Q9UPT9 (UBP22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	USP22
Synonyms:	KIAA1063, USP3L

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	525 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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 process	Cell cycle Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Activator Chromatin regulator Hydrolase Protease Thiol protease
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW 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-dependent Inferred from mutant phenotype Ref.6. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	SAGA complex Inferred from direct assay Ref.5Ref.6. Source: UniProtKB
Molecular_function	ligand-dependent nuclear receptor transcription coactivator activity Inferred from mutant phenotype Ref.5. Source: UniProtKB ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Inferred from direct assay Ref.4. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 525	525	Ubiquitin carboxyl-terminal hydrolase 22		PRO_0000080650
Regions
	Zinc finger	61 – 121	61	UBP-type
Sites
	Active site	185	1	Nucleophile By similarity
	Active site	479	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	129	1	N6-acetyllysine Ref.8
Natural variations
	Alternative sequence	1 – 57	57	MVSRP…ARKRK → MAPGWPSLSAGSRQEAPQLA AGGSAYQAVGRQFQPRATAL QGPSQ in isoform 2.		VSP_036720
Experimental info
	Mutagenesis	471	1	H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-479. Ref.5
	Mutagenesis	479	1	H → A: Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-471. Ref.5
	Sequence conflict	85	1	F → L in AAI26899. Ref.2
	Sequence conflict	380	1	K → T in CAE45893. Ref.3
	Sequence conflict	496	1	D → V in AAH25317. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 13, 2005. Version 2. Checksum: D18BFE84BE8E5915	FASTA	525	59,961
	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
	Isoform 2 [UniParc]. Checksum: 79C5E8674661256E	FASTA	513	58,179
	10 20 30 40 50 60 MAPGWPSLSA GSRQEAPQLA AGGSAYQAVG RQFQPRATAL QGPSQAKSCI CHVCGVHLNR 70 80 90 100 110 120 LHSCLYCVFF GCFTKKHIHE HAKAKRHNLA IDLMYGGIYC FLCQDYIYDK DMEIIAKEEQ 130 140 150 160 170 180 RKAWKMQGVG EKFSTWEPTK RELELLKHNP KRRKITSNCT IGLRGLINLG NTCFMNCIVQ 190 200 210 220 230 240 ALTHTPLLRD FFLSDRHRCE MQSPSSCLVC EMSSLFQEFY SGHRSPHIPY KLLHLVWTHA 250 260 270 280 290 300 RHLAGYEQQD AHEFLIAALD VLHRHCKGDD NGKKANNPNH CNCIIDQIFT GGLQSDVTCQ 310 320 330 340 350 360 VCHGVSTTID PFWDISLDLP GSSTPFWPLS PGSEGNVVNG ESHVSGTTTL TDCLRRFTRP 370 380 390 400 410 420 EHLGSSAKIK CSGCHSYQES TKQLTMKKLP IVACFHLKRF EHSAKLRRKI TTYVSFPLEL 430 440 450 460 470 480 DMTPFMASSK ESRMNGQYQQ PTDSLNNDNK YSLFAVVNHQ GTLESGHYTS FIRQHKDQWF 490 500 510 KCDDAIITKA SIKDVLDSEG YLLFYHKQFL EYE

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY.
+	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.
IPI	IPI00852960. IPI00923593.
RefSeq	NP_056091.1. NM_015276.1.
UniGene	Hs.462492.
3D structure databases
ProteinModelPortal	Q9UPT9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UPT9. 32 interactions.
MINT	MINT-1390273.
STRING	9606.ENSP00000261497.
Protein family/group databases
MEROPS	C19.035.
PTM databases
PhosphoSite	Q9UPT9.
Polymorphism databases
DMDM	78103328.
Proteomic databases
PaxDb	Q9UPT9.
PRIDE	Q9UPT9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261497; ENSP00000261497; ENSG00000124422. ENST00000537526; ENSP00000440950; ENSG00000124422.
GeneID	23326.
KEGG	hsa:23326.
UCSC	uc002gyl.4. human. uc002gyn.4. human.
Organism-specific databases
CTD	23326.
GeneCards	GC17M020902.
HGNC	HGNC:12621. USP22.
HPA	HPA044980.
MIM	612116. gene.
neXtProt	NX_Q9UPT9.
PharmGKB	PA37247.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5533.
HOGENOM	HOG000007260.
HOVERGEN	HBG058014.
InParanoid	Q9UPT9.
KO	K11366.
OrthoDB	EOG48PMJS.
Gene expression databases
ArrayExpress	Q9UPT9.
Bgee	Q9UPT9.
CleanEx	HS_USP22.
Genevestigator	Q9UPT9.
GermOnline	ENSG00000124422. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR013083. Znf_RING/FYVE/PHD. IPR001607. Znf_UBP. [Graphical view]
Pfam	PF00443. UCH. 1 hit. PF02148. zf-UBP. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS50271. ZF_UBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	USP22. human.
GenomeRNAi	23326.
NextBio	45232.
SOURCE	Search...

Entry information

Entry name

UBP22_HUMAN

Accession

Primary (citable) accession number: Q9UPT9
Secondary accession number(s): A0JNS3 , Q2NLE2, Q6MZY4, Q8TBS8, Q96IW5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	September 13, 2005
Last modified:	May 1, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.