OTU1_MOUSE
ID OTU1_MOUSE Reviewed; 343 AA.
AC Q8CB27; B2RSW9; Q8BPM9; Q8CB24;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Ubiquitin thioesterase OTU1;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q5VVQ6};
GN Name=Yod1;
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; TISSUE=Eye, and Vagina;
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 TISSUE=Brain;
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 [LARGE SCALE ANALYSIS].
RC TISSUE=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).
RN [4]
RP STRUCTURE BY NMR OF 42-126.
RG Northeast structural genomics consortium (NESG);
RT "Northeast structural genomics consortium target mmt2a.";
RL Submitted (AUG-2010) to the PDB data bank.
CC -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from proteins
CC and participates in endoplasmic reticulum-associated degradation (ERAD)
CC for misfolded lumenal proteins. May act by triming the ubiquitin chain
CC on the associated substrate to facilitate their threading through the
CC VCP/p97 pore. Ubiquitin moieties on substrates may present a steric
CC impediment to the threading process when the substrate is transferred
CC to the VCP pore and threaded through VCP's axial channel. Mediates
CC deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked
CC polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin
CC chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in
CC macroautophagy, regulating for instance the clearance of damaged
CC lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome
CC membranes decorated with K48-linked ubiquitin chains and remove these
CC chains allowing autophagosome formation.
CC {ECO:0000250|UniProtKB:Q5VVQ6}.
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:Q5VVQ6};
CC -!- SUBUNIT: Interacts with VCP; the interaction is direct. Interacts with
CC FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on
CC the UBAX-like region, suggesting that it may be indirect. Interacts
CC with PLAA, UBXN6 and VCP; may form a complex involved in
CC macroautophagy. {ECO:0000250|UniProtKB:Q5VVQ6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q5VVQ6}.
CC Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin
CC chains. {ECO:0000250|UniProtKB:Q5VVQ6}.
CC -!- DOMAIN: The UBAX-like region mediates the interaction with VCP.
CC {ECO:0000250|UniProtKB:Q5VVQ6}.
CC -!- DOMAIN: The C2H2-type zinc finger mediates specificity for 'Lys-27'-,
CC 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-
CC 11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin
CC chains is provided by recognition of the sequence surrounding 'Lys-11'
CC in ubiquitin. The S2 site region provides specificity for longer 'Lys-
CC 11'-linked ubiquitin chains. {ECO:0000250|UniProtKB:Q5VVQ6}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC29661.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC35495.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK036938; BAC29646.1; -; mRNA.
DR EMBL; AK036991; BAC29661.1; ALT_FRAME; mRNA.
DR EMBL; AK053730; BAC35495.1; ALT_SEQ; mRNA.
DR EMBL; BC139034; AAI39035.1; -; mRNA.
DR CCDS; CCDS48351.1; -.
DR RefSeq; NP_848806.2; NM_178691.4.
DR PDB; 2KZR; NMR; -; A=42-126.
DR PDBsum; 2KZR; -.
DR AlphaFoldDB; Q8CB27; -.
DR BMRB; Q8CB27; -.
DR SMR; Q8CB27; -.
DR BioGRID; 230509; 4.
DR STRING; 10090.ENSMUSP00000055318; -.
DR MEROPS; C85.007; -.
DR iPTMnet; Q8CB27; -.
DR PhosphoSitePlus; Q8CB27; -.
DR MaxQB; Q8CB27; -.
DR PaxDb; Q8CB27; -.
DR PRIDE; Q8CB27; -.
DR ProteomicsDB; 295489; -.
DR Antibodypedia; 34591; 167 antibodies from 27 providers.
DR DNASU; 226418; -.
DR Ensembl; ENSMUST00000049813; ENSMUSP00000055318; ENSMUSG00000046404.
DR GeneID; 226418; -.
DR KEGG; mmu:226418; -.
DR UCSC; uc007cmh.2; mouse.
DR CTD; 55432; -.
DR MGI; MGI:2442596; Yod1.
DR VEuPathDB; HostDB:ENSMUSG00000046404; -.
DR eggNOG; KOG3288; Eukaryota.
DR GeneTree; ENSGT00390000009989; -.
DR HOGENOM; CLU_049327_1_0_1; -.
DR InParanoid; Q8CB27; -.
DR OMA; NEEYCDW; -.
DR OrthoDB; 1327072at2759; -.
DR PhylomeDB; Q8CB27; -.
DR TreeFam; TF323700; -.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 226418; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Yod1; mouse.
DR PRO; PR:Q8CB27; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8CB27; protein.
DR Bgee; ENSMUSG00000046404; Expressed in blood and 211 other tissues.
DR Genevisible; Q8CB27; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:1904153; P:negative regulation of retrograde protein transport, ER to cytosol; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:1990167; P:protein K27-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0035523; P:protein K29-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:1990168; P:protein K33-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR InterPro; IPR039138; OTU1_2_3.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR13312; PTHR13312; 1.
DR Pfam; PF02338; OTU; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50802; OTU; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Hydrolase; Metal-binding; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway;
KW Unfolded protein response; Zinc; Zinc-finger.
FT CHAIN 1..343
FT /note="Ubiquitin thioesterase OTU1"
FT /id="PRO_0000282357"
FT DOMAIN 144..269
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT ZN_FING 313..337
FT /note="C2H2-type"
FT REGION 45..123
FT /note="UBX-like"
FT REGION 149..155
FT /note="Cys-loop"
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT REGION 208..218
FT /note="Variable-loop"
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT REGION 258..262
FT /note="His-loop"
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT REGION 286..291
FT /note="S2 site"
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT ACT_SITE 152
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT ACT_SITE 155
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT ACT_SITE 262
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT ACT_SITE 337
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT BINDING 261
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:2KZR"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:2KZR"
FT HELIX 64..74
FT /evidence="ECO:0007829|PDB:2KZR"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:2KZR"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:2KZR"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:2KZR"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:2KZR"
SQ SEQUENCE 343 AA; 37485 MW; C07F3F69F1CA86D8 CRC64;
MFGGAKGGHF GVPPAGYSGA VPQSEAGTKA GPAGGRPADT MWRVRCKAKG GTHLLQGLSS
RTRLRELQGQ IAAITGIAPG SQRILVGYPP ECLDLSDRDI TLGDLPIQSG DMLIVEEDQT
RPKASPAFSK YGAPSYVREA LPVLTRTAVP ADNSCLFTSV YYVVEGGVLN PACAPEMRRL
IAQIVASDPV LYSEAILGKT NEDYCDWIRR DDTWGGAIEI SILSKFYQCE ICVVDTQTVR
IDRFGEDAGY TKRVLLIYDG IHYDPLQRNF PDPDTPPLTI FSSNDDIVLV QALELADEAR
RKRQFTDVNR FTLRCMICQK GLTGQAEARD HARETGHTNF GEV
