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Protein

C-C motif chemokine 4

Gene

CCL4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • CCR1 chemokine receptor binding Source: UniProtKB
  • CCR5 chemokine receptor binding Source: UniProtKB
  • chemokine activity Source: ProtInc
  • cytokine activity Source: ProtInc
  • identical protein binding Source: IntAct

GO - Biological processi

  • cell adhesion Source: ProtInc
  • cell-cell signaling Source: ProtInc
  • cellular response to interferon-gamma Source: GO_Central
  • cellular response to interleukin-1 Source: GO_Central
  • cellular response to tumor necrosis factor Source: GO_Central
  • chemokine-mediated signaling pathway Source: GO_Central
  • establishment or maintenance of cell polarity Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: GO_Central
  • immune response Source: ProtInc
  • inflammatory response Source: ProtInc
  • monocyte chemotaxis Source: GO_Central
  • movement of cell or subcellular component Source: ProtInc
  • negative regulation by host of viral transcription Source: UniProtKB
  • neutrophil chemotaxis Source: GO_Central
  • positive regulation of calcium ion transport Source: UniProtKB
  • positive regulation of calcium-mediated signaling Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: GO_Central
  • positive regulation of GTPase activity Source: GO_Central
  • positive regulation of inflammatory response Source: GO_Central
  • positive regulation of natural killer cell chemotaxis Source: UniProtKB
  • response to toxic substance Source: UniProtKB
  • response to virus Source: ProtInc
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129277-MONOMER.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:10630. CCL4.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: Reactome
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi388372.
6351.
9560.
OpenTargetsiENSG00000275302.
ENSG00000275824.
ENSG00000277943.
PharmGKBiPA35563.

Polymorphism and mutation databases

BioMutaiCCL4.
DMDMi127080.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Add BLAST23
ChainiPRO_000000516424 – 92C-C motif chemokine 4Add BLAST69
ChainiPRO_000000516526 – 92MIP-1-beta(3-69)Add BLAST67

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 58By similarity
Disulfide bondi35 ↔ 74By 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

BgeeiENSG00000129277.
CleanExiHS_CCL4.
ExpressionAtlasiP13236. baseline and differential.
GenevisibleiP13236. HS.

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
SLC30A2Q9BRI35EBI-2873970,EBI-8644112

GO - Molecular functioni

  • CCR1 chemokine receptor binding Source: UniProtKB
  • CCR5 chemokine receptor binding Source: UniProtKB
  • chemokine activity Source: ProtInc
  • cytokine activity Source: ProtInc
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi112254. 6 interactors.
DIPiDIP-5840N.
IntActiP13236. 5 interactors.
MINTiMINT-140523.
STRINGi9606.ENSP00000250151.

Structurei

Secondary structure

192
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 28Combined sources3
Turni30 – 32Combined sources3
Helixi45 – 47Combined sources3
Beta strandi48 – 53Combined sources6
Beta strandi58 – 60Combined sources3
Beta strandi63 – 67Combined sources5
Beta strandi68 – 70Combined sources3
Beta strandi72 – 75Combined sources4
Helixi80 – 90Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4RALX-ray3.15D/E24-92[»]
ProteinModelPortaliP13236.
SMRiP13236.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13236.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J4I9. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00860000133690.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
InParanoidiP13236.
KOiK12964.
OMAiEASEFCS.
OrthoDBiEOG091G14Y2.
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

        10         20         30         40         50
MKLCVTVLSL LMLVAAFCSP ALSAPMGSDP PTACCFSYTA RKLPRNFVVD
60 70 80 90
YYETSSLCSQ PAVVFQTKRS KQVCADPSES WVQEYVYDLE LN
Length:92
Mass (Da):10,212
Last modified:January 1, 1990 - v1
Checksum:iF2EA7CF341B0E258
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6T → C in AAA36752 (PubMed:2809212).Curated1
Sequence conflicti15A → S in AAB00790 (PubMed:1894635).Curated1
Sequence conflicti40 – 45ARKLPR → REASS in AAA36656 (PubMed:2521353).Curated6
Sequence conflicti56S → I in AAA36752 (PubMed:2809212).Curated1
Sequence conflicti70S → G in CAA37722 (PubMed:1894635).Curated1
Sequence conflicti70S → G in AAB00790 (PubMed:1894635).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04870212M → V.Corresponds to variant rs9635771dbSNPEnsembl.1
Natural variantiVAR_04870320P → L.Corresponds to variant rs1130750dbSNPEnsembl.1
Natural variantiVAR_05921180S → T.2 PublicationsCorresponds to variant rs1719152dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_002984.3.
NP_996890.1. NM_207007.3.
UniGeneiHs.449862.
Hs.515183.
Hs.75703.

Genome annotation databases

EnsembliENST00000615863; ENSP00000482259; ENSG00000275302.
ENST00000617322; ENSP00000480345; ENSG00000275824.
ENST00000621600; ENSP00000478708; ENSG00000277943.
GeneIDi388372.
6351.
KEGGihsa:388372.
hsa:6351.
UCSCiuc002hkw.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Macrophage inflammatory protein entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_002984.3.
NP_996890.1. NM_207007.3.
UniGeneiHs.449862.
Hs.515183.
Hs.75703.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4RALX-ray3.15D/E24-92[»]
ProteinModelPortaliP13236.
SMRiP13236.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112254. 6 interactors.
DIPiDIP-5840N.
IntActiP13236. 5 interactors.
MINTiMINT-140523.
STRINGi9606.ENSP00000250151.

Polymorphism and mutation databases

BioMutaiCCL4.
DMDMi127080.

Proteomic databases

PaxDbiP13236.
PeptideAtlasiP13236.
PRIDEiP13236.

Protocols and materials databases

DNASUi388372.
9560.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000615863; ENSP00000482259; ENSG00000275302.
ENST00000617322; ENSP00000480345; ENSG00000275824.
ENST00000621600; ENSP00000478708; ENSG00000277943.
GeneIDi388372.
6351.
KEGGihsa:388372.
hsa:6351.
UCSCiuc002hkw.3. human.

Organism-specific databases

CTDi388372.
6351.
DisGeNETi388372.
6351.
9560.
GeneCardsiCCL4.
HGNCiHGNC:10630. CCL4.
HPAiCAB007805.
MIMi182284. gene.
neXtProtiNX_P13236.
OpenTargetsiENSG00000275302.
ENSG00000275824.
ENSG00000277943.
PharmGKBiPA35563.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J4I9. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00860000133690.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
InParanoidiP13236.
KOiK12964.
OMAiEASEFCS.
OrthoDBiEOG091G14Y2.
PhylomeDBiP13236.
TreeFamiTF334888.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129277-MONOMER.

Miscellaneous databases

ChiTaRSiCCL4. human.
EvolutionaryTraceiP13236.
GeneWikiiCCL4.
PROiP13236.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129277.
CleanExiHS_CCL4.
ExpressionAtlasiP13236. baseline and differential.
GenevisibleiP13236. HS.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 177 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 thought to be a ligand for CCR8.1 Publication

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.