OTUB1_MOUSE
ID OTUB1_MOUSE Reviewed; 271 AA.
AC Q7TQI3; Q3ULV9; Q3V408; Q8C326; Q8R5F2;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Ubiquitin thioesterase OTUB1;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q96FW1};
DE AltName: Full=Deubiquitinating enzyme OTUB1;
DE AltName: Full=OTU domain-containing ubiquitin aldehyde-binding protein 1;
DE AltName: Full=Otubain-1;
DE AltName: Full=Ubiquitin-specific-processing protease OTUB1;
GN Name=Otub1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Corpora quadrigemina, Embryo, Mammary gland, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, and Mammary tumor;
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 [3]
RP PROTEIN SEQUENCE OF 189-198, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [4]
RP FUNCTION.
RX PubMed=14661020; DOI=10.1038/ni1017;
RA Soares L., Seroogy C., Skrenta H., Anandasabapathy N., Lovelace P.,
RA Chung C.D., Engleman E., Fathman C.G.;
RT "Two isoforms of otubain 1 regulate T cell anergy via GRAIL.";
RL Nat. Immunol. 5:45-54(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Hydrolase that can specifically remove compared to 'Lys-48'-
CC linked conjugated ubiquitin from proteins and plays an important
CC regulatory role at the level of protein turnover by preventing
CC degradation. Regulator of T-cell anergy, a phenomenon that occurs when
CC T-cells are rendered unresponsive to antigen rechallenge and no longer
CC respond to their cognate antigen. Acts via its interaction with
CC RNF128/GRAIL. Surprisingly, it regulates RNF128-mediated
CC ubiquitination, but does not deubiquitinate polyubiquitinated RNF128.
CC Deubiquitinates estrogen receptor alpha (ESR1). Mediates
CC deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-
CC 63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also
CC capable of removing NEDD8 from NEDD8 conjugates, but with a much lower
CC preference compared to 'Lys-48'-linked ubiquitin.
CC {ECO:0000269|PubMed:14661020}.
CC -!- FUNCTION: Plays a key non-catalytic role in DNA repair regulation by
CC inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that
CC promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA
CC damage sites. Inhibits RNF168 independently of ubiquitin thioesterase
CC activity by binding and inhibiting UBE2N/UBC13, the E2 partner of
CC RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and
CC H2AX marks. Inhibition occurs by binding to free ubiquitin: free
CC ubiquitin acts as an allosteric regulator that increases affinity for
CC UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-
CC UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a
CC cleaved 'Lys48'-linked di-ubiquitin chain (By similarity).
CC {ECO:0000250}.
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:0000250|UniProtKB:Q96FW1};
CC -!- ACTIVITY REGULATION: By free ubiquitin: binding of free ubiquitin
CC triggers conformational changes in the OTU domain and formation of a
CC ubiquitin-binding helix in the N-terminus, promoting binding of the
CC conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with RNF128. Forms a ternary complex with RNF128 and
CC USP8. Interacts with FUS, ESR1 and RACK1. Interacts with UBE2N/UBC13
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C65 family. {ECO:0000305}.
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DR EMBL; AK027996; BAE20433.1; -; mRNA.
DR EMBL; AK140070; BAE24227.1; -; mRNA.
DR EMBL; AK145273; BAE26339.1; -; mRNA.
DR EMBL; AK145970; BAE26795.1; -; mRNA.
DR EMBL; BC022575; AAH22575.1; -; mRNA.
DR EMBL; BC054410; AAH54410.1; -; mRNA.
DR CCDS; CCDS29520.1; -.
DR RefSeq; NP_598911.1; NM_134150.2.
DR AlphaFoldDB; Q7TQI3; -.
DR SMR; Q7TQI3; -.
DR BioGRID; 223228; 20.
DR IntAct; Q7TQI3; 4.
DR MINT; Q7TQI3; -.
DR STRING; 10090.ENSMUSP00000025679; -.
DR MEROPS; C65.001; -.
DR iPTMnet; Q7TQI3; -.
DR PhosphoSitePlus; Q7TQI3; -.
DR SwissPalm; Q7TQI3; -.
DR REPRODUCTION-2DPAGE; Q7TQI3; -.
DR EPD; Q7TQI3; -.
DR jPOST; Q7TQI3; -.
DR MaxQB; Q7TQI3; -.
DR PaxDb; Q7TQI3; -.
DR PeptideAtlas; Q7TQI3; -.
DR PRIDE; Q7TQI3; -.
DR ProteomicsDB; 294083; -.
DR Antibodypedia; 29104; 499 antibodies from 35 providers.
DR DNASU; 107260; -.
DR Ensembl; ENSMUST00000025679; ENSMUSP00000025679; ENSMUSG00000024767.
DR GeneID; 107260; -.
DR KEGG; mmu:107260; -.
DR UCSC; uc008gki.1; mouse.
DR CTD; 55611; -.
DR MGI; MGI:2147616; Otub1.
DR VEuPathDB; HostDB:ENSMUSG00000024767; -.
DR eggNOG; KOG3991; Eukaryota.
DR GeneTree; ENSGT00390000006979; -.
DR InParanoid; Q7TQI3; -.
DR OMA; VRVRYMD; -.
DR OrthoDB; 1257066at2759; -.
DR PhylomeDB; Q7TQI3; -.
DR TreeFam; TF314145; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 107260; 10 hits in 111 CRISPR screens.
DR ChiTaRS; Otub1; mouse.
DR PRO; PR:Q7TQI3; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q7TQI3; protein.
DR Bgee; ENSMUSG00000024767; Expressed in embryonic brain and 255 other tissues.
DR ExpressionAtlas; Q7TQI3; baseline and differential.
DR Genevisible; Q7TQI3; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0019784; F:deNEDDylase activity; ISS:UniProtKB.
DR GO; GO:0101005; F:deubiquitinase activity; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:2000780; P:negative regulation of double-strand break repair; ISS:UniProtKB.
DR GO; GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISO:MGI.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR Gene3D; 1.20.1300.20; -; 1.
DR Gene3D; 3.30.200.60; -; 1.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR030298; OTUB1.
DR InterPro; IPR016615; Otubain.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR019400; Peptidase_C65_otubain.
DR InterPro; IPR042468; Peptidase_C65_otubain_sub1.
DR InterPro; IPR042467; Peptidase_C65_otubain_sub2.
DR PANTHER; PTHR12931; PTHR12931; 1.
DR PANTHER; PTHR12931:SF19; PTHR12931:SF19; 1.
DR Pfam; PF10275; Peptidase_C65; 1.
DR PIRSF; PIRSF013503; Ubiquitin_thioesterase_Otubain; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50802; OTU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Adaptive immunity; Cytoplasm; Direct protein sequencing;
KW DNA damage; DNA repair; Hydrolase; Immunity; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT CHAIN 2..271
FT /note="Ubiquitin thioesterase OTUB1"
FT /id="PRO_0000221009"
FT DOMAIN 80..271
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT REGION 130..138
FT /note="Ubiquitin-conjugating enzyme E2 binding"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT REGION 169..177
FT /note="Ubiquitin-conjugating enzyme E2 binding"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT REGION 189..195
FT /note="Free ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT REGION 206..213
FT /note="Ubiquitin-conjugating enzyme E2 binding"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT REGION 214..221
FT /note="Free ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT REGION 245..251
FT /note="Free ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT ACT_SITE 88
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT ACT_SITE 91
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT ACT_SITE 265
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT SITE 221
FT /note="Interacts with free ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT SITE 235
FT /note="Interacts with free ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT SITE 237
FT /note="Interacts with free ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT SITE 261
FT /note="Interacts with free ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT SITE 266
FT /note="Interacts with free ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT CONFLICT 186
FT /note="E -> D (in Ref. 1; BAE20433)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 271 AA; 31270 MW; 32F78EE1DC5FD679 CRC64;
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE RLELSVLYKE
YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH LEALLDDSKE LQRFKAVSAK
SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE KQTSVADLLA SFNDQSTSDY LVVYLRLLTS
GYLQRESKFF EHFIEGGRTV KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE
GGTTNPHVFP EGSEPKVYLL YRPGHYDILY K
