Reviewed, UniProtKB/Swiss-Prot P13501 (CCL5_HUMAN)

Names and origin

Protein names

Recommended name:
    C-C motif chemokine 5
Alternative name(s):
    Small-inducible cytokine A5
    T-cell-specific protein RANTES
    SIS-delta
    T cell-specific protein P228
      Short name=TCP228
    Eosinophil-chemotactic cytokine
    EoCP
Cleaved into the following 2 chains:
    1- Recommended name:
            RANTES(3-68)
    2- Recommended name:
            RANTES(4-68)

Gene names

Name:	CCL5
Synonyms:	D17S136E, SCYA5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Traceable author statement. Source: ProtInc cell motion Traceable author statement. Source: ProtInc cell-cell signaling Traceable author statement. Source: ProtInc cellular calcium ion homeostasis Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc exocytosis Traceable author statement. Source: ProtInc immune response Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc negative regulation of viral genome replication Inferred from direct assay. Source: UniProtKB response to oxidative stress Traceable author statement. Source: ProtInc response to virus Traceable author statement. Source: ProtInc signal transduction Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	chemoattractant activity Inferred from direct assay. Source: UniProtKB chemokine activity Traceable author statement. Source: ProtInc signal transducer activity Traceable author statement. Source: ProtInc
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

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)
	P13501-1 [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: 2456327] [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: 10213461] [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: 16791620] [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: 15489334] [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: 1380064] [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: 7524281] [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: 8525373] [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: 9516414] [Abstract] Cited for: IDENTIFICATION OF RANTES(3-68), PROTEOLYTIC PROCESSING OF N-TERMINAL, 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: 15923218] [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: 7537088] [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: 7542919] [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: 9889151] [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

EMBLGenBankDDBJ

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.

UniGene

Hs.514821

3D structure databases

PDBPDBe

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	[»]
2VXW	X-ray	1.70	A/B/C/D	33-91	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:31N.
DIP:5841N.

Proteomic databases

PeptideAtlas

P13501.

Genome annotation databases

Ensembl

ENSG00000161570. Homo sapiens. [Contig view]

GeneID

6352.

KEGG

hsa:6352.

Organism-specific databases

GeneCards

GC17M031222.

H-InvDB

HIX0020441.

HGNC

HGNC:10632. CCL5.

MIM

187011. gene.

PharmGKB

PA35564.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P13501.

HOVERGEN

P13501.

OMA

P13501. VFVTRKN.

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_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

P13501.

Bgee

P13501.

CleanEx

HS_CCL5.

GermOnline

ENSG00000161570. Homo sapiens.

Family and domain databases

InterPro

IPR000827. CC_chemkine_sml_CS.
IPR001811. Chemokine_IL8.
[Graphical view]

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

SMART

SM00199. SCY. 1 hit.
[Graphical view]

PROSITE

PS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	June 16, 2009
This is version 111 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)