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P13236

- CCL4_HUMAN

UniProt

P13236 - CCL4_HUMAN

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Protein
C-C motif chemokine 4
Gene
CCL4, LAG1, MIP1B, SCYA4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  1. CCR1 chemokine receptor binding Source: UniProtKB
  2. CCR5 chemokine receptor binding Source: UniProtKB
  3. chemokine activity Source: ProtInc
  4. cytokine activity Source: ProtInc
  5. identical protein binding Source: IntAct
  6. protein binding Source: IntAct

GO - Biological processi

  1. cell adhesion Source: ProtInc
  2. cell chemotaxis Source: GOC
  3. cell-cell signaling Source: ProtInc
  4. cellular component movement Source: ProtInc
  5. establishment or maintenance of cell polarity Source: ProtInc
  6. immune response Source: ProtInc
  7. inflammatory response Source: ProtInc
  8. negative regulation by host of viral transcription Source: UniProtKB
  9. positive regulation of calcium ion transport Source: UniProtKB
  10. positive regulation of calcium-mediated signaling Source: UniProtKB
  11. positive regulation of natural killer cell chemotaxis Source: UniProtKB
  12. response to toxic substance Source: UniProtKB
  13. response to virus Source: ProtInc
  14. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Enzyme and pathway databases

ReactomeiREACT_15344. Chemokine receptors bind chemokines.

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:CCL4
Synonyms:LAG1, MIP1B, SCYA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:10630. CCL4.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35563.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323
Add
BLAST
Chaini24 – 9269C-C motif chemokine 4
PRO_0000005164Add
BLAST
Chaini26 – 9267MIP-1-beta(3-69)
PRO_0000005165Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi34 ↔ 58 By similarity
Disulfide bondi35 ↔ 74 By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP13236.
PeptideAtlasiP13236.
PRIDEiP13236.

Expressioni

Inductioni

By mitogens.

Gene expression databases

ArrayExpressiP13236.
BgeeiP13236.
CleanExiHS_CCL4.
GenevestigatoriP13236.

Organism-specific databases

HPAiCAB007805.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-2873970,EBI-2873970
CCR5P516812EBI-6625160,EBI-489374

Protein-protein interaction databases

BioGridi112254. 2 interactions.
DIPiDIP-5840N.
IntActiP13236. 4 interactions.
MINTiMINT-140523.
STRINGi9606.ENSP00000250151.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 283
Turni30 – 323
Helixi45 – 473
Beta strandi48 – 536
Beta strandi58 – 603
Beta strandi63 – 675
Beta strandi68 – 703
Beta strandi72 – 754
Helixi80 – 9011

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP13236.
SMRiP13236. Positions 27-92.

Miscellaneous databases

EvolutionaryTraceiP13236.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG124416.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
KOiK12964.
OMAiPSCISIV.
OrthoDBiEOG7CVQ1F.
PhylomeDBiP13236.
TreeFamiTF334888.

Family and domain databases

InterProiIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.
PROSITEiPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P13236-1 [UniParc]FASTAAdd to Basket

« Hide

MKLCVTVLSL LMLVAAFCSP ALSAPMGSDP PTACCFSYTA RKLPRNFVVD   50
YYETSSLCSQ PAVVFQTKRS KQVCADPSES WVQEYVYDLE LN 92
Length:92
Mass (Da):10,212
Last modified:January 1, 1990 - v1
Checksum:iF2EA7CF341B0E258
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121M → V.
Corresponds to variant rs9635771 [ dbSNP | Ensembl ].
VAR_048702
Natural varianti20 – 201P → L.
Corresponds to variant rs1130750 [ dbSNP | Ensembl ].
VAR_048703
Natural varianti80 – 801S → T.2 Publications
Corresponds to variant rs1719152 [ dbSNP | Ensembl ].
VAR_059211

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61T → C in AAA36752. 1 Publication
Sequence conflicti15 – 151A → S in AAB00790. 1 Publication
Sequence conflicti40 – 456ARKLPR → REASS in AAA36656. 1 Publication
Sequence conflicti56 – 561S → I in AAA36752. 1 Publication
Sequence conflicti70 – 701S → G in CAA37722. 1 Publication
Sequence conflicti70 – 701S → G in AAB00790. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS11308.1.
PIRiJH0319. A31767.
RefSeqiNP_002975.1. NM_002984.2.
NP_996890.1. NM_207007.3.
UniGeneiHs.449862.
Hs.515183.
Hs.75703.

Genome annotation databases

EnsembliENST00000250151; ENSP00000250151; ENSG00000129277.
GeneIDi388372.
6351.
KEGGihsa:388372.
hsa:6351.
hsa:9560.
UCSCiuc002hkw.1. human.

Polymorphism databases

DMDMi127080.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Macrophage inflammatory protein entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS11308.1.
PIRi JH0319. A31767.
RefSeqi NP_002975.1. NM_002984.2.
NP_996890.1. NM_207007.3.
UniGenei Hs.449862.
Hs.515183.
Hs.75703.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HUM NMR - A/B 24-92 [» ]
1HUN NMR - A/B 24-92 [» ]
1JE4 NMR - A 24-92 [» ]
2FFK NMR - B 24-92 [» ]
2FIN NMR - B 24-92 [» ]
2X6L X-ray 2.60 A/B/C/D/E 24-92 [» ]
3TN2 X-ray 1.60 A 24-91 [» ]
ProteinModelPortali P13236.
SMRi P13236. Positions 27-92.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112254. 2 interactions.
DIPi DIP-5840N.
IntActi P13236. 4 interactions.
MINTi MINT-140523.
STRINGi 9606.ENSP00000250151.

Polymorphism databases

DMDMi 127080.

Proteomic databases

PaxDbi P13236.
PeptideAtlasi P13236.
PRIDEi P13236.

Protocols and materials databases

DNASUi 388372.
9560.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000250151 ; ENSP00000250151 ; ENSG00000129277 .
GeneIDi 388372.
6351.
KEGGi hsa:388372.
hsa:6351.
hsa:9560.
UCSCi uc002hkw.1. human.

Organism-specific databases

CTDi 388372.
6351.
9560.
GeneCardsi GC17P034431.
HGNCi HGNC:10630. CCL4.
HPAi CAB007805.
MIMi 182284. gene.
neXtProti NX_P13236.
PharmGKBi PA35563.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG124416.
HOGENOMi HOG000036685.
HOVERGENi HBG017871.
KOi K12964.
OMAi PSCISIV.
OrthoDBi EOG7CVQ1F.
PhylomeDBi P13236.
TreeFami TF334888.

Enzyme and pathway databases

Reactomei REACT_15344. Chemokine receptors bind chemokines.

Miscellaneous databases

ChiTaRSi CCL4. human.
EvolutionaryTracei P13236.
GeneWikii CCL4.
NextBioi 102005.
PROi P13236.
SOURCEi Search...

Gene expression databases

ArrayExpressi P13236.
Bgeei P13236.
CleanExi HS_CCL4.
Genevestigatori P13236.

Family and domain databases

InterProi IPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view ]
Pfami PF00048. IL8. 1 hit.
[Graphical view ]
SMARTi SM00199. SCY. 1 hit.
[Graphical view ]
SUPFAMi SSF54117. SSF54117. 1 hit.
PROSITEi PS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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.

Entry informationi

Entry nameiCCL4_HUMAN
AccessioniPrimary (citable) accession number: P13236
Secondary accession number(s): P22617
, Q13704, Q3SXL8, Q6FGI8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: September 3, 2014
This is version 155 of the entry and version 1 of the sequence. [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

Caution

Was originally (1 Publication) thought to be a ligand for CCR8.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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