IL21_MOUSE
ID IL21_MOUSE Reviewed; 146 AA.
AC Q9ES17;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Interleukin-21;
DE Short=IL-21;
DE Flags: Precursor;
GN Name=Il21;
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].
RC STRAIN=BALB/cJ;
RX PubMed=11081504; DOI=10.1038/35040504;
RA Parrish-Novak J., Dillon S.R., Nelson A., Hammond A., Sprecher C.,
RA Gross J.A., Johnston J., Madden K., Xu W., West J., Schrader S.,
RA Burkhead S., Heipel M., Brandt C., Kuijper J.L., Kramer J., Conklin D.,
RA Presnell S.R., Berry J., Shiota F., Bort S., Hambly K., Mudri S., Clegg C.,
RA Moore M., Grant F.J., Lofton-Day C., Gilbert T., Raymond F., Ching A.,
RA Yao L., Smith D., Webster P., Whitmore T., Maurer M., Kaushansky K.,
RA Holly R.D., Foster D.;
RT "Interleukin 21 and its receptor are involved in NK cell expansion and
RT regulation of lymphocyte function.";
RL Nature 408:57-63(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Guobing C., Jun D., Junsong C., Fenshu Z.;
RT "Mouse interleukin 21 can improve the anti-tumor effect of LAK cells.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11970879; DOI=10.1016/s1074-7613(02)00295-9;
RA Kasaian M.T., Whitters M.J., Carter L.L., Lowe L.D., Jussif J.M., Deng B.,
RA Johnson K.A., Witek J.S., Senices M., Konz R.F., Wurster A.L.,
RA Donaldson D.D., Collins M., Young D.A., Grusby M.J.;
RT "IL-21 limits NK cell responses and promotes antigen-specific T cell
RT activation: a mediator of the transition from innate to adaptive
RT immunity.";
RL Immunity 16:559-569(2002).
RN [4]
RP FUNCTION.
RX PubMed=12893770; DOI=10.1182/blood-2003-03-0669;
RA Brandt K., Bulfone-Paus S., Foster D.C., Rueckert R.;
RT "Interleukin-21 inhibits dendritic cell activation and maturation.";
RL Blood 102:4090-4098(2003).
RN [5]
RP FUNCTION.
RX PubMed=15100251; DOI=10.4049/jimmunol.172.9.5154;
RA Pene J., Gauchat J.-F., Lecart S., Drouet E., Guglielmi P., Boulay V.,
RA Delwail A., Foster D., Lecron J.C., Yssel H.;
RT "IL-21 is a switch factor for the production of IgG1 and IgG3 by human B
RT cells.";
RL J. Immunol. 172:5154-5157(2004).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INDUCTION BY VIRAL
RP INFECTION.
RX PubMed=23045607; DOI=10.1084/jem.20111504;
RA Karnowski A., Chevrier S., Belz G.T., Mount A., Emslie D., D'Costa K.,
RA Tarlinton D.M., Kallies A., Corcoran L.M.;
RT "B and T cells collaborate in antiviral responses via IL-6, IL-21, and
RT transcriptional activator and coactivator, Oct2 and OBF-1.";
RL J. Exp. Med. 209:2049-2064(2012).
CC -!- FUNCTION: Cytokine with immunoregulatory activity. May promote the
CC transition between innate and adaptive immunity. Induces the production
CC of IgG(1) and IgG(3) in B-cells (PubMed:15100251). Implicated in the
CC generation and maintenance of T follicular helper (Tfh) cells and the
CC formation of germinal-centers. Together with IL6, control the early
CC generation of Tfh cells and are critical for an effective antibody
CC response to acute viral infection (PubMed:23045607). May play a role in
CC proliferation and maturation of natural killer (NK) cells in synergy
CC with IL15 (PubMed:11970879). May regulate proliferation of mature
CC B- and T-cells in response to activating stimuli. In synergy with IL15
CC and IL18 stimulates interferon gamma production in T-cells and NK cells
CC (By similarity). During T-cell mediated immune response may inhibit
CC dendritic cells (DC) activation and maturation (PubMed:12893770).
CC {ECO:0000250|UniProtKB:Q9HBE4, ECO:0000269|PubMed:11970879,
CC ECO:0000269|PubMed:12893770, ECO:0000269|PubMed:15100251,
CC ECO:0000269|PubMed:23045607}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11970879}.
CC -!- TISSUE SPECIFICITY: Expressed in CD4(+) T cells.
CC {ECO:0000269|PubMed:23045607}.
CC -!- INDUCTION: In CD4(+) T cells, expression is induced upon influenza
CC virus infection by IL6. {ECO:0000269|PubMed:23045607}.
CC -!- DISRUPTION PHENOTYPE: Mutants infected with influenza virus do not show
CC a significant difference on germinal center B cells compared to wild-
CC types (PubMed:23045607). Double knockouts for IL21 and IL6 infected
CC with influenza virus show a significant reduction in germinal centers
CC in both the draining lymphatic nodes and the spleens compared to wild-
CC types. Animals show a significant reduction in virus-specific IgM and
CC IgG (PubMed:23045607). {ECO:0000269|PubMed:23045607}.
CC -!- SIMILARITY: Belongs to the IL-15/IL-21 family. {ECO:0000305}.
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DR EMBL; AF254070; AAG29349.1; -; mRNA.
DR EMBL; AY428162; AAR06254.1; -; mRNA.
DR CCDS; CCDS17317.1; -.
DR RefSeq; NP_068554.1; NM_021782.3.
DR AlphaFoldDB; Q9ES17; -.
DR SMR; Q9ES17; -.
DR STRING; 10090.ENSMUSP00000029273; -.
DR GlyGen; Q9ES17; 1 site.
DR PhosphoSitePlus; Q9ES17; -.
DR PaxDb; Q9ES17; -.
DR PRIDE; Q9ES17; -.
DR Antibodypedia; 15937; 842 antibodies from 45 providers.
DR DNASU; 60505; -.
DR Ensembl; ENSMUST00000029273; ENSMUSP00000029273; ENSMUSG00000027718.
DR GeneID; 60505; -.
DR KEGG; mmu:60505; -.
DR UCSC; uc008paj.2; mouse.
DR CTD; 59067; -.
DR MGI; MGI:1890474; Il21.
DR VEuPathDB; HostDB:ENSMUSG00000027718; -.
DR eggNOG; ENOG502SES1; Eukaryota.
DR GeneTree; ENSGT00390000010494; -.
DR HOGENOM; CLU_127182_1_0_1; -.
DR InParanoid; Q9ES17; -.
DR OMA; MIHQHLR; -.
DR OrthoDB; 1439856at2759; -.
DR PhylomeDB; Q9ES17; -.
DR TreeFam; TF336380; -.
DR Reactome; R-MMU-9020958; Interleukin-21 signaling.
DR BioGRID-ORCS; 60505; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q9ES17; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9ES17; protein.
DR Bgee; ENSMUSG00000027718; Expressed in spermatocyte and 7 other tissues.
DR ExpressionAtlas; Q9ES17; baseline and differential.
DR Genevisible; Q9ES17; MM.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005126; F:cytokine receptor binding; IDA:MGI.
DR GO; GO:0005134; F:interleukin-2 receptor binding; ISO:MGI.
DR GO; GO:0001783; P:B cell apoptotic process; NAS:UniProtKB.
DR GO; GO:0048469; P:cell maturation; ISO:MGI.
DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB.
DR GO; GO:0002314; P:germinal center B cell differentiation; IMP:UniProtKB.
DR GO; GO:0001779; P:natural killer cell differentiation; IDA:MGI.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:MGI.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; NAS:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IDA:MGI.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IDA:MGI.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0061470; P:T follicular helper cell differentiation; IMP:UniProtKB.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; ISO:MGI.
DR Gene3D; 1.20.1250.70; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR003443; IL-15/IL-21_fam.
DR PANTHER; PTHR14356; PTHR14356; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
PE 2: Evidence at transcript level;
KW Cytokine; Disulfide bond; Glycoprotein; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000250|UniProtKB:Q76LU5"
FT CHAIN 18..146
FT /note="Interleukin-21"
FT /id="PRO_0000015506"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 64..115
FT /evidence="ECO:0000250|UniProtKB:Q9HBE4"
FT DISULFID 71..118
FT /evidence="ECO:0000250|UniProtKB:Q9HBE4"
SQ SEQUENCE 146 AA; 16811 MW; D2527ED95BA15194 CRC64;
MERTLVCLVV IFLGTVAHKS SPQGPDRLLI RLRHLIDIVE QLKIYENDLD PELLSAPQDV
KGHCEHAAFA CFQKAKLKPS NPGNNKTFII DLVAQLRRRL PARRGGKKQK HIAKCPSCDS
YEKRTPKEFL ERLKWLLQKM IHQHLS
