O94782 (UBP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

USP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	785 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Molecular function	Hydrolase Protease Thiol protease
PTM	Autocatalytic cleavage Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement. Source: Reactome monoubiquitinated protein deubiquitination Inferred from mutant phenotype PubMed 20129063. Source: UniProtKB regulation of DNA repair Inferred from direct assay Ref.9. Source: UniProtKB response to UV Inferred from direct assay Ref.9. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	cysteine-type endopeptidase activity Traceable author statement PubMed 9827704. Source: ProtInc ubiquitin thiolesterase activity Inferred from direct assay Ref.9. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 785	785	Ubiquitin carboxyl-terminal hydrolase 1		PRO_0000080615
Sites
	Active site	90	1	Nucleophile
	Active site	593	1	Proton acceptor By similarity
	Site	671 – 672	2	Cleavage; by autolysis
Amino acid modifications
	Modified residue	42	1	Phosphoserine Ref.10 Ref.12
	Modified residue	67	1	Phosphoserine Ref.11
	Modified residue	475	1	Phosphoserine Ref.13
Experimental info
	Mutagenesis	90	1	C → S: Loss of catalytic activity including autolysis. Ref.7 Ref.8
	Mutagenesis	670 – 671	2	GG → AA: Loss of autolysis-mediated degradation upon UV irradiation. No effect on catalytic activity.
	Sequence conflict	621	1	I → M in AAD11441. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O94782 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 50AA2817A60810AF	FASTA	785	88,207
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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, MASS SPECTROMETRY.
+	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.
IPI	IPI00304379.
PIR	T17309.
RefSeq	NP_001017415.1. NM_001017415.1. NP_001017416.1. NM_001017416.1. NP_003359.3. NM_003368.4.
UniGene	Hs.35086.
3D structure databases
ProteinModelPortal	O94782.
ModBase	Search...
Protein-protein interaction databases
IntAct	O94782. 22 interactions.
MINT	MINT-4719170.
STRING	9606.ENSP00000343526.
Protein family/group databases
MEROPS	C19.019.
PTM databases
PhosphoSite	O94782.
2D gel databases
OGP	O94782.
Proteomic databases
PaxDb	O94782.
PRIDE	O94782.
Protocols and materials databases
DNASU	7398.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000339950; ENSP00000343526; ENSG00000162607. ENST00000371146; ENSP00000360188; ENSG00000162607.
GeneID	7398.
KEGG	hsa:7398.
UCSC	uc001daj.2. human.
Organism-specific databases
CTD	7398.
GeneCards	GC01P062837.
H-InvDB	HIX0159950.
HGNC	HGNC:12607. USP1.
HPA	HPA028440.
MIM	603478. gene.
neXtProt	NX_O94782.
PharmGKB	PA37233.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5077.
HOVERGEN	HBG017288.
InParanoid	O94782.
KO	K11832.
OMA	ISSGHYT.
OrthoDB	EOG4XSKP7.
PhylomeDB	O94782.
Enzyme and pathway databases
Reactome	REACT_216. DNA Repair.
Gene expression databases
ArrayExpress	O94782.
Bgee	O94782.
CleanEx	HS_USP1.
Genevestigator	O94782.
GermOnline	ENSG00000162607. Homo sapiens.
Family and domain databases
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
Pfam	PF00443. UCH. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1795087.
GenomeRNAi	7398.
NextBio	28954.
SOURCE	Search...

Entry information

Entry name

UBP1_HUMAN

Accession

Primary (citable) accession number: O94782
Secondary accession number(s): A0PJ95 , D3DQ57, Q05BX7, Q59H66, Q9UFR0, Q9UNJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 1999
Last modified:	May 29, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.