P84444 (CC21A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C motif chemokine 21a

Alternative name(s):
6Ckine
Beta-chemokine exodus-2
Small-inducible cytokine A21a
Thymus-derived chemotactic agent 4
Short name=TCA4

Gene names

Name:	Ccl21a
Synonyms:	Scya21, Scya21a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	133 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. Potent mesangial cell chemoattractant. 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 and to CXCR3.
Subcellular location	Secreted.
Tissue specificity	Expressed strongly in lung, spleen, thymus, peripheral and mesentric lymph nodes. Also expressed in the testis, kidney, liver, and heart.
Involvement in disease	Mice carrying an autosomal recessive mutation designated paucity of lymph node T-cells (plt) show dramatically reduced numbers of T-cells in lymph nodes, Peyer patches, and the white pulp of the spleen. Plt seems to correspond to Scya21b.
Miscellaneous	Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c produce identical proteins while the protein produced by Ccl21a differs at only one position. Ccl21b and Ccl21c have 'Leu-65' (6Ckine-Leu) while Ccl21a has Ser-65 (6Ckine-Ser).
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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Inferred from direct assay PubMed 15845453. Source: BHF-UCL activation of Rho GTPase activity Inferred from sequence or structural similarity. Source: BHF-UCL cell maturation Inferred from direct assay PubMed 15845453. Source: BHF-UCL dendritic cell chemotaxis Inferred from direct assay PubMed 12200351. Source: BHF-UCL dendritic cell dendrite assembly Inferred from direct assay PubMed 12200351. Source: BHF-UCL establishment of T cell polarity Inferred from sequence or structural similarity. Source: BHF-UCL immune response Inferred from electronic annotation. Source: InterPro immunological synapse formation Inferred from direct assay PubMed 15845453. Source: BHF-UCL inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW mesangial cell-matrix adhesion Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of dendritic cell dendrite assembly Inferred from direct assay PubMed 12200351. Source: BHF-UCL negative regulation of leukocyte apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of JNK cascade Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of actin filament polymerization Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell adhesion mediated by integrin Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell-matrix adhesion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of dendritic cell antigen processing and presentation Inferred from direct assay PubMed 15845453. Source: BHF-UCL positive regulation of filopodium assembly Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of glycoprotein biosynthetic process Inferred from direct assay PubMed 15845453. Source: BHF-UCL positive regulation of macrophage chemotaxis Non-traceable author statement PubMed 20605225. Source: BHF-UCL positive regulation of myeloid dendritic cell chemotaxis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of neutrophil chemotaxis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of pseudopodium assembly Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of receptor-mediated endocytosis Inferred from direct assay PubMed 12609829. Source: BHF-UCL release of sequestered calcium ion into cytosol Inferred from sequence or structural similarity. Source: BHF-UCL response to prostaglandin E stimulus Inferred from sequence or structural similarity. Source: BHF-UCL ruffle organization Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	chemokine activity Inferred from direct assay PubMed 12200351. 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	Potential
	Chain	24 – 133	110	C-C motif chemokine 21a		PRO_0000005223
Regions
	Region	98 – 133	36	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)
	P84444 [UniParc]. Last modified March 1, 2005. Version 1. Checksum: ABD2750A320B3719	FASTA	133	14,558
	10 20 30 40 50 60 MAQMMTLSLL SLVLALCIPW TQGSDGGGQD CCLKYSQKKI PYSIVRGYRK QEPSLGCPIP 70 80 90 100 110 120 AILFSPRKHS KPELCANPEE GWVQNLMRRL DQPPAPGKQS PGCRKNRGTS KSGKKGKGSK 130 GCKRTEQTQP SRG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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].
[2]	"Identification of a new mouse beta-chemokine, thymus-derived chemotactic agent 4, with activity on T lymphocytes and mesangial cells." Tanabe S., Lu Z., Luo Y., Quackenbush E.J., Berman M.A., Collins-Racie L.A., Mi S., Reilly C., Lo D., Jacobs K.A., Dorf M.E. J. Immunol. 159:5671-5679(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c and C57BL/6J. Tissue: Thymus.
[3]	"The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes." Vassileva G., Soto H., Zlotnik A., Nakano H., Kakiuchi T., Hedrick J.A., Lira S.A. J. Exp. Med. 190:1183-1188(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/SvJ. Tissue: Embryonic stem cell.
[4]	"Gene duplications at the chemokine locus on mouse chromosome 4: multiple strain-specific haplotypes and the deletion of secondary lymphoid-organ chemokine and EBI-1 ligand chemokine genes in the plt mutation." Nakano H., Gunn M.D. J. Immunol. 166:361-369(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Ola.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Lymph node and Spleen.
[6]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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]. Strain: C57BL/6J and FVB/N. Tissue: Colon and Mammary gland.
[8]	"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: CHARACTERIZATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF001980 mRNA. Translation: AAB86595.1. AF006637 mRNA. Translation: AAB61440.1. AF171086 Genomic DNA. Translation: AAF16901.1. AF035684 Genomic DNA. Translation: AAC82613.1. AF307985 Genomic DNA. Translation: AAG45833.1. AK144258 mRNA. Translation: BAE25802.1. AK155924 mRNA. Translation: BAE33505.1. AL772334 Genomic DNA. No translation available. BC025974 mRNA. Translation: AAH25974.1. BC028747 mRNA. Translation: AAH28747.1. BC038120 mRNA. Translation: AAH38120.1.
IPI	IPI00113732.
RefSeq	NP_001180596.1. NM_001193667.1. NP_035254.1. NM_011124.4.
UniGene	Mm.220853. Mm.458815.
3D structure databases
ProteinModelPortal	P84444.
SMR	P84444. Positions 24-92.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000103647.
Proteomic databases
PaxDb	P84444.
PRIDE	P84444.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000095114; ENSMUSP00000092732; ENSMUSG00000094686. ENSMUST00000178919; ENSMUSP00000136780; ENSMUSG00000095320.
GeneID	100504362. 18829.
KEGG	mmu:100504362. mmu:18829.
UCSC	uc008smd.2. mouse.
Organism-specific databases
CTD	18829.
MGI	MGI:1349183. Ccl21a.
Phylogenomic databases
eggNOG	NOG46090.
GeneTree	ENSGT00530000063771.
HOGENOM	HOG000036685.
HOVERGEN	HBG017871.
InParanoid	P84444.
KO	K16062.
OMA	CPISAIL.
OrthoDB	EOG4CRM1R.
Gene expression databases
Bgee	P84444.
CleanEx	MM_CCL21B.
Genevestigator	P84444.
GermOnline	ENSMUSG00000071003. Mus musculus.
Family and domain databases
InterPro	IPR001811. Chemokine_IL8-like_dom. [Graphical view]
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	295204.
SOURCE	Search...

Entry information

Entry name

CC21A_MOUSE

Accession

Primary (citable) accession number: P84444
Secondary accession number(s): O09002 , O09006, Q3U1J2, Q91V84

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	March 1, 2005
Last modified:	April 3, 2013
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program