UBP3_HUMAN
ID UBP3_HUMAN Reviewed; 520 AA.
AC Q9Y6I4; B4DVU5; F5H1A6; Q8WVD0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 3;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 3;
DE AltName: Full=Ubiquitin thioesterase 3;
DE AltName: Full=Ubiquitin-specific-processing protease 3;
GN Name=USP3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10480896; DOI=10.1074/jbc.274.38.26878;
RA Sloper-Mould K.E., Eyre H.J., Wang X.-W., Sutherland G.R., Baker R.T.;
RT "Characterization and chromosomal localization of USP3, a novel human
RT ubiquitin-specific protease.";
RL J. Biol. Chem. 274:26878-26884(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH H2A, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-56
RP AND CYS-168, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17980597; DOI=10.1016/j.cub.2007.10.034;
RA Nicassio F., Corrado N., Vissers J.H., Areces L.B., Bergink S.,
RA Marteijn J.A., Geverts B., Houtsmuller A.B., Vermeulen W., Di Fiore P.P.,
RA Citterio E.;
RT "Human USP3 is a chromatin modifier required for S phase progression and
RT genome stability.";
RL Curr. Biol. 17:1972-1977(2007).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
CC -!- FUNCTION: Hydrolase that deubiquitinates monoubiquitinated target
CC proteins such as histone H2A and H2B. Required for proper progression
CC through S phase and subsequent mitotic entry. May regulate the DNA
CC damage response (DDR) checkpoint through deubiquitination of H2A at DNA
CC damage sites. Associates with the chromatin.
CC {ECO:0000269|PubMed:17980597}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12;
CC -!- SUBUNIT: Interacts (via UBP-type domain) with H2A; the interaction is
CC less efficient than with monoubiquitinated H2A.
CC {ECO:0000269|PubMed:17980597}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17980597}.
CC Note=Localizes preferentially with monoubiquitinated H2A to chromatin.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y6I4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y6I4-2; Sequence=VSP_044712;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined, with strongest
CC expression in pancreas.
CC -!- DOMAIN: Both protease activity and an intact zinc finger are required
CC for H2A monodeubiquitination.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP3 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD42992.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF073344; AAD42992.1; ALT_FRAME; mRNA.
DR EMBL; BT007269; AAP35933.1; -; mRNA.
DR EMBL; AK301236; BAG62807.1; -; mRNA.
DR EMBL; AC007950; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC118274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77651.1; -; Genomic_DNA.
DR EMBL; BC018113; AAH18113.1; -; mRNA.
DR EMBL; BC065300; AAH65300.1; -; mRNA.
DR EMBL; BC107137; AAI07138.1; -; mRNA.
DR EMBL; BC107138; AAI07139.1; -; mRNA.
DR CCDS; CCDS32265.1; -. [Q9Y6I4-1]
DR CCDS; CCDS58370.1; -. [Q9Y6I4-2]
DR RefSeq; NP_001243631.1; NM_001256702.1. [Q9Y6I4-2]
DR RefSeq; NP_006528.2; NM_006537.3. [Q9Y6I4-1]
DR AlphaFoldDB; Q9Y6I4; -.
DR SMR; Q9Y6I4; -.
DR BioGRID; 115285; 61.
DR DIP; DIP-53585N; -.
DR IntAct; Q9Y6I4; 27.
DR MINT; Q9Y6I4; -.
DR STRING; 9606.ENSP00000369681; -.
DR MEROPS; C19.026; -.
DR iPTMnet; Q9Y6I4; -.
DR PhosphoSitePlus; Q9Y6I4; -.
DR SwissPalm; Q9Y6I4; -.
DR BioMuta; USP3; -.
DR DMDM; 205371844; -.
DR EPD; Q9Y6I4; -.
DR jPOST; Q9Y6I4; -.
DR MassIVE; Q9Y6I4; -.
DR MaxQB; Q9Y6I4; -.
DR PaxDb; Q9Y6I4; -.
DR PeptideAtlas; Q9Y6I4; -.
DR PRIDE; Q9Y6I4; -.
DR ProteomicsDB; 25594; -.
DR ProteomicsDB; 86692; -. [Q9Y6I4-1]
DR Antibodypedia; 13304; 311 antibodies from 33 providers.
DR DNASU; 9960; -.
DR Ensembl; ENST00000380324.8; ENSP00000369681.3; ENSG00000140455.17. [Q9Y6I4-1]
DR Ensembl; ENST00000540797.5; ENSP00000445828.1; ENSG00000140455.17. [Q9Y6I4-2]
DR GeneID; 9960; -.
DR KEGG; hsa:9960; -.
DR MANE-Select; ENST00000380324.8; ENSP00000369681.3; NM_006537.4; NP_006528.2.
DR UCSC; uc002amf.5; human. [Q9Y6I4-1]
DR CTD; 9960; -.
DR DisGeNET; 9960; -.
DR GeneCards; USP3; -.
DR HGNC; HGNC:12626; USP3.
DR HPA; ENSG00000140455; Low tissue specificity.
DR MIM; 604728; gene.
DR neXtProt; NX_Q9Y6I4; -.
DR OpenTargets; ENSG00000140455; -.
DR PharmGKB; PA37251; -.
DR VEuPathDB; HostDB:ENSG00000140455; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000157850; -.
DR InParanoid; Q9Y6I4; -.
DR OMA; PSTKKFW; -.
DR OrthoDB; 929408at2759; -.
DR PhylomeDB; Q9Y6I4; -.
DR TreeFam; TF315281; -.
DR PathwayCommons; Q9Y6I4; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9Y6I4; -.
DR BioGRID-ORCS; 9960; 16 hits in 1088 CRISPR screens.
DR ChiTaRS; USP3; human.
DR GenomeRNAi; 9960; -.
DR Pharos; Q9Y6I4; Tbio.
DR PRO; PR:Q9Y6I4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9Y6I4; protein.
DR Bgee; ENSG00000140455; Expressed in monocyte and 196 other tissues.
DR ExpressionAtlas; Q9Y6I4; baseline and differential.
DR Genevisible; Q9Y6I4; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0090543; C:Flemming body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:0042393; F:histone binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0016578; P:histone deubiquitination; IDA:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell cycle; Chromatin regulator;
KW DNA damage; Hydrolase; Metal-binding; Nucleus; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..520
FT /note="Ubiquitin carboxyl-terminal hydrolase 3"
FT /id="PRO_0000080619"
FT DOMAIN 159..511
FT /note="USP"
FT ZN_FING 1..121
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT ACT_SITE 168
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 471
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 3
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 5
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 32
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 41
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 49
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 56
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT VAR_SEQ 51..95
FT /note="RYVNGHAKKHYEDAQVPLTNHKKSEKQDKVQHTVCMDCSSYSTYC -> S
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044712"
FT VARIANT 360
FT /note="P -> T (in dbSNP:rs34776764)"
FT /id="VAR_051521"
FT MUTAGEN 56
FT /note="H->A: Does not reduce monoubiquitinated H2A and H2B
FT stability. Interaction with monoubiquitinated H2A is
FT strongly inhibited."
FT /evidence="ECO:0000269|PubMed:17980597"
FT MUTAGEN 168
FT /note="C->S: Does not reduce H2A stability. Interacts more
FT strongly with monoubiquitinated H2A than with
FT nonubiquitinated H2A. Its nuclear localization to chromatin
FT is enhanced."
FT /evidence="ECO:0000269|PubMed:17980597"
FT CONFLICT 439
FT /note="C -> W (in Ref. 1; AAD42992)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="T -> I (in Ref. 3; BAG62807)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 58897 MW; AC27FE9BD0438893 CRC64;
MECPHLSSSV CIAPDSAKFP NGSPSSWCCS VCRSNKSPWV CLTCSSVHCG RYVNGHAKKH
YEDAQVPLTN HKKSEKQDKV QHTVCMDCSS YSTYCYRCDD FVVNDTKLGL VQKVREHLQN
LENSAFTADR HKKRKLLENS TLNSKLLKVN GSTTAICATG LRNLGNTCFM NAILQSLSNI
EQFCCYFKEL PAVELRNGKT AGRRTYHTRS QGDNNVSLVE EFRKTLCALW QGSQTAFSPE
SLFYVVWKIM PNFRGYQQQD AHEFMRYLLD HLHLELQGGF NGVSRSAILQ ENSTLSASNK
CCINGASTVV TAIFGGILQN EVNCLICGTE SRKFDPFLDL SLDIPSQFRS KRSKNQENGP
VCSLRDCLRS FTDLEELDET ELYMCHKCKK KQKSTKKFWI QKLPKVLCLH LKRFHWTAYL
RNKVDTYVEF PLRGLDMKCY LLEPENSGPE SCLYDLAAVV VHHGSGVGSG HYTAYATHEG
RWFHFNDSTV TLTDEETVVK AKAYILFYVE HQAKAGSDKL
