UniProtKB - P13236 (CCL4_HUMAN)
Protein
C-C motif chemokine 4
Gene
CCL4
Organism
Homo sapiens (Human)
Status
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
- CCR chemokine receptor binding Source: GO_Central
- 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
- eosinophil chemotaxis 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: GO_Central
- lymphocyte chemotaxis 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 function | Cytokine |
Biological process | Chemotaxis, Inflammatory response |
Enzyme and pathway databases
PathwayCommonsi | P13236 |
Reactomei | R-HSA-380108, Chemokine receptors bind chemokines R-HSA-418594, G alpha (i) signalling events R-HSA-6783783, Interleukin-10 signaling |
SIGNORi | P13236 |
Names & Taxonomyi
Protein namesi | Recommended name: C-C motif chemokine 4Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000275302.1 |
HGNCi | HGNC:10630, CCL4 |
MIMi | 182284, gene |
neXtProti | NX_P13236 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Keywords - Cellular componenti
SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 388372 6351 |
OpenTargetsi | ENSG00000275302 |
Miscellaneous databases
Pharosi | P13236, Tbio |
Polymorphism and mutation databases
BioMutai | CCL4 |
DMDMi | 127080 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | Add BLAST | 23 | |
ChainiPRO_0000005164 | 24 – 92 | C-C motif chemokine 4Add BLAST | 69 | |
ChainiPRO_0000005165 | 26 – 92 | MIP-1-beta(3-69)Add BLAST | 67 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 34 ↔ 58 | By similarity | ||
Disulfide bondi | 35 ↔ 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 bondProteomic databases
MassIVEi | P13236 |
PaxDbi | P13236 |
PeptideAtlasi | P13236 |
PRIDEi | P13236 |
ProteomicsDBi | 52904 |
Expressioni
Inductioni
By mitogens.
Gene expression databases
Bgeei | ENSG00000275302, Expressed in granulocyte and 180 other tissues |
ExpressionAtlasi | P13236, baseline and differential |
Genevisiblei | P13236, HS |
Organism-specific databases
HPAi | ENSG00000275302, Group enriched (blood, lung, lymphoid tissue) |
Interactioni
Subunit structurei
Homodimer and heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69).
1 PublicationBinary interactionsi
Hide detailsP13236
MIP-1-beta(3-69) (PRO_0000005165)
With | #Exp. | IntAct |
---|---|---|
CCR5 [P51681] | 2 | EBI-6625160,EBI-489374 |
GO - Molecular functioni
- CCR1 chemokine receptor binding Source: UniProtKB
- CCR5 chemokine receptor binding Source: UniProtKB
- CCR chemokine receptor binding Source: GO_Central
- chemokine activity Source: GO_Central
- cytokine activity Source: ProtInc
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 112254, 24 interactors |
DIPi | DIP-5840N |
IntActi | P13236, 26 interactors |
MINTi | P13236 |
STRINGi | 9606.ENSP00000482259 |
Chemistry databases
BindingDBi | P13236 |
Miscellaneous databases
RNActi | P13236, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P13236 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P13236 |
Family & Domainsi
Sequence similaritiesi
Belongs to the intercrine beta (chemokine CC) family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502S8M4, Eukaryota |
GeneTreei | ENSGT01000000214365 |
HOGENOMi | CLU_141716_4_0_1 |
InParanoidi | P13236 |
OMAi | VDYYDTN |
OrthoDBi | 1575018at2759 |
PhylomeDBi | P13236 |
TreeFami | TF334888 |
Family and domain databases
InterProi | View protein in InterPro IPR039809, Chemokine_b/g/d IPR000827, Chemokine_CC_CS IPR001811, Chemokine_IL8-like_dom IPR036048, Interleukin_8-like_sf |
PANTHERi | PTHR12015, PTHR12015, 1 hit |
Pfami | View protein in Pfam PF00048, IL8, 1 hit |
SMARTi | View protein in SMART SM00199, SCY, 1 hit |
SUPFAMi | SSF54117, SSF54117, 1 hit |
PROSITEi | View protein in PROSITE PS00472, SMALL_CYTOKINES_CC, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P13236-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKLCVTVLSL LMLVAAFCSP ALSAPMGSDP PTACCFSYTA RKLPRNFVVD
60 70 80 90
YYETSSLCSQ PAVVFQTKRS KQVCADPSES WVQEYVYDLE LN
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ7M4M2 | Q7M4M2_HUMAN | C-C motif chemokine 4 | CCL4 | 52 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 6 | T → C in AAA36752 (PubMed:2809212).Curated | 1 | |
Sequence conflicti | 15 | A → S in AAB00790 (PubMed:1894635).Curated | 1 | |
Sequence conflicti | 40 – 45 | ARKLPR → REASS in AAA36656 (PubMed:2521353).Curated | 6 | |
Sequence conflicti | 56 | S → I in AAA36752 (PubMed:2809212).Curated | 1 | |
Sequence conflicti | 70 | S → G in CAA37722 (PubMed:1894635).Curated | 1 | |
Sequence conflicti | 70 | S → G in AAB00790 (PubMed:1894635).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048702 | 12 | M → V. Corresponds to variant dbSNP:rs1049752Ensembl. | 1 | |
Natural variantiVAR_048703 | 20 | P → L. Corresponds to variant dbSNP:rs1130750Ensembl. | 1 | |
Natural variantiVAR_059211 | 80 | S → 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 |
CCDSi | CCDS11308.1 |
PIRi | JH0319, A31767 |
RefSeqi | NP_002975.1, NM_002984.3 NP_996890.1, NM_207007.3 |
Genome annotation databases
Ensembli | ENST00000615863; ENSP00000482259; ENSG00000275302 ENST00000617322; ENSP00000480345; ENSG00000275824 ENST00000621600; ENSP00000478708; ENSG00000277943 |
GeneIDi | 388372 6351 |
KEGGi | hsa:388372 hsa:6351 |
UCSCi | uc002hkw.3, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS11308.1 |
PIRi | JH0319, A31767 |
RefSeqi | NP_002975.1, NM_002984.3 NP_996890.1, NM_207007.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
4RAL | X-ray | 3.15 | D/E | 24-92 | [»] | |
SMRi | P13236 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112254, 24 interactors |
DIPi | DIP-5840N |
IntActi | P13236, 26 interactors |
MINTi | P13236 |
STRINGi | 9606.ENSP00000482259 |
Chemistry databases
BindingDBi | P13236 |
Polymorphism and mutation databases
BioMutai | CCL4 |
DMDMi | 127080 |
Proteomic databases
MassIVEi | P13236 |
PaxDbi | P13236 |
PeptideAtlasi | P13236 |
PRIDEi | P13236 |
ProteomicsDBi | 52904 |
Protocols and materials databases
Antibodypediai | 72629, 585 antibodies |
DNASUi | 388372 9560 |
Genome annotation databases
Ensembli | ENST00000615863; ENSP00000482259; ENSG00000275302 ENST00000617322; ENSP00000480345; ENSG00000275824 ENST00000621600; ENSP00000478708; ENSG00000277943 |
GeneIDi | 388372 6351 |
KEGGi | hsa:388372 hsa:6351 |
UCSCi | uc002hkw.3, human |
Organism-specific databases
CTDi | 388372 6351 |
DisGeNETi | 388372 6351 |
EuPathDBi | HostDB:ENSG00000275302.1 |
GeneCardsi | CCL4 |
HGNCi | HGNC:10630, CCL4 |
HPAi | ENSG00000275302, Group enriched (blood, lung, lymphoid tissue) |
MIMi | 182284, gene |
neXtProti | NX_P13236 |
OpenTargetsi | ENSG00000275302 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S8M4, Eukaryota |
GeneTreei | ENSGT01000000214365 |
HOGENOMi | CLU_141716_4_0_1 |
InParanoidi | P13236 |
OMAi | VDYYDTN |
OrthoDBi | 1575018at2759 |
PhylomeDBi | P13236 |
TreeFami | TF334888 |
Enzyme and pathway databases
PathwayCommonsi | P13236 |
Reactomei | R-HSA-380108, Chemokine receptors bind chemokines R-HSA-418594, G alpha (i) signalling events R-HSA-6783783, Interleukin-10 signaling |
SIGNORi | P13236 |
Miscellaneous databases
BioGRID-ORCSi | 388372, 2 hits in 82 CRISPR screens 6351, 3 hits in 817 CRISPR screens |
ChiTaRSi | CCL4, human |
EvolutionaryTracei | P13236 |
GeneWikii | CCL4 |
Pharosi | P13236, Tbio |
PROi | PR:P13236 |
RNActi | P13236, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000275302, Expressed in granulocyte and 180 other tissues |
ExpressionAtlasi | P13236, baseline and differential |
Genevisiblei | P13236, HS |
Family and domain databases
InterProi | View protein in InterPro IPR039809, Chemokine_b/g/d IPR000827, Chemokine_CC_CS IPR001811, Chemokine_IL8-like_dom IPR036048, Interleukin_8-like_sf |
PANTHERi | PTHR12015, PTHR12015, 1 hit |
Pfami | View protein in Pfam PF00048, IL8, 1 hit |
SMARTi | View protein in SMART SM00199, SCY, 1 hit |
SUPFAMi | SSF54117, SSF54117, 1 hit |
PROSITEi | View protein in PROSITE PS00472, SMALL_CYTOKINES_CC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CCL4_HUMAN | |
Accessioni | P13236Primary (citable) accession number: P13236 Secondary accession number(s): P22617 Q6FGI8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | January 1, 1990 | |
Last modified: | December 2, 2020 | |
This is version 208 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations