ID IL22_MOUSE Reviewed; 179 AA.
AC Q9JJY9; Q14BB3;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 27-MAR-2024, entry version 153.
DE RecName: Full=Interleukin-22;
DE Short=IL-22;
DE AltName: Full=IL-10-related T-cell-derived-inducible factor;
DE Short=IL-TIF;
DE AltName: Full=IL-TIF alpha;
DE AltName: Full=Interleukin-22a;
DE Short=IL-22a;
DE Flags: Precursor;
GN Name=Il22; Synonyms=Il22a, Iltif, Iltifa;
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=AKR/J;
RX PubMed=10657629; DOI=10.4049/jimmunol.164.4.1814;
RA Dumoutier L., Louahed J., Renauld J.-C.;
RT "Cloning and characterization of IL-10-related T cell-derived inducible
RT factor (IL-TIF), a novel cytokine structurally related to IL-10 and
RT inducible by IL-9.";
RL J. Immunol. 164:1814-1819(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=129;
RX PubMed=11197690; DOI=10.1038/sj.gene.6363716;
RA Dumoutier L., Van Roost E., Colau D., Ameye G., Michaux L., Renauld J.-C.;
RT "IL-TIF/IL-22: genomic organization and mapping of the human and mouse
RT genes.";
RL Genes Immun. 1:488-494(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION.
RX PubMed=24742671; DOI=10.1074/jbc.m114.551747;
RA Weathington N.M., Snavely C.A., Chen B.B., Zhao J., Zhao Y.,
RA Mallampalli R.K.;
RT "Glycogen synthase kinase-3beta stabilizes the interleukin (IL)-22 receptor
RT from proteasomal degradation in murine lung epithelia.";
RL J. Biol. Chem. 289:17610-17619(2014).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33912578; DOI=10.3389/fmed.2021.656047;
RA Delbue D., Lebenheim L., Cardoso-Silva D., Dony V., Krug S.M.,
RA Richter J.F., Manna S., Munoz M., Wolk K., Heldt C., Heimesaat M.M.,
RA Sabat R., Siegmund B., Schumann M.;
RT "Reprogramming Intestinal Epithelial Cell Polarity by Interleukin-22.";
RL Front. Med. 8:656047-656047(2021).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=35525330; DOI=10.1016/j.taap.2022.116044;
RA Ulu A., Sveiven S., Bilg A., Velazquez J.V., Diaz M., Mukherjee M.,
RA Yuil-Valdes A.G., Kota S., Burr A., Najera A., Nordgren T.M.;
RT "IL-22 regulates inflammatory responses to agricultural dust-induced airway
RT inflammation.";
RL Toxicol. Appl. Pharmacol. 446:116044-116044(2022).
RN [7] {ECO:0007744|PDB:6WEO}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 34-179, DISULFIDE BONDS, AND
RP FUNCTION.
RX PubMed=33852830; DOI=10.1016/j.immuni.2021.03.008;
RA Saxton R.A., Henneberg L.T., Calafiore M., Su L., Jude K.M., Hanash A.M.,
RA Garcia K.C.;
RT "The tissue protective functions of interleukin-22 can be decoupled from
RT pro-inflammatory actions through structure-based design.";
RL Immunity 54:660-672.e9(2021).
CC -!- FUNCTION: Cytokine that plays a critical role in modulating tissue
CC responses during inflammation (PubMed:35525330, PubMed:33852830). Plays
CC an essential role in the regeneration of epithelial cells to maintain
CC barrier function after injury and for the prevention of further tissue
CC damage (PubMed:33912578). Unlike most of the cytokines, has no effect
CC on immune cells. Signals through a heterodimeric receptor composed of
CC two subunits, the specific receptor IL22RA1 which is present on non-
CC immune cells in many organs and the shared subunit IL10RB. Ligation of
CC IL22RA1 with IL22 induces activation of the tyrosine kinases JAK1 and
CC TYK2, which in turn activates STAT3. In turn, promotes cell survival
CC and proliferation through STAT3, ERK1/2 and PI3K/AKT pathways. Promotes
CC phosphorylation of GSK3B at 'Ser-9' and CTTN (PubMed:24742671).
CC Promotes epithelial cell spreading (PubMed:24742671).
CC {ECO:0000250|UniProtKB:Q9GZX6, ECO:0000269|PubMed:24742671,
CC ECO:0000269|PubMed:33852830, ECO:0000269|PubMed:33912578,
CC ECO:0000269|PubMed:35525330}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISRUPTION PHENOTYPE: Deletion mice have an enhanced response to
CC agricultural dust as evidenced by an exacerbated increase in
CC infiltrating immune cells and lung pathology as compared to wild-type
CC controls (PubMed:35525330). In addition, T-gondii-infected mice display
CC a significant defect of the epithelial barrier and an increase in
CC macromolecular permeability when compared to wild-type mice
CC (PubMed:33912578). {ECO:0000269|PubMed:33912578,
CC ECO:0000269|PubMed:35525330}.
CC -!- SIMILARITY: Belongs to the IL-10 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ249491; CAB75546.1; -; mRNA.
DR EMBL; AJ294727; CAC19435.1; -; Genomic_DNA.
DR EMBL; BC116235; AAI16236.1; -; mRNA.
DR CCDS; CCDS36070.1; -.
DR RefSeq; NP_058667.1; NM_016971.2.
DR RefSeq; XP_006513928.1; XM_006513865.3.
DR PDB; 6WEO; X-ray; 2.60 A; 2/5/8/D/G/J/L/N/Q/T/W/Z=34-179.
DR PDBsum; 6WEO; -.
DR AlphaFoldDB; Q9JJY9; -.
DR SMR; Q9JJY9; -.
DR MINT; Q9JJY9; -.
DR STRING; 10090.ENSMUSP00000094449; -.
DR GlyCosmos; Q9JJY9; 3 sites, No reported glycans.
DR GlyGen; Q9JJY9; 3 sites.
DR PhosphoSitePlus; Q9JJY9; -.
DR PaxDb; 10090-ENSMUSP00000094449; -.
DR ABCD; Q9JJY9; 4 sequenced antibodies.
DR DNASU; 50929; -.
DR Ensembl; ENSMUST00000096691.5; ENSMUSP00000094449.5; ENSMUSG00000074695.4.
DR GeneID; 50929; -.
DR KEGG; mmu:50929; -.
DR UCSC; uc007hdv.2; mouse.
DR AGR; MGI:1355307; -.
DR CTD; 50616; -.
DR MGI; MGI:1355307; Il22.
DR VEuPathDB; HostDB:ENSMUSG00000074695; -.
DR eggNOG; ENOG502S5PC; Eukaryota.
DR GeneTree; ENSGT00510000048550; -.
DR HOGENOM; CLU_127397_0_0_1; -.
DR InParanoid; Q9JJY9; -.
DR OMA; INFQQPY; -.
DR OrthoDB; 5322174at2759; -.
DR PhylomeDB; Q9JJY9; -.
DR TreeFam; TF333253; -.
DR BioGRID-ORCS; 50929; 2 hits in 56 CRISPR screens.
DR PRO; PR:Q9JJY9; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9JJY9; Protein.
DR Bgee; ENSMUSG00000074695; Expressed in blastoderm cell in morula and 11 other cell types or tissues.
DR Genevisible; Q9JJY9; MM.
DR GO; GO:0005615; C:extracellular space; IDA:UniProt.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProt.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProt.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IDA:MGI.
DR GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; IDA:MGI.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR020423; IL-10_CS.
DR InterPro; IPR020453; IL-22.
DR PANTHER; PTHR48400; INTERLEUKIN-22; 1.
DR PANTHER; PTHR48400:SF1; INTERLEUKIN-22; 1.
DR Pfam; PF14565; IL22; 1.
DR PIRSF; PIRSF037726; Interleukin-22; 1.
DR PRINTS; PR01936; INTRLEUKIN22.
DR SUPFAM; SSF47266; 4-helical cytokines; 1.
DR PROSITE; PS00520; INTERLEUKIN_10; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytokine; Disulfide bond; Glycoprotein; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..179
FT /note="Interleukin-22"
FT /id="PRO_0000015384"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..132
FT /evidence="ECO:0000269|PubMed:33852830,
FT ECO:0007744|PDB:6WEO"
FT DISULFID 89..178
FT /evidence="ECO:0000269|PubMed:33852830,
FT ECO:0007744|PDB:6WEO"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:6WEO"
FT HELIX 50..64
FT /evidence="ECO:0007829|PDB:6WEO"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:6WEO"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:6WEO"
FT HELIX 88..102
FT /evidence="ECO:0007829|PDB:6WEO"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:6WEO"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:6WEO"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:6WEO"
FT HELIX 139..154
FT /evidence="ECO:0007829|PDB:6WEO"
FT HELIX 156..165
FT /evidence="ECO:0007829|PDB:6WEO"
FT HELIX 167..178
FT /evidence="ECO:0007829|PDB:6WEO"
SQ SEQUENCE 179 AA; 20106 MW; ACB0F5574AA79274 CRC64;
MAVLQKSMSF SLMGTLAASC LLLIALWAQE ANALPVNTRC KLEVSNFQQP YIVNRTFMLA
KEASLADNNT DVRLIGEKLF RGVSAKDQCY LMKQVLNFTL EDVLLPQSDR FQPYMQEVVP
FLTKLSNQLS SCHISGDDQN IQKNVRRLKE TVKKLGESGE IKAIGELDLL FMSLRNACV
//
