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P10147

- CCL3_HUMAN

UniProt

P10147 - CCL3_HUMAN

Protein

C-C motif chemokine 3

Gene

CCL3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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 binding Source: UniProtKB
    10. 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

    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

    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

    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.
    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. 4 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 – 283
    Beta strandi31 – 333
    Helixi44 – 463
    Beta strandi47 – 526
    Beta strandi57 – 593
    Beta strandi62 – 665
    Beta strandi71 – 744
    Helixi79 – 879

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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[»]
    3TN1X-ray2.60A/B/C/D/E25-91[»]
    ProteinModelPortaliP10147.
    SMRiP10147. Positions 26-91.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP10147.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG42742.
    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

    MQVSTAALAV LLCTMALCNQ FSASLAADTP TACCFSYTSR QIPQNFIADY   50
    FETSSQCSKP GVIFLTKRSR QVCADPSEEW VQKYVSDLEL SA 92
    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:
    EMBL
    GenBank
    DDBJ
    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

    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS11307.1.
    PIRi A35673. A30574.
    RefSeqi NP_002974.1. NM_002983.2.
    UniGenei Hs.514107.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1B50 NMR - A/B 24-92 [» ]
    1B53 NMR - A/B 24-92 [» ]
    2X69 X-ray 2.65 A/B/C/D/E 23-92 [» ]
    2X6G X-ray 2.18 A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R 23-92 [» ]
    3FPU X-ray 1.76 B 24-92 [» ]
    3H44 X-ray 3.00 C/D 23-92 [» ]
    3KBX X-ray 2.65 A/B/C/D/E 23-92 [» ]
    3TN1 X-ray 2.60 A/B/C/D/E 25-91 [» ]
    ProteinModelPortali P10147.
    SMRi P10147. Positions 26-91.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112252. 4 interactions.
    DIPi DIP-5837N.
    IntActi P10147. 1 interaction.
    MINTi MINT-103148.
    STRINGi 9606.ENSP00000225245.

    Polymorphism databases

    DMDMi 127078.

    Proteomic databases

    PaxDbi P10147.
    PRIDEi P10147.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 6348.
    KEGGi hsa:6348.
    UCSCi uc002hkv.3. human.

    Organism-specific databases

    CTDi 6348.
    GeneCardsi GC17M034415.
    HGNCi HGNC:10627. CCL3.
    MIMi 182283. gene.
    neXtProti NX_P10147.
    PharmGKBi PA35559.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42742.
    HOGENOMi HOG000036685.
    HOVERGENi HBG017871.
    InParanoidi P10147.
    KOi K05408.
    OMAi NTPTACC.
    OrthoDBi EOG7CVQ1F.
    PhylomeDBi P10147.
    TreeFami TF334888.

    Enzyme and pathway databases

    Reactomei REACT_15344. Chemokine receptors bind chemokines.

    Miscellaneous databases

    EvolutionaryTracei P10147.
    GeneWikii CCL3.
    GenomeRNAii 6348.
    NextBioi 24664.
    PROi P10147.
    SOURCEi Search...

    Gene expression databases

    Bgeei P10147.
    CleanExi HS_CCL3.
    Genevestigatori P10147.

    Family and domain databases

    InterProi IPR000827. Chemokine_CC_CS.
    IPR001811. Chemokine_IL8-like_dom.
    [Graphical view ]
    Pfami PF00048. IL8. 1 hit.
    [Graphical view ]
    SMARTi SM00199. SCY. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54117. SSF54117. 1 hit.
    PROSITEi PS00472. SMALL_CYTOKINES_CC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 162 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