OTU1_RAT
ID OTU1_RAT Reviewed; 343 AA.
AC Q32Q05; Q6IE74;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Ubiquitin thioesterase OTU1;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q5VVQ6};
GN Name=Yod1; Synonyms=Hshin7;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [2]
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).
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}.
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DR EMBL; BC107904; AAI07905.1; -; mRNA.
DR EMBL; BN000319; CAE48374.1; -; mRNA.
DR RefSeq; NP_001008889.1; NM_001008889.1.
DR AlphaFoldDB; Q32Q05; -.
DR SMR; Q32Q05; -.
DR BioGRID; 264526; 1.
DR STRING; 10116.ENSRNOP00000031836; -.
DR MEROPS; C85.007; -.
DR iPTMnet; Q32Q05; -.
DR PhosphoSitePlus; Q32Q05; -.
DR PaxDb; Q32Q05; -.
DR Ensembl; ENSRNOT00000030476; ENSRNOP00000031836; ENSRNOG00000025704.
DR GeneID; 363982; -.
DR KEGG; rno:363982; -.
DR UCSC; RGD:1359726; rat.
DR CTD; 55432; -.
DR RGD; 1359726; Yod1.
DR eggNOG; KOG3288; Eukaryota.
DR GeneTree; ENSGT00390000009989; -.
DR HOGENOM; CLU_049327_1_0_1; -.
DR InParanoid; Q32Q05; -.
DR OMA; NEEYCDW; -.
DR OrthoDB; 1327072at2759; -.
DR PhylomeDB; Q32Q05; -.
DR TreeFam; TF323700; -.
DR Reactome; R-RNO-5689896; Ovarian tumor domain proteases.
DR PRO; PR:Q32Q05; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000025704; Expressed in esophagus and 18 other tissues.
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:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
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:RGD.
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 2: Evidence at transcript level;
KW Cytoplasm; Hydrolase; Metal-binding; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway; Unfolded protein response; Zinc;
KW Zinc-finger.
FT CHAIN 1..343
FT /note="Ubiquitin thioesterase OTU1"
FT /id="PRO_0000282358"
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"
SQ SEQUENCE 343 AA; 37402 MW; AD23FFBF8A4AC502 CRC64;
MFGGAKGGHF GVPPAGCSGA VSQAAAGTKA GPAGGRPADT MWRLRCKAKG GTHVLQGLSN
RTRLRELQGQ IAAITGIAPG SQRILVGYPP ECLDLSDRDI TLGDLPIQSG DMLIVEEDQT
RPKASPAFSK HGAPSYVRET LPVLTRTAVP ADNSCLFTSV YYVVEGGVLN PACAPEMRRL
IAQIVASDPD LYSEAILGKT NEEYCDWIRR DDTWGGAIEI SILSKFYQCE ICVVDTQTVR
IDRFGEDAGY TKRVLLIYDG IHYDPLQRNF PDPDTPPLTI FSSNDDIVLV QALELADEAR
RKRQFTDVNR FTLRCMLCQK GLTGQAEARD HARETGHTNF GEV
