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P10147 (CCL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. MIP-1-alpha(4-69)
    Alternative name(s):
    LD78-alpha(4-69)
Gene names
Name:CCL3
Synonyms:G0S19-1, MIP1A, SCYA3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length92 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.8

Subunit structure

Self-associates. Also heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69). Ref.11

Subcellular location

Secreted.

Induction

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

Post-translational modification

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

Sequence similarities

Belongs to the intercrine beta (chemokine CC) family.

Ontologies

Keywords
   Biological processChemotaxis
Inflammatory response
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB

T cell chemotaxis

Inferred from direct assay PubMed 10706735. Source: UniProtKB

astrocyte cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

behavior

Inferred from direct assay PubMed 20167378. Source: UniProtKB

calcium ion transport

Inferred from direct assay PubMed 10734056. Source: UniProtKB

calcium-mediated signaling

Inferred from direct assay PubMed 10072545PubMed 19523456. Source: UniProtKB

cell activation

Inferred from direct assay PubMed 10706735. Source: UniProtKB

cell-cell signaling

Inferred from direct assay PubMed 10679098. Source: UniProtKB

cellular calcium ion homeostasis

Inferred from direct assay PubMed 10072545PubMed 10734056PubMed 21403648. Source: UniProtKB

cellular response to interferon-gamma

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

cellular response to interleukin-1

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

cellular response to organic cyclic compound

Inferred from direct assay PubMed 21147091. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 9407497. Source: UniProtKB

chemotaxis

Inferred from direct assay PubMed 10679098. Source: UniProtKB

cytoskeleton organization

Inferred from direct assay PubMed 10072545. Source: UniProtKB

eosinophil chemotaxis

Inferred from direct assay PubMed 10072545. Source: UniProtKB

eosinophil degranulation

Inferred from direct assay PubMed 10706735. Source: UniProtKB

exocytosis

Inferred from direct assay PubMed 10734056. Source: UniProtKB

granulocyte chemotaxis

Inferred from direct assay PubMed 10706735. Source: UniProtKB

inflammatory response

Inferred from direct assay PubMed 10679098PubMed 10706735PubMed 21147091. Source: UniProtKB

lipopolysaccharide-mediated signaling pathway

Inferred from direct assay PubMed 21147091. Source: UniProtKB

lymphocyte chemotaxis

Inferred from direct assay PubMed 10706735. Source: UniProtKB

macrophage chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

monocyte chemotaxis

Inferred from direct assay PubMed 10706735. Source: UniProtKB

negative regulation by host of viral transcription

Inferred from direct assay PubMed 10841574. Source: UniProtKB

negative regulation of bone mineralization

Inferred from direct assay PubMed 21403648. Source: UniProtKB

negative regulation of gene expression

Inferred from direct assay PubMed 21403648. Source: UniProtKB

negative regulation of osteoclast differentiation

Inferred from direct assay PubMed 21403648. Source: UniProtKB

neutrophil chemotaxis

Inferred from direct assay PubMed 10706735. Source: UniProtKB

osteoblast differentiation

Inferred from expression pattern PubMed 21403648. Source: UniProtKB

positive chemotaxis

Inferred from direct assay PubMed 10072545PubMed 10660125PubMed 10706735PubMed 15001559. Source: GOC

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 21403648. Source: UniProtKB

positive regulation of calcium ion import

Traceable author statement PubMed 10925302. Source: BHF-UCL

positive regulation of calcium ion transport

Inferred from direct assay PubMed 15764707PubMed 8699119. Source: UniProtKB

positive regulation of calcium-mediated signaling

Inferred from mutant phenotype PubMed 10679098. Source: UniProtKB

positive regulation of catalytic activity

Inferred from direct assay PubMed 10734056. Source: GOC

positive regulation of cell migration

Inferred from direct assay PubMed 10706735PubMed 7545673. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 10706735. Source: UniProtKB

positive regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-1 beta secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of natural killer cell chemotaxis

Inferred from direct assay PubMed 7545673. Source: UniProtKB

positive regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from expression pattern PubMed 21403648. Source: UniProtKB

positive regulation of tumor necrosis factor production

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase B signaling

Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 10734056PubMed 15764707. Source: GOC

regulation of cell shape

Inferred from direct assay PubMed 10072545. Source: UniProtKB

regulation of sensory perception of pain

Inferred from direct assay PubMed 15764707. Source: UniProtKB

release of sequestered calcium ion into cytosol by sarcoplasmic reticulum

Inferred from direct assay PubMed 19523456. Source: UniProtKB

response to cholesterol

Inferred from direct assay PubMed 19523456. Source: UniProtKB

response to toxic substance

Inferred from direct assay PubMed 10841574. Source: UniProtKB

signaling

Inferred from expression pattern PubMed 12032188. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 21784977. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 19523456. Source: UniProtKB

extracellular region

Inferred from direct assay PubMed 20041150. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 20167378PubMed 21403648. Source: UniProtKB

intracellular

Inferred from direct assay PubMed 10072545. Source: UniProtKB

   Molecular_functionCCR1 chemokine receptor binding

Inferred from physical interaction PubMed 10660125PubMed 15764707PubMed 7545673PubMed 8699119. Source: UniProtKB

CCR5 chemokine receptor binding

Inferred from physical interaction PubMed 10679098PubMed 8699119. Source: UniProtKB

calcium-dependent protein kinase C activity

Inferred from direct assay PubMed 15764707. Source: UniProtKB

chemoattractant activity

Inferred from direct assay PubMed 10072545PubMed 10660125PubMed 10706735PubMed 15001559. Source: UniProtKB

chemokine activity

Inferred from direct assay PubMed 10072545PubMed 10660125. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 20959807. Source: IntAct

kinase activity

Inferred from direct assay PubMed 21403648. Source: UniProtKB

phospholipase activator activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 21784977. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-8459634,EBI-8459634
IDEP147353EBI-8459634,EBI-2556886

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.7
Chain24 – 9269C-C motif chemokine 3
PRO_0000005156
Chain27 – 9266MIP-1-alpha(4-69)
PRO_0000005157

Sites

Site401Involved in GAG binding
Site681Involved in GAG binding
Site701Involved in GAG binding

Amino acid modifications

Disulfide bond33 ↔ 57 By similarity
Disulfide bond34 ↔ 73 By similarity

Natural variations

Natural variant781E → D.
Corresponds to variant rs34171309 [ dbSNP | Ensembl ].
VAR_048701

Experimental info

Mutagenesis401R → A: Slightly reduces heparin binding. Ref.10
Mutagenesis491D → A: Reduces self-association; in BB-10010: Improved pharmaceutical properties. Ref.7 Ref.13
Mutagenesis681R → A: Strongly reduces heparin binding. Ref.10
Mutagenesis701R → A: Reduces heparin binding. Ref.10
Mutagenesis891E → A: Reduces self-association. Ref.13

Secondary structure

................ 92
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10147 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 517865D5D6776CA8

FASTA9210,085
        10         20         30         40         50         60 
MQVSTAALAV LLCTMALCNQ FSASLAADTP TACCFSYTSR QIPQNFIADY FETSSQCSKP 

        70         80         90 
GVIFLTKRSR QVCADPSEEW VQKYVSDLEL SA 

« Hide

References

« Hide 'large scale' references
[1]"A cDNA clone used to study mRNA inducible in human tonsillar lymphocytes by a tumor promoter."
Obaru K., Fukuda M., Maeda S., Shimada K.
J. Biochem. 99:885-894(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Lymphocyte.
[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].
Tissue: T-cell.
[3]"Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation."
Blum S., Forsdyke R.E., Forsdyke D.R.
DNA Cell Biol. 9:589-602(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Lymphocyte.
[4]"Structures of human genes coding for cytokine LD78 and their expression."
Nakao M., Nomiyama H., Shimada K.
Mol. Cell. Biol. 10:3646-3658(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Lymphocyte.
[5]"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].
Tissue: Natural killer cell.
[6]Jang J.S., Kim B.E.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-92.
Tissue: Leukocyte.
[7]"BB-10010: an active variant of human macrophage inflammatory protein-1 alpha with improved pharmaceutical properties."
Hunter M.G., Bawden L., Brotherton D., Craig S., Cribbes S., Czaplewski L.G., Dexter T.M., Drummond A.H., Gearing A.H., Heyworth C.M., Lord B.I., Mccourt M., Varley P.G., Wood L.M., Edwards R.M., Lewis P.J.
Blood 86:4400-4408(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-92, MUTAGENESIS OF ASP-49.
[8]"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: PROTEIN SEQUENCE OF 27-40 AND 71-83, FUNCTION.
[9]"Identification of MIP-1 alpha/LD78 as a monocyte chemoattractant released by the HTLV-I-transformed cell line MT4."
Bertini R., Luini W., Sozzani S., Bottazzi B., Ruggiero P., Boraschi D., Saggioro D., Chieco-Bianchi L., Proost P., van Damme J., Mantovani A.
AIDS Res. Hum. Retroviruses 11:155-160(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-51, IDENTIFICATION OF LD78-ALPHA(4-69).
[10]"Identification of a glycosaminoglycan-binding site in chemokine macrophage inflammatory protein-1alpha."
Koopmann W., Krangel M.S.
J. Biol. Chem. 272:10103-10109(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: GAG BINDING SITES ARG-40; ARG-68 AND ARG-70, MUTAGENESIS OF ARG-40; ARG-68 AND ARG-70.
[11]"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: SUBUNIT, INTERACTION WITH MIP-1-BETA(3-69).
[12]"Macrophage inflammatory protein-1."
Menten P., Wuyts A., Van Damme J.
Cytokine Growth Factor Rev. 13:455-481(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants."
Czaplewski L.G., McKeating J., Craven C.J., Higgins L.D., Appay V., Brown A., Dudgeon T., Howard L.A., Meyers T., Owen J., Palan S.R., Tan P., Wilson G., Woods N.R., Heyworth C.M., Lord B.I., Brotherton D., Christison R. expand/collapse author list , Craig S., Cribbes S., Edwards R.M., Evans S.J., Gilbert R., Morgan P., Eliot Randle E., Schofield N., Varley P.G., Fisher J., Jonathan P., Waltho J.P., Hunter M.G.
J. Biol. Chem. 274:16077-16084(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 24-92, MUTAGENESIS OF ASP-49 AND GLU-89.
+Additional computationally mapped references.

Web resources

Wikipedia

Macrophage inflammatory protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11307.1.
PIRA30574. A35673.
RefSeqNP_002974.1. NM_002983.2.
UniGeneHs.514107.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
3TN1X-ray2.60A/B/C/D/E25-91[»]
ProteinModelPortalP10147.
SMRP10147. Positions 26-91.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112252. 4 interactions.
DIPDIP-5837N.
IntActP10147. 1 interaction.
MINTMINT-103148.
STRING9606.ENSP00000225245.

Polymorphism databases

DMDM127078.

Proteomic databases

PaxDbP10147.
PRIDEP10147.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225245; ENSP00000225245; ENSG00000006075.
GeneID6348.
KEGGhsa:6348.
UCSCuc002hkv.3. human.

Organism-specific databases

CTD6348.
GeneCardsGC17M034415.
HGNCHGNC:10627. CCL3.
MIM182283. gene.
neXtProtNX_P10147.
PharmGKBPA35559.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42742.
HOGENOMHOG000036685.
HOVERGENHBG017871.
InParanoidP10147.
KOK05408.
OMANTPTACC.
OrthoDBEOG7CVQ1F.
PhylomeDBP10147.
TreeFamTF334888.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP10147.
CleanExHS_CCL3.
GenevestigatorP10147.

Family and domain databases

InterProIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamPF00048. IL8. 1 hit.
[Graphical view]
SMARTSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMSSF54117. SSF54117. 1 hit.
PROSITEPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10147.
GeneWikiCCL3.
GenomeRNAi6348.
NextBio24664.
PROP10147.
SOURCESearch...

Entry information

Entry nameCCL3_HUMAN
AccessionPrimary (citable) accession number: P10147
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM