ID CCL5_HUMAN Reviewed; 91 AA.
AC P13501; O43646; Q0QVW8; Q4ZGJ1; Q9NYA2; Q9UBG2; Q9UC99;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 3.
DT 01-MAY-2013, entry version 151.
DE RecName: Full=C-C motif chemokine 5;
DE AltName: Full=EoCP;
DE AltName: Full=Eosinophil chemotactic cytokine;
DE AltName: Full=SIS-delta;
DE AltName: Full=Small-inducible cytokine A5;
DE AltName: Full=T cell-specific protein P228;
DE Short=TCP228;
DE AltName: Full=T-cell-specific protein RANTES;
DE Contains:
DE RecName: Full=RANTES(3-68);
DE Contains:
DE RecName: Full=RANTES(4-68);
DE Flags: Precursor;
GN Name=CCL5; Synonyms=D17S136E, SCYA5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2456327;
RA Schall T.J., Jongstra J., Dyer B.J., Jorgensen J., Clayberger C.,
RA Davis M.M., Krensky A.M.;
RT "A human T cell-specific molecule is a member of a new gene family.";
RL J. Immunol. 141:1018-1025(1988).
RN [2]
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
RT 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, LEC, and
RT RANTES.";
RL J. Interferon Cytokine Res. 19:227-234(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND VARIANT PHE-24.
RC TISSUE=Blood;
RX PubMed=16791620; DOI=10.1007/s00251-006-0133-2;
RA Capoulade-Metay C., Ayouba A., Kfutwah A., Lole K., Petres S.,
RA Dudoit Y., Deterre P., Menu E., Barre-Sinoussi F., Debre P.,
RA Theodorou I.;
RT "A natural CCL5/RANTES variant antagonist for CCR1 and CCR3.";
RL Immunogenetics 58:533-541(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Leukocyte;
RA Jang J.S., Kim B.E.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zeng Q.P., Yang R.Y., Fu L.C.;
RT "The complete sequence of human beta-chemokine RANTES mRNA.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 24-55, FUNCTION, MASS SPECTROMETRY, GLYCOSYLATION
RP AT SER-27 AND SER-28, AND OXIDATION AT MET-90.
RX PubMed=1380064; DOI=10.1084/jem.176.2.587;
RA Kameyoshi Y., Doerschner A., Mallet A.I., Christophers E.,
RA Schroeder J.-M.;
RT "Cytokine RANTES released by thrombin-stimulated platelets is a potent
RT attractant for human eosinophils.";
RL J. Exp. Med. 176:587-592(1992).
RN [9]
RP PROTEIN SEQUENCE OF 24-55.
RX PubMed=7524281;
RA Schroeder J.-M., Kameyoshi Y., Christophers E.;
RT "Platelets secrete an eosinophil-chemotactic cytokine which is a
RT member of the C-C-chemokine family.";
RL Adv. Exp. Med. Biol. 351:119-128(1993).
RN [10]
RP PROTEIN SEQUENCE OF 49-56; 71-79 AND 83-91, AND FUNCTION.
RX PubMed=8525373; DOI=10.1126/science.270.5243.1811;
RA Cocchi F., DeVico A.L., Garzino-Demo A., Arya S.K., Gallo R.C.,
RA Lusso P.;
RT "Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major
RT HIV-suppressive factors produced by CD8+ T cells.";
RL Science 270:1811-1815(1995).
RN [11]
RP IDENTIFICATION OF RANTES(3-68), PROTEOLYTIC PROCESSING OF N-TERMINUS,
RP AND FUNCTION.
RX PubMed=9516414; DOI=10.1074/jbc.273.13.7222;
RA Proost P., De Meester I., Schols D., Struyf S., Lambeir A.-M.,
RA Wuyts A., Opdenakker G., De Clercq E., Scharpe S., Van Damme J.;
RT "Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase
RT IV. Conversion of RANTES into a potent inhibitor of monocyte
RT chemotaxis and HIV-1-infection.";
RL J. Biol. Chem. 273:7222-7227(1998).
RN [12]
RP IDENTIFICATION OF RANTES(4-68), MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=15923218; DOI=10.1189/jlb.0305161;
RA Lim J.K., Burns J.M., Lu W., DeVico A.L.;
RT "Multiple pathways of amino terminal processing produce two truncated
RT variants of RANTES/CCL5.";
RL J. Leukoc. Biol. 78:442-452(2005).
RN [13]
RP STRUCTURE BY NMR.
RX PubMed=7537088; DOI=10.1021/bi00016a004;
RA Skelton N.J., Aspiras F., Ogez J., Schall T.J.;
RT "Proton NMR assignments and solution conformation of RANTES, a
RT chemokine of the C-C type.";
RL Biochemistry 34:5329-5342(1995).
RN [14]
RP STRUCTURE BY NMR.
RX PubMed=7542919; DOI=10.1021/bi00029a005;
RA Chung C.-W., Cooke R.M., Proudfoot A.E.I., Wells T.N.C.;
RT "The three-dimensional solution structure of RANTES.";
RL Biochemistry 34:9307-9314(1995).
RN [15]
RP SYNTHESIS, AND X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=9889151; DOI=10.1016/S1074-5521(99)80019-2;
RA Wilken J., Hoover D., Thompson D.A., Barlow P.N., McSparron H.,
RA Picard L., Wlodawer A., Lubkowski J., Kent S.B.;
RT "Total chemical synthesis and high-resolution crystal structure of the
RT potent anti-HIV protein AOP-RANTES.";
RL Chem. Biol. 6:43-51(1999).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RA Hoover D.M., Shaw J., Gryczynski Z., Proudfoot A.E.I., Wells T.N.C.,
RA Lubkowski J.;
RT "The crystal structure of Met-RANTES: comparison with native RANTES
RT and AOP-RANTES.";
RL Protein Pept. Lett. 7:73-82(2000).
CC -!- FUNCTION: Chemoattractant for blood monocytes, memory T-helper
CC cells and eosinophils. Causes the release of histamine from
CC basophils and activates eosinophils. Binds to CCR1, CCR3, CCR4 and
CC CCR5. One of the major HIV-suppressive factors produced by CD8+ T-
CC cells. Recombinant RANTES protein induces a dose-dependent
CC inhibition of different strains of HIV-1, HIV-2, and simian
CC immunodeficiency virus (SIV). The processed form RANTES(3-68) acts
CC as a natural chemotaxis inhibitor and is a more potent inhibitor
CC of HIV-1-infection. The second processed form RANTES(4-68)
CC exhibits reduced chemotactic and HIV-suppressive activity compared
CC with RANTES(1-68) and RANTES(3-68) and is generated by an
CC unidentified enzyme associated with monocytes and neutrophils.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: T-cell and macrophage specific.
CC -!- INDUCTION: By mitogens.
CC -!- PTM: N-terminal processed form RANTES(3-68) is produced by
CC proteolytic cleavage, probably by DPP4, after secretion from
CC peripheral blood leukocytes and cultured sarcoma cells.
CC -!- PTM: The identity of the O-linked saccharides at Ser-27 and Ser-28
CC are not reported in PubMed:1380064. They are assigned by
CC similarity.
CC -!- MASS SPECTROMETRY: Mass=7515; Mass_error=1; Method=SELDI;
CC Range=27-91; Source=PubMed:15923218;
CC -!- MASS SPECTROMETRY: Mass=7862.8; Mass_error=1.1;
CC Method=Electrospray; Range=24-91; Source=PubMed:1380064;
CC -!- MASS SPECTROMETRY: Mass=8355; Mass_error=10; Method=Electrospray;
CC Range=24-91; Note=O-glycosylated; Source=PubMed:1380064;
CC -!- POLYMORPHISM: The variant Phe-24 is an antagonist of the chemokine
CC receptors CCR1 and CCR3.
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ccl5/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=RANTES entry;
CC URL="http://en.wikipedia.org/wiki/RANTES";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M21121; AAA36725.1; -; mRNA.
DR EMBL; AF088219; AAC63331.1; -; Genomic_DNA.
DR EMBL; DQ230537; ABB69929.1; -; mRNA.
DR EMBL; AF043341; AAC03541.1; -; mRNA.
DR EMBL; AF266753; AAF73070.1; -; mRNA.
DR EMBL; DQ017060; AAY22177.1; -; Genomic_DNA.
DR EMBL; BC008600; AAH08600.1; -; mRNA.
DR IPI; IPI00009309; -.
DR PIR; A28815; A28815.
DR RefSeq; NP_002976.2; NM_002985.2.
DR UniGene; Hs.514821; -.
DR PDB; 1B3A; X-ray; 1.60 A; A/B=25-91.
DR PDB; 1EQT; X-ray; 1.60 A; A/B=26-91.
DR PDB; 1HRJ; NMR; -; A/B=24-91.
DR PDB; 1RTN; NMR; -; A/B=24-91.
DR PDB; 1RTO; NMR; -; A/B=24-91.
DR PDB; 1U4L; X-ray; 2.00 A; A/B=24-91.
DR PDB; 1U4M; X-ray; 2.00 A; A/B=24-91.
DR PDB; 1U4P; X-ray; 1.70 A; A/B=24-91.
DR PDB; 1U4R; X-ray; 2.20 A; A/B/C/D=24-91.
DR PDB; 2L9H; Other; -; A/B/C/D=24-91.
DR PDB; 2VXW; X-ray; 1.70 A; A/B/C/D=33-91.
DR PDBsum; 1B3A; -.
DR PDBsum; 1EQT; -.
DR PDBsum; 1HRJ; -.
DR PDBsum; 1RTN; -.
DR PDBsum; 1RTO; -.
DR PDBsum; 1U4L; -.
DR PDBsum; 1U4M; -.
DR PDBsum; 1U4P; -.
DR PDBsum; 1U4R; -.
DR PDBsum; 2L9H; -.
DR PDBsum; 2VXW; -.
DR ProteinModelPortal; P13501; -.
DR DIP; DIP-31N; -.
DR IntAct; P13501; 11.
DR STRING; 9606.ENSP00000293272; -.
DR PhosphoSite; P13501; -.
DR DMDM; 6175077; -.
DR PaxDb; P13501; -.
DR PeptideAtlas; P13501; -.
DR PRIDE; P13501; -.
DR DNASU; 6352; -.
DR Ensembl; ENST00000293272; ENSP00000293272; ENSG00000161570.
DR Ensembl; ENST00000366113; ENSP00000375216; ENSG00000161570.
DR GeneID; 6352; -.
DR KEGG; hsa:6352; -.
DR UCSC; uc002hkf.3; human.
DR CTD; 6352; -.
DR GeneCards; GC17M034198; -.
DR HGNC; HGNC:10632; CCL5.
DR MIM; 187011; gene.
DR neXtProt; NX_P13501; -.
DR PharmGKB; PA35564; -.
DR eggNOG; NOG38896; -.
DR HOVERGEN; HBG017871; -.
DR InParanoid; P13501; -.
DR KO; K12499; -.
DR OMA; QEYFYTS; -.
DR OrthoDB; EOG4W3SPN; -.
DR PhylomeDB; P13501; -.
DR Pathway_Interaction_DB; syndecan_1_pathway; Syndecan-1-mediated signaling events.
DR Pathway_Interaction_DB; syndecan_4_pathway; Syndecan-4-mediated signaling events.
DR Reactome; REACT_111102; Signal Transduction.
DR BindingDB; P13501; -.
DR ChEMBL; CHEMBL1275217; -.
DR EvolutionaryTrace; P13501; -.
DR GenomeRNAi; 6352; -.
DR NextBio; 24676; -.
DR PMAP-CutDB; P13501; -.
DR ArrayExpress; P13501; -.
DR Bgee; P13501; -.
DR CleanEx; HS_CCL5; -.
DR Genevestigator; P13501; -.
DR GermOnline; ENSG00000161570; Homo sapiens.
DR GO; GO:0005737; C:cytoplasm; IEA:Compara.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0031726; F:CCR1 chemokine receptor binding; IDA:BHF-UCL.
DR GO; GO:0031729; F:CCR4 chemokine receptor binding; TAS:BHF-UCL.
DR GO; GO:0042056; F:chemoattractant activity; IDA:UniProtKB.
DR GO; GO:0008009; F:chemokine activity; NAS:UniProtKB.
DR GO; GO:0046817; F:chemokine receptor antagonist activity; IDA:BHF-UCL.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0016004; F:phospholipase activator activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:BHF-UCL.
DR GO; GO:0030298; F:receptor signaling protein tyrosine kinase activator activity; IDA:BHF-UCL.
DR GO; GO:0031584; P:activation of phospholipase D activity; IDA:BHF-UCL.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; IDA:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0043623; P:cellular protein complex assembly; IDA:BHF-UCL.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; TAS:BHF-UCL.
DR GO; GO:0002407; P:dendritic cell chemotaxis; TAS:BHF-UCL.
DR GO; GO:0048245; P:eosinophil chemotaxis; IDA:BHF-UCL.
DR GO; GO:0006887; P:exocytosis; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0048246; P:macrophage chemotaxis; TAS:BHF-UCL.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0002548; P:monocyte chemotaxis; IC:UniProtKB.
DR GO; GO:0043922; P:negative regulation by host of viral transcription; IDA:UniProtKB.
DR GO; GO:0045744; P:negative regulation of G-protein coupled receptor protein signaling pathway; IDA:UniProtKB.
DR GO; GO:2000110; P:negative regulation of macrophage apoptotic process; IEA:Compara.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL.
DR GO; GO:0042119; P:neutrophil activation; IDA:BHF-UCL.
DR GO; GO:0010535; P:positive regulation of activation of JAK2 kinase activity; TAS:BHF-UCL.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:UniProtKB.
DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; IDA:BHF-UCL.
DR GO; GO:0034112; P:positive regulation of homotypic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0045089; P:positive regulation of innate immune response; TAS:BHF-UCL.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IDA:BHF-UCL.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:BHF-UCL.
DR GO; GO:2000503; P:positive regulation of natural killer cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IDA:BHF-UCL.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IDA:BHF-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0070234; P:positive regulation of T cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IDA:BHF-UCL.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0045948; P:positive regulation of translational initiation; NAS:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
DR GO; GO:0045070; P:positive regulation of viral genome replication; TAS:BHF-UCL.
DR GO; GO:0043491; P:protein kinase B signaling cascade; IMP:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:BHF-UCL.
DR GO; GO:0002676; P:regulation of chronic inflammatory response; TAS:BHF-UCL.
DR GO; GO:0009636; P:response to toxin; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; TAS:BHF-UCL.
DR InterPro; IPR000827; Chemokine_CC_CS.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; Chemokine_IL8; 1.
DR PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chemotaxis; Complete proteome; Cytokine;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Inflammatory response; Polymorphism; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1 23
FT CHAIN 24 91 C-C motif chemokine 5.
FT /FTId=PRO_0000005175.
FT CHAIN 26 91 RANTES(3-68).
FT /FTId=PRO_0000005176.
FT CHAIN 27 91 RANTES(4-68).
FT /FTId=PRO_0000005177.
FT SITE 25 26 Cleavage; by DPP4.
FT SITE 90 90 Susceptible to oxidation.
FT CARBOHYD 27 27 O-linked (GalNAc...); partial.
FT CARBOHYD 28 28 O-linked (GalNAc...); partial.
FT DISULFID 33 57
FT DISULFID 34 73
FT VARIANT 24 24 S -> F.
FT /FTId=VAR_043043.
FT CONFLICT 7 7 A -> R (in Ref. 1; AAA36725 and 5;
FT AAF73070).
FT CONFLICT 14 14 A -> V (in Ref. 5; AAF73070).
FT STRAND 31 33
FT STRAND 35 40
FT HELIX 44 46
FT STRAND 47 52
FT STRAND 57 59
FT STRAND 62 66
FT STRAND 71 74
FT HELIX 79 89
SQ SEQUENCE 91 AA; 9990 MW; FB0BFAF9A87C620F CRC64;
MKVSAAALAV ILIATALCAP ASASPYSSDT TPCCFAYIAR PLPRAHIKEY FYTSGKCSNP
AVVFVTRKNR QVCANPEKKW VREYINSLEM S
//
