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P13501 (CCL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-C motif chemokine 5
Alternative name(s):
EoCP
Eosinophil chemotactic cytokine
SIS-delta
Small-inducible cytokine A5
T cell-specific protein P228
Short name=TCP228
T-cell-specific protein RANTES

Cleaved into the following 2 chains:

  1. RANTES(3-68)
  2. RANTES(4-68)
Gene names
Name:CCL5
Synonyms:D17S136E, SCYA5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length91 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. Binds to CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils. Ref.3 Ref.8 Ref.10 Ref.11 Ref.12

Subcellular location

Secreted.

Tissue specificity

T-cell and macrophage specific.

Induction

By mitogens.

Post-translational modification

N-terminal processed form RANTES(3-68) is produced by proteolytic cleavage, probably by DPP4, after secretion from peripheral blood leukocytes and cultured sarcoma cells.

The identity of the O-linked saccharides at Ser-27 and Ser-28 are not reported in Ref.8. They are assigned by similarity.

Polymorphism

The variant Phe-24 is an antagonist of the chemokine receptors CCR1 and CCR3.

Sequence similarities

Belongs to the intercrine beta (chemokine CC) family.

Mass spectrometry

Molecular mass is 7515±1 Da from positions 27 - 91. Determined by SELDI. Ref.12

Molecular mass is 7862.8±1.1 Da from positions 24 - 91. Determined by ESI. Ref.8

Molecular mass is 8355±10 Da from positions 24 - 91. Determined by ESI. O-glycosylated. Ref.8

Ontologies

Keywords
   Biological processChemotaxis
Inflammatory response
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB

activation of phospholipase D activity

Inferred from direct assay PubMed 9469451. Source: BHF-UCL

calcium ion transport

Inferred from direct assay PubMed 10734056. Source: UniProtKB

cell-cell signaling

Inferred from direct assay PubMed 8558019. Source: BHF-UCL

cellular calcium ion homeostasis

Inferred from direct assay PubMed 10734056. Source: UniProtKB

cellular protein complex assembly

Inferred from direct assay PubMed 18337562. Source: BHF-UCL

cellular response to fibroblast growth factor stimulus

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

cellular response to interferon-gamma

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

cellular response to interleukin-1

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

cellular response to organic cyclic compound

Inferred from direct assay PubMed 21147091. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

chemokine-mediated signaling pathway

Traceable author statement PubMed 18337562. Source: BHF-UCL

chemotaxis

Non-traceable author statement Ref.8. Source: UniProtKB

dendritic cell chemotaxis

Traceable author statement PubMed 18337562. Source: BHF-UCL

eosinophil chemotaxis

Inferred from direct assay PubMed 16778803. Source: BHF-UCL

exocytosis

Inferred from direct assay PubMed 10734056. Source: UniProtKB

inflammatory response

Inferred from direct assay PubMed 21147091. Source: UniProtKB

leukocyte cell-cell adhesion

Inferred from direct assay PubMed 8558019. Source: BHF-UCL

lipopolysaccharide-mediated signaling pathway

Inferred from direct assay PubMed 21147091. Source: UniProtKB

macrophage chemotaxis

Traceable author statement PubMed 18337562. Source: BHF-UCL

monocyte chemotaxis

Inferred by curator PubMed 10660125. Source: UniProtKB

negative regulation by host of viral transcription

Inferred from direct assay PubMed 10841574. Source: UniProtKB

negative regulation of G-protein coupled receptor protein signaling pathway

Inferred from direct assay PubMed 10734056. Source: UniProtKB

negative regulation of T cell apoptotic process

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

negative regulation of chemokine-mediated signaling pathway

Inferred from direct assay PubMed 8631850. Source: GOC

negative regulation of macrophage apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of viral genome replication

Inferred from direct assay PubMed 10490959. Source: BHF-UCL

neutrophil activation

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

positive chemotaxis

Inferred from direct assay PubMed 15001559. Source: GOC

positive regulation of JAK-STAT cascade

Traceable author statement PubMed 11278738. Source: BHF-UCL

positive regulation of T cell apoptotic process

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

positive regulation of T cell chemotaxis

Inferred from direct assay PubMed 16778803PubMed 1699135PubMed 18337562PubMed 7544376. Source: BHF-UCL

positive regulation of T cell migration

Inferred from direct assay PubMed 23620790. Source: MGI

positive regulation of T cell proliferation

Inferred from direct assay PubMed 18832695. Source: BHF-UCL

positive regulation of activation of JAK2 kinase activity

Traceable author statement PubMed 11278738. Source: BHF-UCL

positive regulation of calcium ion transport

Inferred from direct assay PubMed 8699119. Source: UniProtKB

positive regulation of cell adhesion

Inferred from direct assay PubMed 10910894. Source: BHF-UCL

positive regulation of cell migration

Inferred from direct assay PubMed 7545673. Source: UniProtKB

positive regulation of cell-cell adhesion mediated by integrin

Inferred from direct assay PubMed 8558019. Source: BHF-UCL

positive regulation of cellular biosynthetic process

Inferred from direct assay PubMed 18337562. Source: BHF-UCL

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of homotypic cell-cell adhesion

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

positive regulation of innate immune response

Traceable author statement PubMed 21148810. Source: BHF-UCL

positive regulation of macrophage chemotaxis

Inferred from direct assay PubMed 16778803. Source: BHF-UCL

positive regulation of monocyte chemotaxis

Inferred from direct assay PubMed 1699135PubMed 19779041. Source: BHF-UCL

positive regulation of natural killer cell chemotaxis

Inferred from direct assay PubMed 7545673. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from direct assay PubMed 7544376. Source: BHF-UCL

positive regulation of phosphorylation

Inferred from direct assay PubMed 18337562. Source: BHF-UCL

positive regulation of protein tyrosine kinase activity

Inferred from direct assay PubMed 10488085. Source: GOC

positive regulation of smooth muscle cell migration

Inferred from direct assay PubMed 21297082. Source: BHF-UCL

positive regulation of smooth muscle cell proliferation

Inferred from direct assay PubMed 21297082. Source: BHF-UCL

positive regulation of translational initiation

Non-traceable author statement PubMed 18337562. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of STAT protein

Inferred from direct assay PubMed 9417081. Source: BHF-UCL

positive regulation of viral genome replication

Traceable author statement PubMed 10488085. Source: BHF-UCL

protein kinase B signaling

Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 10734056. Source: GOC

protein tetramerization

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

regulation of T cell activation

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

regulation of chronic inflammatory response

Traceable author statement PubMed 10488085. Source: BHF-UCL

response to toxic substance

Inferred from direct assay PubMed 10841574. Source: UniProtKB

response to virus

Traceable author statement PubMed 10488085. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionCCR1 chemokine receptor binding

Inferred from physical interaction PubMed 10660125PubMed 10734056PubMed 7545673PubMed 8699119. Source: UniProtKB

CCR4 chemokine receptor binding

Traceable author statement PubMed 9417081. Source: BHF-UCL

CCR5 chemokine receptor binding

Inferred from physical interaction PubMed 9139699. Source: BHF-UCL

chemoattractant activity

Inferred from direct assay PubMed 15001559. Source: UniProtKB

chemokine activity

Non-traceable author statement Ref.9. Source: UniProtKB

chemokine receptor antagonist activity

Inferred from direct assay PubMed 8631850. Source: BHF-UCL

chemokine receptor binding

Inferred from physical interaction PubMed 7517217PubMed 9139699. Source: BHF-UCL

phosphatidylinositol phospholipase C activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

phospholipase activator activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 8699119. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

protein kinase activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

protein self-association

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

receptor signaling protein tyrosine kinase activator activity

Inferred from direct assay PubMed 10488085. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CCR5P516814EBI-2848366,EBI-489374

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.8 Ref.9
Chain24 – 9168C-C motif chemokine 5
PRO_0000005175
Chain26 – 9166RANTES(3-68)
PRO_0000005176
Chain27 – 9165RANTES(4-68)
PRO_0000005177

Sites

Site25 – 262Cleavage; by DPP4
Site901Susceptible to oxidation

Amino acid modifications

Glycosylation271O-linked (GalNAc...); partial Ref.8
Glycosylation281O-linked (GalNAc...); partial Ref.8
Disulfide bond33 ↔ 57
Disulfide bond34 ↔ 73

Natural variations

Natural variant241S → F. Ref.3
VAR_043043

Experimental info

Sequence conflict71A → R in AAA36725. Ref.1
Sequence conflict71A → R in AAF73070. Ref.5
Sequence conflict141A → V in AAF73070. Ref.5

Secondary structure

................ 91
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P13501 [UniParc].

Last modified July 15, 1999. Version 3.
Checksum: FB0BFAF9A87C620F

FASTA919,990
        10         20         30         40         50         60 
MKVSAAALAV ILIATALCAP ASASPYSSDT TPCCFAYIAR PLPRAHIKEY FYTSGKCSNP 

        70         80         90 
AVVFVTRKNR QVCANPEKKW VREYINSLEM S 

« Hide

References

« Hide 'large scale' references
[1]"A human T cell-specific molecule is a member of a new gene family."
Schall T.J., Jongstra J., Dyer B.J., Jorgensen J., Clayberger C., Davis M.M., Krensky A.M.
J. Immunol. 141:1018-1025(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Organization of the chemokine gene cluster on human chromosome 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, LEC, and RANTES."
Nomiyama H., Fukuda S., Iio M., Tanase S., Miura R., Yoshie O.
J. Interferon Cytokine Res. 19:227-234(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"A natural CCL5/RANTES variant antagonist for CCR1 and CCR3."
Capoulade-Metay C., Ayouba A., Kfutwah A., Lole K., Petres S., Dudoit Y., Deterre P., Menu E., Barre-Sinoussi F., Debre P., Theodorou I.
Immunogenetics 58:533-541(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT PHE-24.
Tissue: Blood.
[4]Jang J.S., Kim B.E.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Leukocyte.
[5]"The complete sequence of human beta-chemokine RANTES mRNA."
Zeng Q.P., Yang R.Y., Fu L.C.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]NIEHS SNPs program
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[8]"Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils."
Kameyoshi Y., Doerschner A., Mallet A.I., Christophers E., Schroeder J.-M.
J. Exp. Med. 176:587-592(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-55, FUNCTION, MASS SPECTROMETRY, GLYCOSYLATION AT SER-27 AND SER-28, OXIDATION AT MET-90.
[9]"Platelets secrete an eosinophil-chemotactic cytokine which is a member of the C-C-chemokine family."
Schroeder J.-M., Kameyoshi Y., Christophers E.
Adv. Exp. Med. Biol. 351:119-128(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-55.
[10]"Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells."
Cocchi F., DeVico A.L., Garzino-Demo A., Arya S.K., Gallo R.C., Lusso P.
Science 270:1811-1815(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 49-56; 71-79 AND 83-91, FUNCTION.
[11]"Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection."
Proost P., De Meester I., Schols D., Struyf S., Lambeir A.-M., Wuyts A., Opdenakker G., De Clercq E., Scharpe S., Van Damme J.
J. Biol. Chem. 273:7222-7227(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF RANTES(3-68), PROTEOLYTIC PROCESSING OF N-TERMINUS, FUNCTION.
[12]"Multiple pathways of amino terminal processing produce two truncated variants of RANTES/CCL5."
Lim J.K., Burns J.M., Lu W., DeVico A.L.
J. Leukoc. Biol. 78:442-452(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF RANTES(4-68), MASS SPECTROMETRY, FUNCTION.
[13]"Proton NMR assignments and solution conformation of RANTES, a chemokine of the C-C type."
Skelton N.J., Aspiras F., Ogez J., Schall T.J.
Biochemistry 34:5329-5342(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[14]"The three-dimensional solution structure of RANTES."
Chung C.-W., Cooke R.M., Proudfoot A.E.I., Wells T.N.C.
Biochemistry 34:9307-9314(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[15]"Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES."
Wilken J., Hoover D., Thompson D.A., Barlow P.N., McSparron H., Picard L., Wlodawer A., Lubkowski J., Kent S.B.
Chem. Biol. 6:43-51(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SYNTHESIS, X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
[16]"The crystal structure of Met-RANTES: comparison with native RANTES and AOP-RANTES."
Hoover D.M., Shaw J., Gryczynski Z., Proudfoot A.E.I., Wells T.N.C., Lubkowski J.
Protein Pept. Lett. 7:73-82(2000)
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M21121 mRNA. Translation: AAA36725.1.
AF088219 Genomic DNA. Translation: AAC63331.1.
DQ230537 mRNA. Translation: ABB69929.1.
AF043341 mRNA. Translation: AAC03541.1.
AF266753 mRNA. Translation: AAF73070.1.
DQ017060 Genomic DNA. Translation: AAY22177.1.
BC008600 mRNA. Translation: AAH08600.1.
CCDSCCDS11300.1.
PIRA28815.
RefSeqNP_002976.2. NM_002985.2.
UniGeneHs.514821.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1B3AX-ray1.60A/B25-91[»]
1EQTX-ray1.60A/B26-91[»]
1HRJNMR-A/B24-91[»]
1RTNNMR-A/B24-91[»]
1RTONMR-A/B24-91[»]
1U4LX-ray2.00A/B24-91[»]
1U4MX-ray2.00A/B24-91[»]
1U4PX-ray1.70A/B24-91[»]
1U4RX-ray2.20A/B/C/D24-91[»]
2L9HOther-A/B/C/D24-91[»]
2VXWX-ray1.70A/B/C/D33-91[»]
ProteinModelPortalP13501.
SMRP13501. Positions 25-91.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112255. 16 interactions.
DIPDIP-31N.
IntActP13501. 13 interactions.
MINTMINT-103226.
STRING9606.ENSP00000293272.

Chemistry

BindingDBP13501.
ChEMBLCHEMBL1275217.

PTM databases

PhosphoSiteP13501.

Polymorphism databases

DMDM6175077.

Proteomic databases

PaxDbP13501.
PeptideAtlasP13501.
PRIDEP13501.

Protocols and materials databases

DNASU6352.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293272; ENSP00000293272; ENSG00000161570.
ENST00000366113; ENSP00000375216; ENSG00000161570.
ENST00000603197; ENSP00000474412; ENSG00000271503.
ENST00000605140; ENSP00000475057; ENSG00000271503.
GeneID6352.
KEGGhsa:6352.
UCSCuc002hkf.3. human.

Organism-specific databases

CTD6352.
GeneCardsGC17M034198.
HGNCHGNC:10632. CCL5.
MIM187011. gene.
neXtProtNX_P13501.
PharmGKBPA35564.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG38896.
HOVERGENHBG017871.
InParanoidP13501.
KOK12499.
OrthoDBEOG7CVQ1F.
PhylomeDBP13501.
TreeFamTF334888.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP13501.
BgeeP13501.
CleanExHS_CCL5.
GenevestigatorP13501.

Family and domain databases

InterProIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamPF00048. IL8. 1 hit.
[Graphical view]
SMARTSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMSSF54117. SSF54117. 1 hit.
PROSITEPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP13501.
GeneWikiCCL5.
GenomeRNAi6352.
NextBio24676.
PMAP-CutDBP13501.
PROP13501.
SOURCESearch...

Entry information

Entry nameCCL5_HUMAN
AccessionPrimary (citable) accession number: P13501
Secondary accession number(s): O43646 expand/collapse secondary AC list , Q0QVW8, Q4ZGJ1, Q9NYA2, Q9UBG2, Q9UC99
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 15, 1999
Last modified: July 9, 2014
This is version 162 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM