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Q9UPT9 (UBP22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:USP22
Synonyms:KIAA1063, USP3L
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length525 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.7

Catalytic activity

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). Ref.6

Subunit structure

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. Ref.5

Subcellular location

Nucleus Probable.

Tissue specificity

Moderately expressed in various tissues including heart and skeletal muscle, and weakly expressed in lung and liver. Ref.4

Sequence similarities

Belongs to the peptidase C19 family. UBP8 subfamily.

Contains 1 UBP-type zinc finger.

Contains 1 USP domain.

Sequence caution

The sequence AAH25317.1 differs from that shown. Reason: Frameshift at position 355.

The sequence BAA83015.1 differs from that shown. Reason: Erroneous initiation.

Isoform 2: The sequence AAI10500.1 differs from that shown. Reason: Frameshift at position 3.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
Ubl conjugation pathway
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionActivator
Chromatin regulator
Hydrolase
Protease
Thiol protease
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

chromatin organization

Traceable author statement. Source: Reactome

embryo development

Non-traceable author statement Ref.4. Source: UniProtKB

histone H4 acetylation

Inferred from direct assay Ref.6. Source: GOC

histone deubiquitination

Inferred from direct assay Ref.5Ref.6. Source: UniProtKB

histone ubiquitination

Inferred from direct assay Ref.7. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.6. Source: UniProtKB

protein deubiquitination

Inferred from direct assay Ref.4. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentSAGA complex

Inferred from direct assay Ref.5Ref.6. Source: UniProtKB

   Molecular_functionenzyme binding

Inferred from physical interaction PubMed 23382074. Source: UniProt

ligand-dependent nuclear receptor transcription coactivator activity

Inferred from mutant phenotype Ref.5. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

transcription coactivator activity

Inferred from direct assay Ref.5. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.4. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FUBP1Q96AE43EBI-723510,EBI-711404
NFATC2Q134692EBI-723510,EBI-716258

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UPT9-1)

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.
Isoform 2 (identifier: Q9UPT9-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 525525Ubiquitin carboxyl-terminal hydrolase 22
PRO_0000080650

Regions

Domain176 – 520345USP
Zinc finger61 – 12161UBP-type

Sites

Active site1851Nucleophile By similarity
Active site4791Proton acceptor By similarity

Amino acid modifications

Modified residue1291N6-acetyllysine Ref.8

Natural variations

Alternative sequence1 – 5757MVSRP…ARKRK → MAPGWPSLSAGSRQEAPQLA AGGSAYQAVGRQFQPRATAL QGPSQ in isoform 2.
VSP_036720

Experimental info

Mutagenesis4711H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-479. Ref.5
Mutagenesis4791H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-471. Ref.5
Sequence conflict851F → L in AAI26899. Ref.2
Sequence conflict3801K → T in CAE45893. Ref.3
Sequence conflict4961D → V in AAH25317. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 13, 2005. Version 2.
Checksum: D18BFE84BE8E5915

FASTA52559,961
        10         20         30         40         50         60 
MVSRPEPEGE AMDAELAVAP PGCSHLGSFK VDNWKQNLRA IYQCFVWSGT AEARKRKAKS 

        70         80         90        100        110        120 
CICHVCGVHL NRLHSCLYCV FFGCFTKKHI HEHAKAKRHN LAIDLMYGGI YCFLCQDYIY 

       130        140        150        160        170        180 
DKDMEIIAKE EQRKAWKMQG VGEKFSTWEP TKRELELLKH NPKRRKITSN CTIGLRGLIN 

       190        200        210        220        230        240 
LGNTCFMNCI VQALTHTPLL RDFFLSDRHR CEMQSPSSCL VCEMSSLFQE FYSGHRSPHI 

       250        260        270        280        290        300 
PYKLLHLVWT HARHLAGYEQ QDAHEFLIAA LDVLHRHCKG DDNGKKANNP NHCNCIIDQI 

       310        320        330        340        350        360 
FTGGLQSDVT CQVCHGVSTT IDPFWDISLD LPGSSTPFWP LSPGSEGNVV NGESHVSGTT 

       370        380        390        400        410        420 
TLTDCLRRFT RPEHLGSSAK IKCSGCHSYQ ESTKQLTMKK LPIVACFHLK RFEHSAKLRR 

       430        440        450        460        470        480 
KITTYVSFPL ELDMTPFMAS SKESRMNGQY QQPTDSLNND NKYSLFAVVN HQGTLESGHY 

       490        500        510        520 
TSFIRQHKDQ WFKCDDAIIT KASIKDVLDS EGYLLFYHKQ FLEYE 

« Hide

Isoform 2 [UniParc].

Checksum: 79C5E8674661256E
Show »

FASTA51358,179

References

« Hide 'large scale' references
[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(1999) [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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Uterus.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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(2006) [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(2008) [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(2008) [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(2008) [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(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS42285.1. [Q9UPT9-1]
RefSeqNP_056091.1. NM_015276.1. [Q9UPT9-1]
UniGeneHs.462492.

3D structure databases

ProteinModelPortalQ9UPT9.
SMRQ9UPT9. Positions 76-517.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116914. 40 interactions.
IntActQ9UPT9. 35 interactions.
MINTMINT-1390273.
STRING9606.ENSP00000261497.

Protein family/group databases

MEROPSC19.035.

PTM databases

PhosphoSiteQ9UPT9.

Polymorphism databases

DMDM78103328.

Proteomic databases

MaxQBQ9UPT9.
PaxDbQ9UPT9.
PRIDEQ9UPT9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261497; ENSP00000261497; ENSG00000124422. [Q9UPT9-1]
ENST00000537526; ENSP00000440950; ENSG00000124422. [Q9UPT9-2]
GeneID23326.
KEGGhsa:23326.
UCSCuc002gyl.4. human. [Q9UPT9-1]
uc002gyn.4. human. [Q9UPT9-2]

Organism-specific databases

CTD23326.
GeneCardsGC17M020902.
HGNCHGNC:12621. USP22.
HPAHPA044980.
MIM612116. gene.
neXtProtNX_Q9UPT9.
PharmGKBPA37247.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5533.
HOGENOMHOG000007260.
HOVERGENHBG058014.
InParanoidQ9UPT9.
KOK11366.
OMAYCQMCDD.
OrthoDBEOG7FR7G7.
PhylomeDBQ9UPT9.
TreeFamTF323554.

Enzyme and pathway databases

ReactomeREACT_172623. Chromatin organization.

Gene expression databases

ArrayExpressQ9UPT9.
BgeeQ9UPT9.
CleanExHS_USP22.
GenevestigatorQ9UPT9.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUSP22. human.
GenomeRNAi23326.
NextBio45232.
PROQ9UPT9.
SOURCESearch...

Entry information

Entry nameUBP22_HUMAN
AccessionPrimary (citable) accession number: Q9UPT9
Secondary accession number(s): A0JNS3 expand/collapse secondary AC list , Q2NLE2, Q6MZY4, Q8TBS8, Q96IW5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: September 13, 2005
Last modified: July 9, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM