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P13236 (CCL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. 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 4
Alternative name(s):
G-26 T-lymphocyte-secreted protein
HC21
Lymphocyte activation gene 1 protein
Short name=LAG-1
MIP-1-beta(1-69)
Macrophage inflammatory protein 1-beta
Short name=MIP-1-beta
PAT 744
Protein H400
SIS-gamma
Small-inducible cytokine A4
T-cell activation protein 2
Short name=ACT-2

Cleaved into the following chain:

  1. MIP-1-beta(3-69)
Gene names
Name:CCL4
Synonyms:LAG1, MIP1B, SCYA4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length92 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B Ref.13 Ref.14 Ref.15

Subunit structure

Homodimer and heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69). Ref.15

Subcellular location

Secreted.

Induction

By mitogens.

Post-translational modification

N-terminal processed form MIP-1-beta(3-69) is produced by proteolytic cleavage after secretion from peripheral blood lymphocytes.

Sequence similarities

Belongs to the intercrine beta (chemokine CC) family.

Caution

Was originally (Ref.12) thought to be a ligand for CCR8.

Ontologies

Keywords
   Biological processChemotaxis
Inflammatory response
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell adhesion

Traceable author statement PubMed 10929056. Source: ProtInc

cell chemotaxis

Traceable author statement PubMed 10929056. Source: GOC

cell-cell signaling

Traceable author statement Ref.2. Source: ProtInc

cellular component movement

Traceable author statement PubMed 9759849. Source: ProtInc

establishment or maintenance of cell polarity

Traceable author statement PubMed 9759849. Source: ProtInc

immune response

Traceable author statement PubMed 10929056. Source: ProtInc

inflammatory response

Traceable author statement Ref.2. Source: ProtInc

negative regulation by host of viral transcription

Inferred from direct assay PubMed 10841574. Source: UniProtKB

positive regulation of calcium ion transport

Inferred from direct assay PubMed 8699119. Source: UniProtKB

positive regulation of calcium-mediated signaling

Inferred from mutant phenotype PubMed 10679098. Source: UniProtKB

positive regulation of natural killer cell chemotaxis

Inferred from direct assay PubMed 7545673. Source: UniProtKB

response to toxic substance

Inferred from direct assay PubMed 10841574. Source: UniProtKB

response to virus

Traceable author statement PubMed 9743377. Source: ProtInc

signal transduction

Traceable author statement PubMed 10929056PubMed 9558100. Source: ProtInc

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Traceable author statement Ref.2. Source: ProtInc

   Molecular_functionCCR1 chemokine receptor binding

Inferred from physical interaction PubMed 7545673. Source: UniProtKB

CCR5 chemokine receptor binding

Inferred from physical interaction PubMed 10679098. Source: UniProtKB

chemokine activity

Traceable author statement PubMed 10929056. Source: ProtInc

cytokine activity

Traceable author statement Ref.1. Source: ProtInc

identical protein binding

Inferred from physical interaction PubMed 20959807. Source: IntAct

protein binding

Inferred from physical interaction PubMed 23597562. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-2873970,EBI-2873970
CCR5P516812EBI-6625160,EBI-489374

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323
Chain24 – 9269C-C motif chemokine 4
PRO_0000005164
Chain26 – 9267MIP-1-beta(3-69)
PRO_0000005165

Amino acid modifications

Disulfide bond34 ↔ 58 By similarity
Disulfide bond35 ↔ 74 By similarity

Natural variations

Natural variant121M → V.
Corresponds to variant rs9635771 [ dbSNP | Ensembl ].
VAR_048702
Natural variant201P → L.
Corresponds to variant rs1130750 [ dbSNP | Ensembl ].
VAR_048703
Natural variant801S → T. Ref.10 Ref.11
Corresponds to variant rs1719152 [ dbSNP | Ensembl ].
VAR_059211

Experimental info

Sequence conflict61T → C in AAA36752. Ref.11
Sequence conflict151A → S in AAB00790. Ref.6
Sequence conflict40 – 456ARKLPR → REASS in AAA36656. Ref.3
Sequence conflict561S → I in AAA36752. Ref.11
Sequence conflict701S → G in CAA37722. Ref.6
Sequence conflict701S → G in AAB00790. Ref.6

Secondary structure

................. 92
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P13236 [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: F2EA7CF341B0E258

FASTA9210,212
        10         20         30         40         50         60 
MKLCVTVLSL LMLVAAFCSP ALSAPMGSDP PTACCFSYTA RKLPRNFVVD YYETSSLCSQ 

        70         80         90 
PAVVFQTKRS KQVCADPSES WVQEYVYDLE LN 

« Hide

References

« Hide 'large scale' references
[1]"Identification, cloning, and characterization of an immune activation gene."
Lipes M.A., Napolitano M., Jeang K.-T., Chang N.T., Leonard W.J.
Proc. Natl. Acad. Sci. U.S.A. 85:9704-9708(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors."
Zipfel P.F., Balke J., Irving S.G., Kelly K., Siebenlist U.
J. Immunol. 142:1582-1590(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes."
Brown K.D., Zurawski S.M., Mosmann T.R., Zurawski G.
J. Immunol. 142:679-687(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: T-cell.
[4]"Cloning and expression of a lymphocyte activation gene (LAG-1)."
Baixeras E., Roman-Roman S., Jitsukawa S., Genevee C., Mechiche S., Viegas-Pequignot E., Hercend T., Triebel F.
Mol. Immunol. 27:1091-1102(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Natural killer cell.
[5]"Isolation and characterization of a cDNA encoding a putative cytokine which is induced by stimulation via the CD2 structure on human T lymphocytes."
Chang H.C., Reinherz E.L.
Eur. J. Immunol. 19:1045-1051(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: T-cell.
[6]"The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization."
Napolitano M., Modi W.S., Cevario S.J., Gnarra J.R., Seuanez H.N., Leonard W.J.
J. Biol. Chem. 266:17531-17536(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV+ patients."
Colobran R., Adreani P., Ashhab Y., Llano A., Este J.A., Dominguez O., Pujol-Borrell R., Juan M.
J. Immunol. 174:5655-5664(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[8]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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], VARIANT THR-80.
[11]"A novel polypeptide secreted by activated human T lymphocytes."
Miller M.D., Hata S., Waal Malefyt R., Krangel M.S.
J. Immunol. 143:2907-2916(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-92, VARIANT THR-80.
Tissue: T-cell.
[12]"Identification of the CC chemokines TARC and macrophage inflammatory protein-1 beta as novel functional ligands for the CCR8 receptor."
Bernardini G., Hedrick J., Sozzani S., Luini W., Spinetti G., Weiss M., Menon S., Zlotnik A., Mantovani A., Santoni A., Napolitano M.
Eur. J. Immunol. 28:582-588(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR INTERACTION.
[13]"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: FUNCTION.
[14]"The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8."
Garlisi C.G., Xiao H., Tian F., Hedrick J.A., Billah M.M., Egan R.W., Umland S.P.
Eur. J. Immunol. 29:3210-3215(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Natural truncation of the chemokine MIP-1beta/CCL4 affects receptor specificity but not anti-HIV-1 activity."
Guan E., Wang J., Roderiquez G., Norcross M.A.
J. Biol. Chem. 277:32348-32352(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF MIP-1-BETA(3-69) BY MASS SPECTROMETRY, FUNCTION, SUBUNIT.
[16]"Macrophage inflammatory protein-1."
Menten P., Wuyts A., Van Damme J.
Cytokine Growth Factor Rev. 13:455-481(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[17]"High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR."
Lodi P.J., Garrett D.S., Kuscewski J., Tsang M.L.S., Weatherbee J.A., Leonard W.J., Gronenborn A.M., Clore G.M.
Science 263:1762-1767(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
+Additional computationally mapped references.

Web resources

Wikipedia

Macrophage inflammatory protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04130 mRNA. Translation: AAA51576.1.
M25316 mRNA. Translation: AAA57256.1.
M23502 mRNA. Translation: AAA36656.1.
X53683 mRNA. Translation: CAA37723.1.
X53682 Genomic DNA. Translation: CAA37722.2. Sequence problems.
X16166 mRNA. Translation: CAA34291.1.
M69203, M69201, M69202 Genomic DNA. Translation: AAB00790.1.
AY766446 mRNA. Translation: AAX07305.1.
AY766459 Genomic DNA. Translation: AAX07292.1.
CR542119 mRNA. Translation: CAG46916.1.
AC003976 Genomic DNA. No translation available.
BC104226 mRNA. Translation: AAI04227.1.
BC104227 mRNA. Translation: AAI04228.1.
BC107433 mRNA. Translation: AAI07434.1.
M57503 mRNA. Translation: AAA36752.1.
CCDSCCDS11308.1.
PIRA31767. JH0319.
RefSeqNP_002975.1. NM_002984.2.
NP_996890.1. NM_207007.3.
UniGeneHs.449862.
Hs.515183.
Hs.75703.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HUMNMR-A/B24-92[»]
1HUNNMR-A/B24-92[»]
1JE4NMR-A24-92[»]
2FFKNMR-B24-92[»]
2FINNMR-B24-92[»]
2X6LX-ray2.60A/B/C/D/E24-92[»]
3TN2X-ray1.60A24-91[»]
ProteinModelPortalP13236.
SMRP13236. Positions 27-92.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112254. 2 interactions.
DIPDIP-5840N.
IntActP13236. 4 interactions.
MINTMINT-140523.
STRING9606.ENSP00000250151.

Polymorphism databases

DMDM127080.

Proteomic databases

PaxDbP13236.
PeptideAtlasP13236.
PRIDEP13236.

Protocols and materials databases

DNASU388372.
9560.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250151; ENSP00000250151; ENSG00000129277.
GeneID388372.
6351.
KEGGhsa:388372.
hsa:6351.
hsa:9560.
UCSCuc002hkw.1. human.

Organism-specific databases

CTD388372.
6351.
9560.
GeneCardsGC17P034431.
HGNCHGNC:10630. CCL4.
HPACAB007805.
MIM182284. gene.
neXtProtNX_P13236.
PharmGKBPA35563.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG124416.
HOGENOMHOG000036685.
HOVERGENHBG017871.
KOK12964.
OMAPSCISIV.
OrthoDBEOG7CVQ1F.
PhylomeDBP13236.
TreeFamTF334888.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP13236.
BgeeP13236.
CleanExHS_CCL4.
GenevestigatorP13236.

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

ChiTaRSCCL4. human.
EvolutionaryTraceP13236.
GeneWikiCCL4.
CCL4L1.
NextBio102005.
PROP13236.
SOURCESearch...

Entry information

Entry nameCCL4_HUMAN
AccessionPrimary (citable) accession number: P13236
Secondary accession number(s): P22617 expand/collapse secondary AC list , Q13704, Q3SXL8, Q6FGI8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: July 9, 2014
This is version 154 of the entry and version 1 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