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Protein

C-C motif chemokine 5

Gene

CCL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including 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 (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485).7 Publications

GO - Molecular functioni

  • CCR1 chemokine receptor binding Source: BHF-UCL
  • CCR4 chemokine receptor binding Source: BHF-UCL
  • CCR5 chemokine receptor binding Source: BHF-UCL
  • chemoattractant activity Source: UniProtKB
  • chemokine activity Source: BHF-UCL
  • chemokine receptor antagonist activity Source: BHF-UCL
  • chemokine receptor binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • phosphatidylinositol phospholipase C activity Source: UniProtKB
  • phospholipase activator activity Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL
  • protein kinase activity Source: UniProtKB
  • protein self-association Source: BHF-UCL
  • receptor signaling protein tyrosine kinase activator activity Source: BHF-UCL

GO - Biological processi

  • activation of phospholipase D activity Source: BHF-UCL
  • calcium ion transport Source: UniProtKB
  • cell-cell signaling Source: BHF-UCL
  • cellular calcium ion homeostasis Source: UniProtKB
  • cellular response to fibroblast growth factor stimulus Source: UniProtKB
  • cellular response to interferon-gamma Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to organic cyclic compound Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • chemokine-mediated signaling pathway Source: UniProtKB
  • chemotaxis Source: UniProtKB
  • cytokine-mediated signaling pathway Source: Reactome
  • dendritic cell chemotaxis Source: BHF-UCL
  • eosinophil chemotaxis Source: BHF-UCL
  • exocytosis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • leukocyte cell-cell adhesion Source: BHF-UCL
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • macrophage chemotaxis Source: BHF-UCL
  • MAPK cascade Source: UniProtKB
  • monocyte chemotaxis Source: UniProtKB
  • negative regulation by host of viral transcription Source: UniProtKB
  • negative regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
  • negative regulation of macrophage apoptotic process Source: Ensembl
  • negative regulation of T cell apoptotic process Source: BHF-UCL
  • negative regulation of viral genome replication Source: BHF-UCL
  • neutrophil activation Source: BHF-UCL
  • neutrophil chemotaxis Source: GO_Central
  • positive regulation of activation of Janus kinase activity Source: BHF-UCL
  • positive regulation of calcium ion transport Source: UniProtKB
  • positive regulation of cell adhesion Source: BHF-UCL
  • positive regulation of cell-cell adhesion mediated by integrin Source: BHF-UCL
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cellular biosynthetic process Source: BHF-UCL
  • positive regulation of epithelial cell proliferation Source: Ensembl
  • positive regulation of ERK1 and ERK2 cascade Source: GO_Central
  • positive regulation of GTPase activity Source: GO_Central
  • positive regulation of homotypic cell-cell adhesion Source: BHF-UCL
  • positive regulation of innate immune response Source: BHF-UCL
  • positive regulation of JAK-STAT cascade Source: BHF-UCL
  • positive regulation of macrophage chemotaxis Source: BHF-UCL
  • positive regulation of monocyte chemotaxis Source: BHF-UCL
  • positive regulation of natural killer cell chemotaxis Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • positive regulation of phosphorylation Source: BHF-UCL
  • positive regulation of smooth muscle cell migration Source: BHF-UCL
  • positive regulation of smooth muscle cell proliferation Source: BHF-UCL
  • positive regulation of T cell apoptotic process Source: BHF-UCL
  • positive regulation of T cell chemotaxis Source: BHF-UCL
  • positive regulation of T cell migration Source: MGI
  • positive regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of translational initiation Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
  • positive regulation of viral genome replication Source: BHF-UCL
  • protein kinase B signaling Source: UniProtKB
  • protein tetramerization Source: BHF-UCL
  • regulation of chronic inflammatory response Source: BHF-UCL
  • regulation of insulin secretion Source: UniProtKB
  • regulation of neuron death Source: UniProtKB
  • regulation of T cell activation Source: BHF-UCL
  • response to toxic substance Source: UniProtKB
  • response to virus Source: BHF-UCL

Keywordsi

Molecular functionCytokine
Biological processChemotaxis, Inflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-380108 Chemokine receptors bind chemokines
R-HSA-418594 G alpha (i) signalling events
R-HSA-6783783 Interleukin-10 signaling
SIGNORiP13501

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:CCL5
Synonyms:D17S136E, SCYA5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000271503.5
HGNCiHGNC:10632 CCL5
MIMi187011 gene
neXtProtiNX_P13501

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi6352
OpenTargetsiENSG00000271503
PharmGKBiPA35564

Chemistry databases

ChEMBLiCHEMBL1275217
DrugBankiDB02322 Heparin Disaccharide I-S
DB02353 Heparin Disaccharide Iii-S

Polymorphism and mutation databases

BioMutaiCCL5
DMDMi6175077

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 232 PublicationsAdd BLAST23
ChainiPRO_000000517524 – 91C-C motif chemokine 5Add BLAST68
ChainiPRO_000000517626 – 91RANTES(3-68)Add BLAST66
ChainiPRO_000000517727 – 91RANTES(4-68)Add BLAST65

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi27O-linked (GalNAc...) serine; partial1 Publication1
Glycosylationi28O-linked (GalNAc...) serine; partial1 Publication1
Disulfide bondi33 ↔ 57
Disulfide bondi34 ↔ 73
Modified residuei90Methionine sulfoxide1 Publication1

Post-translational modificationi

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.1 Publication
The identity of the O-linked saccharides at Ser-27 and Ser-28 are not reported in PubMed:1380064. They are assigned by similarity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei25 – 26Cleavage; by DPP42

Keywords - PTMi

Disulfide bond, Glycoprotein, Oxidation

Proteomic databases

EPDiP13501
PaxDbiP13501
PeptideAtlasiP13501
PRIDEiP13501
ProteomicsDBi52922
TopDownProteomicsiP13501

PTM databases

iPTMnetiP13501
PhosphoSitePlusiP13501

Miscellaneous databases

PMAP-CutDBiP13501

Expressioni

Tissue specificityi

Expressed in the follicular fluid (at protein level). T-cell and macrophage specific.2 Publications

Inductioni

By mitogens.

Gene expression databases

BgeeiENSG00000271503
CleanExiHS_CCL5
ExpressionAtlasiP13501 baseline and differential
GenevisibleiP13501 HS

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • CCR1 chemokine receptor binding Source: BHF-UCL
  • CCR4 chemokine receptor binding Source: BHF-UCL
  • CCR5 chemokine receptor binding Source: BHF-UCL
  • chemoattractant activity Source: UniProtKB
  • chemokine activity Source: BHF-UCL
  • chemokine receptor antagonist activity Source: BHF-UCL
  • chemokine receptor binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: BHF-UCL
  • protein self-association Source: BHF-UCL

Protein-protein interaction databases

BioGridi112255, 35 interactors
DIPiDIP-31N
IntActiP13501, 26 interactors
MINTiP13501
STRINGi9606.ENSP00000293272

Chemistry databases

BindingDBiP13501

Structurei

Secondary structure

191
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi31 – 33Combined sources3
Beta strandi35 – 40Combined sources6
Helixi44 – 46Combined sources3
Beta strandi47 – 52Combined sources6
Beta strandi57 – 59Combined sources3
Beta strandi62 – 66Combined sources5
Beta strandi71 – 74Combined sources4
Helixi79 – 88Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5CMDX-ray3.09A/B/C/D/E/F27-91[»]
5COYX-ray1.44A/B27-91[»]
5DNFX-ray2.55A/B/C/D/E/F/G/H/I27-91[»]
5L2UX-ray2.28A/B/C/D/E/F/G/H/I27-91[»]
5UIWX-ray2.20B33-91[»]
6FGPNMR-B24-91[»]
ProteinModelPortaliP13501
SMRiP13501
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13501

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J0XH Eukaryota
ENOG410ZUYI LUCA
GeneTreeiENSGT00900000140870
HOVERGENiHBG017871
InParanoidiP13501
KOiK12499
PhylomeDBiP13501
TreeFamiTF334888

Family and domain databases

InterProiView protein in InterPro
IPR030595 CCL5
IPR000827 Chemokine_CC_CS
IPR001811 Chemokine_IL8-like_dom
IPR036048 Interleukin_8-like_sf
PANTHERiPTHR12015:SF82 PTHR12015:SF82, 1 hit
PfamiView protein in Pfam
PF00048 IL8, 1 hit
SMARTiView protein in SMART
SM00199 SCY, 1 hit
SUPFAMiSSF54117 SSF54117, 1 hit
PROSITEiView protein in PROSITE
PS00472 SMALL_CYTOKINES_CC, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P13501-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVSAAALAV ILIATALCAP ASASPYSSDT TPCCFAYIAR PLPRAHIKEY
60 70 80 90
FYTSGKCSNP AVVFVTRKNR QVCANPEKKW VREYINSLEM S
Length:91
Mass (Da):9,990
Last modified:July 15, 1999 - v3
Checksum:iFB0BFAF9A87C620F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7A → R in AAA36725 (PubMed:2456327).Curated1
Sequence conflicti7A → R in AAF73070 (Ref. 5) Curated1
Sequence conflicti14A → V in AAF73070 (Ref. 5) Curated1

Mass spectrometryi

Molecular mass is 7515±1 Da from positions 27 - 91. Determined by SELDI. 1 Publication
Molecular mass is 7862.8±1.1 Da from positions 24 - 91. Determined by ESI. 1 Publication
Molecular mass is 8355±10 Da from positions 24 - 91. Determined by ESI. O-glycosylated.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04304324S → F Polymorphism; antagonist of the chemokine receptors CCR1 and CCR3. 1 PublicationCorresponds to variant dbSNP:rs377415776Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS11300.1
PIRiA28815
RefSeqiNP_002976.2, NM_002985.2
UniGeneiHs.514821

Genome annotation databases

EnsembliENST00000603197; ENSP00000474412; ENSG00000271503
ENST00000605140; ENSP00000475057; ENSG00000271503
ENST00000613606; ENSP00000479894; ENSG00000274233
ENST00000618639; ENSP00000484921; ENSG00000274233
GeneIDi6352
KEGGihsa:6352
UCSCiuc002hkf.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCCL5_HUMAN
AccessioniPrimary (citable) accession number: P13501
Secondary accession number(s): O43646
, Q0QVW8, Q4ZGJ1, Q9NYA2, Q9UBG2, Q9UC99
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 15, 1999
Last modified: June 20, 2018
This is version 191 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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