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Protein

Ubiquitin carboxyl-terminal hydrolase 3

Gene

USP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei168NucleophilePROSITE-ProRule annotation1
Active sitei471Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri27 – 104UBP-typePROSITE-ProRule annotationAdd BLAST78

GO - Molecular functioni

  • chromatin binding Source: Ensembl
  • core promoter sequence-specific DNA binding Source: Ensembl
  • histone binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • DNA repair Source: UniProtKB
  • histone deubiquitination Source: UniProtKB
  • mitotic cell cycle Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • regulation of protein stability Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Cell cycle, DNA damage, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS06718-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.026.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:USP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:12626. USP3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • intracellular membrane-bounded organelle Source: HPA
  • nuclear chromatin Source: UniProtKB
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi56H → A: Does not reduce monoubiquitinated H2A and H2B stability. Interaction with monoubiquitinated H2A is strongly inhibited. 1 Publication1
Mutagenesisi168C → S: Does not reduce H2A stability. Interacts more strongly with monoubiquitinated H2A than with nonubiquitinated H2A. Its nuclear localization to chromatin is enhanced. 1 Publication1

Organism-specific databases

DisGeNETi9960.
OpenTargetsiENSG00000140455.
PharmGKBiPA37251.

Polymorphism and mutation databases

BioMutaiUSP3.
DMDMi205371844.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806191 – 520Ubiquitin carboxyl-terminal hydrolase 3Add BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9Y6I4.
MaxQBiQ9Y6I4.
PaxDbiQ9Y6I4.
PeptideAtlasiQ9Y6I4.
PRIDEiQ9Y6I4.

PTM databases

iPTMnetiQ9Y6I4.
PhosphoSitePlusiQ9Y6I4.

Expressioni

Tissue specificityi

Expressed in all tissues examined, with strongest expression in pancreas.

Gene expression databases

BgeeiENSG00000140455.
CleanExiHS_USP3.
ExpressionAtlasiQ9Y6I4. baseline and differential.
GenevisibleiQ9Y6I4. HS.

Organism-specific databases

HPAiHPA071327.

Interactioni

Subunit structurei

Interacts (via UBP-type domain) with H2A; the interaction is less efficient than with monoubiquitinated H2A.1 Publication

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115285. 37 interactors.
DIPiDIP-53585N.
IntActiQ9Y6I4. 20 interactors.
STRINGi9606.ENSP00000369681.

Structurei

3D structure databases

ProteinModelPortaliQ9Y6I4.
SMRiQ9Y6I4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini159 – 511USPAdd BLAST353

Domaini

Both protease activity and an intact zinc finger are required for H2A monodeubiquitination.

Sequence similaritiesi

Belongs to the peptidase C19 family. USP3 subfamily.Curated
Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri27 – 104UBP-typePROSITE-ProRule annotationAdd BLAST78

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1867. Eukaryota.
ENOG410XQQ0. LUCA.
GeneTreeiENSGT00860000133682.
HOGENOMiHOG000231498.
HOVERGENiHBG103589.
InParanoidiQ9Y6I4.
KOiK11986.
OMAiDETELYM.
OrthoDBiEOG091G05JL.
PhylomeDBiQ9Y6I4.
TreeFamiTF315281.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR033302. USP3_animal.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PANTHERiPTHR24006:SF356. PTHR24006:SF356. 3 hits.
PfamiPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTiSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9Y6I4-1) [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
MECPHLSSSV CIAPDSAKFP NGSPSSWCCS VCRSNKSPWV CLTCSSVHCG
60 70 80 90 100
RYVNGHAKKH YEDAQVPLTN HKKSEKQDKV QHTVCMDCSS YSTYCYRCDD
110 120 130 140 150
FVVNDTKLGL VQKVREHLQN LENSAFTADR HKKRKLLENS TLNSKLLKVN
160 170 180 190 200
GSTTAICATG LRNLGNTCFM NAILQSLSNI EQFCCYFKEL PAVELRNGKT
210 220 230 240 250
AGRRTYHTRS QGDNNVSLVE EFRKTLCALW QGSQTAFSPE SLFYVVWKIM
260 270 280 290 300
PNFRGYQQQD AHEFMRYLLD HLHLELQGGF NGVSRSAILQ ENSTLSASNK
310 320 330 340 350
CCINGASTVV TAIFGGILQN EVNCLICGTE SRKFDPFLDL SLDIPSQFRS
360 370 380 390 400
KRSKNQENGP VCSLRDCLRS FTDLEELDET ELYMCHKCKK KQKSTKKFWI
410 420 430 440 450
QKLPKVLCLH LKRFHWTAYL RNKVDTYVEF PLRGLDMKCY LLEPENSGPE
460 470 480 490 500
SCLYDLAAVV VHHGSGVGSG HYTAYATHEG RWFHFNDSTV TLTDEETVVK
510 520
AKAYILFYVE HQAKAGSDKL
Length:520
Mass (Da):58,897
Last modified:September 2, 2008 - v2
Checksum:iAC27FE9BD0438893
GO
Isoform 2 (identifier: Q9Y6I4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     51-95: RYVNGHAKKHYEDAQVPLTNHKKSEKQDKVQHTVCMDCSSYSTYC → S

Note: No experimental confirmation available.
Show »
Length:476
Mass (Da):53,743
Checksum:i5F201F63795E938A
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti439C → W in AAD42992 (PubMed:10480896).Curated1
Sequence conflicti473T → I in BAG62807 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051521360P → T.Corresponds to variant rs34776764dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04471251 – 95RYVNG…YSTYC → S in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32265.1. [Q9Y6I4-1]
CCDS58370.1. [Q9Y6I4-2]
RefSeqiNP_001243631.1. NM_001256702.1. [Q9Y6I4-2]
NP_006528.2. NM_006537.3. [Q9Y6I4-1]
UniGeneiHs.458499.

Genome annotation databases

EnsembliENST00000380324; ENSP00000369681; ENSG00000140455. [Q9Y6I4-1]
ENST00000540797; ENSP00000445828; ENSG00000140455. [Q9Y6I4-2]
GeneIDi9960.
KEGGihsa:9960.
UCSCiuc002amf.5. human. [Q9Y6I4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32265.1. [Q9Y6I4-1]
CCDS58370.1. [Q9Y6I4-2]
RefSeqiNP_001243631.1. NM_001256702.1. [Q9Y6I4-2]
NP_006528.2. NM_006537.3. [Q9Y6I4-1]
UniGeneiHs.458499.

3D structure databases

ProteinModelPortaliQ9Y6I4.
SMRiQ9Y6I4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115285. 37 interactors.
DIPiDIP-53585N.
IntActiQ9Y6I4. 20 interactors.
STRINGi9606.ENSP00000369681.

Protein family/group databases

MEROPSiC19.026.

PTM databases

iPTMnetiQ9Y6I4.
PhosphoSitePlusiQ9Y6I4.

Polymorphism and mutation databases

BioMutaiUSP3.
DMDMi205371844.

Proteomic databases

EPDiQ9Y6I4.
MaxQBiQ9Y6I4.
PaxDbiQ9Y6I4.
PeptideAtlasiQ9Y6I4.
PRIDEiQ9Y6I4.

Protocols and materials databases

DNASUi9960.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380324; ENSP00000369681; ENSG00000140455. [Q9Y6I4-1]
ENST00000540797; ENSP00000445828; ENSG00000140455. [Q9Y6I4-2]
GeneIDi9960.
KEGGihsa:9960.
UCSCiuc002amf.5. human. [Q9Y6I4-1]

Organism-specific databases

CTDi9960.
DisGeNETi9960.
GeneCardsiUSP3.
H-InvDBHIX0012328.
HGNCiHGNC:12626. USP3.
HPAiHPA071327.
MIMi604728. gene.
neXtProtiNX_Q9Y6I4.
OpenTargetsiENSG00000140455.
PharmGKBiPA37251.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1867. Eukaryota.
ENOG410XQQ0. LUCA.
GeneTreeiENSGT00860000133682.
HOGENOMiHOG000231498.
HOVERGENiHBG103589.
InParanoidiQ9Y6I4.
KOiK11986.
OMAiDETELYM.
OrthoDBiEOG091G05JL.
PhylomeDBiQ9Y6I4.
TreeFamiTF315281.

Enzyme and pathway databases

BioCyciZFISH:HS06718-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiUSP3. human.
GenomeRNAii9960.
PROiQ9Y6I4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140455.
CleanExiHS_USP3.
ExpressionAtlasiQ9Y6I4. baseline and differential.
GenevisibleiQ9Y6I4. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR033302. USP3_animal.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PANTHERiPTHR24006:SF356. PTHR24006:SF356. 3 hits.
PfamiPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTiSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6I4
Secondary accession number(s): B4DVU5, F5H1A6, Q8WVD0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: September 2, 2008
Last modified: November 30, 2016
This is version 145 of the entry and version 2 of the sequence. [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. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.