TRI22_HUMAN
ID TRI22_HUMAN Reviewed; 498 AA.
AC Q8IYM9; Q05CQ0; Q15521;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM22;
DE EC=2.3.2.27;
DE AltName: Full=50 kDa-stimulated trans-acting factor;
DE AltName: Full=RING finger protein 94;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM22 {ECO:0000305};
DE AltName: Full=Staf-50;
DE AltName: Full=Tripartite motif-containing protein 22;
GN Name=TRIM22; Synonyms=RNF94, STAF50;
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] (ISOFORM 2), INDUCTION, TISSUE SPECIFICITY, AND
RP VARIANT THR-242.
RX PubMed=7797467; DOI=10.1074/jbc.270.25.14891;
RA Tissot C., Mechti N.;
RT "Molecular cloning of a new interferon-induced factor that represses human
RT immunodeficiency virus type 1 long terminal repeat expression.";
RL J. Biol. Chem. 270:14891-14898(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-155.
RC TISSUE=Lung, and Testis;
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 [3]
RP SUBCELLULAR LOCATION.
RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140;
RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L.,
RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S.,
RA Pelicci P.G., Ballabio A.;
RT "The tripartite motif family identifies cell compartments.";
RL EMBO J. 20:2140-2151(2001).
RN [4]
RP INDUCTION.
RX PubMed=15064739; DOI=10.1038/sj.onc.1207524;
RA Obad S., Brunnstrom H., Vallon-Christersson J., Borg A., Drott K.,
RA Gullberg U.;
RT "Staf50 is a novel p53 target gene conferring reduced clonogenic growth of
RT leukemic U-937 cells.";
RL Oncogene 23:4050-4059(2004).
RN [5]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17156811; DOI=10.1016/j.virol.2006.10.035;
RA Li X., Gold B., O'hUigin C., Diaz-Griffero F., Song B., Si Z., Li Y.,
RA Yuan W., Stremlau M., Mische C., Javanbakht H., Scally M., Winkler C.,
RA Dean M., Sodroski J.;
RT "Unique features of TRIM5alpha among closely related human TRIM family
RT members.";
RL Virology 360:419-433(2007).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AUTOUBIQUITINATION, AND MUTAGENESIS OF
RP CYS-15.
RX PubMed=18656448; DOI=10.1016/j.bbrc.2008.07.070;
RA Duan Z., Gao B., Xu W., Xiong S.;
RT "Identification of TRIM22 as a RING finger E3 ubiquitin ligase.";
RL Biochem. Biophys. Res. Commun. 374:502-506(2008).
RN [7]
RP FUNCTION, INDUCTION, INTERACTION WITH HIV-1 GAG POLYPROTEIN (MICROBIAL
RP INFECTION), AND MUTAGENESIS OF CYS-15 AND CYS-18.
RX PubMed=18389079; DOI=10.1371/journal.ppat.1000007;
RA Barr S.D., Smiley J.R., Bushman F.D.;
RT "The interferon response inhibits HIV particle production by induction of
RT TRIM22.";
RL PLoS Pathog. 4:E1000007-E1000007(2008).
RN [8]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=19331816; DOI=10.1016/j.yexcr.2009.01.028;
RA Sivaramakrishnan G., Sun Y., Tan S.K., Lin V.C.;
RT "Dynamic localization of tripartite motif-containing 22 in nuclear and
RT nucleolar bodies.";
RL Exp. Cell Res. 315:1521-1532(2009).
RN [9]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-15; CYS-18 AND
RP 493-VAL-CYS-494.
RX PubMed=19481078; DOI=10.1016/j.febslet.2009.05.036;
RA Sivaramakrishnan G., Sun Y., Rajmohan R., Lin V.C.;
RT "B30.2/SPRY domain in tripartite motif-containing 22 is essential for the
RT formation of distinct nuclear bodies.";
RL FEBS Lett. 583:2093-2099(2009).
RN [10]
RP FUNCTION.
RX PubMed=19585648; DOI=10.1002/hep.23011;
RA Gao B., Duan Z., Xu W., Xiong S.;
RT "Tripartite motif-containing 22 inhibits the activity of hepatitis B virus
RT core promoter, which is dependent on nuclear-located RING domain.";
RL Hepatology 50:424-433(2009).
RN [11]
RP FUNCTION, AND INTERACTION WITH EMCV PROTEASE 3C (MICROBIAL INFECTION).
RX PubMed=19218198; DOI=10.1099/vir.0.006288-0;
RA Eldin P., Papon L., Oteiza A., Brocchi E., Lawson T.G., Mechti N.;
RT "TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral
RT activity against encephalomyocarditis virus.";
RL J. Gen. Virol. 90:536-545(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Interferon-induced antiviral protein involved in cell innate
CC immunity. The antiviral activity could in part be mediated by TRIM22-
CC dependent ubiquitination of viral proteins. Plays a role in restricting
CC the replication of HIV-1, encephalomyocarditis virus (EMCV) and
CC hepatitis B virus (HBV). Acts as a transcriptional repressor of HBV
CC core promoter. May have E3 ubiquitin-protein ligase activity.
CC {ECO:0000269|PubMed:18389079, ECO:0000269|PubMed:18656448,
CC ECO:0000269|PubMed:19218198, ECO:0000269|PubMed:19585648}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homotrimer (PubMed:17156811). {ECO:0000269|PubMed:17156811}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Gag polyprotein;
CC this interaction seems to reduce gag production or virus budding.
CC {ECO:0000269|PubMed:18389079}.
CC -!- SUBUNIT: (Microbial infection) Interacts with EMCV protease 3C; this
CC interaction leads to viral protease ubiquitination.
CC {ECO:0000269|PubMed:19218198}.
CC -!- INTERACTION:
CC Q8IYM9; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-954123, EBI-742388;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17156811}. Nucleus
CC {ECO:0000269|PubMed:17156811}. Nucleus speckle. Nucleus, Cajal body.
CC Note=Localizes predominantly to the nucleus, found in cytoplasm to some
CC extent. Forms distinct nuclear bodies that undergo dynamic changes
CC during cell cycle progression. Nuclear bodies start to form in the
CC early G0/G1 phase but become speckle-like in the S-phase and completely
CC dispersed in mitosis. 35% of TRIM22 nuclear bodies overlap or are found
CC adjacent to Cajal bodies.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IYM9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IYM9-2; Sequence=VSP_012060;
CC -!- TISSUE SPECIFICITY: Strongly expressed in peripheral blood leukocytes,
CC spleen, thymus, and ovary. Expressed at basal levels in other tissues.
CC {ECO:0000269|PubMed:7797467}.
CC -!- INDUCTION: By interferons alpha and beta. Up-regulated by p53/TP53.
CC Dramatically induced by progesterone in MDA-MB-231-derived ABC28 cells
CC and T47D cells. {ECO:0000269|PubMed:15064739,
CC ECO:0000269|PubMed:18389079, ECO:0000269|PubMed:19331816,
CC ECO:0000269|PubMed:7797467}.
CC -!- DOMAIN: The C-terminal SPRY domain is required for the transcriptional
CC suppressor activity, probably by mediating correct nuclear
CC localization. Residues 491-494 are essential for nuclear localization
CC and nuclear bodies formation.
CC -!- DOMAIN: The RING domain is essential for antiviral activity and for
CC TRIM22 nuclear bodies (NB) formation but is not necessary for nuclear
CC localization.
CC -!- PTM: Auto-ubiquitinated. {ECO:0000269|PubMed:18656448}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA57684.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X82200; CAA57684.1; ALT_FRAME; mRNA.
DR EMBL; BC022281; AAH22281.1; -; mRNA.
DR EMBL; BC035582; AAH35582.1; -; mRNA.
DR CCDS; CCDS41612.1; -. [Q8IYM9-1]
DR PIR; A57041; A57041.
DR RefSeq; NP_001186502.1; NM_001199573.1. [Q8IYM9-2]
DR RefSeq; NP_006065.2; NM_006074.4. [Q8IYM9-1]
DR AlphaFoldDB; Q8IYM9; -.
DR SMR; Q8IYM9; -.
DR BioGRID; 115628; 24.
DR IntAct; Q8IYM9; 16.
DR MINT; Q8IYM9; -.
DR STRING; 9606.ENSP00000369299; -.
DR iPTMnet; Q8IYM9; -.
DR PhosphoSitePlus; Q8IYM9; -.
DR SwissPalm; Q8IYM9; -.
DR BioMuta; TRIM22; -.
DR DMDM; 47606181; -.
DR EPD; Q8IYM9; -.
DR jPOST; Q8IYM9; -.
DR MassIVE; Q8IYM9; -.
DR MaxQB; Q8IYM9; -.
DR PaxDb; Q8IYM9; -.
DR PeptideAtlas; Q8IYM9; -.
DR PRIDE; Q8IYM9; -.
DR ProteomicsDB; 71205; -. [Q8IYM9-1]
DR ProteomicsDB; 71206; -. [Q8IYM9-2]
DR Antibodypedia; 1279; 285 antibodies from 26 providers.
DR DNASU; 10346; -.
DR Ensembl; ENST00000379965.8; ENSP00000369299.3; ENSG00000132274.16. [Q8IYM9-1]
DR GeneID; 10346; -.
DR KEGG; hsa:10346; -.
DR MANE-Select; ENST00000379965.8; ENSP00000369299.3; NM_006074.5; NP_006065.2.
DR UCSC; uc001mbr.4; human. [Q8IYM9-1]
DR CTD; 10346; -.
DR DisGeNET; 10346; -.
DR GeneCards; TRIM22; -.
DR HGNC; HGNC:16379; TRIM22.
DR HPA; ENSG00000132274; Low tissue specificity.
DR MIM; 606559; gene.
DR neXtProt; NX_Q8IYM9; -.
DR OpenTargets; ENSG00000132274; -.
DR PharmGKB; PA38129; -.
DR VEuPathDB; HostDB:ENSG00000132274; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000163787; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q8IYM9; -.
DR OMA; VLGCQHF; -.
DR PhylomeDB; Q8IYM9; -.
DR TreeFam; TF342569; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q8IYM9; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; Q8IYM9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 10346; 3 hits in 1105 CRISPR screens.
DR ChiTaRS; TRIM22; human.
DR GeneWiki; TRIM22; -.
DR GenomeRNAi; 10346; -.
DR Pharos; Q8IYM9; Tbio.
DR PRO; PR:Q8IYM9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8IYM9; protein.
DR Bgee; ENSG00000132274; Expressed in monocyte and 200 other tissues.
DR ExpressionAtlas; Q8IYM9; baseline and differential.
DR Genevisible; Q8IYM9; HS.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:ARUK-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc.
DR GO; GO:0046596; P:regulation of viral entry into host cell; IBA:GO_Central.
DR GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR CDD; cd15824; SPRY_PRY_TRIM22; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR003879; Butyrophylin_SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR035827; PRY/SPRY_TRIM22.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Coiled coil; Cytoplasm;
KW Host-virus interaction; Metal-binding; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..498
FT /note="E3 ubiquitin-protein ligase TRIM22"
FT /id="PRO_0000056232"
FT DOMAIN 283..498
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 15..60
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 92..133
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 132..248
FT /evidence="ECO:0000255"
FT MOTIF 257..275
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 119
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT VAR_SEQ 174..177
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7797467"
FT /id="VSP_012060"
FT VARIANT 155
FT /note="D -> N (in dbSNP:rs7935564)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_052134"
FT VARIANT 232
FT /note="T -> A (in dbSNP:rs2291843)"
FT /id="VAR_052135"
FT VARIANT 242
FT /note="R -> T (in dbSNP:rs1063303)"
FT /evidence="ECO:0000269|PubMed:7797467"
FT /id="VAR_052136"
FT VARIANT 321
FT /note="R -> K (in dbSNP:rs12364019)"
FT /id="VAR_052137"
FT MUTAGEN 15
FT /note="C->A: Loss of E3 ubiquitin-protein ligase activity,
FT reduces auto-ubiquitination and not affect nuclear bodies
FT formation. Loss of antiviral activity; when associated with
FT A-18."
FT /evidence="ECO:0000269|PubMed:18389079,
FT ECO:0000269|PubMed:18656448, ECO:0000269|PubMed:19481078"
FT MUTAGEN 18
FT /note="C->A: Loss of antiviral activity and not affect
FT nuclear bodies formation; when associated with A-15."
FT /evidence="ECO:0000269|PubMed:18389079,
FT ECO:0000269|PubMed:19481078"
FT MUTAGEN 493..494
FT /note="VC->AA: Reduces formation of regular nuclear
FT bodies."
FT /evidence="ECO:0000269|PubMed:19481078"
FT CONFLICT 464
FT /note="A -> R (in Ref. 1; CAA57684)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 498 AA; 56947 MW; AFADB968DE76F7DD CRC64;
MDFSVKVDIE KEVTCPICLE LLTEPLSLDC GHSFCQACIT AKIKESVIIS RGESSCPVCQ
TRFQPGNLRP NRHLANIVER VKEVKMSPQE GQKRDVCEHH GKKLQIFCKE DGKVICWVCE
LSQEHQGHQT FRINEVVKEC QEKLQVALQR LIKEDQEAEK LEDDIRQERT AWKNYIQIER
QKILKGFNEM RVILDNEEQR ELQKLEEGEV NVLDNLAAAT DQLVQQRQDA STLISDLQRR
LRGSSVEMLQ DVIDVMKRSE SWTLKKPKSV SKKLKSVFRV PDLSGMLQVL KELTDVQYYW
VDVMLNPGSA TSNVAISVDQ RQVKTVRTCT FKNSNPCDFS AFGVFGCQYF SSGKYYWEVD
VSGKIAWILG VHSKISSLNK RKSSGFAFDP SVNYSKVYSR YRPQYGYWVI GLQNTCEYNA
FEDSSSSDPK VLTLFMAVPP CRIGVFLDYE AGIVSFFNVT NHGALIYKFS GCRFSRPAYP
YFNPWNCLVP MTVCPPSS
