OTUB1_RAT
ID OTUB1_RAT Reviewed; 271 AA.
AC B2RYG6;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Ubiquitin thioesterase OTUB1 {ECO:0000250|UniProtKB:Q7TQI3};
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q96FW1};
DE AltName: Full=Deubiquitinating enzyme OTUB1 {ECO:0000250|UniProtKB:Q7TQI3};
DE AltName: Full=OTU domain-containing ubiquitin aldehyde-binding protein 1 {ECO:0000250|UniProtKB:Q7TQI3};
DE AltName: Full=Otubain-1 {ECO:0000250|UniProtKB:Q7TQI3};
DE AltName: Full=Ubiquitin-specific-processing protease OTUB1 {ECO:0000250|UniProtKB:Q7TQI3};
GN Name=Otub1 {ECO:0000312|EMBL:AAI66771.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:EDM12666.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:AAI66771.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate {ECO:0000312|EMBL:AAI66771.1};
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 IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=19343716; DOI=10.1002/pmic.200800664;
RA Maurya D.K., Sundaram C.S., Bhargava P.;
RT "Proteome profile of the mature rat olfactory bulb.";
RL Proteomics 9:2593-2599(2009).
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 (By similarity).
CC {ECO:0000250}.
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.
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:0000269|PubMed:19343716}.
CC -!- SIMILARITY: Belongs to the peptidase C65 family. {ECO:0000255}.
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DR EMBL; CH473953; EDM12666.1; -; Genomic_DNA.
DR EMBL; BC166771; AAI66771.1; -; mRNA.
DR RefSeq; NP_001099802.1; NM_001106332.1.
DR AlphaFoldDB; B2RYG6; -.
DR SMR; B2RYG6; -.
DR BioGRID; 254414; 3.
DR IntAct; B2RYG6; 2.
DR MINT; B2RYG6; -.
DR STRING; 10116.ENSRNOP00000028752; -.
DR iPTMnet; B2RYG6; -.
DR PhosphoSitePlus; B2RYG6; -.
DR SwissPalm; B2RYG6; -.
DR World-2DPAGE; 0004:B2RYG6; -.
DR jPOST; B2RYG6; -.
DR PaxDb; B2RYG6; -.
DR PeptideAtlas; B2RYG6; -.
DR PRIDE; B2RYG6; -.
DR Ensembl; ENSRNOT00000101186; ENSRNOP00000088887; ENSRNOG00000021175.
DR GeneID; 293705; -.
DR KEGG; rno:293705; -.
DR UCSC; RGD:1311329; rat.
DR CTD; 55611; -.
DR RGD; 1311329; Otub1.
DR eggNOG; KOG3991; Eukaryota.
DR GeneTree; ENSGT00390000006979; -.
DR HOGENOM; CLU_014832_3_0_1; -.
DR InParanoid; B2RYG6; -.
DR OMA; VRVRYMD; -.
DR OrthoDB; 1257066at2759; -.
DR PhylomeDB; B2RYG6; -.
DR TreeFam; TF314145; -.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-5689896; Ovarian tumor domain proteases.
DR PRO; PR:B2RYG6; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000021175; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; B2RYG6; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0019784; F:deNEDDylase activity; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
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:0071347; P:cellular response to interleukin-1; IEP:RGD.
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: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; DNA damage; DNA repair;
KW Hydrolase; Immunity; Phosphoprotein; Protease; Reference proteome;
KW 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_0000349125"
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 23
FT /note="Required for proximal ubiquitin-binding"
FT /evidence="ECO:0000250"
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"
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
