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P13236

- CCL4_HUMAN

UniProt

P13236 - CCL4_HUMAN

Protein

C-C motif chemokine 4

Gene

CCL4

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 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

    GO - Molecular functioni

    1. CCR1 chemokine receptor binding Source: UniProtKB
    2. CCR5 chemokine receptor binding Source: UniProtKB
    3. chemokine activity Source: ProtInc
    4. cytokine activity Source: ProtInc
    5. identical protein binding Source: IntAct
    6. protein binding Source: IntAct

    GO - Biological processi

    1. cell adhesion Source: ProtInc
    2. cell-cell signaling Source: ProtInc
    3. cell chemotaxis Source: GOC
    4. cellular component movement Source: ProtInc
    5. establishment or maintenance of cell polarity Source: ProtInc
    6. immune response Source: ProtInc
    7. inflammatory response Source: ProtInc
    8. negative regulation by host of viral transcription Source: UniProtKB
    9. positive regulation of calcium ion transport Source: UniProtKB
    10. positive regulation of calcium-mediated signaling Source: UniProtKB
    11. positive regulation of natural killer cell chemotaxis Source: UniProtKB
    12. response to toxic substance Source: UniProtKB
    13. response to virus Source: ProtInc
    14. signal transduction Source: ProtInc

    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 4
    Alternative 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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:10630. CCL4.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. extracellular space Source: ProtInc

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA35563.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Add
    BLAST
    Chaini24 – 9269C-C motif chemokine 4PRO_0000005164Add
    BLAST
    Chaini26 – 9267MIP-1-beta(3-69)PRO_0000005165Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi34 ↔ 58By similarity
    Disulfide bondi35 ↔ 74By 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 bond

    Proteomic databases

    PaxDbiP13236.
    PeptideAtlasiP13236.
    PRIDEiP13236.

    Expressioni

    Inductioni

    By mitogens.

    Gene expression databases

    ArrayExpressiP13236.
    BgeeiP13236.
    CleanExiHS_CCL4.
    GenevestigatoriP13236.

    Organism-specific databases

    HPAiCAB007805.

    Interactioni

    Subunit structurei

    Homodimer and heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69).1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-2873970,EBI-2873970
    CCR5P516812EBI-6625160,EBI-489374

    Protein-protein interaction databases

    BioGridi112254. 2 interactions.
    DIPiDIP-5840N.
    IntActiP13236. 4 interactions.
    MINTiMINT-140523.
    STRINGi9606.ENSP00000250151.

    Structurei

    Secondary structure

    1
    92
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi26 – 283
    Turni30 – 323
    Helixi45 – 473
    Beta strandi48 – 536
    Beta strandi58 – 603
    Beta strandi63 – 675
    Beta strandi68 – 703
    Beta strandi72 – 754
    Helixi80 – 9011

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1HUMNMR-A/B24-92[»]
    1HUNNMR-A/B24-92[»]
    1JE4NMR-A24-92[»]
    2FFKNMR-B24-92[»]
    2FINNMR-B24-92[»]
    2X6LX-ray2.60A/B/C/D/E24-92[»]
    3TN2X-ray1.60A24-91[»]
    ProteinModelPortaliP13236.
    SMRiP13236. Positions 27-92.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP13236.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG124416.
    HOGENOMiHOG000036685.
    HOVERGENiHBG017871.
    KOiK12964.
    OMAiPSCISIV.
    OrthoDBiEOG7CVQ1F.
    PhylomeDBiP13236.
    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.

    P13236-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKLCVTVLSL LMLVAAFCSP ALSAPMGSDP PTACCFSYTA RKLPRNFVVD   50
    YYETSSLCSQ PAVVFQTKRS KQVCADPSES WVQEYVYDLE LN 92
    Length:92
    Mass (Da):10,212
    Last modified:January 1, 1990 - v1
    Checksum:iF2EA7CF341B0E258
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti6 – 61T → C in AAA36752. (PubMed:2809212)Curated
    Sequence conflicti15 – 151A → S in AAB00790. (PubMed:1894635)Curated
    Sequence conflicti40 – 456ARKLPR → REASS in AAA36656. (PubMed:2521353)Curated
    Sequence conflicti56 – 561S → I in AAA36752. (PubMed:2809212)Curated
    Sequence conflicti70 – 701S → G in CAA37722. (PubMed:1894635)Curated
    Sequence conflicti70 – 701S → G in AAB00790. (PubMed:1894635)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121M → V.
    Corresponds to variant rs9635771 [ dbSNP | Ensembl ].
    VAR_048702
    Natural varianti20 – 201P → L.
    Corresponds to variant rs1130750 [ dbSNP | Ensembl ].
    VAR_048703
    Natural varianti80 – 801S → T.2 Publications
    Corresponds to variant rs1719152 [ dbSNP | Ensembl ].
    VAR_059211

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSiCCDS11308.1.
    PIRiJH0319. A31767.
    RefSeqiNP_002975.1. NM_002984.2.
    NP_996890.1. NM_207007.3.
    UniGeneiHs.449862.
    Hs.515183.
    Hs.75703.

    Genome annotation databases

    GeneIDi388372.
    6351.
    KEGGihsa:388372.
    hsa:6351.
    hsa:9560.
    UCSCiuc002hkw.1. human.

    Polymorphism databases

    DMDMi127080.

    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
    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_002984.2.
    NP_996890.1. NM_207007.3.
    UniGenei Hs.449862.
    Hs.515183.
    Hs.75703.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P13236.
    SMRi P13236. Positions 27-92.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112254. 2 interactions.
    DIPi DIP-5840N.
    IntActi P13236. 4 interactions.
    MINTi MINT-140523.
    STRINGi 9606.ENSP00000250151.

    Polymorphism databases

    DMDMi 127080.

    Proteomic databases

    PaxDbi P13236.
    PeptideAtlasi P13236.
    PRIDEi P13236.

    Protocols and materials databases

    DNASUi 388372.
    9560.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 388372.
    6351.
    KEGGi hsa:388372.
    hsa:6351.
    hsa:9560.
    UCSCi uc002hkw.1. human.

    Organism-specific databases

    CTDi 388372.
    6351.
    GeneCardsi GC17P034431.
    HGNCi HGNC:10630. CCL4.
    HPAi CAB007805.
    MIMi 182284. gene.
    neXtProti NX_P13236.
    PharmGKBi PA35563.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG124416.
    HOGENOMi HOG000036685.
    HOVERGENi HBG017871.
    KOi K12964.
    OMAi PSCISIV.
    OrthoDBi EOG7CVQ1F.
    PhylomeDBi P13236.
    TreeFami TF334888.

    Enzyme and pathway databases

    Reactomei REACT_15344. Chemokine receptors bind chemokines.

    Miscellaneous databases

    ChiTaRSi CCL4. human.
    EvolutionaryTracei P13236.
    GeneWikii CCL4.
    NextBioi 102005.
    PROi P13236.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P13236.
    Bgeei P13236.
    CleanExi HS_CCL4.
    Genevestigatori P13236.

    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. "Identification, cloning, and characterization of an immune activation gene."
      Lipes M.A., Napolitano M., Jeang K.-T., Chang N.T., Leonard W.J.
      Proc. Natl. Acad. Sci. U.S.A. 85:9704-9708(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    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].
    3. "A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes."
      Brown K.D., Zurawski S.M., Mosmann T.R., Zurawski G.
      J. Immunol. 142:679-687(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: T-cell.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Tissue: Natural killer cell.
    5. "Isolation and characterization of a cDNA encoding a putative cytokine which is induced by stimulation via the CD2 structure on human T lymphocytes."
      Chang H.C., Reinherz E.L.
      Eur. J. Immunol. 19:1045-1051(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: T-cell.
    6. "The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization."
      Napolitano M., Modi W.S., Cevario S.J., Gnarra J.R., Seuanez H.N., Leonard W.J.
      J. Biol. Chem. 266:17531-17536(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. "Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV+ patients."
      Colobran R., Adreani P., Ashhab Y., Llano A., Este J.A., Dominguez O., Pujol-Borrell R., Juan M.
      J. Immunol. 174:5655-5664(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    8. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    9. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. "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], VARIANT THR-80.
    11. "A novel polypeptide secreted by activated human T lymphocytes."
      Miller M.D., Hata S., Waal Malefyt R., Krangel M.S.
      J. Immunol. 143:2907-2916(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-92, VARIANT THR-80.
      Tissue: T-cell.
    12. "Identification of the CC chemokines TARC and macrophage inflammatory protein-1 beta as novel functional ligands for the CCR8 receptor."
      Bernardini G., Hedrick J., Sozzani S., Luini W., Spinetti G., Weiss M., Menon S., Zlotnik A., Mantovani A., Santoni A., Napolitano M.
      Eur. J. Immunol. 28:582-588(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: RECEPTOR INTERACTION.
    13. "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: FUNCTION.
    14. "The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8."
      Garlisi C.G., Xiao H., Tian F., Hedrick J.A., Billah M.M., Egan R.W., Umland S.P.
      Eur. J. Immunol. 29:3210-3215(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "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: IDENTIFICATION OF MIP-1-BETA(3-69) BY MASS SPECTROMETRY, FUNCTION, SUBUNIT.
    16. Cited for: REVIEW.
    17. "High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR."
      Lodi P.J., Garrett D.S., Kuscewski J., Tsang M.L.S., Weatherbee J.A., Leonard W.J., Gronenborn A.M., Clore G.M.
      Science 263:1762-1767(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.

    Entry informationi

    Entry nameiCCL4_HUMAN
    AccessioniPrimary (citable) accession number: P13236
    Secondary accession number(s): P22617
    , Q13704, Q3SXL8, Q6FGI8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: January 1, 1990
    Last modified: October 1, 2014
    This is version 156 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

    Caution

    Was originally thought to be a ligand for CCR8.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, 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