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O94782 (UBP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:USP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length785 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9

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). Ref.9

Subunit structure

Interacts with FANCD2 and PCNA. Interacts with WDR48. Ref.7 Ref.9

Subcellular location

Nucleus Ref.7.

Developmental stage

Cell cycle-regulated. Highest level during S phase. Ref.7

Induction

Down-regulated following DNA damage. Ref.9

Post-translational modification

Autocatalytic cleavage of USP1 following UV irradiation inactivates it leading to an increase in ubiquitinated PCNA, recruitment of POLH and translesion synthesis.

Ubiquitinated; leading to its subsequent proteasomal degradation By similarity. Ref.7

Miscellaneous

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

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 USP domain.

Biophysicochemical properties

Kinetic parameters:

KM=0.7 µM for ubiquitin vinyl sulfone (in presence of WDR48) Ref.9

KM=1.4 µM for ubiquitin vinyl sulfone (in absence of WDR48)

Sequence caution

The sequence AAH18745.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

The sequence AAH32364.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

The sequence BAD92130.1 differs from that shown. Reason: Frameshift at position 230.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 785785Ubiquitin carboxyl-terminal hydrolase 1
PRO_0000080615

Regions

Domain81 – 785705USP

Sites

Active site901Nucleophile
Active site5931Proton acceptor By similarity
Site671 – 6722Cleavage; by autolysis

Amino acid modifications

Modified residue421Phosphoserine Ref.10 Ref.13
Modified residue671Phosphoserine Ref.11
Modified residue4751Phosphoserine Ref.14

Experimental info

Mutagenesis901C → S: Loss of catalytic activity including autolysis. Ref.7 Ref.8
Mutagenesis670 – 6712GG → AA: Loss of autolysis-mediated degradation upon UV irradiation. No effect on catalytic activity.
Sequence conflict6211I → M in AAD11441. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O94782 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 50AA2817A60810AF

FASTA78588,207
        10         20         30         40         50         60 
MPGVIPSESN GLSRGSPSKK NRLSLKFFQK KETKRALDFT DSQENEEKAS EYRASEIDQV 

        70         80         90        100        110        120 
VPAAQSSPIN CEKRENLLPF VGLNNLGNTC YLNSILQVLY FCPGFKSGVK HLFNIISRKK 

       130        140        150        160        170        180 
EALKDEANQK DKGNCKEDSL ASYELICSLQ SLIISVEQLQ ASFLLNPEKY TDELATQPRR 

       190        200        210        220        230        240 
LLNTLRELNP MYEGYLQHDA QEVLQCILGN IQETCQLLKK EEVKNVAELP TKVEEIPHPK 

       250        260        270        280        290        300 
EEMNGINSIE MDSMRHSEDF KEKLPKGNGK RKSDTEFGNM KKKVKLSKEH QSLEENQRQT 

       310        320        330        340        350        360 
RSKRKATSDT LESPPKIIPK YISENESPRP SQKKSRVKIN WLKSATKQPS ILSKFCSLGK 

       370        380        390        400        410        420 
ITTNQGVKGQ SKENECDPEE DLGKCESDNT TNGCGLESPG NTVTPVNVNE VKPINKGEEQ 

       430        440        450        460        470        480 
IGFELVEKLF QGQLVLRTRC LECESLTERR EDFQDISVPV QEDELSKVEE SSEISPEPKT 

       490        500        510        520        530        540 
EMKTLRWAIS QFASVERIVG EDKYFCENCH HYTEAERSLL FDKMPEVITI HLKCFAASGL 

       550        560        570        580        590        600 
EFDCYGGGLS KINTPLLTPL KLSLEEWSTK PTNDSYGLFA VVMHSGITIS SGHYTASVKV 

       610        620        630        640        650        660 
TDLNSLELDK GNFVVDQMCE IGKPEPLNEE EARGVVENYN DEEVSIRVGG NTQPSKVLNK 

       670        680        690        700        710        720 
KNVEAIGLLG GQKSKADYEL YNKASNPDKV ASTAFAENRN SETSDTTGTH ESDRNKESSD 

       730        740        750        760        770        780 
QTGINISGFE NKISYVVQSL KEYEGKWLLF DDSEVKVTEE KDFLNSLSPS TSPTSTPYLL 


FYKKL 

« Hide

References

« Hide 'large scale' references
[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]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
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]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 (SEP-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].
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]"Regulation of monoubiquitinated PCNA by DUB autocleavage."
Huang T.T., Nijman S.M.B., Mirchandani K.D., Galardy P.J., Cohn M.A., Haas W., Gygi S.P., Ploegh H.L., Bernards R., D'Andrea A.D.
Nat. Cell Biol. 8:339-347(2006) [PubMed] [Europe PMC] [Abstract]
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]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT17309.
RefSeqNP_001017415.1. NM_001017415.1.
NP_001017416.1. NM_001017416.1.
NP_003359.3. NM_003368.4.
UniGeneHs.35086.

3D structure databases

ProteinModelPortalO94782.
SMRO94782. Positions 78-216, 395-599.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113241. 38 interactions.
IntActO94782. 22 interactions.
MINTMINT-4719170.
STRING9606.ENSP00000343526.

Chemistry

ChEMBLCHEMBL1795087.

Protein family/group databases

MEROPSC19.019.

PTM databases

PhosphoSiteO94782.

2D gel databases

OGPO94782.

Proteomic databases

PaxDbO94782.
PRIDEO94782.

Protocols and materials databases

DNASU7398.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339950; ENSP00000343526; ENSG00000162607.
ENST00000371146; ENSP00000360188; ENSG00000162607.
GeneID7398.
KEGGhsa:7398.
UCSCuc001daj.2. human.

Organism-specific databases

CTD7398.
GeneCardsGC01P062837.
H-InvDBHIX0159950.
HGNCHGNC:12607. USP1.
HPAHPA028440.
MIM603478. gene.
neXtProtNX_O94782.
PharmGKBPA37233.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOVERGENHBG017288.
InParanoidO94782.
KOK11832.
OMAFAVVMHS.
OrthoDBEOG7JT6VZ.
PhylomeDBO94782.
TreeFamTF331057.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressO94782.
BgeeO94782.
CleanExHS_USP1.
GenevestigatorO94782.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 2 hits.
[Graphical view]
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUSP1.
GenomeRNAi7398.
NextBio28954.
PROO94782.
SOURCESearch...

Entry information

Entry nameUBP1_HUMAN
AccessionPrimary (citable) accession number: O94782
Secondary accession number(s): A0PJ95 expand/collapse secondary AC list , D3DQ57, Q05BX7, Q59H66, Q9UFR0, Q9UNJ3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 124 of the entry and version 1 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 chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM