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Protein

Ubiquitin carboxyl-terminal hydrolase 22

Gene

USP22

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complex SAGA. Catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a coactivator. Recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation and cell cycle progression.3 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei185 – 1851NucleophilePROSITE-ProRule annotation
Active sitei479 – 4791Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri61 – 12161UBP-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: GO_Central
  2. enzyme binding Source: UniProtKB
  3. ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  4. transcription coactivator activity Source: UniProtKB
  5. ubiquitin-specific protease activity Source: UniProtKB
  6. zinc ion binding Source: InterPro

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. chromatin organization Source: Reactome
  3. embryo development Source: UniProtKB
  4. histone deubiquitination Source: UniProtKB
  5. histone H4 acetylation Source: GOC
  6. histone ubiquitination Source: UniProtKB
  7. positive regulation of mitotic cell cycle Source: UniProtKB
  8. positive regulation of transcription, DNA-templated Source: UniProtKB
  9. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  10. protein deubiquitination Source: UniProtKB
  11. regulation of proteasomal protein catabolic process Source: GO_Central
  12. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Cell cycle, Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_264245. HATs acetylate histones.

Protein family/group databases

MEROPSiC19.035.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 22 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 22
Ubiquitin thioesterase 22
Ubiquitin-specific-processing protease 22
Gene namesi
Name:USP22
Synonyms:KIAA1063, USP3L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:12621. USP22.

Subcellular locationi

Nucleus Curated

GO - Cellular componenti

  1. SAGA complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi471 – 4711H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-479. 1 Publication
Mutagenesisi479 – 4791H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-471. 1 Publication

Organism-specific databases

PharmGKBiPA37247.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 525525Ubiquitin carboxyl-terminal hydrolase 22PRO_0000080650Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei129 – 1291N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ9UPT9.
PaxDbiQ9UPT9.
PRIDEiQ9UPT9.

PTM databases

PhosphoSiteiQ9UPT9.

Expressioni

Tissue specificityi

Moderately expressed in various tissues including heart and skeletal muscle, and weakly expressed in lung and liver.1 Publication

Gene expression databases

BgeeiQ9UPT9.
CleanExiHS_USP22.
ExpressionAtlasiQ9UPT9. baseline and differential.
GenevestigatoriQ9UPT9.

Organism-specific databases

HPAiHPA044980.

Interactioni

Subunit structurei

Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H, TAF10, TRRAP and USP22. Within the SAGA complex, ATXN7L3, ENY2 and USP22 form a subcomplex required for histone deubiquitination. Interacts directly with ATXN7L3; leading to its recritment to the SAGA complex.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FUBP1Q96AE43EBI-723510,EBI-711404
NFATC2Q134692EBI-723510,EBI-716258

Protein-protein interaction databases

BioGridi116914. 55 interactions.
IntActiQ9UPT9. 35 interactions.
MINTiMINT-1390273.
STRINGi9606.ENSP00000261497.

Structurei

3D structure databases

ProteinModelPortaliQ9UPT9.
SMRiQ9UPT9. Positions 76-517.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini176 – 520345USPAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C19 family. UBP8 subfamily.Curated
Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri61 – 12161UBP-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00780000121889.
HOGENOMiHOG000007260.
HOVERGENiHBG058014.
InParanoidiQ9UPT9.
KOiK11366.
OMAiIHEHAKA.
OrthoDBiEOG7FR7G7.
PhylomeDBiQ9UPT9.
TreeFamiTF323554.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UPT9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVSRPEPEGE AMDAELAVAP PGCSHLGSFK VDNWKQNLRA IYQCFVWSGT
60 70 80 90 100
AEARKRKAKS CICHVCGVHL NRLHSCLYCV FFGCFTKKHI HEHAKAKRHN
110 120 130 140 150
LAIDLMYGGI YCFLCQDYIY DKDMEIIAKE EQRKAWKMQG VGEKFSTWEP
160 170 180 190 200
TKRELELLKH NPKRRKITSN CTIGLRGLIN LGNTCFMNCI VQALTHTPLL
210 220 230 240 250
RDFFLSDRHR CEMQSPSSCL VCEMSSLFQE FYSGHRSPHI PYKLLHLVWT
260 270 280 290 300
HARHLAGYEQ QDAHEFLIAA LDVLHRHCKG DDNGKKANNP NHCNCIIDQI
310 320 330 340 350
FTGGLQSDVT CQVCHGVSTT IDPFWDISLD LPGSSTPFWP LSPGSEGNVV
360 370 380 390 400
NGESHVSGTT TLTDCLRRFT RPEHLGSSAK IKCSGCHSYQ ESTKQLTMKK
410 420 430 440 450
LPIVACFHLK RFEHSAKLRR KITTYVSFPL ELDMTPFMAS SKESRMNGQY
460 470 480 490 500
QQPTDSLNND NKYSLFAVVN HQGTLESGHY TSFIRQHKDQ WFKCDDAIIT
510 520
KASIKDVLDS EGYLLFYHKQ FLEYE
Length:525
Mass (Da):59,961
Last modified:September 12, 2005 - v2
Checksum:iD18BFE84BE8E5915
GO
Isoform 2 (identifier: Q9UPT9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: MVSRPEPEGE...SGTAEARKRK → MAPGWPSLSA...RATALQGPSQ

Show »
Length:513
Mass (Da):58,179
Checksum:i79C5E8674661256E
GO

Sequence cautioni

The sequence AAH25317.1 differs from that shown. Reason: Frameshift at position 355. Curated
Isoform 2 : The sequence AAI10500.1 differs from that shown. Reason: Frameshift at position 3. Curated
The sequence BAA83015.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti85 – 851F → L in AAI26899 (PubMed:15489334).Curated
Sequence conflicti380 – 3801K → T in CAE45893 (PubMed:17974005).Curated
Sequence conflicti496 – 4961D → V in AAH25317 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5757MVSRP…ARKRK → MAPGWPSLSAGSRQEAPQLA AGGSAYQAVGRQFQPRATAL QGPSQ in isoform 2. 1 PublicationVSP_036720Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028986 mRNA. Translation: BAA83015.1. Different initiation.
BC007196 mRNA. Translation: AAH07196.1.
BC025317 mRNA. Translation: AAH25317.1. Frameshift.
BC110499 mRNA. Translation: AAI10500.1. Frameshift.
BC126898 mRNA. Translation: AAI26899.1.
BX640815 mRNA. Translation: CAE45893.1.
CCDSiCCDS42285.1. [Q9UPT9-1]
RefSeqiNP_056091.1. NM_015276.1. [Q9UPT9-1]
UniGeneiHs.462492.

Genome annotation databases

EnsembliENST00000261497; ENSP00000261497; ENSG00000124422. [Q9UPT9-1]
ENST00000537526; ENSP00000440950; ENSG00000124422. [Q9UPT9-2]
GeneIDi23326.
KEGGihsa:23326.
UCSCiuc002gyl.4. human. [Q9UPT9-1]
uc002gyn.4. human. [Q9UPT9-2]

Polymorphism databases

DMDMi78103328.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028986 mRNA. Translation: BAA83015.1. Different initiation.
BC007196 mRNA. Translation: AAH07196.1.
BC025317 mRNA. Translation: AAH25317.1. Frameshift.
BC110499 mRNA. Translation: AAI10500.1. Frameshift.
BC126898 mRNA. Translation: AAI26899.1.
BX640815 mRNA. Translation: CAE45893.1.
CCDSiCCDS42285.1. [Q9UPT9-1]
RefSeqiNP_056091.1. NM_015276.1. [Q9UPT9-1]
UniGeneiHs.462492.

3D structure databases

ProteinModelPortaliQ9UPT9.
SMRiQ9UPT9. Positions 76-517.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116914. 55 interactions.
IntActiQ9UPT9. 35 interactions.
MINTiMINT-1390273.
STRINGi9606.ENSP00000261497.

Protein family/group databases

MEROPSiC19.035.

PTM databases

PhosphoSiteiQ9UPT9.

Polymorphism databases

DMDMi78103328.

Proteomic databases

MaxQBiQ9UPT9.
PaxDbiQ9UPT9.
PRIDEiQ9UPT9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261497; ENSP00000261497; ENSG00000124422. [Q9UPT9-1]
ENST00000537526; ENSP00000440950; ENSG00000124422. [Q9UPT9-2]
GeneIDi23326.
KEGGihsa:23326.
UCSCiuc002gyl.4. human. [Q9UPT9-1]
uc002gyn.4. human. [Q9UPT9-2]

Organism-specific databases

CTDi23326.
GeneCardsiGC17M020902.
HGNCiHGNC:12621. USP22.
HPAiHPA044980.
MIMi612116. gene.
neXtProtiNX_Q9UPT9.
PharmGKBiPA37247.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00780000121889.
HOGENOMiHOG000007260.
HOVERGENiHBG058014.
InParanoidiQ9UPT9.
KOiK11366.
OMAiIHEHAKA.
OrthoDBiEOG7FR7G7.
PhylomeDBiQ9UPT9.
TreeFamiTF323554.

Enzyme and pathway databases

ReactomeiREACT_264245. HATs acetylate histones.

Miscellaneous databases

ChiTaRSiUSP22. human.
GenomeRNAii23326.
NextBioi45232.
PROiQ9UPT9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UPT9.
CleanExiHS_USP22.
ExpressionAtlasiQ9UPT9. baseline and differential.
GenevestigatoriQ9UPT9.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 6:197-205(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Uterus.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-525.
    Tissue: Colon endothelium.
  4. "The expression patterns of deubiquitinating enzymes, USP22 and Usp22."
    Lee H.-J., Kim M.-S., Shin J.-M., Park T.-J., Chung H.-M., Baek K.-H.
    Gene Expr. Patterns 6:277-284(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing."
    Zhao Y., Lang G., Ito S., Bonnet J., Metzger E., Sawatsubashi S., Suzuki E., Le Guezennec X., Stunnenberg H.G., Krasnov A., Georgieva S.G., Schuele R., Takeyama K., Kato S., Tora L., Devys D.
    Mol. Cell 29:92-101(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HISTONE DEUBIQUITINATION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SAGA COMPLEX, MUTAGENESIS OF HIS-471 AND HIS-479.
  6. "The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression."
    Zhang X.-Y., Varthi M., Sykes S.M., Phillips C., Warzecha C., Zhu W., Wyce A., Thorne A.W., Berger S.L., McMahon S.B.
    Mol. Cell 29:102-111(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HISTONE H2A DEUBIQUITINATION, CATALYTIC ACTIVITY.
  7. "USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A."
    Zhang X.-Y., Pfeiffer H.K., Thorne A.W., McMahon S.B.
    Cell Cycle 7:1522-1524(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HISTONE H2B DEUBIQUITINATION.
  8. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiUBP22_HUMAN
AccessioniPrimary (citable) accession number: Q9UPT9
Secondary accession number(s): A0JNS3
, Q2NLE2, Q6MZY4, Q8TBS8, Q96IW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 26, 2002
Last sequence update: September 12, 2005
Last modified: March 31, 2015
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.