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O00585 (CCL21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CCL21
Synonyms:SCYA21
ORF Names:UNQ784/PRO1600
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length134 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Monomer. Binds to CCR7. Ref.8 Ref.9 Ref.10

Subcellular location

Secreted.

Tissue specificity

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.

Sequence similarities

Belongs to the intercrine beta (chemokine CC) family.

Ontologies

Keywords
   Biological processChemotaxis
Inflammatory response
   Cellular componentSecreted
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processT cell costimulation

Inferred from sequence or structural similarity. Source: BHF-UCL

activation of Rho GTPase activity

Inferred from direct assay PubMed 15778365. Source: BHF-UCL

cell maturation

Inferred from sequence or structural similarity. Source: BHF-UCL

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

dendritic cell chemotaxis

Inferred from direct assay PubMed 15778365. Source: BHF-UCL

dendritic cell dendrite assembly

Inferred from sequence or structural similarity. Source: BHF-UCL

establishment of T cell polarity

Inferred from direct assay PubMed 12729902. Source: BHF-UCL

immune response

Traceable author statement PubMed 10861057. Source: ProtInc

immunological synapse formation

Inferred from sequence or structural similarity. Source: BHF-UCL

inflammatory response

Non-traceable author statement PubMed 14592837. Source: BHF-UCL

mesangial cell-matrix adhesion

Inferred from direct assay PubMed 15569314. Source: BHF-UCL

negative regulation of dendritic cell dendrite assembly

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of leukocyte apoptotic process

Inferred from direct assay PubMed 15059845. Source: BHF-UCL

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 12729902PubMed 15778365. Source: BHF-UCL

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 15059845. Source: BHF-UCL

positive regulation of JNK cascade

Inferred from direct assay PubMed 15778365. Source: BHF-UCL

positive regulation of actin filament polymerization

Inferred from direct assay PubMed 11242036. Source: BHF-UCL

positive regulation of cell adhesion mediated by integrin

Inferred from direct assay PubMed 15569314. Source: BHF-UCL

positive regulation of cell motility

Inferred from direct assay PubMed 15778365. Source: BHF-UCL

positive regulation of cell-matrix adhesion

Inferred from direct assay PubMed 15569314. Source: BHF-UCL

positive regulation of chemotaxis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of dendritic cell antigen processing and presentation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of filopodium assembly

Inferred from direct assay PubMed 15569314. Source: BHF-UCL

positive regulation of glycoprotein biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of myeloid dendritic cell chemotaxis

Inferred from direct assay PubMed 14592837. Source: BHF-UCL

positive regulation of neutrophil chemotaxis

Inferred from direct assay PubMed 21051556. Source: BHF-UCL

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from direct assay PubMed 15059845PubMed 15778365. Source: BHF-UCL

positive regulation of protein kinase B signaling

Inferred from direct assay PubMed 15059845PubMed 15778365. Source: BHF-UCL

positive regulation of protein kinase activity

Inferred from direct assay PubMed 15059845. Source: BHF-UCL

positive regulation of pseudopodium assembly

Inferred from direct assay PubMed 11242036. Source: BHF-UCL

positive regulation of receptor-mediated endocytosis

Inferred from sequence or structural similarity. Source: BHF-UCL

release of sequestered calcium ion into cytosol

Inferred from direct assay PubMed 14592837. Source: BHF-UCL

response to prostaglandin E

Inferred from direct assay PubMed 14592837. Source: BHF-UCL

ruffle organization

Inferred from direct assay PubMed 15569314. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionCCR7 chemokine receptor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

chemokine activity

Inferred from direct assay PubMed 15778365. Source: BHF-UCL

chemokine receptor binding

Inferred from direct assay Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.3
Chain24 – 134111C-C motif chemokine 21
PRO_0000005220

Regions

Region98 – 13437C-terminal basic extension

Amino acid modifications

Disulfide bond31 ↔ 57 Ref.10
Disulfide bond32 ↔ 75 Ref.10
Disulfide bond103 ↔ 122 Potential

Secondary structure

............ 134
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00585 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: FB48C2F71CB4A9D2

FASTA13414,646
        10         20         30         40         50         60 
MAQSLALSLL ILVLAFGIPR TQGSDGGAQD CCLKYSQRKI PAKVVRSYRK QEPSLGCSIP 

        70         80         90        100        110        120 
AILFLPRKRS QAELCADPKE LWVQQLMQHL DKTPSPQKPA QGCRKDRGAS KTGKKGKGSK 

       130 
GCKRTERSQT PKGP 

« Hide

References

« Hide 'large scale' references
[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]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Wikipedia

CCL21 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_002980.1. NM_002989.3.
UniGeneHs.57907.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L4NNMR-A24-134[»]
ProteinModelPortalO00585.
SMRO00585. Positions 24-93.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112269. 5 interactions.
DIPDIP-5854N.
IntActO00585. 5 interactions.
MINTMINT-123964.
STRING9606.ENSP00000259607.

PTM databases

PhosphoSiteO00585.

Proteomic databases

PaxDbO00585.
PRIDEO00585.

Protocols and materials databases

DNASU6366.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259607; ENSP00000259607; ENSG00000137077.
GeneID6366.
KEGGhsa:6366.
UCSCuc003zvo.4. human.

Organism-specific databases

CTD6366.
GeneCardsGC09M034709.
HGNCHGNC:10620. CCL21.
HPACAB005067.
MIM602737. gene.
neXtProtNX_O00585.
PharmGKBPA35552.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46090.
HOGENOMHOG000036685.
HOVERGENHBG017871.
InParanoidO00585.
KOK16062.
OMACCLKYSL.
OrthoDBEOG7GXPDG.
PhylomeDBO00585.
TreeFamTF338224.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressO00585.
BgeeO00585.
CleanExHS_CCL21.
GenevestigatorO00585.

Family and domain databases

InterProIPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamPF00048. IL8. 1 hit.
[Graphical view]
SMARTSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMSSF54117. SSF54117. 1 hit.
ProtoNetSearch...

Other

GeneWikiCCL21.
GenomeRNAi6366.
NextBio24734.
PMAP-CutDBO00585.
PROO00585.
SOURCESearch...

Entry information

Entry nameCCL21_HUMAN
AccessionPrimary (citable) accession number: O00585
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM