UBP22_HUMAN
ID UBP22_HUMAN Reviewed; 525 AA.
AC Q9UPT9; A0JNS3; Q2NLE2; Q6MZY4; Q8TBS8; Q96IW5;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 22;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 22;
DE AltName: Full=Ubiquitin thioesterase 22;
DE AltName: Full=Ubiquitin-specific-processing protease 22;
GN Name=USP22; Synonyms=KIAA1063, USP3L;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-525.
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=16378762; DOI=10.1016/j.modgep.2005.07.007;
RA Lee H.-J., Kim M.-S., Shin J.-M., Park T.-J., Chung H.-M., Baek K.-H.;
RT "The expression patterns of deubiquitinating enzymes, USP22 and Usp22.";
RL Gene Expr. Patterns 6:277-284(2006).
RN [5]
RP FUNCTION IN HISTONE DEUBIQUITINATION, IDENTIFICATION BY MASS SPECTROMETRY,
RP IDENTIFICATION IN THE SAGA COMPLEX, AND MUTAGENESIS OF HIS-471 AND HIS-479.
RX PubMed=18206972; DOI=10.1016/j.molcel.2007.12.011;
RA Zhao Y., Lang G., Ito S., Bonnet J., Metzger E., Sawatsubashi S.,
RA Suzuki E., Le Guezennec X., Stunnenberg H.G., Krasnov A., Georgieva S.G.,
RA Schuele R., Takeyama K., Kato S., Tora L., Devys D.;
RT "A TFTC/STAGA module mediates histone H2A and H2B deubiquitination,
RT coactivates nuclear receptors, and counteracts heterochromatin silencing.";
RL Mol. Cell 29:92-101(2008).
RN [6]
RP FUNCTION IN HISTONE H2A DEUBIQUITINATION, AND CATALYTIC ACTIVITY.
RX PubMed=18206973; DOI=10.1016/j.molcel.2007.12.015;
RA Zhang X.-Y., Varthi M., Sykes S.M., Phillips C., Warzecha C., Zhu W.,
RA Wyce A., Thorne A.W., Berger S.L., McMahon S.B.;
RT "The putative cancer stem cell marker USP22 is a subunit of the human SAGA
RT complex required for activated transcription and cell-cycle progression.";
RL Mol. Cell 29:102-111(2008).
RN [7]
RP FUNCTION IN HISTONE H2B DEUBIQUITINATION.
RX PubMed=18469533; DOI=10.4161/cc.7.11.5962;
RA Zhang X.-Y., Pfeiffer H.K., Thorne A.W., McMahon S.B.;
RT "USP22, an hSAGA subunit and potential cancer stem cell marker, reverses
RT the polycomb-catalyzed ubiquitylation of histone H2A.";
RL Cell Cycle 7:1522-1524(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-129, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP IDENTIFICATION IN THE SAGA COMPLEX, AND INTERACTION WITH ATXN7L3 AND
RP ATXN7L3B.
RX PubMed=27601583; DOI=10.1128/mcb.00193-16;
RA Li W., Atanassov B.S., Lan X., Mohan R.D., Swanson S.K., Farria A.T.,
RA Florens L., Washburn M.P., Workman J.L., Dent S.Y.;
RT "Cytoplasmic ATXN7L3B interferes with nuclear functions of the SAGA
RT deubiquitinase module.";
RL Mol. Cell. Biol. 36:2855-2866(2016).
CC -!- FUNCTION: Histone deubiquitinating component of the transcription
CC regulatory histone acetylation (HAT) complex SAGA. Catalyzes the
CC deubiquitination of both histones H2A and H2B, thereby acting as a
CC coactivator. Recruited to specific gene promoters by activators such as
CC MYC, where it is required for transcription. Required for nuclear
CC receptor-mediated transactivation and cell cycle progression.
CC {ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:18206973,
CC ECO:0000269|PubMed:18469533}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:18206973};
CC -!- SUBUNIT: Component of some SAGA transcription coactivator-HAT
CC complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H,
CC TAF10, TRRAP and USP22. Within the SAGA complex, ATXN7L3, ENY2 and
CC USP22 form a subcomplex required for histone deubiquitination
CC (PubMed:18206972, PubMed:27601583). Interacts directly with ATXN7L3;
CC leading to its recruitment to the SAGA complex (PubMed:18206972).
CC Interacts with ATXN7L3 and weakly with ATXN7L3B (PubMed:27601583).
CC {ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:27601583}.
CC -!- INTERACTION:
CC Q9UPT9; Q9NRN7: AASDHPPT; NbExp=6; IntAct=EBI-723510, EBI-740884;
CC Q9UPT9; Q96AE4: FUBP1; NbExp=3; IntAct=EBI-723510, EBI-711404;
CC Q9UPT9; Q13469: NFATC2; NbExp=2; IntAct=EBI-723510, EBI-716258;
CC Q9UPT9-2; Q9NRN7: AASDHPPT; NbExp=11; IntAct=EBI-12074414, EBI-740884;
CC Q9UPT9-2; Q14CW9: ATXN7L3; NbExp=3; IntAct=EBI-12074414, EBI-949215;
CC Q9UPT9-2; O95429: BAG4; NbExp=3; IntAct=EBI-12074414, EBI-2949658;
CC Q9UPT9-2; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-12074414, EBI-11522433;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q5DU02}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UPT9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UPT9-2; Sequence=VSP_036720;
CC -!- TISSUE SPECIFICITY: Moderately expressed in various tissues including
CC heart and skeletal muscle, and weakly expressed in lung and liver.
CC {ECO:0000269|PubMed:16378762}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. UBP8 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH25317.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA83015.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 2]:
CC Sequence=AAI10500.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB028986; BAA83015.1; ALT_INIT; mRNA.
DR EMBL; BC007196; AAH07196.1; -; mRNA.
DR EMBL; BC025317; AAH25317.1; ALT_FRAME; mRNA.
DR EMBL; BC110499; AAI10500.1; ALT_FRAME; mRNA.
DR EMBL; BC126898; AAI26899.1; -; mRNA.
DR EMBL; BX640815; CAE45893.1; -; mRNA.
DR CCDS; CCDS42285.1; -. [Q9UPT9-1]
DR RefSeq; NP_056091.1; NM_015276.1. [Q9UPT9-1]
DR AlphaFoldDB; Q9UPT9; -.
DR SMR; Q9UPT9; -.
DR BioGRID; 116914; 124.
DR ComplexPortal; CPX-6802; SAGA complex, KAT2B variant.
DR ComplexPortal; CPX-900; SAGA complex, KAT2A variant.
DR ComplexPortal; CPX-903; TFTC histone acetylation complex.
DR CORUM; Q9UPT9; -.
DR IntAct; Q9UPT9; 62.
DR MINT; Q9UPT9; -.
DR STRING; 9606.ENSP00000261497; -.
DR MEROPS; C19.035; -.
DR GlyGen; Q9UPT9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UPT9; -.
DR PhosphoSitePlus; Q9UPT9; -.
DR BioMuta; USP22; -.
DR DMDM; 78103328; -.
DR EPD; Q9UPT9; -.
DR jPOST; Q9UPT9; -.
DR MassIVE; Q9UPT9; -.
DR MaxQB; Q9UPT9; -.
DR PaxDb; Q9UPT9; -.
DR PeptideAtlas; Q9UPT9; -.
DR PRIDE; Q9UPT9; -.
DR ProteomicsDB; 85443; -. [Q9UPT9-1]
DR ProteomicsDB; 85444; -. [Q9UPT9-2]
DR Antibodypedia; 26118; 345 antibodies from 32 providers.
DR DNASU; 23326; -.
DR Ensembl; ENST00000261497.9; ENSP00000261497.4; ENSG00000124422.12. [Q9UPT9-1]
DR Ensembl; ENST00000537526.6; ENSP00000440950.2; ENSG00000124422.12. [Q9UPT9-2]
DR GeneID; 23326; -.
DR KEGG; hsa:23326; -.
DR MANE-Select; ENST00000261497.9; ENSP00000261497.4; NM_015276.2; NP_056091.1.
DR UCSC; uc002gym.4; human. [Q9UPT9-1]
DR CTD; 23326; -.
DR DisGeNET; 23326; -.
DR GeneCards; USP22; -.
DR HGNC; HGNC:12621; USP22.
DR HPA; ENSG00000124422; Low tissue specificity.
DR MIM; 612116; gene.
DR neXtProt; NX_Q9UPT9; -.
DR OpenTargets; ENSG00000124422; -.
DR PharmGKB; PA37247; -.
DR VEuPathDB; HostDB:ENSG00000124422; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000156623; -.
DR HOGENOM; CLU_008279_11_0_1; -.
DR InParanoid; Q9UPT9; -.
DR OMA; FMSVILQ; -.
DR OrthoDB; 929408at2759; -.
DR PhylomeDB; Q9UPT9; -.
DR TreeFam; TF323554; -.
DR PathwayCommons; Q9UPT9; -.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9UPT9; -.
DR SIGNOR; Q9UPT9; -.
DR BioGRID-ORCS; 23326; 45 hits in 1096 CRISPR screens.
DR ChiTaRS; USP22; human.
DR GenomeRNAi; 23326; -.
DR Pharos; Q9UPT9; Tbio.
DR PRO; PR:Q9UPT9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9UPT9; protein.
DR Bgee; ENSG00000124422; Expressed in paraflocculus and 204 other tissues.
DR ExpressionAtlas; Q9UPT9; baseline and differential.
DR Genevisible; Q9UPT9; HS.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000124; C:SAGA complex; IDA:UniProtKB.
DR GO; GO:0033276; C:transcription factor TFTC complex; IC:ComplexPortal.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IMP:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; NAS:UniProtKB.
DR GO; GO:0016578; P:histone deubiquitination; IDA:UniProtKB.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:ComplexPortal.
DR GO; GO:0043967; P:histone H4 acetylation; IEA:GOC.
DR GO; GO:0016574; P:histone ubiquitination; IDA:UniProtKB.
DR GO; GO:0035521; P:monoubiquitinated histone deubiquitination; IDA:ComplexPortal.
DR GO; GO:0035522; P:monoubiquitinated histone H2A deubiquitination; IDA:ComplexPortal.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:0043484; P:regulation of RNA splicing; IC:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Cell cycle;
KW Chromatin regulator; Hydrolase; Metal-binding; Nucleus; Protease;
KW Reference proteome; Thiol protease; Transcription;
KW Transcription regulation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..525
FT /note="Ubiquitin carboxyl-terminal hydrolase 22"
FT /id="PRO_0000080650"
FT DOMAIN 176..520
FT /note="USP"
FT ZN_FING 21..138
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT ACT_SITE 185
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 479
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 23
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 25
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 66
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 129
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..57
FT /note="MVSRPEPEGEAMDAELAVAPPGCSHLGSFKVDNWKQNLRAIYQCFVWSGTAE
FT ARKRK -> MAPGWPSLSAGSRQEAPQLAAGGSAYQAVGRQFQPRATALQGPSQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036720"
FT MUTAGEN 471
FT /note="H->A: Impairs its function as a positive modulator
FT of androgen receptor transactivation; when associated with
FT A-479."
FT /evidence="ECO:0000269|PubMed:18206972"
FT MUTAGEN 479
FT /note="H->A: Impairs its function as a positive modulator
FT of androgen receptor transactivation; when associated with
FT A-471."
FT /evidence="ECO:0000269|PubMed:18206972"
FT CONFLICT 85
FT /note="F -> L (in Ref. 2; AAI26899)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="K -> T (in Ref. 3; CAE45893)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="D -> V (in Ref. 2; AAH25317)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 59961 MW; D18BFE84BE8E5915 CRC64;
MVSRPEPEGE AMDAELAVAP PGCSHLGSFK VDNWKQNLRA IYQCFVWSGT AEARKRKAKS
CICHVCGVHL NRLHSCLYCV FFGCFTKKHI HEHAKAKRHN LAIDLMYGGI YCFLCQDYIY
DKDMEIIAKE EQRKAWKMQG VGEKFSTWEP TKRELELLKH NPKRRKITSN CTIGLRGLIN
LGNTCFMNCI VQALTHTPLL RDFFLSDRHR CEMQSPSSCL VCEMSSLFQE FYSGHRSPHI
PYKLLHLVWT HARHLAGYEQ QDAHEFLIAA LDVLHRHCKG DDNGKKANNP NHCNCIIDQI
FTGGLQSDVT CQVCHGVSTT IDPFWDISLD LPGSSTPFWP LSPGSEGNVV NGESHVSGTT
TLTDCLRRFT RPEHLGSSAK IKCSGCHSYQ ESTKQLTMKK LPIVACFHLK RFEHSAKLRR
KITTYVSFPL ELDMTPFMAS SKESRMNGQY QQPTDSLNND NKYSLFAVVN HQGTLESGHY
TSFIRQHKDQ WFKCDDAIIT KASIKDVLDS EGYLLFYHKQ FLEYE
