I22R2_HUMAN
ID I22R2_HUMAN Reviewed; 263 AA.
AC Q969J5; Q08AH7; Q6UWM1; Q96A41; Q96QR0;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Interleukin-22 receptor subunit alpha-2;
DE Short=IL-22 receptor subunit alpha-2;
DE Short=IL-22R-alpha-2;
DE Short=IL-22RA2;
DE AltName: Full=Cytokine receptor class-II member 10;
DE AltName: Full=Cytokine receptor family 2 member 10;
DE Short=CRF2-10;
DE AltName: Full=Cytokine receptor family type 2, soluble 1;
DE Short=CRF2-S1;
DE AltName: Full=Interleukin-22-binding protein;
DE Short=IL-22BP;
DE Short=IL22BP;
DE AltName: Full=ZcytoR16;
DE Flags: Precursor;
GN Name=IL22RA2; ORFNames=UNQ5793/PRO19598/PRO19822;
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] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Mammary gland, and Placenta;
RX PubMed=11607789; DOI=10.1038/sj.gene.6363786;
RA Gruenberg B.H., Schoenemeyer A., Weiss B., Toschi L., Kunz S., Wolk K.,
RA Asadullah K., Sabat R.;
RT "A novel, soluble homologue of the human IL-10 receptor with preferential
RT expression in placenta.";
RL Genes Immun. 2:329-334(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND FUNCTION.
RX PubMed=11390454; DOI=10.4049/jimmunol.166.12.7096;
RA Kotenko S.V., Izotova L.S., Mirochnitchenko O.V., Esterova E.,
RA Dickensheets H., Donnelly R.P., Pestka S.;
RT "Identification, cloning, and characterization of a novel soluble receptor
RT that binds IL-22 and neutralizes its activity.";
RL J. Immunol. 166:7096-7103(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND FUNCTION.
RC TISSUE=Mammary gland;
RX PubMed=11390453; DOI=10.4049/jimmunol.166.12.7090;
RA Dumoutier L., Lejeune D., Colau D., Renauld J.-C.;
RT "Cloning and characterization of IL-22 binding protein, a natural
RT antagonist of IL-10-related T cell-derived inducible factor/IL-22.";
RL J. Immunol. 166:7090-7095(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11481447; DOI=10.1073/pnas.171303198;
RA Xu W., Presnell S.R., Parrish-Novak J., Kindsvogel W., Jaspers S., Chen Z.,
RA Dillon S.R., Gao Z., Gilbert T., Madden K., Schlutsmeyer S., Yao L.,
RA Whitmore T.E., Chandrasekher Y., Grant F.J., Maurer M., Jelinek L.,
RA Storey H., Brender T., Hammond A., Topouzis S., Clegg C.H., Foster D.C.;
RT "A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring
RT IL-22 antagonist.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9511-9516(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-16 AND LYS-190.
RG SeattleSNPs variation discovery resource;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [10]
RP PROTEIN SEQUENCE OF 22-36.
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 [11]
RP TISSUE SPECIFICITY.
RX PubMed=15201862; DOI=10.1038/sj.gene.6364104;
RA Weiss B., Wolk K., Gruenberg B.H., Volk H.D., Sterry W., Asadullah K.,
RA Sabat R.;
RT "Cloning of murine IL-22 receptor alpha 2 and comparison with its human
RT counterpart.";
RL Genes Immun. 5:330-336(2004).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=12700595; DOI=10.1038/sj.gene.6363947;
RA Wei C.-C., Ho T.-W., Liang W.-G., Chen G.-Y., Chang M.-S.;
RT "Cloning and characterization of mouse IL-22 binding protein.";
RL Genes Immun. 4:204-211(2003).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS) OF 21-231 (ISOFORM 2), AND DISULFIDE
RP BOND.
RX PubMed=19285080; DOI=10.1016/j.febslet.2009.03.006;
RA de Moura P.R., Watanabe L., Bleicher L., Colau D., Dumoutier L.,
RA Lemaire M.M., Renauld J.C., Polikarpov I.;
RT "Crystal structure of a soluble decoy receptor IL-22BP bound to
RT interleukin-22.";
RL FEBS Lett. 583:1072-1077(2009).
CC -!- FUNCTION: Isoform 2 is a receptor for IL22. Binds to IL22, prevents
CC interaction with the functional IL-22R complex and blocks the activity
CC of IL22 (in vitro). May play an important role as an IL22 antagonist in
CC the regulation of inflammatory responses.
CC -!- FUNCTION: Isoform 1 may play a role in establishing and maintaining
CC successful pregnancy.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12700595}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long, CRF2-10L, CRF2-s1-long;
CC IsoId=Q969J5-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, CRF2-10, CRF2-s1-short;
CC IsoId=Q969J5-2; Sequence=VSP_013105;
CC Name=3; Synonyms=CRF2-10S;
CC IsoId=Q969J5-3; Sequence=VSP_013105, VSP_013106, VSP_013107;
CC -!- TISSUE SPECIFICITY: Expressed in placenta, spleen, breast, skin and
CC lung. Also detected in intestinal tract, testis, brain, heart and
CC thymus. No expression found in prostate, bladder, kidney, ovary,
CC muscle, bone marrow, liver and uterus. Isoform 1 is expressed only in
CC placenta. Isoform 2 is expressed in placenta and breast and at lower
CC level in spleen, skin, thymus and stomach.
CC {ECO:0000269|PubMed:11481447, ECO:0000269|PubMed:11607789,
CC ECO:0000269|PubMed:15201862}.
CC -!- SIMILARITY: Belongs to the type II cytokine receptor family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ89097.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il22ra2/";
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DR EMBL; AJ313161; CAC85634.1; -; mRNA.
DR EMBL; AJ313162; CAC85635.1; -; mRNA.
DR EMBL; AY040566; AAK85714.1; -; mRNA.
DR EMBL; AY040567; AAK85715.1; -; mRNA.
DR EMBL; AY040568; AAK85716.1; -; mRNA.
DR EMBL; AJ297262; CAC83097.1; -; mRNA.
DR EMBL; AY044429; AAK91775.1; -; mRNA.
DR EMBL; AY358111; AAQ88478.1; -; mRNA.
DR EMBL; AY358737; AAQ89097.1; ALT_INIT; mRNA.
DR EMBL; AY779023; AAV31775.1; -; Genomic_DNA.
DR EMBL; AL050337; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47933.1; -; Genomic_DNA.
DR EMBL; BC125167; AAI25168.1; -; mRNA.
DR EMBL; BC125168; AAI25169.1; -; mRNA.
DR CCDS; CCDS5182.1; -. [Q969J5-1]
DR CCDS; CCDS5183.1; -. [Q969J5-2]
DR CCDS; CCDS5184.1; -. [Q969J5-3]
DR RefSeq; NP_443194.1; NM_052962.2. [Q969J5-1]
DR RefSeq; NP_851826.1; NM_181309.1. [Q969J5-2]
DR RefSeq; NP_851827.1; NM_181310.1. [Q969J5-3]
DR PDB; 3G9V; X-ray; 2.76 A; A/C=21-263.
DR PDBsum; 3G9V; -.
DR AlphaFoldDB; Q969J5; -.
DR SMR; Q969J5; -.
DR BioGRID; 125503; 20.
DR DIP; DIP-46036N; -.
DR IntAct; Q969J5; 4.
DR MINT; Q969J5; -.
DR STRING; 9606.ENSP00000296980; -.
DR BindingDB; Q969J5; -.
DR GlyGen; Q969J5; 1 site.
DR PhosphoSitePlus; Q969J5; -.
DR BioMuta; IL22RA2; -.
DR DMDM; 61213728; -.
DR PaxDb; Q969J5; -.
DR PeptideAtlas; Q969J5; -.
DR PRIDE; Q969J5; -.
DR ProteomicsDB; 75775; -. [Q969J5-1]
DR ProteomicsDB; 75776; -. [Q969J5-2]
DR Antibodypedia; 19779; 370 antibodies from 35 providers.
DR DNASU; 116379; -.
DR Ensembl; ENST00000296980.7; ENSP00000296980.2; ENSG00000164485.15. [Q969J5-1]
DR Ensembl; ENST00000339602.3; ENSP00000340920.3; ENSG00000164485.15. [Q969J5-3]
DR Ensembl; ENST00000349184.8; ENSP00000296979.4; ENSG00000164485.15. [Q969J5-2]
DR GeneID; 116379; -.
DR KEGG; hsa:116379; -.
DR MANE-Select; ENST00000296980.7; ENSP00000296980.2; NM_052962.3; NP_443194.1.
DR UCSC; uc003qhl.4; human. [Q969J5-1]
DR CTD; 116379; -.
DR DisGeNET; 116379; -.
DR GeneCards; IL22RA2; -.
DR HGNC; HGNC:14901; IL22RA2.
DR HPA; ENSG00000164485; Group enriched (breast, lymphoid tissue).
DR MIM; 606648; gene.
DR neXtProt; NX_Q969J5; -.
DR OpenTargets; ENSG00000164485; -.
DR PharmGKB; PA134983729; -.
DR VEuPathDB; HostDB:ENSG00000164485; -.
DR eggNOG; ENOG502S2NT; Eukaryota.
DR GeneTree; ENSGT00940000161124; -.
DR HOGENOM; CLU_081158_1_0_1; -.
DR InParanoid; Q969J5; -.
DR OMA; SMENYYE; -.
DR OrthoDB; 1078220at2759; -.
DR PhylomeDB; Q969J5; -.
DR TreeFam; TF332537; -.
DR PathwayCommons; Q969J5; -.
DR Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR SignaLink; Q969J5; -.
DR SIGNOR; Q969J5; -.
DR BioGRID-ORCS; 116379; 9 hits in 1073 CRISPR screens.
DR ChiTaRS; IL22RA2; human.
DR EvolutionaryTrace; Q969J5; -.
DR GenomeRNAi; 116379; -.
DR Pharos; Q969J5; Tbio.
DR PRO; PR:Q969J5; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q969J5; protein.
DR Bgee; ENSG00000164485; Expressed in vermiform appendix and 28 other tissues.
DR Genevisible; Q969J5; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0042017; F:interleukin-22 binding; IDA:UniProtKB.
DR GO; GO:0042018; F:interleukin-22 receptor activity; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015373; Interferon/interleukin_rcp_dom.
DR Pfam; PF09294; Interfer-bind; 1.
DR Pfam; PF01108; Tissue_fac; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Receptor; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 22..263
FT /note="Interleukin-22 receptor subunit alpha-2"
FT /id="PRO_0000011016"
FT DOMAIN 26..68
FT /note="Fibronectin type-III 1"
FT DOMAIN 100..161
FT /note="Fibronectin type-III 2"
FT DOMAIN 162..263
FT /note="Fibronectin type-III 3"
FT SITE 99
FT /note="Critical for IL22-binding"
FT /evidence="ECO:0000250"
FT SITE 151
FT /note="Critical for IL22-binding"
FT /evidence="ECO:0000250"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 238..259
FT /evidence="ECO:0000269|PubMed:19285080"
FT VAR_SEQ 67..98
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11390453,
FT ECO:0000303|PubMed:11390454, ECO:0000303|PubMed:11481447,
FT ECO:0000303|PubMed:11607789, ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013105"
FT VAR_SEQ 158..162
FT /note="TKIDP -> RAKGL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11390454"
FT /id="VSP_013106"
FT VAR_SEQ 163..263
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11390454"
FT /id="VSP_013107"
FT VARIANT 16
FT /note="L -> P (in dbSNP:rs28385692)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_021493"
FT VARIANT 190
FT /note="E -> K (in dbSNP:rs28362173)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_021494"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 59..66
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 105..113
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3G9V"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 131..139
FT /evidence="ECO:0007829|PDB:3G9V"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:3G9V"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:3G9V"
FT HELIX 195..198
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 216..223
FT /evidence="ECO:0007829|PDB:3G9V"
FT STRAND 239..245
FT /evidence="ECO:0007829|PDB:3G9V"
FT TURN 246..249
FT /evidence="ECO:0007829|PDB:3G9V"
SQ SEQUENCE 263 AA; 30550 MW; C96ECEC5D78AC79B CRC64;
MMPKHCFLGF LISFFLTGVA GTQSTHESLK PQRVQFQSRN FHNILQWQPG RALTGNSSVY
FVQYKIMFSC SMKSSHQKPS GCWQHISCNF PGCRTLAKYG QRQWKNKEDC WGTQELSCDL
TSETSDIQEP YYGRVRAASA GSYSEWSMTP RFTPWWETKI DPPVMNITQV NGSLLVILHA
PNLPYRYQKE KNVSIEDYYE LLYRVFIINN SLEKEQKVYE GAHRAVEIEA LTPHSSYCVV
AEIYQPMLDR RSQRSEERCV EIP
