Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ubiquitin carboxyl-terminal hydrolase 1

Gene

USP1

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

Functioni

Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2. Also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity.3 Publications

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).1 Publication

Kineticsi

  1. KM=0.7 µM for ubiquitin vinyl sulfone (in presence of WDR48)1 Publication
  2. KM=1.4 µM for ubiquitin vinyl sulfone (in absence of WDR48)1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei90 – 901Nucleophile
    Active sitei593 – 5931Proton acceptorPROSITE-ProRule annotation
    Sitei671 – 6722Cleavage; by autolysis

    GO - Molecular functioni

    • cysteine-type endopeptidase activity Source: ProtInc
    • ubiquitin-specific protease activity Source: UniProtKB

    GO - Biological processi

    • DNA damage response, detection of DNA damage Source: Reactome
    • DNA repair Source: Reactome
    • monoubiquitinated protein deubiquitination Source: UniProtKB
    • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
    • protein deubiquitination Source: UniProtKB
    • regulation of DNA repair Source: UniProtKB
    • regulation of proteasomal protein catabolic process Source: GO_Central
    • response to UV Source: UniProtKB
    • skeletal system development Source: Ensembl
    • translesion synthesis Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    DNA damage, DNA repair, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_18265. Regulation of the Fanconi anemia pathway.
    REACT_355480. Recognition of DNA damage by PCNA-containing replication complex.

    Protein family/group databases

    MEROPSiC19.019.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 1 (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme 1
    Short name:
    hUBP
    Ubiquitin thioesterase 1
    Ubiquitin-specific-processing protease 1
    Gene namesi
    Name:USP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:12607. USP1.

    Subcellular locationi

    GO - Cellular componenti

    • nucleoplasm Source: Reactome
    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi90 – 901C → S: Loss of catalytic activity including autolysis. 2 Publications
    Mutagenesisi670 – 6712GG → AA: Loss of autolysis-mediated degradation upon UV irradiation. No effect on catalytic activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA37233.

    Polymorphism and mutation databases

    BioMutaiUSP1.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 785785Ubiquitin carboxyl-terminal hydrolase 1PRO_0000080615Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei42 – 421Phosphoserine2 Publications
    Modified residuei67 – 671Phosphoserine1 Publication
    Modified residuei475 – 4751Phosphoserine1 Publication

    Post-translational modificationi

    Autocatalytic cleavage of USP1 following UV irradiation inactivates it leading to an increase in ubiquitinated PCNA, recruitment of POLH and translesion synthesis.2 Publications
    Ubiquitinated; leading to its subsequent proteasomal degradation.By similarity

    Keywords - PTMi

    Autocatalytic cleavage, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO94782.
    PaxDbiO94782.
    PRIDEiO94782.

    2D gel databases

    OGPiO94782.

    PTM databases

    PhosphoSiteiO94782.

    Expressioni

    Developmental stagei

    Cell cycle-regulated. Highest level during S phase.1 Publication

    Inductioni

    Down-regulated following DNA damage.1 Publication

    Gene expression databases

    BgeeiO94782.
    CleanExiHS_USP1.
    ExpressionAtlasiO94782. baseline and differential.
    GenevisibleiO94782. HS.

    Organism-specific databases

    HPAiHPA028440.

    Interactioni

    Subunit structurei

    Interacts with FANCD2 and PCNA. Interacts with WDR48.2 Publications

    Protein-protein interaction databases

    BioGridi113241. 46 interactions.
    IntActiO94782. 22 interactions.
    MINTiMINT-4719170.
    STRINGi9606.ENSP00000343526.

    Structurei

    3D structure databases

    ProteinModelPortaliO94782.
    SMRiO94782. Positions 395-599.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini81 – 785705USPAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C19 family.Curated
    Contains 1 USP domain.Curated

    Phylogenomic databases

    eggNOGiCOG5077.
    GeneTreeiENSGT00650000093027.
    HOVERGENiHBG017288.
    InParanoidiO94782.
    KOiK11832.
    OMAiEYRASEI.
    OrthoDBiEOG7JT6VZ.
    PhylomeDBiO94782.
    TreeFamiTF331057.

    Family and domain databases

    InterProiIPR001394. Peptidase_C19_UCH.
    IPR018200. USP_CS.
    IPR028889. USP_dom.
    [Graphical view]
    PfamiPF00443. UCH. 2 hits.
    [Graphical view]
    PROSITEiPS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O94782-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPGVIPSESN GLSRGSPSKK NRLSLKFFQK KETKRALDFT DSQENEEKAS
    60 70 80 90 100
    EYRASEIDQV VPAAQSSPIN CEKRENLLPF VGLNNLGNTC YLNSILQVLY
    110 120 130 140 150
    FCPGFKSGVK HLFNIISRKK EALKDEANQK DKGNCKEDSL ASYELICSLQ
    160 170 180 190 200
    SLIISVEQLQ ASFLLNPEKY TDELATQPRR LLNTLRELNP MYEGYLQHDA
    210 220 230 240 250
    QEVLQCILGN IQETCQLLKK EEVKNVAELP TKVEEIPHPK EEMNGINSIE
    260 270 280 290 300
    MDSMRHSEDF KEKLPKGNGK RKSDTEFGNM KKKVKLSKEH QSLEENQRQT
    310 320 330 340 350
    RSKRKATSDT LESPPKIIPK YISENESPRP SQKKSRVKIN WLKSATKQPS
    360 370 380 390 400
    ILSKFCSLGK ITTNQGVKGQ SKENECDPEE DLGKCESDNT TNGCGLESPG
    410 420 430 440 450
    NTVTPVNVNE VKPINKGEEQ IGFELVEKLF QGQLVLRTRC LECESLTERR
    460 470 480 490 500
    EDFQDISVPV QEDELSKVEE SSEISPEPKT EMKTLRWAIS QFASVERIVG
    510 520 530 540 550
    EDKYFCENCH HYTEAERSLL FDKMPEVITI HLKCFAASGL EFDCYGGGLS
    560 570 580 590 600
    KINTPLLTPL KLSLEEWSTK PTNDSYGLFA VVMHSGITIS SGHYTASVKV
    610 620 630 640 650
    TDLNSLELDK GNFVVDQMCE IGKPEPLNEE EARGVVENYN DEEVSIRVGG
    660 670 680 690 700
    NTQPSKVLNK KNVEAIGLLG GQKSKADYEL YNKASNPDKV ASTAFAENRN
    710 720 730 740 750
    SETSDTTGTH ESDRNKESSD QTGINISGFE NKISYVVQSL KEYEGKWLLF
    760 770 780
    DDSEVKVTEE KDFLNSLSPS TSPTSTPYLL FYKKL
    Length:785
    Mass (Da):88,207
    Last modified:May 1, 1999 - v1
    Checksum:i50AA2817A60810AF
    GO

    Sequence cautioni

    The sequence AAH18745.1 differs from that shown.Contaminating sequence. Potential poly-A sequence.Curated
    The sequence AAH32364.1 differs from that shown.Contaminating sequence. Potential poly-A sequence.Curated
    The sequence BAD92130.1 differs from that shown. Reason: Frameshift at position 230. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti621 – 6211I → M in AAD11441 (Ref. 2) Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB014458 mRNA. Translation: BAA34703.1.
    AF117386 mRNA. Translation: AAD11441.1.
    AL117575 mRNA. Translation: CAB55999.1.
    AL117503 mRNA. Translation: CAB55967.1.
    AB208893 mRNA. Translation: BAD92130.1. Frameshift.
    CH471059 Genomic DNA. Translation: EAX06585.1.
    CH471059 Genomic DNA. Translation: EAX06586.1.
    BC050525 mRNA. Translation: AAH50525.1.
    BC018745 mRNA. Translation: AAH18745.1. Sequence problems.
    BC032364 mRNA. Translation: AAH32364.1. Sequence problems.
    CCDSiCCDS621.1.
    PIRiT17309.
    RefSeqiNP_001017415.1. NM_001017415.1.
    NP_001017416.1. NM_001017416.1.
    NP_003359.3. NM_003368.4.
    UniGeneiHs.35086.

    Genome annotation databases

    EnsembliENST00000339950; ENSP00000343526; ENSG00000162607.
    ENST00000371146; ENSP00000360188; ENSG00000162607.
    GeneIDi7398.
    KEGGihsa:7398.
    UCSCiuc001daj.2. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB014458 mRNA. Translation: BAA34703.1.
    AF117386 mRNA. Translation: AAD11441.1.
    AL117575 mRNA. Translation: CAB55999.1.
    AL117503 mRNA. Translation: CAB55967.1.
    AB208893 mRNA. Translation: BAD92130.1. Frameshift.
    CH471059 Genomic DNA. Translation: EAX06585.1.
    CH471059 Genomic DNA. Translation: EAX06586.1.
    BC050525 mRNA. Translation: AAH50525.1.
    BC018745 mRNA. Translation: AAH18745.1. Sequence problems.
    BC032364 mRNA. Translation: AAH32364.1. Sequence problems.
    CCDSiCCDS621.1.
    PIRiT17309.
    RefSeqiNP_001017415.1. NM_001017415.1.
    NP_001017416.1. NM_001017416.1.
    NP_003359.3. NM_003368.4.
    UniGeneiHs.35086.

    3D structure databases

    ProteinModelPortaliO94782.
    SMRiO94782. Positions 395-599.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi113241. 46 interactions.
    IntActiO94782. 22 interactions.
    MINTiMINT-4719170.
    STRINGi9606.ENSP00000343526.

    Chemistry

    ChEMBLiCHEMBL1795087.
    GuidetoPHARMACOLOGYi2428.

    Protein family/group databases

    MEROPSiC19.019.

    PTM databases

    PhosphoSiteiO94782.

    Polymorphism and mutation databases

    BioMutaiUSP1.

    2D gel databases

    OGPiO94782.

    Proteomic databases

    MaxQBiO94782.
    PaxDbiO94782.
    PRIDEiO94782.

    Protocols and materials databases

    DNASUi7398.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000339950; ENSP00000343526; ENSG00000162607.
    ENST00000371146; ENSP00000360188; ENSG00000162607.
    GeneIDi7398.
    KEGGihsa:7398.
    UCSCiuc001daj.2. human.

    Organism-specific databases

    CTDi7398.
    GeneCardsiGC01P062837.
    H-InvDBHIX0159950.
    HGNCiHGNC:12607. USP1.
    HPAiHPA028440.
    MIMi603478. gene.
    neXtProtiNX_O94782.
    PharmGKBiPA37233.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG5077.
    GeneTreeiENSGT00650000093027.
    HOVERGENiHBG017288.
    InParanoidiO94782.
    KOiK11832.
    OMAiEYRASEI.
    OrthoDBiEOG7JT6VZ.
    PhylomeDBiO94782.
    TreeFamiTF331057.

    Enzyme and pathway databases

    ReactomeiREACT_18265. Regulation of the Fanconi anemia pathway.
    REACT_355480. Recognition of DNA damage by PCNA-containing replication complex.

    Miscellaneous databases

    ChiTaRSiUSP1. human.
    GeneWikiiUSP1.
    GenomeRNAii7398.
    NextBioi28954.
    PROiO94782.
    SOURCEiSearch...

    Gene expression databases

    BgeeiO94782.
    CleanExiHS_USP1.
    ExpressionAtlasiO94782. baseline and differential.
    GenevisibleiO94782. HS.

    Family and domain databases

    InterProiIPR001394. Peptidase_C19_UCH.
    IPR018200. USP_CS.
    IPR028889. USP_dom.
    [Graphical view]
    PfamiPF00443. UCH. 2 hits.
    [Graphical view]
    PROSITEiPS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Identification and chromosomal assignment of USP1, a novel gene encoding a human ubiquitin-specific protease."
      Fjiwara T., Saito A., Suzuki M., Shinomiya H., Suzuki T., Takahashi E., Tanigami A., Ichiyama A., Chung C.H., Nakamura Y., Tanaka K.
      Genomics 54:155-158(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal brain.
    2. "Molecular cloning of a novel human ubiquitin-specific protease."
      Seibold S., Marx M.
      Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    4. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
      Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    5. 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].
      Tissue: Eye, Testis and Uterus.
    7. "The deubiquitinating enzyme USP1 regulates the Fanconi Anemia pathway."
      Nijman S.M.B., Huang T.T., Dirac A.M.G., Brummelkamp T.R., Kerkhoven R.M., D'Andrea A.D., Bernards R.
      Mol. Cell 17:331-339(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, UBIQUITINATION, INTERACTION WITH FANCD2, MUTAGENESIS OF CYS-90.
    8. Cited for: FUNCTION, CLEAVAGE SITE, MUTAGENESIS OF CYS-90 AND 670-GLY-GLY-671.
    9. "A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway."
      Cohn M.A., Kowal P., Yang K., Haas W., Huang T.T., Gygi S.P., D'Andrea A.D.
      Mol. Cell 28:786-797(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, INTERACTION WITH WDR48, INDUCTION.
    10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. "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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    14. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-475, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiUBP1_HUMAN
    AccessioniPrimary (citable) accession number: O94782
    Secondary accession number(s): A0PJ95
    , D3DQ57, Q05BX7, Q59H66, Q9UFR0, Q9UNJ3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 1, 1999
    Last modified: June 24, 2015
    This is version 137 of the entry and version 1 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

    Miscellaneous

    HEK293T cells expressing reduced levels of USP1 show a higher level of ubiquitinated PCNA and an increase in point mutations upon UV irradiation.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.