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 24-JAN-2024, entry version 192. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 66. 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; 9606-ENSP00000369681; -. DR PeptideAtlas; Q9Y6I4; -. DR ProteomicsDB; 25594; -. DR ProteomicsDB; 86692; -. [Q9Y6I4-1] DR Pumba; Q9Y6I4; -. DR Antibodypedia; 13304; 342 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 AGR; HGNC:12626; -. 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; AGKRIYN; -. DR OrthoDB; 227085at2759; -. 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; 17 hits in 1165 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 198 other cell types or tissues. DR ExpressionAtlas; Q9Y6I4; baseline and differential. 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:0140950; F:histone H2A deubiquitinase activity; IMP:UniProtKB. DR GO; GO:0140936; F:histone H2B deubiquitinase activity; IMP:UniProtKB. DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB. DR GO; GO:0140861; P:DNA repair-dependent chromatin remodeling; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF19; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 3; 1. DR Pfam; PF00443; UCH; 1. DR Pfam; PF02148; zf-UBP; 1. DR SMART; SM00290; ZnF_UBP; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF57850; RING/U-box; 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. DR Genevisible; Q9Y6I4; HS. 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 //