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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

GO - Biological processi

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 Expressed in 187 organ(s), highest expression level in blood
CleanExiHS_CCL5
ExpressionAtlasiP13501 baseline and differential
GenevisibleiP13501 HS

Interactioni

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112255, 35 interactors
DIPiDIP-31N
IntActiP13501, 53 interactors
MINTiP13501
STRINGi9606.ENSP00000293272

Chemistry databases

BindingDBiP13501

Structurei

Secondary structure

191
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A075B7C5A0A075B7C5_HUMAN
C-C motif chemokine 5
CCL5
150Annotation score:

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

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

RANTES entry

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

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...

Protein-protein interaction databases

BioGridi112255, 35 interactors
DIPiDIP-31N
IntActiP13501, 53 interactors
MINTiP13501
STRINGi9606.ENSP00000293272

Chemistry databases

BindingDBiP13501
ChEMBLiCHEMBL1275217
DrugBankiDB02322 Heparin Disaccharide I-S
DB02353 Heparin Disaccharide Iii-S

PTM databases

iPTMnetiP13501
PhosphoSitePlusiP13501

Polymorphism and mutation databases

BioMutaiCCL5
DMDMi6175077

Proteomic databases

EPDiP13501
PaxDbiP13501
PeptideAtlasiP13501
PRIDEiP13501
ProteomicsDBi52922
TopDownProteomicsiP13501

Protocols and materials databases

DNASUi6352
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6352
DisGeNETi6352
EuPathDBiHostDB:ENSG00000271503.5
GeneCardsiCCL5
HGNCiHGNC:10632 CCL5
MIMi187011 gene
neXtProtiNX_P13501
OpenTargetsiENSG00000271503
PharmGKBiPA35564
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0XH Eukaryota
ENOG410ZUYI LUCA
GeneTreeiENSGT00900000140870
HOVERGENiHBG017871
InParanoidiP13501
KOiK12499
PhylomeDBiP13501
TreeFamiTF334888

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

Miscellaneous databases

ChiTaRSiCCL5 human
EvolutionaryTraceiP13501
GeneWikiiCCL5
GenomeRNAii6352
PMAP-CutDBiP13501
PROiPR:P13501
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000271503 Expressed in 187 organ(s), highest expression level in blood
CleanExiHS_CCL5
ExpressionAtlasiP13501 baseline and differential
GenevisibleiP13501 HS

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
ProtoNetiSearch...

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: September 12, 2018
This is version 192 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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Main funding by: National Institutes of Health

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