192.10.1501;
RA Detheux M., Staendker L., Vakili J., Muench J., Forssmann U., Adermann K.,
RA Poehlmann S., Vassart G., Kirchhoff F., Parmentier M., Forssmann W.-G.;
RT "Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a
RT potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV
RT properties.";
RL J. Exp. Med. 192:1501-1508(2000).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 28-93.
RX PubMed=17691823; DOI=10.1021/bi700936w;
RA Blain K.Y., Kwiatkowski W., Zhao Q., La Fleur D., Naik C., Chun T.-W.,
RA Tsareva T., Kanakaraj P., Laird M.W., Shah R., George L., Sanyal I.,
RA Moore P.A., Demeler B., Choe S.;
RT "Structural and functional characterization of CC chemokine CCL14.";
RL Biochemistry 46:10008-10015(2007).
CC -!- FUNCTION: Has weak activities on human monocytes and acts via receptors
CC that also recognize MIP-1 alpha. It induces intracellular Ca(2+)
CC changes and enzyme release, but no chemotaxis, at concentrations of
CC 100-1,000 nM, and is inactive on T-lymphocytes, neutrophils, and
CC eosinophil leukocytes. Enhances the proliferation of CD34 myeloid
CC progenitor cells. The processed form HCC-1(9-74) is a chemotactic
CC factor that attracts monocytes, eosinophils, and T-cells and is a
CC ligand for CCR1, CCR3 and CCR5. {ECO:0000269|PubMed:11085751}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=HCC-1;
CC IsoId=Q16627-1; Sequence=Displayed;
CC Name=HCC-3;
CC IsoId=Q16627-2; Sequence=VSP_001060;
CC -!- TISSUE SPECIFICITY: Expressed constitutively in several normal tissues:
CC spleen, liver, skeletal and heart muscle, gut, and bone marrow, present
CC at high concentrations (1-80 nM) in plasma.
CC {ECO:0000269|PubMed:9600961}.
CC -!- PTM: The N-terminal processed forms HCC-1(3-74), HCC-1(4-74) and HCC-
CC 1(9-74) are produced in small amounts by proteolytic cleavage after
CC secretion in blood.
CC -!- PTM: HCC-1(1-74), but not HCC-1(3-74) and HCC-1(4-74), is partially O-
CC glycosylated; the O-linked glycan consists of one Gal-GalNAc
CC disaccharide, further modified by two N-acetylneuraminic acids.
CC {ECO:0000269|PubMed:10978165}.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL14 entry;
CC URL="https://en.wikipedia.org/wiki/CCL14";
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DR EMBL; Z49270; CAA89264.1; -; mRNA.
DR EMBL; Z70292; CAA94307.1; -; mRNA.
DR EMBL; Z70293; CAA94309.1; -; mRNA.
DR EMBL; Z49269; CAA89263.1; -; Genomic_DNA.
DR EMBL; AF088219; AAC63329.1; -; Genomic_DNA.
DR EMBL; AF088219; AAF23982.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80105.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80106.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80107.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80108.1; -; Genomic_DNA.
DR EMBL; BC038289; AAH38289.1; -; mRNA.
DR EMBL; BC045165; AAH45165.1; -; mRNA.
DR CCDS; CCDS32624.1; -. [Q16627-1]
DR CCDS; CCDS45652.1; -. [Q16627-2]
DR RefSeq; NP_116738.1; NM_032962.4. [Q16627-2]
DR RefSeq; NP_116739.1; NM_032963.3. [Q16627-1]
DR PDB; 2Q8R; X-ray; 1.82 A; E/F/G/H=28-93.
DR PDB; 2Q8T; X-ray; 2.23 A; A/B/C/D=20-93.
DR PDBsum; 2Q8R; -.
DR PDBsum; 2Q8T; -.
DR AlphaFoldDB; Q16627; -.
DR SMR; Q16627; -.
DR BioGRID; 112261; 26.
DR DIP; DIP-5861N; -.
DR IntAct; Q16627; 11.
DR GlyGen; Q16627; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q16627; -.
DR PhosphoSitePlus; Q16627; -.
DR BioMuta; CCL14; -.
DR DMDM; 2493670; -.
DR MassIVE; Q16627; -.
DR PeptideAtlas; Q16627; -.
DR PRIDE; Q16627; -.
DR ProteomicsDB; 60974; -. [Q16627-1]
DR ProteomicsDB; 60975; -. [Q16627-2]
DR Antibodypedia; 73663; 330 antibodies from 29 providers.
DR DNASU; 6358; -.
DR Ensembl; ENST00000618404.5; ENSP00000481023.1; ENSG00000276409.5. [Q16627-1]
DR Ensembl; ENST00000619040.4; ENSP00000483302.1; ENSG00000277236.4. [Q16627-2]
DR Ensembl; ENST00000622526.1; ENSP00000479097.1; ENSG00000276409.5. [Q16627-2]
DR Ensembl; ENST00000632700.1; ENSP00000487948.1; ENSG00000277236.4. [Q16627-1]
DR GeneID; 6358; -.
DR KEGG; hsa:6358; -.
DR MANE-Select; ENST00000618404.5; ENSP00000481023.1; NM_032963.4; NP_116739.1.
DR UCSC; uc010wcq.2; human. [Q16627-1]
DR CTD; 6358; -.
DR DisGeNET; 6358; -.
DR GeneCards; CCL14; -.
DR HGNC; HGNC:10612; CCL14.
DR HPA; ENSG00000276409; Tissue enhanced (lymphoid).
DR MIM; 601392; gene.
DR neXtProt; NX_Q16627; -.
DR OpenTargets; ENSG00000276409; -.
DR PharmGKB; PA35545; -.
DR VEuPathDB; HostDB:ENSG00000276409; -.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_4_2_1; -.
DR InParanoid; Q16627; -.
DR OMA; GHSVCAN; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; Q16627; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; Q16627; -.
DR SignaLink; Q16627; -.
DR BioGRID-ORCS; 6358; 8 hits in 1056 CRISPR screens.
DR ChiTaRS; CCL14; human.
DR EvolutionaryTrace; Q16627; -.
DR GenomeRNAi; 6358; -.
DR Pharos; Q16627; Tbio.
DR PRO; PR:Q16627; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q16627; protein.
DR Bgee; ENSG00000276409; Expressed in spleen and 93 other tissues.
DR ExpressionAtlas; Q16627; baseline and differential.
DR Genevisible; Q16627; 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:0008009; F:chemokine activity; IBA:GO_Central.
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: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:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
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; Alternative splicing; Cytokine; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:10978165,
FT ECO:0000269|PubMed:11085751, ECO:0000269|PubMed:8551235"
FT CHAIN 20..93
FT /note="C-C motif chemokine 14"
FT /id="PRO_0000005204"
FT CHAIN 22..93
FT /note="HCC-1(3-74)"
FT /id="PRO_0000005205"
FT CHAIN 23..93
FT /note="HCC-1(4-74)"
FT /id="PRO_0000005206"
FT CHAIN 28..93
FT /note="HCC-1(9-74)"
FT /id="PRO_0000005207"
FT CARBOHYD 26
FT /note="O-linked (GalNAc...) serine; partial"
FT /evidence="ECO:0000269|PubMed:10978165"
FT DISULFID 35..59
FT DISULFID 36..75
FT VAR_SEQ 27
FT /note="R -> QTGGKPKVVKIQLKLVG (in isoform HCC-3)"
FT /evidence="ECO:0000303|PubMed:9600961"
FT /id="VSP_001060"
FT VARIANT 61
FT /note="K -> E (in dbSNP:rs16971802)"
FT /id="VAR_048707"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2Q8R"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2Q8R"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:2Q8R"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2Q8R"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:2Q8R"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:2Q8R"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:2Q8R"
SQ SEQUENCE 93 AA; 10678 MW; DDDB899DC9148836 CRC64;
MKISVAAIPF FLLITIALGT KTESSSRGPY HPSECCFTYT TYKIPRQRIM DYYETNSQCS
KPGIVFITKR GHSVCTNPSD KWVQDYIKDM KEN
