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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei40 – 401Involved in GAG binding
Sitei68 – 681Involved in GAG binding
Sitei70 – 701Involved in GAG binding

GO - Molecular functioni

  1. calcium-dependent protein kinase C activity Source: UniProtKB
  2. CCR1 chemokine receptor binding Source: UniProtKB
  3. CCR5 chemokine receptor binding Source: UniProtKB
  4. chemoattractant activity Source: UniProtKB
  5. chemokine activity Source: UniProtKB
  6. identical protein binding Source: IntAct
  7. kinase activity Source: UniProtKB
  8. phospholipase activator activity Source: UniProtKB
  9. protein kinase activity Source: UniProtKB

GO - Biological processi

  1. astrocyte cell migration Source: UniProtKB
  2. behavior Source: UniProtKB
  3. calcium ion transport Source: UniProtKB
  4. calcium-mediated signaling Source: UniProtKB
  5. cell activation Source: UniProtKB
  6. cell-cell signaling Source: UniProtKB
  7. cellular calcium ion homeostasis Source: UniProtKB
  8. cellular response to interferon-gamma Source: UniProtKB
  9. cellular response to interleukin-1 Source: UniProtKB
  10. cellular response to organic cyclic compound Source: UniProtKB
  11. cellular response to tumor necrosis factor Source: UniProtKB
  12. chemotaxis Source: UniProtKB
  13. cytoskeleton organization Source: UniProtKB
  14. eosinophil chemotaxis Source: UniProtKB
  15. eosinophil degranulation Source: UniProtKB
  16. exocytosis Source: UniProtKB
  17. granulocyte chemotaxis Source: UniProtKB
  18. inflammatory response Source: UniProtKB
  19. lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  20. lymphocyte chemotaxis Source: UniProtKB
  21. macrophage chemotaxis Source: UniProtKB
  22. MAPK cascade Source: UniProtKB
  23. monocyte chemotaxis Source: UniProtKB
  24. negative regulation by host of viral transcription Source: UniProtKB
  25. negative regulation of bone mineralization Source: UniProtKB
  26. negative regulation of gene expression Source: UniProtKB
  27. negative regulation of osteoclast differentiation Source: UniProtKB
  28. neutrophil chemotaxis Source: UniProtKB
  29. osteoblast differentiation Source: UniProtKB
  30. positive chemotaxis Source: GOC
  31. positive regulation of calcium ion import Source: BHF-UCL
  32. positive regulation of calcium ion transport Source: UniProtKB
  33. positive regulation of calcium-mediated signaling Source: UniProtKB
  34. positive regulation of catalytic activity Source: GOC
  35. positive regulation of cell migration Source: UniProtKB
  36. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  37. positive regulation of gene expression Source: UniProtKB
  38. positive regulation of inflammatory response Source: UniProtKB
  39. positive regulation of interleukin-1 beta secretion Source: UniProtKB
  40. positive regulation of natural killer cell chemotaxis Source: UniProtKB
  41. positive regulation of neuron apoptotic process Source: UniProtKB
  42. positive regulation of protein kinase B signaling Source: UniProtKB
  43. positive regulation of tumor necrosis factor production Source: UniProtKB
  44. protein kinase B signaling Source: UniProtKB
  45. protein phosphorylation Source: GOC
  46. regulation of cell shape Source: UniProtKB
  47. regulation of sensory perception of pain Source: UniProtKB
  48. release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: UniProtKB
  49. response to cholesterol Source: UniProtKB
  50. response to toxic substance Source: UniProtKB
  51. signaling Source: UniProtKB
  52. T cell chemotaxis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Enzyme and pathway databases

ReactomeiREACT_15344. Chemokine receptors bind chemokines.

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
ProteomesiUP000005640: Chromosome 17, UP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:10627. CCL3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: UniProtKB
  3. extracellular region Source: BHF-UCL
  4. extracellular space Source: UniProtKB
  5. intracellular Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi40 – 401R → A: Slightly reduces heparin binding. 1 Publication
Mutagenesisi49 – 491D → A: Reduces self-association; in BB-10010: Improved pharmaceutical properties. 2 Publications
Mutagenesisi68 – 681R → A: Strongly reduces heparin binding. 1 Publication
Mutagenesisi70 – 701R → A: Reduces heparin binding. 1 Publication
Mutagenesisi89 – 891E → A: Reduces self-association. 1 Publication

Organism-specific databases

PharmGKBiPA35559.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23231 PublicationAdd
BLAST
Chaini24 – 9269C-C motif chemokine 3PRO_0000005156Add
BLAST
Chaini27 – 9266MIP-1-alpha(4-69)PRO_0000005157Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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.
PRIDEiP10147.

Expressioni

Inductioni

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

Gene expression databases

BgeeiP10147.
CleanExiHS_CCL3.
ExpressionAtlasiP10147. baseline and differential.
GenevestigatoriP10147.

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

Protein-protein interaction databases

BioGridi112252. 5 interactions.
DIPiDIP-5837N.
IntActiP10147. 1 interaction.
MINTiMINT-103148.
STRINGi9606.ENSP00000225245.

Structurei

Secondary structure

1
92
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi26 – 283Combined sources
Beta strandi31 – 333Combined sources
Helixi44 – 463Combined sources
Beta strandi47 – 526Combined sources
Beta strandi57 – 593Combined sources
Beta strandi62 – 665Combined sources
Beta strandi71 – 744Combined sources
Helixi79 – 879Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP10147.
SMRiP10147. Positions 26-91.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10147.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG42742.
GeneTreeiENSGT00730000110278.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
InParanoidiP10147.
KOiK05408.
OMAiNTPTACC.
OrthoDBiEOG7CVQ1F.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781E → D.
Corresponds to variant rs34171309 [ dbSNP | Ensembl ].
VAR_048701

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.3. human.

Polymorphism databases

DMDMi127078.

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
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[»]
ProteinModelPortaliP10147.
SMRiP10147. Positions 26-91.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112252. 5 interactions.
DIPiDIP-5837N.
IntActiP10147. 1 interaction.
MINTiMINT-103148.
STRINGi9606.ENSP00000225245.

Polymorphism databases

DMDMi127078.

Proteomic databases

PaxDbiP10147.
PRIDEiP10147.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000613396; ENSP00000480753; ENSG00000278567.
ENST00000613922; ENSP00000477908; ENSG00000277632.
ENST00000616221; ENSP00000483712; ENSG00000274221.
GeneIDi6348.
KEGGihsa:6348.
UCSCiuc002hkv.3. human.

Organism-specific databases

CTDi6348.
GeneCardsiGC17M034415.
HGNCiHGNC:10627. CCL3.
MIMi182283. gene.
neXtProtiNX_P10147.
PharmGKBiPA35559.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42742.
GeneTreeiENSGT00730000110278.
HOGENOMiHOG000036685.
HOVERGENiHBG017871.
InParanoidiP10147.
KOiK05408.
OMAiNTPTACC.
OrthoDBiEOG7CVQ1F.
PhylomeDBiP10147.
TreeFamiTF334888.

Enzyme and pathway databases

ReactomeiREACT_15344. Chemokine receptors bind chemokines.

Miscellaneous databases

EvolutionaryTraceiP10147.
GeneWikiiCCL3.
GenomeRNAii6348.
NextBioi24664.
PROiP10147.
SOURCEiSearch...

Gene expression databases

BgeeiP10147.
CleanExiHS_CCL3.
ExpressionAtlasiP10147. baseline and differential.
GenevestigatoriP10147.

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...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.

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: March 4, 2015
This is version 166 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

External Data

Dasty 3

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 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.