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Protein

Ubiquitin carboxyl-terminal hydrolase 22

Gene

USP22

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Active sitei185NucleophilePROSITE-ProRule annotation1
Active sitei479Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri61 – 121UBP-typePROSITE-ProRule annotationAdd BLAST61

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • nuclear receptor transcription coactivator activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: Reactome
  • transcription coactivator activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Hydrolase, Protease, Thiol protease
Biological processCell cycle, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3214847 HATs acetylate histones
R-HSA-5689880 Ub-specific processing proteases

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
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000124422.11
HGNCiHGNC:12621 USP22
MIMi612116 gene
neXtProtiNX_Q9UPT9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi471H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-479. 1 Publication1
Mutagenesisi479H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-471. 1 Publication1

Organism-specific databases

DisGeNETi23326
OpenTargetsiENSG00000124422
PharmGKBiPA37247

Polymorphism and mutation databases

BioMutaiUSP22
DMDMi78103328

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806501 – 525Ubiquitin carboxyl-terminal hydrolase 22Add BLAST525

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei129N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9UPT9
PaxDbiQ9UPT9
PeptideAtlasiQ9UPT9
PRIDEiQ9UPT9
ProteomicsDBi85443
85444 [Q9UPT9-2]

PTM databases

iPTMnetiQ9UPT9
PhosphoSitePlusiQ9UPT9

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

BgeeiENSG00000124422 Expressed in 239 organ(s), highest expression level in cerebellum
CleanExiHS_USP22
ExpressionAtlasiQ9UPT9 baseline and differential
GenevisibleiQ9UPT9 HS

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 (PubMed:18206972, PubMed:27601583). Interacts directly with ATXN7L3; leading to its recruitment to the SAGA complex (PubMed:18206972). Interacts with ATXN7L3 and weakly with ATXN7L3B (PubMed:27601583).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116914, 84 interactors
ComplexPortaliCPX-900 SAGA complex
CPX-903 TFTC histone acetylation complex
CORUMiQ9UPT9
IntActiQ9UPT9, 39 interactors
MINTiQ9UPT9
STRINGi9606.ENSP00000261497

Structurei

3D structure databases

ProteinModelPortaliQ9UPT9
SMRiQ9UPT9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini176 – 520USPAdd BLAST345

Sequence similaritiesi

Belongs to the peptidase C19 family. UBP8 subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri61 – 121UBP-typePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1867 Eukaryota
ENOG410XQQ0 LUCA
GeneTreeiENSGT00890000139343
HOGENOMiHOG000007260
HOVERGENiHBG058014
InParanoidiQ9UPT9
KOiK11366
OMAiCDDHLIT
OrthoDBiEOG091G09GI
PhylomeDBiQ9UPT9
TreeFamiTF323554

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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 13, 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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ESK0K7ESK0_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP22
107Annotation score:
K7ERX6K7ERX6_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP22
125Annotation score:
J3QS30J3QS30_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP22
102Annotation score:
J3QRV6J3QRV6_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP22
194Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti85F → L in AAI26899 (PubMed:15489334).Curated1
Sequence conflicti380K → T in CAE45893 (PubMed:17974005).Curated1
Sequence conflicti496D → V in AAH25317 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0367201 – 57MVSRP…ARKRK → MAPGWPSLSAGSRQEAPQLA AGGSAYQAVGRQFQPRATAL QGPSQ in isoform 2. 1 PublicationAdd BLAST57

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
UCSCiuc002gym.4 human [Q9UPT9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116914, 84 interactors
ComplexPortaliCPX-900 SAGA complex
CPX-903 TFTC histone acetylation complex
CORUMiQ9UPT9
IntActiQ9UPT9, 39 interactors
MINTiQ9UPT9
STRINGi9606.ENSP00000261497

Protein family/group databases

MEROPSiC19.035

PTM databases

iPTMnetiQ9UPT9
PhosphoSitePlusiQ9UPT9

Polymorphism and mutation databases

BioMutaiUSP22
DMDMi78103328

Proteomic databases

EPDiQ9UPT9
PaxDbiQ9UPT9
PeptideAtlasiQ9UPT9
PRIDEiQ9UPT9
ProteomicsDBi85443
85444 [Q9UPT9-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261497; ENSP00000261497; ENSG00000124422 [Q9UPT9-1]
ENST00000537526; ENSP00000440950; ENSG00000124422 [Q9UPT9-2]
GeneIDi23326
KEGGihsa:23326
UCSCiuc002gym.4 human [Q9UPT9-1]

Organism-specific databases

CTDi23326
DisGeNETi23326
EuPathDBiHostDB:ENSG00000124422.11
GeneCardsiUSP22
HGNCiHGNC:12621 USP22
HPAiHPA044980
MIMi612116 gene
neXtProtiNX_Q9UPT9
OpenTargetsiENSG00000124422
PharmGKBiPA37247
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1867 Eukaryota
ENOG410XQQ0 LUCA
GeneTreeiENSGT00890000139343
HOGENOMiHOG000007260
HOVERGENiHBG058014
InParanoidiQ9UPT9
KOiK11366
OMAiCDDHLIT
OrthoDBiEOG091G09GI
PhylomeDBiQ9UPT9
TreeFamiTF323554

Enzyme and pathway databases

ReactomeiR-HSA-3214847 HATs acetylate histones
R-HSA-5689880 Ub-specific processing proteases

Miscellaneous databases

ChiTaRSiUSP22 human
GenomeRNAii23326
PROiPR:Q9UPT9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124422 Expressed in 239 organ(s), highest expression level in cerebellum
CleanExiHS_USP22
ExpressionAtlasiQ9UPT9 baseline and differential
GenevisibleiQ9UPT9 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP22_HUMAN
AccessioniPrimary (citable) accession number: Q9UPT9
Secondary accession number(s): A0JNS3
, Q2NLE2, Q6MZY4, Q8TBS8, Q96IW5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: September 13, 2005
Last modified: November 7, 2018
This is version 157 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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