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O00585

- CCL21_HUMAN

UniProt

O00585 - CCL21_HUMAN

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Protein
C-C motif chemokine 21
Gene
CCL21, SCYA21, UNQ784/PRO1600
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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

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
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35552.

PTM / Processingi

Molecule processing

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

Amino acid modifications

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

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 CCR7.3 Publications

Protein-protein interaction databases

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

Structurei

Secondary structure

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.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni98 – 13437C-terminal basic extension
Add
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. 5 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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 131 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

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