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Protein

C-C motif chemokine 4

Gene

CCL4

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

Caution

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

GO - Molecular functioni

  • CCR1 chemokine receptor binding Source: UniProtKB
  • CCR5 chemokine receptor binding Source: UniProtKB
  • chemokine activity Source: GO_Central
  • 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
  • cytokine-mediated signaling pathway Source: Reactome
  • establishment or maintenance of cell polarity Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: GO_Central
  • immune response Source: ProtInc
  • inflammatory response Source: GO_Central
  • monocyte chemotaxis Source: GO_Central
  • 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 natural killer cell chemotaxis Source: UniProtKB
  • response to toxic substance Source: UniProtKB
  • response to virus Source: ProtInc
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionCytokine
Biological processChemotaxis, Inflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-418594 G alpha (i) signalling events
R-HSA-6783783 Interleukin-10 signaling
SIGNORiP13236

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

EuPathDBiHostDB:ENSG00000275302.1
HGNCiHGNC:10630 CCL4
MIMi182284 gene
neXtProtiNX_P13236

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi388372
6351
9560
OpenTargetsiENSG00000275302
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
ProteomicsDBi52904

Expressioni

Inductioni

By mitogens.

Gene expression databases

BgeeiENSG00000275302
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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112254, 6 interactors
DIPiDIP-5840N
IntActiP13236, 23 interactors
MINTiP13236
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

ProteinModelPortaliP13236
SMRiP13236
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13236

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J4I9 Eukaryota
ENOG410YXJU LUCA
GeneTreeiENSGT00900000140870
HOGENOMiHOG000036685
HOVERGENiHBG017871
InParanoidiP13236
KOiK12964
OMAiRSKQVCA
OrthoDBiEOG091G14Y2
PhylomeDBiP13236
TreeFamiTF334888

Family and domain databases

InterProiView protein in InterPro
IPR000827 Chemokine_CC_CS
IPR001811 Chemokine_IL8-like_dom
IPR036048 Interleukin_8-like_sf
PfamiView protein in Pfam
PF00048 IL8, 1 hit
SMARTiView protein in SMART
SM00199 SCY, 1 hit
SUPFAMiSSF54117 SSF54117, 1 hit
PROSITEiView protein in PROSITE
PS00472 SMALL_CYTOKINES_CC, 1 hit

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 dbSNP:rs1049752Ensembl.1
Natural variantiVAR_04870320P → L. Corresponds to variant dbSNP:rs1130750Ensembl.1
Natural variantiVAR_05921180S → T2 PublicationsCorresponds to variant dbSNP:rs1719152Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCCL4_HUMAN
AccessioniPrimary (citable) accession number: P13236
Secondary accession number(s): P22617
, Q13704, Q3SXL8, Q6FGI8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: July 18, 2018
This is version 189 of the entry and version 1 of the sequence. See 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

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

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