CC21A_MOUSE
ID CC21A_MOUSE Reviewed; 133 AA.
AC P84444; O09002; O09006; Q3U1J2; Q91V84;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=C-C motif chemokine 21a;
DE AltName: Full=6Ckine;
DE AltName: Full=Beta-chemokine exodus-2;
DE AltName: Full=Small-inducible cytokine A21a;
DE AltName: Full=Thymus-derived chemotactic agent 4;
DE Short=TCA4;
DE Flags: Precursor;
GN Name=Ccl21a; Synonyms=Scya21, Scya21a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9257816;
RA Hedrick J.A., Zlotnik A.;
RT "Identification and characterization of a novel beta chemokine containing
RT six conserved cysteines.";
RL J. Immunol. 159:1589-1593(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Thymus;
RX PubMed=9548511;
RA Tanabe S., Lu Z., Luo Y., Quackenbush E.J., Berman M.A.,
RA Collins-Racie L.A., Mi S., Reilly C., Lo D., Jacobs K.A., Dorf M.E.;
RT "Identification of a new mouse beta-chemokine, thymus-derived chemotactic
RT agent 4, with activity on T lymphocytes and mesangial cells.";
RL J. Immunol. 159:5671-5679(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN PLT.
RC STRAIN=129/SvJ; TISSUE=Embryonic stem cell;
RX PubMed=10523616; DOI=10.1084/jem.190.8.1183;
RA Vassileva G., Soto H., Zlotnik A., Nakano H., Kakiuchi T., Hedrick J.A.,
RA Lira S.A.;
RT "The reduced expression of 6Ckine in the plt mouse results from the
RT deletion of one of two 6Ckine genes.";
RL J. Exp. Med. 190:1183-1188(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Ola;
RX PubMed=11123313; DOI=10.4049/jimmunol.166.1.361;
RA Nakano H., Gunn M.D.;
RT "Gene duplications at the chemokine locus on mouse chromosome 4: multiple
RT strain-specific haplotypes and the deletion of secondary lymphoid-organ
RT chemokine and EBI-1 ligand chemokine genes in the plt mutation.";
RL J. Immunol. 166:361-369(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Lymph node, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Colon, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP CHARACTERIZATION.
RX PubMed=9419363; DOI=10.1073/pnas.95.1.258;
RA Gunn M.D., Tangemann K., Tam C., Cyster J.G., Rosen S.D., Williams L.T.;
RT "A chemokine expressed in lymphoid high endothelial venules promotes the
RT adhesion and chemotaxis of naive T lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:258-263(1998).
CC -!- FUNCTION: Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic
CC in vitro for thymocytes and activated T-cells, but not for B-cells,
CC macrophages, or neutrophils. Potent mesangial cell chemoattractant.
CC Shows preferential activity towards naive T-cells. May play a role in
CC mediating homing of lymphocytes to secondary lymphoid organs.
CC -!- SUBUNIT: Binds to CCR7 and to CXCR3.Interacts with PDPN; relocalizes
CC PDPN to the basolateral membrane. {ECO:0000250|UniProtKB:O00585}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed strongly in lung, spleen, thymus,
CC peripheral and mesentric lymph nodes. Also expressed in the testis,
CC kidney, liver, and heart.
CC -!- DISEASE: Note=Mice carrying an autosomal recessive mutation designated
CC paucity of lymph node T-cells (plt) show dramatically reduced numbers
CC of T-cells in lymph nodes, Peyer patches, and the white pulp of the
CC spleen. Plt seems to correspond to Scya21b.
CC {ECO:0000269|PubMed:10523616}.
CC -!- MISCELLANEOUS: Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c
CC produce identical proteins while the protein produced by Ccl21a differs
CC at only one position. Ccl21b and Ccl21c have 'Leu-65' (6Ckine-Leu)
CC while Ccl21a has Ser-65 (6Ckine-Ser).
CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC {ECO:0000305}.
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DR EMBL; AF001980; AAB86595.1; -; mRNA.
DR EMBL; AF006637; AAB61440.1; -; mRNA.
DR EMBL; AF171086; AAF16901.1; -; Genomic_DNA.
DR EMBL; AF035684; AAC82613.1; -; Genomic_DNA.
DR EMBL; AF307985; AAG45833.1; -; Genomic_DNA.
DR EMBL; AK144258; BAE25802.1; -; mRNA.
DR EMBL; AK155924; BAE33505.1; -; mRNA.
DR EMBL; AL772334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025974; AAH25974.1; -; mRNA.
DR EMBL; BC028747; AAH28747.1; -; mRNA.
DR EMBL; BC038120; AAH38120.1; -; mRNA.
DR CCDS; CCDS18081.1; -.
DR RefSeq; NP_001180596.1; NM_001193667.1.
DR RefSeq; NP_035254.1; NM_011124.4.
DR AlphaFoldDB; P84444; -.
DR SMR; P84444; -.
DR STRING; 10090.ENSMUSP00000092732; -.
DR EPD; P84444; -.
DR MaxQB; P84444; -.
DR PaxDb; P84444; -.
DR PeptideAtlas; P84444; -.
DR PRIDE; P84444; -.
DR ProteomicsDB; 281247; -.
DR DNASU; 18829; -.
DR Ensembl; ENSMUST00000095114; ENSMUSP00000092732; ENSMUSG00000094686.
DR GeneID; 18829; -.
DR KEGG; mmu:18829; -.
DR UCSC; uc008sny.2; mouse.
DR CTD; 18829; -.
DR MGI; MGI:1349183; Ccl21a.
DR VEuPathDB; HostDB:ENSMUSG00000094686; -.
DR VEuPathDB; HostDB:ENSMUSG00000095320; -.
DR eggNOG; ENOG502S8D1; Eukaryota.
DR GeneTree; ENSGT01050000244920; -.
DR HOGENOM; CLU_141716_3_2_1; -.
DR InParanoid; P84444; -.
DR OMA; CKRTEQP; -.
DR OrthoDB; 1542802at2759; -.
DR PhylomeDB; P84444; -.
DR TreeFam; TF338224; -.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 100504362; 1 hit in 11 CRISPR screens.
DR BioGRID-ORCS; 18829; 3 hits in 23 CRISPR screens.
DR ChiTaRS; Ccl21a; mouse.
DR PRO; PR:P84444; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P84444; protein.
DR Bgee; ENSMUSG00000094686; Expressed in thymus and 43 other tissues.
DR Genevisible; P84444; MM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0031732; F:CCR7 chemokine receptor binding; IPI:BHF-UCL.
DR GO; GO:0008009; F:chemokine activity; IDA:BHF-UCL.
DR GO; GO:0042379; F:chemokine receptor binding; ISO:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; ISS:BHF-UCL.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:MGI.
DR GO; GO:0060326; P:cell chemotaxis; ISO:MGI.
DR GO; GO:0048469; P:cell maturation; IDA:BHF-UCL.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:BHF-UCL.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
DR GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0038116; P:chemokine (C-C motif) ligand 21 signaling pathway; IMP:BHF-UCL.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0002407; P:dendritic cell chemotaxis; IDA:BHF-UCL.
DR GO; GO:0097026; P:dendritic cell dendrite assembly; IDA:BHF-UCL.
DR GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
DR GO; GO:0001768; P:establishment of T cell polarity; ISS:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0001771; P:immunological synapse formation; IDA:BHF-UCL.
DR GO; GO:0050930; P:induction of positive chemotaxis; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0031640; P:killing of cells of another organism; ISO:MGI.
DR GO; GO:0048535; P:lymph node development; IMP:MGI.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0035759; P:mesangial cell-matrix adhesion; ISS:BHF-UCL.
DR GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:2000548; P:negative regulation of dendritic cell dendrite assembly; IDA:BHF-UCL.
DR GO; GO:1903237; P:negative regulation of leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:BHF-UCL.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:BHF-UCL.
DR GO; GO:2000147; P:positive regulation of cell motility; ISS:BHF-UCL.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISS:BHF-UCL.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:BHF-UCL.
DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; IDA:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:BHF-UCL.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:BHF-UCL.
DR GO; GO:0010560; P:positive regulation of glycoprotein biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:BHF-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:BHF-UCL.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; NAS:BHF-UCL.
DR GO; GO:2000529; P:positive regulation of myeloid dendritic cell chemotaxis; ISS:BHF-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISS:BHF-UCL.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:BHF-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:BHF-UCL.
DR GO; GO:0031274; P:positive regulation of pseudopodium assembly; ISS:BHF-UCL.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IDA:BHF-UCL.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISO:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:BHF-UCL.
DR GO; GO:0034695; P:response to prostaglandin E; ISS:BHF-UCL.
DR GO; GO:0031529; P:ruffle organization; ISS:BHF-UCL.
DR GO; GO:0031295; P:T cell costimulation; IDA:BHF-UCL.
DR InterPro; IPR030593; CCL21.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015; PTHR12015; 1.
DR PANTHER; PTHR12015:SF72; PTHR12015:SF72; 1.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
PE 1: Evidence at protein level;
KW Chemotaxis; Cytokine; Disulfide bond; Inflammatory response;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..133
FT /note="C-C motif chemokine 21a"
FT /id="PRO_0000005223"
FT REGION 86..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 98..133
FT /note="C-terminal basic extension"
FT DISULFID 31..57
FT /evidence="ECO:0000250"
FT DISULFID 32..75
FT /evidence="ECO:0000250"
FT DISULFID 103..122
FT /evidence="ECO:0000255"
SQ SEQUENCE 133 AA; 14558 MW; ABD2750A320B3719 CRC64;
MAQMMTLSLL SLVLALCIPW TQGSDGGGQD CCLKYSQKKI PYSIVRGYRK QEPSLGCPIP
AILFSPRKHS KPELCANPEE GWVQNLMRRL DQPPAPGKQS PGCRKNRGTS KSGKKGKGSK
GCKRTEQTQP SRG
