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Protein

C-C motif chemokine 3

Gene

CCL3

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 CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei40Involved in GAG binding1
Sitei68Involved in GAG binding1
Sitei70Involved in GAG binding1

GO - Molecular functioni

  • calcium-dependent protein kinase C activity Source: UniProtKB
  • CCR1 chemokine receptor binding Source: UniProtKB
  • CCR5 chemokine receptor binding Source: UniProtKB
  • chemoattractant activity Source: UniProtKB
  • chemokine activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • kinase activity Source: UniProtKB
  • phospholipase activator activity Source: UniProtKB
  • protein kinase activity Source: UniProtKB

GO - Biological processi

  • astrocyte cell migration Source: UniProtKB
  • behavior Source: UniProtKB
  • calcium ion transport Source: UniProtKB
  • calcium-mediated signaling Source: UniProtKB
  • cell activation Source: UniProtKB
  • cell-cell signaling Source: UniProtKB
  • cellular calcium ion homeostasis Source: UniProtKB
  • cellular response to interferon-gamma Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to organic cyclic compound Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • chemokine-mediated signaling pathway Source: GO_Central
  • chemotaxis Source: UniProtKB
  • cytoskeleton organization Source: UniProtKB
  • eosinophil chemotaxis Source: UniProtKB
  • eosinophil degranulation Source: UniProtKB
  • exocytosis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: GO_Central
  • granulocyte chemotaxis Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • lymphocyte chemotaxis Source: UniProtKB
  • macrophage chemotaxis Source: UniProtKB
  • MAPK cascade Source: UniProtKB
  • monocyte chemotaxis Source: UniProtKB
  • negative regulation by host of viral transcription Source: UniProtKB
  • negative regulation of bone mineralization Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of osteoclast differentiation Source: UniProtKB
  • neutrophil chemotaxis Source: UniProtKB
  • osteoblast differentiation Source: UniProtKB
  • positive regulation of calcium ion import Source: BHF-UCL
  • positive regulation of calcium ion transport Source: UniProtKB
  • positive regulation of calcium-mediated signaling Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of GTPase activity Source: GO_Central
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of interleukin-1 beta secretion Source: UniProtKB
  • positive regulation of natural killer cell chemotaxis Source: UniProtKB
  • positive regulation of neuron apoptotic process Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • protein kinase B signaling Source: UniProtKB
  • regulation of cell shape Source: UniProtKB
  • regulation of sensory perception of pain Source: UniProtKB
  • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: UniProtKB
  • response to cholesterol Source: UniProtKB
  • response to toxic substance Source: UniProtKB
  • signaling Source: UniProtKB
  • T cell chemotaxis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006075-MONOMER.
SIGNORiP10147.

Names & Taxonomyi

Protein namesi
Recommended name:
C-C motif chemokine 3
Alternative name(s):
G0/G1 switch regulatory protein 19-1
Macrophage inflammatory protein 1-alpha
Short name:
MIP-1-alpha
PAT 464.1
SIS-beta
Small-inducible cytokine A3
Tonsillar lymphocyte LD78 alpha protein
Cleaved into the following chain:
Alternative name(s):
LD78-alpha(4-69)
Gene namesi
Name:CCL3
Synonyms:G0S19-1, MIP1A, SCYA3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:10627. CCL3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular region Source: BHF-UCL
  • extracellular space Source: UniProtKB
  • intracellular Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40R → A: Slightly reduces heparin binding. 1 Publication1
Mutagenesisi49D → A: Reduces self-association; in BB-10010: Improved pharmaceutical properties. 2 Publications1
Mutagenesisi68R → A: Strongly reduces heparin binding. 1 Publication1
Mutagenesisi70R → A: Reduces heparin binding. 1 Publication1
Mutagenesisi89E → A: Reduces self-association. 1 Publication1

Organism-specific databases

DisGeNETi6348.
MalaCardsiCCL3.
OpenTargetsiENSG00000274221.
ENSG00000277632.
ENSG00000278567.
PharmGKBiPA35559.

Polymorphism and mutation databases

BioMutaiCCL3.
DMDMi127078.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000000515624 – 92C-C motif chemokine 3Add BLAST69
ChainiPRO_000000515727 – 92MIP-1-alpha(4-69)Add BLAST66

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 57By similarity
Disulfide bondi34 ↔ 73By similarity

Post-translational modificationi

N-terminal processed form LD78-alpha(4-69) is produced by proteolytic cleavage after secretion from HTLV1-transformed T-cells.

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP10147.
PeptideAtlasiP10147.
PRIDEiP10147.

Expressioni

Inductioni

By TPA or PHA (TPA = 12-O-tetradecanoyl phorbol-13 acetate (tumor promoter); PHA = phytohemagglutinin (T-cell mitogen)).

Gene expression databases

BgeeiENSG00000006075.
CleanExiHS_CCL3.
GenevisibleiP10147. HS.

Interactioni

Subunit structurei

Self-associates. Also heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-8459634,EBI-8459634
IDEP147353EBI-8459634,EBI-2556886

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112252. 5 interactors.
DIPiDIP-5837N.
IntActiP10147. 1 interactor.
MINTiMINT-103148.
STRINGi9606.ENSP00000225245.

Structurei

Secondary structure

192
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi26 – 28Combined sources3
Beta strandi31 – 33Combined sources3
Helixi44 – 46Combined sources3
Beta strandi47 – 52Combined sources6
Beta strandi57 – 59Combined sources3
Beta strandi62 – 66Combined sources5
Beta strandi71 – 74Combined sources4
Beta strandi76 – 78Combined sources3
Helixi79 – 87Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B50NMR-A/B24-92[»]
1B53NMR-A/B24-92[»]
2X69X-ray2.65A/B/C/D/E23-92[»]
2X6GX-ray2.18A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R23-92[»]
3FPUX-ray1.76B24-92[»]
3H44X-ray3.00C/D23-92[»]
3KBXX-ray2.65A/B/C/D/E23-92[»]
4RA8X-ray2.60A/B/C/D/E23-91[»]
4ZKBX-ray2.90B24-92[»]
5CORX-ray2.55A/B/C/D/E/F/G/H/I/J23-92[»]
5D65X-ray3.10A/B/C/D/E23-92[»]
ProteinModelPortaliP10147.
SMRiP10147.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10147.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J4I9. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00860000133690.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
InParanoidiP10147.
KOiK05408.
OMAiNTPTACC.
OrthoDBiEOG091G14Y2.
PhylomeDBiP10147.
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.

P10147-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQVSTAALAV LLCTMALCNQ FSASLAADTP TACCFSYTSR QIPQNFIADY
60 70 80 90
FETSSQCSKP GVIFLTKRSR QVCADPSEEW VQKYVSDLEL SA
Length:92
Mass (Da):10,085
Last modified:July 1, 1989 - v1
Checksum:i517865D5D6776CA8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04870178E → D.Corresponds to variant rs34171309dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00044 mRNA. Translation: BAA00029.1.
X03754 mRNA. Translation: CAA27388.1.
X04018 Genomic DNA. Translation: CAA27643.1. Sequence problems.
M25315 mRNA. Translation: AAA57255.1.
M23452 mRNA. Translation: AAA36316.1.
M23178 Genomic DNA. Translation: AAA35858.1.
D90144 Genomic DNA. Translation: BAA14172.1.
BC071834 mRNA. Translation: AAH71834.1.
AF043339 mRNA. Translation: AAC03539.1.
CCDSiCCDS11307.1.
PIRiA35673. A30574.
RefSeqiNP_002974.1. NM_002983.2.
UniGeneiHs.514107.

Genome annotation databases

EnsembliENST00000613396; ENSP00000480753; ENSG00000278567.
ENST00000613922; ENSP00000477908; ENSG00000277632.
ENST00000616221; ENSP00000483712; ENSG00000274221.
GeneIDi6348.
KEGGihsa:6348.
UCSCiuc002hkv.5. 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
D00044 mRNA. Translation: BAA00029.1.
X03754 mRNA. Translation: CAA27388.1.
X04018 Genomic DNA. Translation: CAA27643.1. Sequence problems.
M25315 mRNA. Translation: AAA57255.1.
M23452 mRNA. Translation: AAA36316.1.
M23178 Genomic DNA. Translation: AAA35858.1.
D90144 Genomic DNA. Translation: BAA14172.1.
BC071834 mRNA. Translation: AAH71834.1.
AF043339 mRNA. Translation: AAC03539.1.
CCDSiCCDS11307.1.
PIRiA35673. A30574.
RefSeqiNP_002974.1. NM_002983.2.
UniGeneiHs.514107.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B50NMR-A/B24-92[»]
1B53NMR-A/B24-92[»]
2X69X-ray2.65A/B/C/D/E23-92[»]
2X6GX-ray2.18A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R23-92[»]
3FPUX-ray1.76B24-92[»]
3H44X-ray3.00C/D23-92[»]
3KBXX-ray2.65A/B/C/D/E23-92[»]
4RA8X-ray2.60A/B/C/D/E23-91[»]
4ZKBX-ray2.90B24-92[»]
5CORX-ray2.55A/B/C/D/E/F/G/H/I/J23-92[»]
5D65X-ray3.10A/B/C/D/E23-92[»]
ProteinModelPortaliP10147.
SMRiP10147.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112252. 5 interactors.
DIPiDIP-5837N.
IntActiP10147. 1 interactor.
MINTiMINT-103148.
STRINGi9606.ENSP00000225245.

Polymorphism and mutation databases

BioMutaiCCL3.
DMDMi127078.

Proteomic databases

PaxDbiP10147.
PeptideAtlasiP10147.
PRIDEiP10147.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000613396; ENSP00000480753; ENSG00000278567.
ENST00000613922; ENSP00000477908; ENSG00000277632.
ENST00000616221; ENSP00000483712; ENSG00000274221.
GeneIDi6348.
KEGGihsa:6348.
UCSCiuc002hkv.5. human.

Organism-specific databases

CTDi6348.
DisGeNETi6348.
GeneCardsiCCL3.
HGNCiHGNC:10627. CCL3.
MalaCardsiCCL3.
MIMi182283. gene.
neXtProtiNX_P10147.
OpenTargetsiENSG00000274221.
ENSG00000277632.
ENSG00000278567.
PharmGKBiPA35559.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J4I9. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00860000133690.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
InParanoidiP10147.
KOiK05408.
OMAiNTPTACC.
OrthoDBiEOG091G14Y2.
PhylomeDBiP10147.
TreeFamiTF334888.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006075-MONOMER.
SIGNORiP10147.

Miscellaneous databases

EvolutionaryTraceiP10147.
GeneWikiiCCL3.
GenomeRNAii6348.
PROiP10147.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000006075.
CleanExiHS_CCL3.
GenevisibleiP10147. 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 nameiCCL3_HUMAN
AccessioniPrimary (citable) accession number: P10147
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 180 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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.