P13501 (CCL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. RANTES(3-68)
2. RANTES(4-68)

Gene names

Name:	CCL5
Synonyms:	D17S136E, SCYA5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	91 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Chemotaxis Inflammatory response
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MAPK 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 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 macrophage apoptotic process Inferred from electronic annotation. Source: Compara 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 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 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-cell adhesion mediated by integrin Inferred from direct assay PubMed 8558019. Source: BHF-UCL 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 cascade Inferred from direct assay PubMed 7544376. Source: BHF-UCL 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 cascade Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB protein tetramerization Inferred from direct assay PubMed 10488085. Source: BHF-UCL regulation of chronic inflammatory response Traceable author statement PubMed 10488085. Source: BHF-UCL response to toxin Inferred from direct assay PubMed 10841574. Source: UniProtKB response to virus Traceable author statement PubMed 10488085. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	CCR1 chemokine receptor binding Inferred from direct assay PubMed 10910894. Source: BHF-UCL CCR4 chemokine receptor binding Traceable author statement PubMed 9417081. 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 phosphatidylinositol phospholipase C activity Inferred from direct assay PubMed 10734056. Source: UniProtKB phospholipase activator activity Inferred from direct assay PubMed 10734056. 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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.8 Ref.9

Chain

24 – 91

68

C-C motif chemokine 5

PRO_0000005175

Chain

26 – 91

66

RANTES(3-68)

PRO_0000005176

Chain

27 – 91

65

RANTES(4-68)

PRO_0000005177

Sites

Site

25 – 26

2

Cleavage; by DPP4

Site

90

1

Susceptible to oxidation

Amino acid modifications

Glycosylation

27

1

O-linked (GalNAc...); partial Ref.8

Glycosylation

28

1

O-linked (GalNAc...); partial Ref.8

Disulfide bond

33 ↔ 57

Disulfide bond

34 ↔ 73

Natural variations

Natural variant

24

1

S → F. Ref.3

VAR_043043

Experimental info

Sequence conflict

7

1

A → R in AAA36725. Ref.1

Sequence conflict

7

1

A → R in AAF73070. Ref.5

Sequence conflict

14

1

A → V in AAF73070. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

91

Helix Strand Turn

Details...

Beta strand

31 – 33

3

Beta strand

35 – 40

6

Helix

44 – 46

3

Beta strand

47 – 52

6

Beta strand

57 – 59

3

Beta strand

62 – 66

5

Beta strand

71 – 74

4

Helix

79 – 89

11

Sequences

	Sequence		Length	Mass (Da)
	P13501 [UniParc]. Last modified July 15, 1999. Version 3. Checksum: FB0BFAF9A87C620F	FASTA	91	9,990
	10 20 30 40 50 60 MKVSAAALAV ILIATALCAP ASASPYSSDT TPCCFAYIAR PLPRAHIKEY FYTSGKCSNP 70 80 90 AVVFVTRKNR QVCANPEKKW VREYINSLEM S

References

	« Hide 'large scale' referencesShow '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

NIEHS-SNPs

Wikipedia

RANTES entry

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.

IPI

IPI00009309.

PIR

A28815.

RefSeq

NP_002976.2. NM_002985.2.

UniGene

Hs.514821.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B3A	X-ray	1.60	A/B	25-91	[»]
1EQT	X-ray	1.60	A/B	26-91	[»]
1HRJ	NMR	-	A/B	24-91	[»]
1RTN	NMR	-	A/B	24-91	[»]
1RTO	NMR	-	A/B	24-91	[»]
1U4L	X-ray	2.00	A/B	24-91	[»]
1U4M	X-ray	2.00	A/B	24-91	[»]
1U4P	X-ray	1.70	A/B	24-91	[»]
1U4R	X-ray	2.20	A/B/C/D	24-91	[»]
2L9H	Other	-	A/B/C/D	24-91	[»]
2VXW	X-ray	1.70	A/B/C/D	33-91	[»]

ProteinModelPortal

P13501.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31N.

IntAct

P13501. 11 interactions.

STRING

9606.ENSP00000293272.

PTM databases

PhosphoSite

P13501.

Polymorphism databases

DMDM

6175077.

Proteomic databases

PaxDb

P13501.

PeptideAtlas

P13501.

PRIDE

P13501.

Protocols and materials databases

DNASU

6352.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000293272; ENSP00000293272; ENSG00000161570.
ENST00000366113; ENSP00000375216; ENSG00000161570.

GeneID

6352.

KEGG

hsa:6352.

UCSC

uc002hkf.3. human.

Organism-specific databases

CTD

6352.

GeneCards

GC17M034198.

HGNC

HGNC:10632. CCL5.

MIM

187011. gene.

neXtProt

NX_P13501.

PharmGKB

PA35564.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG38896.

HOVERGEN

HBG017871.

InParanoid

P13501.

KO

K12499.

OMA

QEYFYTS.

OrthoDB

EOG4W3SPN.

PhylomeDB

P13501.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_1_pathway. Syndecan-1-mediated signaling events.
syndecan_4_pathway. Syndecan-4-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P13501.

Bgee

P13501.

CleanEx

HS_CCL5.

Genevestigator

P13501.

GermOnline

ENSG00000161570. Homo sapiens.

Family and domain databases

InterPro

IPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

SMART

SM00199. SCY. 1 hit.
[Graphical view]

SUPFAM

SSF54117. Chemokine_IL8. 1 hit.

PROSITE

PS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P13501.

ChEMBL

CHEMBL1275217.

EvolutionaryTrace

P13501.

GenomeRNAi

6352.

NextBio

24676.

PMAP-CutDB

P13501.

SOURCE

Search...

Entry information

Entry name

CCL5_HUMAN

Accession

Primary (citable) accession number: P13501
Secondary accession number(s): O43646 , Q0QVW8, Q4ZGJ1, Q9NYA2, Q9UBG2, Q9UC99

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 151 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.