UniProtKB - Q9Y6I4 (UBP3_HUMAN)
Protein
Ubiquitin carboxyl-terminal hydrolase 3
Gene
USP3
Organism
Homo sapiens (Human)
Status
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). EC:3.4.19.12
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 168 | NucleophilePROSITE-ProRule annotation | 1 | |
Active sitei | 471 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 27 – 104 | UBP-typePROSITE-ProRule annotationAdd BLAST | 78 |
GO - Molecular functioni
- cysteine-type peptidase activity Source: UniProtKB-KW
- histone binding Source: UniProtKB
- promoter-specific chromatin binding Source: Ensembl
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: Ensembl
- thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
- 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 by RNA polymerase II Source: Ensembl
- protein deubiquitination Source: Reactome
- regulation of protein stability Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Chromatin regulator, Hydrolase, Protease, Thiol protease |
Biological process | Cell cycle, DNA damage, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9Y6I4 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Protein family/group databases
MEROPSi | C19.026 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12626, USP3 |
MIMi | 604728, gene |
neXtProti | NX_Q9Y6I4 |
VEuPathDBi | HostDB:ENSG00000140455.16 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Note: Localizes preferentially with monoubiquitinated H2A to chromatin.
Nucleus
- nuclear chromatin Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
- cytoplasmic ribonucleoprotein granule Source: HPA
- Flemming body Source: HPA
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 56 | H → A: Does not reduce monoubiquitinated H2A and H2B stability. Interaction with monoubiquitinated H2A is strongly inhibited. 1 Publication | 1 | |
Mutagenesisi | 168 | C → S: Does not reduce H2A stability. Interacts more strongly with monoubiquitinated H2A than with nonubiquitinated H2A. Its nuclear localization to chromatin is enhanced. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9960 |
OpenTargetsi | ENSG00000140455 |
PharmGKBi | PA37251 |
Miscellaneous databases
Pharosi | Q9Y6I4, Tbio |
Genetic variation databases
BioMutai | USP3 |
DMDMi | 205371844 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080619 | 1 – 520 | Ubiquitin carboxyl-terminal hydrolase 3Add BLAST | 520 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q9Y6I4 |
jPOSTi | Q9Y6I4 |
MassIVEi | Q9Y6I4 |
MaxQBi | Q9Y6I4 |
PaxDbi | Q9Y6I4 |
PeptideAtlasi | Q9Y6I4 |
PRIDEi | Q9Y6I4 |
ProteomicsDBi | 25594 86692 [Q9Y6I4-1] |
PTM databases
iPTMneti | Q9Y6I4 |
PhosphoSitePlusi | Q9Y6I4 |
SwissPalmi | Q9Y6I4 |
Expressioni
Tissue specificityi
Expressed in all tissues examined, with strongest expression in pancreas.
Gene expression databases
Bgeei | ENSG00000140455, Expressed in stomach and 228 other tissues |
ExpressionAtlasi | Q9Y6I4, baseline and differential |
Genevisiblei | Q9Y6I4, HS |
Organism-specific databases
HPAi | ENSG00000140455, Low tissue specificity |
Interactioni
Subunit structurei
Interacts (via UBP-type domain) with H2A; the interaction is less efficient than with monoubiquitinated H2A.
1 PublicationGO - Molecular functioni
- histone binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 115285, 53 interactors |
DIPi | DIP-53585N |
IntActi | Q9Y6I4, 26 interactors |
STRINGi | 9606.ENSP00000369681 |
Miscellaneous databases
RNActi | Q9Y6I4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 159 – 511 | USPAdd BLAST | 353 |
Domaini
Both protease activity and an intact zinc finger are required for H2A monodeubiquitination.
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 27 – 104 | UBP-typePROSITE-ProRule annotationAdd BLAST | 78 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG1867, Eukaryota |
GeneTreei | ENSGT00940000157850 |
InParanoidi | Q9Y6I4 |
OMAi | GHWYHFN |
OrthoDBi | 929408at2759 |
PhylomeDBi | Q9Y6I4 |
TreeFami | TF315281 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00443, UCH, 1 hit PF02148, zf-UBP, 1 hit |
SMARTi | View protein in SMART SM00290, ZnF_UBP, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit PS50271, ZF_UBP, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9Y6I4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YMI4 | H0YMI4_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 503 | Annotation score: | ||
Q6JHV3 | Q6JHV3_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 498 | Annotation score: | ||
H0YLB7 | H0YLB7_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 431 | Annotation score: | ||
H0YKU8 | H0YKU8_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 443 | Annotation score: | ||
H0YLG0 | H0YLG0_HUMAN | Ubiquitinyl hydrolase 1 | USP3 | 133 | Annotation score: | ||
H0YM72 | H0YM72_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 106 | Annotation score: | ||
H0YMP6 | H0YMP6_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 132 | Annotation score: | ||
H0YL81 | H0YL81_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 126 | Annotation score: | ||
H0YNX9 | H0YNX9_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 39 | Annotation score: | ||
H0YLJ0 | H0YLJ0_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP3 | 55 | Annotation score: | ||
There are more potential isoformsShow all |
Sequence cautioni
The sequence AAD42992 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 439 | C → W in AAD42992 (PubMed:10480896).Curated | 1 | |
Sequence conflicti | 473 | T → I in BAG62807 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051521 | 360 | P → T. Corresponds to variant dbSNP:rs34776764EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044712 | 51 – 95 | RYVNG…YSTYC → S in isoform 2. 1 PublicationAdd BLAST | 45 |
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 |
CCDSi | CCDS32265.1 [Q9Y6I4-1] CCDS58370.1 [Q9Y6I4-2] |
RefSeqi | NP_001243631.1, NM_001256702.1 [Q9Y6I4-2] NP_006528.2, NM_006537.3 [Q9Y6I4-1] |
Genome annotation databases
Ensembli | ENST00000380324; ENSP00000369681; ENSG00000140455 [Q9Y6I4-1] ENST00000540797; ENSP00000445828; ENSG00000140455 [Q9Y6I4-2] |
GeneIDi | 9960 |
KEGGi | hsa:9960 |
UCSCi | uc002amf.5, human [Q9Y6I4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS32265.1 [Q9Y6I4-1] CCDS58370.1 [Q9Y6I4-2] |
RefSeqi | NP_001243631.1, NM_001256702.1 [Q9Y6I4-2] NP_006528.2, NM_006537.3 [Q9Y6I4-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 115285, 53 interactors |
DIPi | DIP-53585N |
IntActi | Q9Y6I4, 26 interactors |
STRINGi | 9606.ENSP00000369681 |
Protein family/group databases
MEROPSi | C19.026 |
PTM databases
iPTMneti | Q9Y6I4 |
PhosphoSitePlusi | Q9Y6I4 |
SwissPalmi | Q9Y6I4 |
Genetic variation databases
BioMutai | USP3 |
DMDMi | 205371844 |
Proteomic databases
EPDi | Q9Y6I4 |
jPOSTi | Q9Y6I4 |
MassIVEi | Q9Y6I4 |
MaxQBi | Q9Y6I4 |
PaxDbi | Q9Y6I4 |
PeptideAtlasi | Q9Y6I4 |
PRIDEi | Q9Y6I4 |
ProteomicsDBi | 25594 86692 [Q9Y6I4-1] |
Protocols and materials databases
Antibodypediai | 13304, 289 antibodies |
DNASUi | 9960 |
Genome annotation databases
Ensembli | ENST00000380324; ENSP00000369681; ENSG00000140455 [Q9Y6I4-1] ENST00000540797; ENSP00000445828; ENSG00000140455 [Q9Y6I4-2] |
GeneIDi | 9960 |
KEGGi | hsa:9960 |
UCSCi | uc002amf.5, human [Q9Y6I4-1] |
Organism-specific databases
CTDi | 9960 |
DisGeNETi | 9960 |
GeneCardsi | USP3 |
HGNCi | HGNC:12626, USP3 |
HPAi | ENSG00000140455, Low tissue specificity |
MIMi | 604728, gene |
neXtProti | NX_Q9Y6I4 |
OpenTargetsi | ENSG00000140455 |
PharmGKBi | PA37251 |
VEuPathDBi | HostDB:ENSG00000140455.16 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1867, Eukaryota |
GeneTreei | ENSGT00940000157850 |
InParanoidi | Q9Y6I4 |
OMAi | GHWYHFN |
OrthoDBi | 929408at2759 |
PhylomeDBi | Q9Y6I4 |
TreeFami | TF315281 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y6I4 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Miscellaneous databases
BioGRID-ORCSi | 9960, 6 hits in 876 CRISPR screens |
ChiTaRSi | USP3, human |
GenomeRNAii | 9960 |
Pharosi | Q9Y6I4, Tbio |
PROi | PR:Q9Y6I4 |
RNActi | Q9Y6I4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000140455, Expressed in stomach and 228 other tissues |
ExpressionAtlasi | Q9Y6I4, baseline and differential |
Genevisiblei | Q9Y6I4, HS |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00443, UCH, 1 hit PF02148, zf-UBP, 1 hit |
SMARTi | View protein in SMART SM00290, ZnF_UBP, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit PS50271, ZF_UBP, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBP3_HUMAN | |
Accessioni | Q9Y6I4Primary (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: | February 10, 2021 | |
This is version 178 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Peptidase families
Classification of peptidase families and list of entries