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O00585

- CCL21_HUMAN

UniProt

O00585 - CCL21_HUMAN

Protein

C-C motif chemokine 21

Gene

CCL21

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

    Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.

    GO - Molecular functioni

    1. CCR7 chemokine receptor binding Source: BHF-UCL
    2. chemokine activity Source: BHF-UCL
    3. chemokine receptor binding Source: UniProtKB

    GO - Biological processi

    1. activation of Rho GTPase activity Source: BHF-UCL
    2. cell-cell signaling Source: ProtInc
    3. cell maturation Source: BHF-UCL
    4. dendritic cell chemotaxis Source: BHF-UCL
    5. dendritic cell dendrite assembly Source: BHF-UCL
    6. establishment of T cell polarity Source: BHF-UCL
    7. immune response Source: ProtInc
    8. immunological synapse formation Source: BHF-UCL
    9. inflammatory response Source: BHF-UCL
    10. mesangial cell-matrix adhesion Source: BHF-UCL
    11. negative regulation of dendritic cell dendrite assembly Source: BHF-UCL
    12. negative regulation of leukocyte apoptotic process Source: BHF-UCL
    13. positive regulation of actin filament polymerization Source: BHF-UCL
    14. positive regulation of cell adhesion mediated by integrin Source: BHF-UCL
    15. positive regulation of cell-matrix adhesion Source: BHF-UCL
    16. positive regulation of cell motility Source: BHF-UCL
    17. positive regulation of chemotaxis Source: BHF-UCL
    18. positive regulation of dendritic cell antigen processing and presentation Source: BHF-UCL
    19. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
    20. positive regulation of filopodium assembly Source: BHF-UCL
    21. positive regulation of glycoprotein biosynthetic process Source: BHF-UCL
    22. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
    23. positive regulation of JNK cascade Source: BHF-UCL
    24. positive regulation of myeloid dendritic cell chemotaxis Source: BHF-UCL
    25. positive regulation of neutrophil chemotaxis Source: BHF-UCL
    26. positive regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
    27. positive regulation of protein kinase activity Source: BHF-UCL
    28. positive regulation of protein kinase B signaling Source: BHF-UCL
    29. positive regulation of pseudopodium assembly Source: BHF-UCL
    30. positive regulation of receptor-mediated endocytosis Source: BHF-UCL
    31. positive regulation of T cell migration Source: MGI
    32. release of sequestered calcium ion into cytosol Source: BHF-UCL
    33. response to prostaglandin E Source: BHF-UCL
    34. ruffle organization Source: BHF-UCL
    35. T cell costimulation Source: BHF-UCL

    Keywords - Molecular functioni

    Cytokine

    Keywords - Biological processi

    Chemotaxis, Inflammatory response

    Enzyme and pathway databases

    ReactomeiREACT_15344. Chemokine receptors bind chemokines.
    REACT_19231. G alpha (i) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    C-C motif chemokine 21
    Alternative name(s):
    6Ckine
    Beta-chemokine exodus-2
    Secondary lymphoid-tissue chemokine
    Short name:
    SLC
    Small-inducible cytokine A21
    Gene namesi
    Name:CCL21
    Synonyms:SCYA21
    ORF Names:UNQ784/PRO1600
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:10620. CCL21.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. extracellular space Source: UniProtKB-KW

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA35552.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 23231 PublicationAdd
    BLAST
    Chaini24 – 134111C-C motif chemokine 21PRO_0000005220Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi31 ↔ 571 Publication
    Disulfide bondi32 ↔ 751 Publication
    Disulfide bondi103 ↔ 122Sequence Analysis

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiO00585.
    PRIDEiO00585.

    PTM databases

    PhosphoSiteiO00585.

    Miscellaneous databases

    PMAP-CutDBO00585.

    Expressioni

    Tissue specificityi

    Highly expressed in high endothelial venules of lymph nodes, spleen and appendix. Intermediate levels found in small intestine, thyroid gland and trachea. Low level expression in thymus, bone marrow, liver, and pancreas. Also found in tonsil, fetal heart and fetal spleen.

    Gene expression databases

    ArrayExpressiO00585.
    BgeeiO00585.
    CleanExiHS_CCL21.
    GenevestigatoriO00585.

    Organism-specific databases

    HPAiCAB005067.

    Interactioni

    Subunit structurei

    Monomer. Binds to CCR7.1 Publication

    Protein-protein interaction databases

    BioGridi112269. 5 interactions.
    DIPiDIP-5854N.
    IntActiO00585. 7 interactions.
    MINTiMINT-123964.
    STRINGi9606.ENSP00000259607.

    Structurei

    Secondary structure

    1
    134
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni42 – 443
    Beta strandi45 – 506
    Turni53 – 564
    Beta strandi62 – 687
    Beta strandi74 – 763
    Helixi81 – 9111

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2L4NNMR-A24-134[»]
    ProteinModelPortaliO00585.
    SMRiO00585. Positions 24-93.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni98 – 13437C-terminal basic extensionAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG46090.
    HOGENOMiHOG000036685.
    HOVERGENiHBG017871.
    InParanoidiO00585.
    KOiK16062.
    OMAiCCLKYSL.
    OrthoDBiEOG7GXPDG.
    PhylomeDBiO00585.
    TreeFamiTF338224.

    Family and domain databases

    InterProiIPR001811. Chemokine_IL8-like_dom.
    [Graphical view]
    PfamiPF00048. IL8. 1 hit.
    [Graphical view]
    SMARTiSM00199. SCY. 1 hit.
    [Graphical view]
    SUPFAMiSSF54117. SSF54117. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O00585-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAQSLALSLL ILVLAFGIPR TQGSDGGAQD CCLKYSQRKI PAKVVRSYRK    50
    QEPSLGCSIP AILFLPRKRS QAELCADPKE LWVQQLMQHL DKTPSPQKPA 100
    QGCRKDRGAS KTGKKGKGSK GCKRTERSQT PKGP 134
    Length:134
    Mass (Da):14,646
    Last modified:July 1, 1997 - v1
    Checksum:iFB48C2F71CB4A9D2
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB002409 mRNA. Translation: BAA21817.1.
    AF001979 mRNA. Translation: AAB86594.1.
    U88320 mRNA. Translation: AAB91454.1.
    AJ005654 Genomic DNA. Translation: CAA06653.1.
    AY358887 mRNA. Translation: AAQ89246.1.
    BC027918 mRNA. Translation: AAH27918.1.
    CCDSiCCDS6571.1.
    RefSeqiNP_002980.1. NM_002989.3.
    UniGeneiHs.57907.

    Genome annotation databases

    EnsembliENST00000259607; ENSP00000259607; ENSG00000137077.
    GeneIDi6366.
    KEGGihsa:6366.
    UCSCiuc003zvo.4. human.

    Cross-referencesi

    Web resourcesi

    Wikipedia

    CCL21 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB002409 mRNA. Translation: BAA21817.1 .
    AF001979 mRNA. Translation: AAB86594.1 .
    U88320 mRNA. Translation: AAB91454.1 .
    AJ005654 Genomic DNA. Translation: CAA06653.1 .
    AY358887 mRNA. Translation: AAQ89246.1 .
    BC027918 mRNA. Translation: AAH27918.1 .
    CCDSi CCDS6571.1.
    RefSeqi NP_002980.1. NM_002989.3.
    UniGenei Hs.57907.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2L4N NMR - A 24-134 [» ]
    ProteinModelPortali O00585.
    SMRi O00585. Positions 24-93.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112269. 5 interactions.
    DIPi DIP-5854N.
    IntActi O00585. 7 interactions.
    MINTi MINT-123964.
    STRINGi 9606.ENSP00000259607.

    PTM databases

    PhosphoSitei O00585.

    Proteomic databases

    PaxDbi O00585.
    PRIDEi O00585.

    Protocols and materials databases

    DNASUi 6366.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000259607 ; ENSP00000259607 ; ENSG00000137077 .
    GeneIDi 6366.
    KEGGi hsa:6366.
    UCSCi uc003zvo.4. human.

    Organism-specific databases

    CTDi 6366.
    GeneCardsi GC09M034709.
    HGNCi HGNC:10620. CCL21.
    HPAi CAB005067.
    MIMi 602737. gene.
    neXtProti NX_O00585.
    PharmGKBi PA35552.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46090.
    HOGENOMi HOG000036685.
    HOVERGENi HBG017871.
    InParanoidi O00585.
    KOi K16062.
    OMAi CCLKYSL.
    OrthoDBi EOG7GXPDG.
    PhylomeDBi O00585.
    TreeFami TF338224.

    Enzyme and pathway databases

    Reactomei REACT_15344. Chemokine receptors bind chemokines.
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GeneWikii CCL21.
    GenomeRNAii 6366.
    NextBioi 24734.
    PMAP-CutDB O00585.
    PROi O00585.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00585.
    Bgeei O00585.
    CleanExi HS_CCL21.
    Genevestigatori O00585.

    Family and domain databases

    InterProi 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.
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of a novel human CC chemokine secondary lymphoid-tissue chemokine that is a potent chemoattractant for lymphocytes and mapped to chromosome 9p13."
      Nagira M., Imai T., Hieshima K., Kusuda J., Ridanpaeae M., Takagi S., Nishimura M., Kakizaki M., Nomiyama H., Yoshie O.
      J. Biol. Chem. 272:19518-19524(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Identification and characterization of a novel beta chemokine containing six conserved cysteines."
      Hedrick J.A., Zlotnik A.
      J. Immunol. 159:1589-1593(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Isolation and characterization of Exodus-2, a novel C-C chemokine with a unique 37-amino acid carboxyl-terminal extension."
      Hromas R., Kim C.H., Klemsz M., Krathwohl M., Fife K., Cooper S., Schnizlein-Bick C., Broxmeyer H.E.
      J. Immunol. 159:2554-2558(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 24-33.
    4. "A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes."
      Gunn M.D., Tangemann K., Tam C., Cyster J.G., Rosen S.D., Williams L.T.
      Proc. Natl. Acad. Sci. U.S.A. 95:258-263(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
    5. "Genomic organisation of human SLC."
      Reiterer P., Bernhardt G., Lipp M.
      Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. "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: Pancreas and Spleen.
    8. "Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7."
      Yoshida R., Nagira M., Kitaura M., Imagawa N., Imai T., Yoshie O.
      J. Biol. Chem. 273:7118-7122(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: RECEPTOR INTERACTION.
    9. "Beta-arrestin recruitment and G protein signaling by the atypical human chemokine decoy receptor CCX-CKR."
      Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M., van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J., Vischer H.F.
      J. Biol. Chem. 288:7169-7181(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: RECEPTOR INTERACTION.
    10. "Solution structure of CCL21 and identification of a putative CCR7 binding site."
      Love M., Sandberg J.L., Ziarek J.J., Gerarden K.P., Rode R.R., Jensen D.R., McCaslin D.R., Peterson F.C., Veldkamp C.T.
      Biochemistry 51:733-735(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 24-134, SUBUNIT, DISULFIDE BONDS.

    Entry informationi

    Entry nameiCCL21_HUMAN
    AccessioniPrimary (citable) accession number: O00585
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 132 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 9
      Human chromosome 9: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3