Q9Y6I4 (UBP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 3
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 3
Ubiquitin thiolesterase 3
Ubiquitin-specific-processing protease 3

Gene names

Name:

USP3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolase that deubiquitinates monoubiquitinated target proteins such as histone H2A and H2B. Required for proper progression through S phase and subsequent mitotic entry. May regulate the DNA damage response (DDR) checkpoint through deubiquitination of H2A at DNA damage sites. Associates with the chromatin. Ref.6
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).
Subunit structure	Interacts (via UBP-type domain) with H2A; the interaction is less efficient than with monoubiquitinated H2A. Ref.6
Subcellular location	Nucleus. Note: Localizes preferentially with monoubiquitinated H2A to chromatin. Ref.6
Tissue specificity	Expressed in all tissues examined, with strongest expression in pancreas.
Domain	Both protease activity and an intact zinc finger are required for H2A monodeubiquitination.
Sequence similarities	Belongs to the peptidase C19 family. USP3 subfamily. Contains 1 UBP-type zinc finger.
Sequence caution	The sequence AAD42992.1 differs from that shown. Reason: Frameshift at positions 265, 274 and 299.

Ontologies

Keywords
Biological process	Cell cycle DNA damage Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Protease Thiol protease
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from mutant phenotype Ref.6. Source: UniProtKB histone deubiquitination Inferred from direct assay Ref.6. Source: UniProtKB mitotic cell cycle Inferred from mutant phenotype Ref.6. Source: UniProtKB regulation of protein stability Inferred from direct assay Ref.6. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	nuclear chromatin Inferred from direct assay Ref.6. Source: UniProtKB
Molecular function	histone binding Inferred from physical interaction Ref.6. Source: UniProtKB ubiquitin thiolesterase activity Inferred from mutant phenotype Ref.6. Source: UniProtKB ubiquitin-specific protease activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 520	520	Ubiquitin carboxyl-terminal hydrolase 3		PRO_0000080619
Regions
	Zinc finger	27 – 104	78	UBP-type
Sites
	Active site	168	1	Nucleophile By similarity
	Active site	471	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.8
	Modified residue	141	1	Phosphothreonine Ref.7
Natural variations
	Natural variant	360	1	P → T. Corresponds to variant rs34776764 [ dbSNP | Ensembl ].		VAR_051521
Experimental info
	Mutagenesis	56	1	H → A: Does not reduce monoubiquitinated H2A and H2B stability. Interaction with monoubiquitinated H2A is strongly inhibited. Ref.6
	Mutagenesis	168	1	C → S: Does not reduce H2A stability. Interacts more strongly with monoubiquitinated H2A than with nonubiquitinated H2A. Its nuclear localization to chromatin is enhanced. Ref.6
	Sequence conflict	439	1	C → W in AAD42992. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6I4 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: AC27FE9BD0438893	FASTA	520	58,897
	10 20 30 40 50 60 MECPHLSSSV CIAPDSAKFP NGSPSSWCCS VCRSNKSPWV CLTCSSVHCG RYVNGHAKKH 70 80 90 100 110 120 YEDAQVPLTN HKKSEKQDKV QHTVCMDCSS YSTYCYRCDD FVVNDTKLGL VQKVREHLQN 130 140 150 160 170 180 LENSAFTADR HKKRKLLENS TLNSKLLKVN GSTTAICATG LRNLGNTCFM NAILQSLSNI 190 200 210 220 230 240 EQFCCYFKEL PAVELRNGKT AGRRTYHTRS QGDNNVSLVE EFRKTLCALW QGSQTAFSPE 250 260 270 280 290 300 SLFYVVWKIM PNFRGYQQQD AHEFMRYLLD HLHLELQGGF NGVSRSAILQ ENSTLSASNK 310 320 330 340 350 360 CCINGASTVV TAIFGGILQN EVNCLICGTE SRKFDPFLDL SLDIPSQFRS KRSKNQENGP 370 380 390 400 410 420 VCSLRDCLRS FTDLEELDET ELYMCHKCKK KQKSTKKFWI QKLPKVLCLH LKRFHWTAYL 430 440 450 460 470 480 RNKVDTYVEF PLRGLDMKCY LLEPENSGPE SCLYDLAAVV VHHGSGVGSG HYTAYATHEG 490 500 510 520 RWFHFNDSTV TLTDEETVVK AKAYILFYVE HQAKAGSDKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and chromosomal localization of USP3, a novel human ubiquitin-specific protease." Sloper-Mould K.E., Eyre H.J., Wang X.-W., Sutherland G.R., Baker R.T. J. Biol. Chem. 274:26878-26884(1999) [PubMed: 10480896] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Skin.
[6]	"Human USP3 is a chromatin modifier required for S phase progression and genome stability." Nicassio F., Corrado N., Vissers J.H., Areces L.B., Bergink S., Marteijn J.A., Geverts B., Houtsmuller A.B., Vermeulen W., Di Fiore P.P., Citterio E. Curr. Biol. 17:1972-1977(2007) [PubMed: 17980597] [Abstract] Cited for: FUNCTION, INTERACTION WITH H2A, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-56 AND CYS-168, IDENTIFICATION BY MASS SPECTROMETRY.
[7]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-141, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY. Tissue: Embryonic kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF073344 mRNA. Translation: AAD42992.1. Frameshift. BT007269 mRNA. Translation: AAP35933.1. AC007950 Genomic DNA. No translation available. AC118274 Genomic DNA. No translation available. CH471082 Genomic DNA. Translation: EAW77651.1. BC018113 mRNA. Translation: AAH18113.1. BC065300 mRNA. Translation: AAH65300.1. BC107137 mRNA. Translation: AAI07138.1. BC107138 mRNA. Translation: AAI07139.1.
IPI	IPI00002330.
RefSeq	NP_006528.2. NM_006537.2.
UniGene	Hs.458499.
3D structure databases
ProteinModelPortal	Q9Y6I4.
SMR	Q9Y6I4. Positions 1-513.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6I4. 20 interactions.
STRING	Q9Y6I4.
Protein family/group databases
MEROPS	C19.026.
PTM databases
PhosphoSite	Q9Y6I4.
Proteomic databases
PRIDE	Q9Y6I4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000380324; ENSP00000369681; ENSG00000140455.
GeneID	9960.
KEGG	hsa:9960.
Organism-specific databases
CTD	9960.
GeneCards	GC15P063796.
H-InvDB	HIX0012328.
HGNC	HGNC:12626. USP3.
MIM	604728. gene.
neXtProt	NX_Q9Y6I4.
PharmGKB	PA37251.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00590000083075.
HOGENOM	HBG713682.
HOVERGEN	HBG103589.
InParanoid	Q9Y6I4.
OMA	PSSWCCS.
OrthoDB	EOG4G4GQC.
PhylomeDB	Q9Y6I4.
Gene expression databases
ArrayExpress	Q9Y6I4.
Bgee	Q9Y6I4.
CleanEx	HS_USP3.
Genevestigator	Q9Y6I4.
GermOnline	ENSG00000140455. Homo sapiens.
Family and domain databases
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR013083. Znf_RING/FYVE/PHD. IPR001607. Znf_UBP. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KO	K11986.
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
SOURCE	Search...

Entry information

Entry name

UBP3_HUMAN

Accession

Primary (citable) accession number: Q9Y6I4
Secondary accession number(s): Q8WVD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	September 2, 2008
Last modified:	January 25, 2012
This is version 96 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.