UBP51_HUMAN
ID UBP51_HUMAN Reviewed; 711 AA.
AC Q70EK9; Q8IWJ8;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 51 {ECO:0000303|PubMed:27083998};
DE EC=3.4.19.12 {ECO:0000269|PubMed:27083998};
DE AltName: Full=Deubiquitinating enzyme 51;
DE AltName: Full=Ubiquitin thioesterase 51;
DE AltName: Full=Ubiquitin-specific-processing protease 51;
GN Name=USP51 {ECO:0000312|HGNC:HGNC:23086};
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], TISSUE SPECIFICITY, AND ENZYME ACTIVITY.
RX PubMed=14715245; DOI=10.1016/j.bbrc.2003.12.050;
RA Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S.,
RA Lopez-Otin C.;
RT "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific
RT proteases.";
RL Biochem. Biophys. Res. Commun. 314:54-62(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-305.
RC TISSUE=Mammary gland;
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 [4]
RP IDENTIFICATION.
RX PubMed=15060002; DOI=10.1101/gr.1946304;
RA Puente X.S., Lopez-Otin C.;
RT "A genomic analysis of rat proteases and protease inhibitors.";
RL Genome Res. 14:609-622(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, HISTONE BINDING, ACTIVE
RP SITE, AND MUTAGENESIS OF CYS-372 AND HIS-665.
RX PubMed=27083998; DOI=10.1101/gad.271841.115;
RA Wang Z., Zhang H., Liu J., Cheruiyot A., Lee J.H., Ordog T., Lou Z.,
RA You Z., Zhang Z.;
RT "USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response.";
RL Genes Dev. 30:946-959(2016).
CC -!- FUNCTION: Specifically deubiquitinates 'Lys-14' (H2AK13Ub) and 'Lys-
CC 16'(H2AK15Ub) of histone H2A regulating the DNA damage response at
CC double-strand breaks (DSBs) (PubMed:27083998). USP51 is recruited to
CC chromatin after DNA damage and regulates the dynamic
CC assembly/disassembly of TP53BP1 and BRCA1. Exhibits also activity for
CC 'Lys-27' or 'Lys-63'-linked di-ubiquitin (PubMed:27083998).
CC {ECO:0000269|PubMed:27083998}.
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; Evidence={ECO:0000269|PubMed:14715245,
CC ECO:0000269|PubMed:27083998};
CC -!- SUBUNIT: Interacts with H2A (PubMed:27083998).
CC {ECO:0000269|PubMed:27083998}.
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000305|PubMed:27083998}.
CC Note=Upon DNA damage, chromatin-bound USP51 disassociates from
CC chromatin immediately following DNA damage and reassociates with
CC chromatin following DNA repair. {ECO:0000269|PubMed:27083998}.
CC -!- TISSUE SPECIFICITY: Expressed in prostate, brain, lung, aorta and
CC kidney. {ECO:0000269|PubMed:14715245}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH35907.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AJ583823; CAE47750.2; -; mRNA.
DR EMBL; AL732358; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035907; AAH35907.1; ALT_SEQ; mRNA.
DR EMBL; BN000340; CAE48396.2; -; mRNA.
DR CCDS; CCDS14370.1; -.
DR RefSeq; NP_958443.1; NM_201286.3.
DR RefSeq; XP_016884788.1; XM_017029299.1.
DR RefSeq; XP_016884789.1; XM_017029300.1.
DR RefSeq; XP_016884790.1; XM_017029301.1.
DR AlphaFoldDB; Q70EK9; -.
DR SMR; Q70EK9; -.
DR BioGRID; 127720; 38.
DR IntAct; Q70EK9; 2.
DR MINT; Q70EK9; -.
DR STRING; 9606.ENSP00000423333; -.
DR MEROPS; C19.065; -.
DR iPTMnet; Q70EK9; -.
DR PhosphoSitePlus; Q70EK9; -.
DR BioMuta; USP51; -.
DR DMDM; 52000873; -.
DR EPD; Q70EK9; -.
DR jPOST; Q70EK9; -.
DR MassIVE; Q70EK9; -.
DR MaxQB; Q70EK9; -.
DR PaxDb; Q70EK9; -.
DR PeptideAtlas; Q70EK9; -.
DR PRIDE; Q70EK9; -.
DR ProteomicsDB; 68537; -.
DR Antibodypedia; 52206; 37 antibodies from 20 providers.
DR DNASU; 158880; -.
DR Ensembl; ENST00000500968.4; ENSP00000423333.2; ENSG00000247746.5.
DR GeneID; 158880; -.
DR KEGG; hsa:158880; -.
DR MANE-Select; ENST00000500968.4; ENSP00000423333.2; NM_201286.4; NP_958443.1.
DR UCSC; uc004dun.3; human.
DR CTD; 158880; -.
DR DisGeNET; 158880; -.
DR GeneCards; USP51; -.
DR HGNC; HGNC:23086; USP51.
DR HPA; ENSG00000247746; Tissue enriched (epididymis).
DR neXtProt; NX_Q70EK9; -.
DR OpenTargets; ENSG00000247746; -.
DR PharmGKB; PA134888611; -.
DR VEuPathDB; HostDB:ENSG00000247746; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000163664; -.
DR HOGENOM; CLU_008279_11_0_1; -.
DR InParanoid; Q70EK9; -.
DR OMA; KQRKCDK; -.
DR OrthoDB; 929408at2759; -.
DR PhylomeDB; Q70EK9; -.
DR TreeFam; TF323554; -.
DR PathwayCommons; Q70EK9; -.
DR SignaLink; Q70EK9; -.
DR BioGRID-ORCS; 158880; 4 hits in 741 CRISPR screens.
DR GeneWiki; USP51; -.
DR GenomeRNAi; 158880; -.
DR Pharos; Q70EK9; Tbio.
DR PRO; PR:Q70EK9; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q70EK9; protein.
DR Bgee; ENSG00000247746; Expressed in corpus epididymis and 142 other tissues.
DR ExpressionAtlas; Q70EK9; baseline and differential.
DR Genevisible; Q70EK9; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016578; P:histone deubiquitination; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:FlyBase.
DR GO; GO:0010564; P:regulation of cell cycle process; IMP:UniProtKB.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:2001032; P:regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; 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; IPR033383; USP51.
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:SF38; PTHR21646:SF38; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-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 Chromosome; DNA damage; DNA repair; Hydrolase; Metal-binding; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..711
FT /note="Ubiquitin carboxyl-terminal hydrolase 51"
FT /id="PRO_0000080680"
FT DOMAIN 363..706
FT /note="USP"
FT ZN_FING 193..311
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 1..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..66
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..145
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 372
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093,
FT ECO:0000269|PubMed:27083998"
FT ACT_SITE 665
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093,
FT ECO:0000269|PubMed:27083998"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 252
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 262
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 266
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 285
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 288
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MUTAGEN 372
FT /note="C->S: Abolishes ability to deubiquitinate histone
FT H2A; when associated with 665-R. No decrease of total
FT H2AK15ub levels following ionizing radiation; when
FT associated with 665-R."
FT /evidence="ECO:0000269|PubMed:27083998"
FT MUTAGEN 665
FT /note="H->R: Abolishes ability to deubiquitinate histone
FT H2A; when associated with 665-R. Suppresses ionizing
FT radiation-induced H2AK13,15Ub; when associated with 372-R."
FT /evidence="ECO:0000269|PubMed:27083998"
SQ SEQUENCE 711 AA; 79756 MW; B721E620AE7ACE86 CRC64;
MAQVRETSLP SGSGVRWISG GGGGASPEEA VEKAGKMEEA AAGATKASSR REAEEMKLEP
LQEREPAPEE NLTWSSSGGD EKVLPSIPLR CHSSSSPVCP RRKPRPRPQP RARSRSQPGL
SAPPPPPARP PPPPPPPPPP APRPRAWRGS RRRSRPGSRP QTRRSCSGDL DGSGDPGGLG
DWLLEVEFGQ GPTGCSHVES FKVGKNWQKN LRLIYQRFVW SGTPETRKRK AKSCICHVCS
THMNRLHSCL SCVFFGCFTE KHIHKHAETK QHHLAVDLYH GVIYCFMCKD YVYDKDIEQI
AKETKEKILR LLTSTSTDVS HQQFMTSGFE DKQSTCETKE QEPKLVKPKK KRRKKSVYTV
GLRGLINLGN TCFMNCIVQA LTHIPLLKDF FLSDKHKCIM TSPSLCLVCE MSSLFHAMYS
GSRTPHIPYK LLHLIWIHAE HLAGYRQQDA HEFLIAILDV LHRHSKDDSG GQEANNPNCC
NCIIDQIFTG GLQSDVTCQA CHSVSTTIDP CWDISLDLPG SCATFDSQNP ERADSTVSRD
DHIPGIPSLT DCLQWFTRPE HLGSSAKIKC NSCQSYQEST KQLTMKKLPI VACFHLKRFE
HVGKQRRKIN TFISFPLELD MTPFLASTKE SRMKEGQPPT DCVPNENKYS LFAVINHHGT
LESGHYTSFI RQQKDQWFSC DDAIITKATI EDLLYSEGYL LFYHKQGLEK D
