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Protein

Ubiquitin carboxyl-terminal hydrolase 1

Gene

USP1

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

Functioni

Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2 (PubMed:15694335). Also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:16531995). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:18082604, PubMed:26388029).4 Publications

Miscellaneous

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

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).5 Publications

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)DescriptionActionsGraphical viewLength
    Active sitei90Nucleophile3 Publications1
    Active sitei593Proton acceptorPROSITE-ProRule annotation1

    GO - Molecular functioni

    • cysteine-type endopeptidase activity Source: GO_Central
    • peptidase activity Source: Reactome
    • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
    • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Protease, Thiol protease
    Biological processDNA damage, DNA repair, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
    R-HSA-6783310 Fanconi Anemia Pathway

    Protein family/group databases

    MEROPSiC19.019

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 1 (EC:3.4.19.125 Publications)
    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000162607.12
    HGNCiHGNC:12607 USP1
    MIMi603478 gene
    neXtProtiNX_O94782

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi90C → S: Loss of catalytic activity including autolysis. 3 Publications1
    Mutagenesisi444E → K: Strongly reduces interaction with WDR48 and activation by WDR48. 1 Publication1
    Mutagenesisi670 – 671GG → AA: Loss of autolysis-mediated degradation upon UV irradiation. No effect on catalytic activity. 1 Publication2

    Organism-specific databases

    DisGeNETi7398
    OpenTargetsiENSG00000162607
    PharmGKBiPA37233

    Chemistry databases

    ChEMBLiCHEMBL1795087
    GuidetoPHARMACOLOGYi2428

    Polymorphism and mutation databases

    BioMutaiUSP1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000806151 – 785Ubiquitin carboxyl-terminal hydrolase 1Add BLAST785

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei16PhosphoserineCombined sources1
    Modified residuei42PhosphoserineCombined sources1
    Modified residuei67PhosphoserineCombined sources1
    Modified residuei313PhosphoserineCombined sources1
    Modified residuei475PhosphoserineCombined sources1
    Modified residuei768PhosphoserineBy similarity1

    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

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei671 – 672Cleavage; by autolysis1 Publication2

    Keywords - PTMi

    Autocatalytic cleavage, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiO94782
    MaxQBiO94782
    PaxDbiO94782
    PeptideAtlasiO94782
    PRIDEiO94782
    ProteomicsDBi50441

    2D gel databases

    OGPiO94782

    PTM databases

    iPTMnetiO94782
    PhosphoSitePlusiO94782

    Expressioni

    Developmental stagei

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

    Inductioni

    Down-regulated following DNA damage.1 Publication

    Gene expression databases

    BgeeiENSG00000162607 Expressed in 241 organ(s), highest expression level in secondary oocyte
    CleanExiHS_USP1
    ExpressionAtlasiO94782 baseline and differential
    GenevisibleiO94782 HS

    Organism-specific databases

    HPAiHPA028387
    HPA028440

    Interactioni

    Subunit structurei

    Interacts with FANCD2 and PCNA (PubMed:15694335, PubMed:16531995). Interacts with WDR48 (PubMed:18082604, PubMed:26388029).4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    WDR48Q8TAF3-12EBI-2513396,EBI-16178048

    Protein-protein interaction databases

    BioGridi113241, 65 interactors
    CORUMiO94782
    DIPiDIP-53609N
    IntActiO94782, 34 interactors
    STRINGi9606.ENSP00000343526

    Chemistry databases

    BindingDBiO94782

    Structurei

    3D structure databases

    ProteinModelPortaliO94782
    SMRiO94782
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini81 – 785USPAdd BLAST705

    Sequence similaritiesi

    Belongs to the peptidase C19 family.Curated

    Phylogenomic databases

    eggNOGiKOG1864 Eukaryota
    ENOG410XQ81 LUCA
    GeneTreeiENSGT00910000144243
    HOVERGENiHBG017288
    InParanoidiO94782
    KOiK11832
    OMAiKWAISQF
    OrthoDBiEOG091G04D9
    PhylomeDBiO94782
    TreeFamiTF331057

    Family and domain databases

    CDDicd02671 Peptidase_C19O, 1 hit
    InterProiView protein in InterPro
    IPR038765 Papain_like_cys_pep_sf
    IPR001394 Peptidase_C19_UCH
    IPR033815 USP1
    IPR018200 USP_CS
    IPR028889 USP_dom
    PfamiView protein in Pfam
    PF00443 UCH, 1 hit
    SUPFAMiSSF54001 SSF54001, 1 hit
    PROSITEiView protein in PROSITE
    PS00972 USP_1, 1 hit
    PS00973 USP_2, 1 hit
    PS50235 USP_3, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    C9JC88C9JC88_HUMAN
    Ubiquitin carboxyl-terminal hydrola...
    USP1
    186Annotation score:
    C9JWX4C9JWX4_HUMAN
    Ubiquitin carboxyl-terminal hydrola...
    USP1
    87Annotation score:

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti621I → M in AAD11441 (Ref. 2) Curated1

    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.3 human

    Similar proteinsi

    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
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi113241, 65 interactors
    CORUMiO94782
    DIPiDIP-53609N
    IntActiO94782, 34 interactors
    STRINGi9606.ENSP00000343526

    Chemistry databases

    BindingDBiO94782
    ChEMBLiCHEMBL1795087
    GuidetoPHARMACOLOGYi2428

    Protein family/group databases

    MEROPSiC19.019

    PTM databases

    iPTMnetiO94782
    PhosphoSitePlusiO94782

    Polymorphism and mutation databases

    BioMutaiUSP1

    2D gel databases

    OGPiO94782

    Proteomic databases

    EPDiO94782
    MaxQBiO94782
    PaxDbiO94782
    PeptideAtlasiO94782
    PRIDEiO94782
    ProteomicsDBi50441

    Protocols and materials databases

    DNASUi7398
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000339950; ENSP00000343526; ENSG00000162607
    ENST00000371146; ENSP00000360188; ENSG00000162607
    GeneIDi7398
    KEGGihsa:7398
    UCSCiuc001daj.3 human

    Organism-specific databases

    CTDi7398
    DisGeNETi7398
    EuPathDBiHostDB:ENSG00000162607.12
    GeneCardsiUSP1
    H-InvDBiHIX0159950
    HGNCiHGNC:12607 USP1
    HPAiHPA028387
    HPA028440
    MIMi603478 gene
    neXtProtiNX_O94782
    OpenTargetsiENSG00000162607
    PharmGKBiPA37233
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1864 Eukaryota
    ENOG410XQ81 LUCA
    GeneTreeiENSGT00910000144243
    HOVERGENiHBG017288
    InParanoidiO94782
    KOiK11832
    OMAiKWAISQF
    OrthoDBiEOG091G04D9
    PhylomeDBiO94782
    TreeFamiTF331057

    Enzyme and pathway databases

    ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
    R-HSA-6783310 Fanconi Anemia Pathway

    Miscellaneous databases

    ChiTaRSiUSP1 human
    GeneWikiiUSP1
    GenomeRNAii7398
    PROiPR:O94782
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000162607 Expressed in 241 organ(s), highest expression level in secondary oocyte
    CleanExiHS_USP1
    ExpressionAtlasiO94782 baseline and differential
    GenevisibleiO94782 HS

    Family and domain databases

    CDDicd02671 Peptidase_C19O, 1 hit
    InterProiView protein in InterPro
    IPR038765 Papain_like_cys_pep_sf
    IPR001394 Peptidase_C19_UCH
    IPR033815 USP1
    IPR018200 USP_CS
    IPR028889 USP_dom
    PfamiView protein in Pfam
    PF00443 UCH, 1 hit
    SUPFAMiSSF54001 SSF54001, 1 hit
    PROSITEiView protein in PROSITE
    PS00972 USP_1, 1 hit
    PS00973 USP_2, 1 hit
    PS50235 USP_3, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiUBP1_HUMAN
    AccessioniPrimary (citable) accession number: O94782
    Secondary accession number(s): A0PJ95
    , D3DQ57, Q05BX7, Q59H66, Q9UFR0, Q9UNJ3
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 1, 1999
    Last modified: November 7, 2018
    This is version 166 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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