ID   IL22_HUMAN              Reviewed;         179 AA.
AC   Q9GZX6;
DT   16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Interleukin-22;
DE            Short=IL-22;
DE   AltName: Full=Cytokine Zcyto18;
DE   AltName: Full=IL-10-related T-cell-derived-inducible factor;
DE            Short=IL-TIF;
DE   Flags: Precursor;
GN   Name=IL22; Synonyms=ILTIF, ZCYTO18; ORFNames=UNQ3099/PRO10096;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10954742; DOI=10.1073/pnas.170291697;
RA   Dumoutier L., Van Roost E., Colau D., Renauld J.-C.;
RT   "Human interleukin-10-related T cell-derived inducible factor: molecular
RT   cloning and functional characterization as an hepatocyte-stimulating
RT   factor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:10144-10149(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [MRNA], AND FUNCTION.
RX   PubMed=10875937; DOI=10.1074/jbc.m005304200;
RA   Xie M.-H., Aggarwal S., Ho W.-H., Foster J., Zhang Z., Stinson J.,
RA   Wood W.I., Goddard A.D., Gurney A.L.;
RT   "Interleukin (IL)-22, a novel human cytokine that signals through the
RT   interferon receptor-related proteins CRF2-4 and IL-22R.";
RL   J. Biol. Chem. 275:31335-31339(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-158.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Blood;
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   [7]
RP   PROTEIN SEQUENCE OF 34-48.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [8]
RP   FUNCTION.
RX   PubMed=17204547; DOI=10.1152/ajpgi.00239.2006;
RA   Brand S., Dambacher J., Beigel F., Zitzmann K., Heeg M.H.J., Weiss T.S.,
RA   Pruefer T., Olszak T., Steib C.J., Storr M., Goeke B., Diepolder H.,
RA   Bilzer M., Thasler W.E., Auernhammer C.J.;
RT   "IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3
RT   overexpression in vitro.";
RL   Am. J. Physiol. 292:G1019-G1028(2007).
RN   [9]
RP   FUNCTION.
RX   PubMed=25793261; DOI=10.1371/journal.pone.0119872;
RA   Akil H., Abbaci A., Lalloue F., Bessette B., Costes L.M., Domballe L.,
RA   Charreau S., Guilloteau K., Karayan-Tapon L., Bernard F.X., Morel F.,
RA   Jauberteau M.O., Lecron J.C.;
RT   "IL22/IL-22R pathway induces cell survival in human glioblastoma cells.";
RL   PLoS ONE 10:e0119872-e0119872(2015).
RN   [10]
RP   FUNCTION.
RX   PubMed=31311100; DOI=10.3390/ijms20143468;
RA   Moniruzzaman M., Wang R., Jeet V., McGuckin M.A., Hasnain S.Z.;
RT   "Interleukin (IL)-22 from IL-20 Subfamily of Cytokines Induces Colonic
RT   Epithelial Cell Proliferation Predominantly through ERK1/2 Pathway.";
RL   Int. J. Mol. Sci. 20:0-0(2019).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-179.
RX   PubMed=11856845; DOI=10.1107/s0907444902001063;
RA   Nagem R.A., Lucchesi K.W., Colau D., Dumoutier L., Renauld J.-C.,
RA   Polikarpov I.;
RT   "Crystallization and synchrotron X-ray diffraction studies of human
RT   interleukin-22.";
RL   Acta Crystallogr. D 58:529-530(2002).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 38-179, AND GLYCOSYLATION AT
RP   ASN-54 AND ASN-97.
RX   PubMed=15983417; DOI=10.1107/s0907444905009601;
RA   Xu T., Logsdon N.J., Walter M.R.;
RT   "Structure of insect-cell-derived IL-22.";
RL   Acta Crystallogr. D 61:942-950(2005).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 39-179 IN COMPLEX WITH IL22RA1,
RP   DISULFIDE BONDS, AND FUNCTION.
RX   PubMed=18599299; DOI=10.1016/j.str.2008.06.005;
RA   Jones B.C., Logsdon N.J., Walter M.R.;
RT   "Structure of IL-22 bound to its high-affinity IL-22R1 chain.";
RL   Structure 16:1333-1344(2008).
CC   -!- FUNCTION: Cytokine that plays a critical role in modulating tissue
CC       responses during inflammation (PubMed:17204547). Plays an essential
CC       role in the regeneration of epithelial cells to maintain barrier
CC       function after injury and for the prevention of further tissue damage
CC       (PubMed:17204547). Unlike most of the cytokines, has no effect on
CC       immune cells. Signals through a heterodimeric receptor composed of two
CC       subunits, the specific receptor IL22RA1 which is present on non-immune
CC       cells in many organs and the shared subunit IL10RB (PubMed:10875937,
CC       PubMed:18599299). Ligation of IL22RA1 with IL22 induces activation of
CC       the tyrosine kinases JAK1 and TYK2, which in turn activates STAT3. In
CC       turn, promotes cell survival and proliferation through STAT3, ERK1/2
CC       and PI3K/AKT pathways (PubMed:25793261, PubMed:31311100). Promotes
CC       phosphorylation of GSK3B at 'Ser-9' and CTTN (By similarity). Promotes
CC       epithelial cell spreading (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JJY9, ECO:0000269|PubMed:10875937,
CC       ECO:0000269|PubMed:17204547, ECO:0000269|PubMed:18599299,
CC       ECO:0000269|PubMed:25793261, ECO:0000269|PubMed:31311100}.
CC   -!- INTERACTION:
CC       Q9GZX6; Q08334: IL10RB; NbExp=2; IntAct=EBI-8040250, EBI-11175900;
CC       Q9GZX6; Q8N6P7: IL22RA1; NbExp=9; IntAct=EBI-8040250, EBI-3940749;
CC       PRO_0000015383; Q8N6P7: IL22RA1; NbExp=4; IntAct=EBI-11315863, EBI-3940749;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the IL-10 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/il22/";
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/44519/IL22";
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DR   EMBL; AJ277247; CAC06085.1; -; mRNA.
DR   EMBL; AJ277248; CAC19409.1; -; Genomic_DNA.
DR   EMBL; AF279437; AAG22064.1; -; mRNA.
DR   EMBL; AY358890; AAQ89249.1; -; mRNA.
DR   EMBL; AF387519; AAK62468.1; -; Genomic_DNA.
DR   EMBL; BC066263; AAH66263.1; -; mRNA.
DR   EMBL; BC067510; AAH67510.1; -; mRNA.
DR   EMBL; BC069112; AAH69112.1; -; mRNA.
DR   EMBL; BC069308; AAH69308.1; -; mRNA.
DR   EMBL; BC070261; AAH70261.1; -; mRNA.
DR   CCDS; CCDS8982.1; -.
DR   RefSeq; NP_065386.1; NM_020525.4.
DR   PDB; 1M4R; X-ray; 2.00 A; A/B=29-179.
DR   PDB; 1YKB; X-ray; 2.60 A; A/B/C/D/E/F=38-179.
DR   PDB; 3DGC; X-ray; 2.50 A; L/M=39-179.
DR   PDB; 3DLQ; X-ray; 1.90 A; I=29-179.
DR   PDB; 3G9V; X-ray; 2.76 A; B/D=29-179.
DR   PDB; 3Q1S; X-ray; 2.15 A; I=29-179.
DR   PDBsum; 1M4R; -.
DR   PDBsum; 1YKB; -.
DR   PDBsum; 3DGC; -.
DR   PDBsum; 3DLQ; -.
DR   PDBsum; 3G9V; -.
DR   PDBsum; 3Q1S; -.
DR   AlphaFoldDB; Q9GZX6; -.
DR   SMR; Q9GZX6; -.
DR   BioGRID; 119096; 8.
DR   DIP; DIP-46035N; -.
DR   IntAct; Q9GZX6; 3.
DR   MINT; Q9GZX6; -.
DR   STRING; 9606.ENSP00000442424; -.
DR   BindingDB; Q9GZX6; -.
DR   ChEMBL; CHEMBL3712915; -.
DR   GlyCosmos; Q9GZX6; 3 sites, No reported glycans.
DR   GlyGen; Q9GZX6; 3 sites.
DR   iPTMnet; Q9GZX6; -.
DR   PhosphoSitePlus; Q9GZX6; -.
DR   BioMuta; IL22; -.
DR   DMDM; 17366814; -.
DR   jPOST; Q9GZX6; -.
DR   MassIVE; Q9GZX6; -.
DR   PaxDb; 9606-ENSP00000442424; -.
DR   PeptideAtlas; Q9GZX6; -.
DR   ProteomicsDB; 80167; -.
DR   ABCD; Q9GZX6; 35 sequenced antibodies.
DR   Antibodypedia; 16687; 1038 antibodies from 43 providers.
DR   DNASU; 50616; -.
DR   Ensembl; ENST00000328087.6; ENSP00000329384.4; ENSG00000127318.11.
DR   Ensembl; ENST00000538666.6; ENSP00000442424.1; ENSG00000127318.11.
DR   GeneID; 50616; -.
DR   KEGG; hsa:50616; -.
DR   MANE-Select; ENST00000538666.6; ENSP00000442424.1; NM_020525.5; NP_065386.1.
DR   UCSC; uc001sty.2; human.
DR   AGR; HGNC:14900; -.
DR   CTD; 50616; -.
DR   DisGeNET; 50616; -.
DR   GeneCards; IL22; -.
DR   HGNC; HGNC:14900; IL22.
DR   HPA; ENSG00000127318; Tissue enhanced (urinary).
DR   MIM; 605330; gene.
DR   neXtProt; NX_Q9GZX6; -.
DR   OpenTargets; ENSG00000127318; -.
DR   PharmGKB; PA29822; -.
DR   VEuPathDB; HostDB:ENSG00000127318; -.
DR   eggNOG; ENOG502S5PC; Eukaryota.
DR   GeneTree; ENSGT00510000048550; -.
DR   HOGENOM; CLU_127397_0_0_1; -.
DR   InParanoid; Q9GZX6; -.
DR   OMA; INFQQPY; -.
DR   OrthoDB; 5322174at2759; -.
DR   PhylomeDB; Q9GZX6; -.
DR   TreeFam; TF333253; -.
DR   PathwayCommons; Q9GZX6; -.
DR   Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR   SignaLink; Q9GZX6; -.
DR   SIGNOR; Q9GZX6; -.
DR   BioGRID-ORCS; 50616; 10 hits in 1136 CRISPR screens.
DR   ChiTaRS; IL22; human.
DR   EvolutionaryTrace; Q9GZX6; -.
DR   GeneWiki; Interleukin_22; -.
DR   GenomeRNAi; 50616; -.
DR   Pharos; Q9GZX6; Tbio.
DR   PRO; PR:Q9GZX6; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q9GZX6; Protein.
DR   Bgee; ENSG00000127318; Expressed in vermiform appendix and 57 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProt.
DR   GO; GO:0005125; F:cytokine activity; ISS:UniProt.
DR   GO; GO:0045518; F:interleukin-22 receptor binding; NAS:UniProtKB.
DR   GO; GO:0006953; P:acute-phase response; NAS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; NAS:UniProtKB.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProt.
DR   GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
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.
DR   Genevisible; Q9GZX6; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytokine; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           34..179
FT                   /note="Interleukin-22"
FT                   /id="PRO_0000015383"
FT   CARBOHYD        54
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:15983417"
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:0000269|PubMed:15983417"
FT   DISULFID        40..132
FT                   /evidence="ECO:0000269|PubMed:18599299"
FT   DISULFID        89..178
FT                   /evidence="ECO:0000269|PubMed:18599299"
FT   VARIANT         158
FT                   /note="S -> G (in dbSNP:rs2227507)"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="VAR_013078"
FT   HELIX           44..47
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           50..65
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   STRAND          74..76
FT                   /evidence="ECO:0007829|PDB:1M4R"
FT   HELIX           77..80
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           85..87
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           88..102
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   TURN            103..109
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           114..129
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           141..155
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           157..165
FT                   /evidence="ECO:0007829|PDB:3DLQ"
FT   HELIX           167..178
FT                   /evidence="ECO:0007829|PDB:3DLQ"
SQ   SEQUENCE   179 AA;  20011 MW;  3C35E64D60CF8767 CRC64;
     MAALQKSVSS FLMGTLATSC LLLLALLVQG GAAAPISSHC RLDKSNFQQP YITNRTFMLA
     KEASLADNNT DVRLIGEKLF HGVSMSERCY LMKQVLNFTL EEVLFPQSDR FQPYMQEVVP
     FLARLSNRLS TCHIEGDDLH IQRNVQKLKD TVKKLGESGE IKAIGELDLL FMSLRNACI
//