CCL7_HUMAN
ID CCL7_HUMAN Reviewed; 99 AA.
AC P80098; Q569J6;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=C-C motif chemokine 7;
DE AltName: Full=Monocyte chemoattractant protein 3;
DE AltName: Full=Monocyte chemotactic protein 3;
DE Short=MCP-3;
DE AltName: Full=NC28;
DE AltName: Full=Small-inducible cytokine A7;
DE Flags: Precursor;
GN Name=CCL7; Synonyms=MCP3, SCYA6, SCYA7;
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 31-67 AND 71-99.
RX PubMed=8461011; DOI=10.1006/bbrc.1993.1251;
RA Opdenakker G., Froyen G., Fiten P., Proost P., van Damme J.;
RT "Human monocyte chemotactic protein-3 (MCP-3): molecular cloning of the
RT cDNA and comparison with other chemokines.";
RL Biochem. Biophys. Res. Commun. 191:535-542(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=7916328; DOI=10.1006/geno.1994.1283;
RA Opdenakker G., Fiten P., Nys G., Froyen G., van Roy N., Speleman F.,
RA Laureys G., van Damme J.;
RT "The human MCP-3 gene (SCYA7): cloning, sequence analysis, and assignment
RT to the C-C chemokine gene cluster on chromosome 17q11.2-q12.";
RL Genomics 21:403-408(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8318676;
RA Minty A., Chalon P., Guillemot J.-C., Kaghad M., Liauzun P., Magazin M.,
RA Miloux B., Minty C., Ramond P., Vita N., Lupker J., Shire D., Ferrara P.,
RA Caput D.;
RT "Molecular cloning of the MCP-3 chemokine gene and regulation of its
RT expression.";
RL Eur. Cytokine Netw. 4:99-110(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood, and Colon;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-99.
RA Jang J.S., Kim B.E.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 30-99.
RC TISSUE=Osteosarcoma;
RX PubMed=1613466; DOI=10.1084/jem.176.1.59;
RA van Damme J., Proost P., Lenaerts J.-P., Opdenakker G.;
RT "Structural and functional identification of two human, tumor-derived
RT monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine
RT family.";
RL J. Exp. Med. 176:59-65(1992).
RN [7]
RP PROTEIN SEQUENCE OF 24-38, AND PYROGLUTAMATE FORMATION AT GLN-24.
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 [8]
RP INTERACTION WITH TNFAIP6, AND MUTAGENESIS OF LYS-41; LYS-42 AND LYS-45.
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).
RN [9]
RP STRUCTURE BY NMR, AND SUBUNIT.
RX PubMed=8898111; DOI=10.1016/0014-5793(96)01024-1;
RA Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.;
RT "Structural characterization of a monomeric chemokine: monocyte
RT chemoattractant protein-3.";
RL FEBS Lett. 395:277-282(1996).
RN [10]
RP STRUCTURE BY NMR.
RX PubMed=9109648; DOI=10.1021/bi9627929;
RA Meunier S., Bernassau J.-M., Guillemot J.-C., Ferrara P., Darbon H.;
RT "Determination of the three-dimensional structure of CC chemokine monocyte
RT chemoattractant protein 3 by 1H two-dimensional NMR spectroscopy.";
RL Biochemistry 36:4412-4422(1997).
RN [11]
RP STRUCTURE BY NMR.
RA Kwon D., Lee D., Sykes B.D., Kim K.-S.;
RL Submitted (AUG-1998) to the PDB data bank.
CC -!- FUNCTION: Chemotactic factor that attracts monocytes and eosinophils,
CC but not neutrophils. Augments monocyte anti-tumor activity. Also
CC induces the release of gelatinase B. This protein can bind heparin.
CC Binds to CCR1, CCR2 and CCR3.
CC -!- SUBUNIT: Monomer. Interacts with TNFAIP6 (via Link domain).
CC {ECO:0000269|PubMed:27044744, ECO:0000269|PubMed:8898111}.
CC -!- INTERACTION:
CC P80098; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-718759, EBI-741480;
CC P80098; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-718759, EBI-10173939;
CC P80098; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-718759, EBI-947187;
CC P80098; Q2F862; Xeno; NbExp=3; IntAct=EBI-718759, EBI-16161937;
CC PRO_0000005183; P98066: TNFAIP6; NbExp=2; IntAct=EBI-11711410, EBI-11700693;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: O-glycosylated.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA50405.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA50406.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA51055.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL7 entry;
CC URL="https://en.wikipedia.org/wiki/CCL7";
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; X72308; CAA51055.1; ALT_INIT; mRNA.
DR EMBL; X72309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X71087; CAA50407.1; -; mRNA.
DR EMBL; X71087; CAA50406.1; ALT_INIT; mRNA.
DR EMBL; X71087; CAA50405.1; ALT_INIT; mRNA.
DR EMBL; BC092436; AAH92436.1; -; mRNA.
DR EMBL; BC112258; AAI12259.1; -; mRNA.
DR EMBL; BC112260; AAI12261.1; -; mRNA.
DR EMBL; AF043338; AAC03538.1; -; mRNA.
DR CCDS; CCDS11278.1; -.
DR RefSeq; NP_006264.2; NM_006273.3.
DR PDB; 1BO0; NMR; -; A=24-99.
DR PDB; 1NCV; NMR; -; A/B=24-99.
DR PDB; 4ZKC; X-ray; 3.15 A; B=24-99.
DR PDB; 7S58; X-ray; 1.82 A; E/F/H/J=24-99.
DR PDB; 7S59; X-ray; 2.39 A; 2/4=41-99.
DR PDBsum; 1BO0; -.
DR PDBsum; 1NCV; -.
DR PDBsum; 4ZKC; -.
DR PDBsum; 7S58; -.
DR PDBsum; 7S59; -.
DR AlphaFoldDB; P80098; -.
DR BMRB; P80098; -.
DR SMR; P80098; -.
DR BioGRID; 112257; 12.
DR DIP; DIP-5847N; -.
DR IntAct; P80098; 8.
DR STRING; 9606.ENSP00000367832; -.
DR ChEMBL; CHEMBL3217391; -.
DR GlyGen; P80098; 1 site.
DR BioMuta; CCL7; -.
DR DMDM; 1170890; -.
DR MassIVE; P80098; -.
DR PaxDb; P80098; -.
DR PeptideAtlas; P80098; -.
DR PRIDE; P80098; -.
DR ProteomicsDB; 57665; -.
DR Antibodypedia; 15482; 734 antibodies from 35 providers.
DR DNASU; 6354; -.
DR Ensembl; ENST00000378569.2; ENSP00000367832.2; ENSG00000108688.11.
DR GeneID; 6354; -.
DR KEGG; hsa:6354; -.
DR MANE-Select; ENST00000378569.2; ENSP00000367832.2; NM_006273.4; NP_006264.2.
DR UCSC; uc002hhz.5; human.
DR CTD; 6354; -.
DR DisGeNET; 6354; -.
DR GeneCards; CCL7; -.
DR HGNC; HGNC:10634; CCL7.
DR HPA; ENSG00000108688; Tissue enriched (bone).
DR MIM; 158106; gene.
DR neXtProt; NX_P80098; -.
DR OpenTargets; ENSG00000108688; -.
DR PharmGKB; PA35566; -.
DR VEuPathDB; HostDB:ENSG00000108688; -.
DR eggNOG; ENOG502S6ZP; Eukaryota.
DR GeneTree; ENSGT01050000244851; -.
DR HOGENOM; CLU_141716_1_0_1; -.
DR InParanoid; P80098; -.
DR OMA; TTCCYRF; -.
DR OrthoDB; 1575018at2759; -.
DR PhylomeDB; P80098; -.
DR TreeFam; TF334888; -.
DR PathwayCommons; P80098; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR SignaLink; P80098; -.
DR SIGNOR; P80098; -.
DR BioGRID-ORCS; 6354; 17 hits in 1059 CRISPR screens.
DR EvolutionaryTrace; P80098; -.
DR GeneWiki; CCL7; -.
DR GenomeRNAi; 6354; -.
DR Pharos; P80098; Tbio.
DR PRO; PR:P80098; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P80098; protein.
DR Bgee; ENSG00000108688; Expressed in islet of Langerhans and 100 other tissues.
DR ExpressionAtlas; P80098; baseline and differential.
DR Genevisible; P80098; 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:0031726; F:CCR1 chemokine receptor binding; IPI:UniProtKB.
DR GO; GO:0031727; F:CCR2 chemokine receptor binding; IEA:Ensembl.
DR GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; TAS:ProtInc.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
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:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0048245; P:eosinophil chemotaxis; IDA:UniProtKB.
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:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
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:2000503; P:positive regulation of natural killer cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
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; Glycoprotein; Heparin-binding; Inflammatory response;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 24..99
FT /note="C-C motif chemokine 7"
FT /id="PRO_0000005183"
FT MOD_RES 24
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:15340161"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..59
FT DISULFID 35..75
FT MUTAGEN 41
FT /note="K->A: Decreases binding to Link domain of TNFAIP6;
FT when associated with A-42 and A-45."
FT /evidence="ECO:0000269|PubMed:27044744"
FT MUTAGEN 42
FT /note="K->A: Decreases binding to Link domain of TNFAIP6;
FT when associated with A-41 and A-45."
FT /evidence="ECO:0000269|PubMed:27044744"
FT MUTAGEN 45
FT /note="K->A: Decreases binding to Link domain of TNFAIP6;
FT when associated with A-41 and A-42."
FT /evidence="ECO:0000269|PubMed:27044744"
FT CONFLICT 30
FT /note="T -> K (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 68..70
FT /note="Missing (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:1NCV"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:4ZKC"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:4ZKC"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:4ZKC"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:4ZKC"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:4ZKC"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4ZKC"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:4ZKC"
SQ SEQUENCE 99 AA; 11200 MW; 96048B371C25D00E CRC64;
MKASAALLCL LLTAAAFSPQ GLAQPVGINT STTCCYRFIN KKIPKQRLES YRRTTSSHCP
REAVIFKTKL DKEICADPTQ KWVQDFMKHL DKKTQTPKL
