O00585 (CCL21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CCL21
Synonyms:	SCYA21
ORF Names:	UNQ784/PRO1600

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	134 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Subunit structure	Binds to CCR7. Ref.8
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 process	Chemotaxis Inflammatory response
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	T cell costimulation Inferred from sequence or structural similarity. Source: BHF-UCL activation of Rho GTPase activity Inferred from direct assay. Source: BHF-UCL cell maturation Inferred from sequence or structural similarity. Source: BHF-UCL cell-cell signaling Traceable author statement. Source: ProtInc dendritic cell chemotaxis Inferred from direct assay. 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. Source: BHF-UCL immune response Traceable author statement. Source: ProtInc immunological synapse formation Inferred from sequence or structural similarity. Source: BHF-UCL inflammatory response Non-traceable author statement. Source: BHF-UCL mesangial cell-matrix adhesion Inferred from direct assay. Source: BHF-UCL negative regulation of leukocyte apoptosis Inferred from direct assay. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from direct assay. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay. Source: BHF-UCL positive regulation of JNK cascade Inferred from direct assay. Source: BHF-UCL positive regulation of actin filament polymerization Inferred from direct assay. Source: BHF-UCL positive regulation of cell adhesion mediated by integrin Inferred from direct assay. Source: BHF-UCL positive regulation of cell-matrix adhesion Inferred from direct assay. 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. 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. Source: BHF-UCL positive regulation of neutrophil chemotaxis Inferred from direct assay. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase activity Inferred from direct assay. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from direct assay. Source: BHF-UCL positive regulation of protein kinase activity Inferred from direct assay. Source: BHF-UCL positive regulation of pseudopodium assembly Inferred from direct assay. 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. Source: BHF-UCL response to prostaglandin E stimulus Inferred from direct assay. Source: BHF-UCL ruffle organization Inferred from direct assay. Source: BHF-UCL
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	CCR7 chemokine receptor binding Inferred from sequence or structural similarity. Source: BHF-UCL chemokine activity Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.3
	Chain	24 – 134	111	C-C motif chemokine 21		PRO_0000005220
Regions
	Region	98 – 134	37	C-terminal basic extension
Amino acid modifications
	Disulfide bond	31 ↔ 57		By similarity
	Disulfide bond	32 ↔ 75		By similarity
	Disulfide bond	103 ↔ 122		Potential

Sequences

	Sequence		Length	Mass (Da)
	O00585 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: FB48C2F71CB4A9D2	FASTA	134	14,646
	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

References

	« Hide 'large scale' referencesShow '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: 9235955] [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: 9257816] [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: 9300671] [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: 9419363] [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. , 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: 12975309] [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: 15489334] [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: 9507024] [Abstract] Cited for: RECEPTOR INTERACTION.
+	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.

IPI

IPI00012174.

RefSeq

NP_002980.1. NM_002989.2.

UniGene

Hs.57907.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L4N	NMR	-	A	24-134	[»]

ProteinModelPortal

O00585.

SMR

O00585. Positions 26-93.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5854N.

IntAct

O00585. 3 interactions.

MINT

MINT-123964.

STRING

O00585.

PTM databases

PhosphoSite

O00585.

Proteomic databases

PRIDE

O00585.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000259607; ENSP00000259607; ENSG00000137077.

GeneID

6366.

KEGG

hsa:6366.

UCSC

uc003zvo.1. human.

Organism-specific databases

CTD

6366.

GeneCards

GC09M034709.

H-InvDB

HIX0008004.

HGNC

HGNC:10620. CCL21.

HPA

CAB005067.

MIM

602737. gene.

neXtProt

NX_O00585.

PharmGKB

PA35552.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20286.

HOGENOM

HBG126412.

HOVERGEN

HBG017871.

InParanoid

O00585.

OMA

CPISAIL.

OrthoDB

EOG4CRM1R.

PhylomeDB

O00585.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

O00585.

Bgee

O00585.

CleanEx

HS_CCL21.

Genevestigator

O00585.

GermOnline

ENSG00000137077. Homo sapiens.

Family and domain databases

InterPro

IPR001811. Chemokine_IL8-like_dom.
[Graphical view]

KO

K05512.

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

SMART

SM00199. SCY. 1 hit.
[Graphical view]

SUPFAM

SSF54117. Chemokine_IL8. 1 hit.

PROSITE

PS00472. SMALL_CYTOKINES_CC. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

24734.

PMAP-CutDB

O00585.

SOURCE

Search...

Entry information

Entry name

CCL21_HUMAN

Accession

Primary (citable) accession number: O00585

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 1, 1997
Last modified:	January 25, 2012
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.