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Q9Y6I4 (UBP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin carboxyl-terminal hydrolase 3

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme 3
Ubiquitin thioesterase 3
Ubiquitin-specific-processing protease 3
Gene names
Name:USP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length520 AA.
Sequence statusComplete.
Protein existenceEvidence 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.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).

Subunit structure

Interacts (via UBP-type domain) with H2A; the interaction is less efficient than with monoubiquitinated H2A. Ref.7

Subcellular location

Nucleus. Note: Localizes preferentially with monoubiquitinated H2A to chromatin. Ref.7

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.

Contains 1 USP domain.

Sequence caution

The sequence AAD42992.1 differs from that shown. Reason: Frameshift at positions 265, 274 and 299.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y6I4-1)

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: Q9Y6I4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     51-95: RYVNGHAKKHYEDAQVPLTNHKKSEKQDKVQHTVCMDCSSYSTYC → S
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 520520Ubiquitin carboxyl-terminal hydrolase 3
PRO_0000080619

Regions

Domain159 – 511353USP
Zinc finger27 – 10478UBP-type

Sites

Active site1681Nucleophile By similarity
Active site4711Proton acceptor By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8

Natural variations

Alternative sequence51 – 9545RYVNG…YSTYC → S in isoform 2.
VSP_044712
Natural variant3601P → T.
Corresponds to variant rs34776764 [ dbSNP | Ensembl ].
VAR_051521

Experimental info

Mutagenesis561H → A: Does not reduce monoubiquitinated H2A and H2B stability. Interaction with monoubiquitinated H2A is strongly inhibited. Ref.7
Mutagenesis1681C → S: Does not reduce H2A stability. Interacts more strongly with monoubiquitinated H2A than with nonubiquitinated H2A. Its nuclear localization to chromatin is enhanced. Ref.7
Sequence conflict4391C → W in AAD42992. Ref.1
Sequence conflict4731T → I in BAG62807. Ref.3

Sequences

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

Last modified September 2, 2008. Version 2.
Checksum: AC27FE9BD0438893

FASTA52058,897
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 5F201F63795E938A
Show »

FASTA47653,743

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] (ISOFORM 1).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Spleen.
[4]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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].
[6]"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 1).
Tissue: Eye and Skin.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH H2A, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-56 AND CYS-168, IDENTIFICATION BY MASS SPECTROMETRY.
[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] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF073344 mRNA. Translation: AAD42992.1. Frameshift.
BT007269 mRNA. Translation: AAP35933.1.
AK301236 mRNA. Translation: BAG62807.1.
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.
RefSeqNP_001243631.1. NM_001256702.1.
NP_006528.2. NM_006537.3.
UniGeneHs.458499.

3D structure databases

ProteinModelPortalQ9Y6I4.
SMRQ9Y6I4. Positions 1-513.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115285. 26 interactions.
IntActQ9Y6I4. 20 interactions.
STRING9606.ENSP00000369681.

Protein family/group databases

MEROPSC19.026.

PTM databases

PhosphoSiteQ9Y6I4.

Polymorphism databases

DMDM205371844.

Proteomic databases

PaxDbQ9Y6I4.
PRIDEQ9Y6I4.

Protocols and materials databases

DNASU9960.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380324; ENSP00000369681; ENSG00000140455. [Q9Y6I4-1]
ENST00000540797; ENSP00000445828; ENSG00000140455. [Q9Y6I4-2]
GeneID9960.
KEGGhsa:9960.
UCSCuc002amf.4. human. [Q9Y6I4-1]

Organism-specific databases

CTD9960.
GeneCardsGC15P063796.
H-InvDBHIX0012328.
HGNCHGNC:12626. USP3.
MIM604728. gene.
neXtProtNX_Q9Y6I4.
PharmGKBPA37251.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5533.
HOGENOMHOG000231498.
HOVERGENHBG103589.
InParanoidQ9Y6I4.
KOK11986.
OMAESCLYDL.
PhylomeDBQ9Y6I4.
TreeFamTF315281.

Gene expression databases

ArrayExpressQ9Y6I4.
BgeeQ9Y6I4.
CleanExHS_USP3.
GenevestigatorQ9Y6I4.

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

ChiTaRSUSP3. human.
GenomeRNAi9960.
NextBio37582.
PROQ9Y6I4.
SOURCESearch...

Entry information

Entry nameUBP3_HUMAN
AccessionPrimary (citable) accession number: Q9Y6I4
Secondary accession number(s): B4DVU5, F5H1A6, Q8WVD0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: September 2, 2008
Last modified: April 16, 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM