UBP10_BOVIN
ID UBP10_BOVIN Reviewed; 800 AA.
AC A5PJS6;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 10;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q14694};
DE AltName: Full=Deubiquitinating enzyme 10;
DE AltName: Full=Ubiquitin thioesterase 10;
DE AltName: Full=Ubiquitin-specific-processing protease 10;
GN Name=USP10;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from target
CC proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential
CC regulator of p53/TP53 stability: in unstressed cells, specifically
CC deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2
CC action and stabilize p53/TP53. Following DNA damage, translocates to
CC the nucleus and deubiquitinates p53/TP53, leading to regulate the
CC p53/TP53-dependent DNA damage response. Component of a regulatory loop
CC that controls autophagy and p53/TP53 levels: mediates deubiquitination
CC of BECN1, a key regulator of autophagy, leading to stabilize the
CC PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing
CC complexes regulate USP10 stability, suggesting the existence of a
CC regulatory system by which PIK3C3/VPS34-containing complexes regulate
CC p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate
CC MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic
CC recycling. Involved in a TANK-dependent negative feedback response to
CC attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in
CC response to interleukin-1-beta (IL1B) stimulation or upon DNA damage.
CC Deubiquitinates TBX21 leading to its stabilization.
CC {ECO:0000250|UniProtKB:Q14694}.
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:Q14694};
CC -!- ACTIVITY REGULATION: Specifically inhibited by spautin-1 (specific and
CC potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10
CC and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-
CC containing complexes (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Found in a deubiquitination complex with TANK, USP10 and
CC ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta
CC (IL1B)-mediated NF-kappaB activation by promoting IKBKG or TRAF6
CC deubiquitination. Interacts with IKBKG; this interaction increases in
CC response to DNA damage. Interacts with TANK; this interaction increases
CC in response to DNA damage. Interacts with TRAF6; this interaction
CC increases in response to DNA damage. Interacts with ZC3H12A; this
CC interaction increases in response to DNA damage. Interacts with G3BP1
CC (via NTF2-like domain) and G3BP2 (via NTF2-like domain). Interacts with
CC p53/TP53, SNX3 and CFTR. Interacts with TBX21.
CC {ECO:0000250|UniProtKB:Q14694}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14694}. Nucleus
CC {ECO:0000250|UniProtKB:Q14694}. Early endosome
CC {ECO:0000250|UniProtKB:Q14694}. Note=Cytoplasmic in normal conditions
CC (By similarity). After DNA damage, translocates to the nucleus
CC following phosphorylation by ATM (By similarity).
CC {ECO:0000250|UniProtKB:Q14694}.
CC -!- PTM: Phosphorylated by ATM following DNA damage, leading to
CC stablization and translocation it to the nucleus. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Deubiquitinated by USP13 (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP10 subfamily.
CC {ECO:0000305}.
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DR EMBL; BC142223; AAI42224.1; -; mRNA.
DR RefSeq; NP_001092394.1; NM_001098924.1.
DR AlphaFoldDB; A5PJS6; -.
DR SMR; A5PJS6; -.
DR STRING; 9913.ENSBTAP00000012432; -.
DR PaxDb; A5PJS6; -.
DR PRIDE; A5PJS6; -.
DR Ensembl; ENSBTAT00000012432; ENSBTAP00000012432; ENSBTAG00000009446.
DR GeneID; 510164; -.
DR KEGG; bta:510164; -.
DR CTD; 9100; -.
DR VEuPathDB; HostDB:ENSBTAG00000009446; -.
DR VGNC; VGNC:36710; USP10.
DR eggNOG; KOG1871; Eukaryota.
DR GeneTree; ENSGT00550000074994; -.
DR HOGENOM; CLU_008279_4_1_1; -.
DR InParanoid; A5PJS6; -.
DR OrthoDB; 1078977at2759; -.
DR TreeFam; TF323203; -.
DR Proteomes; UP000009136; Chromosome 18.
DR Bgee; ENSBTAG00000009446; Expressed in placenta and 104 other tissues.
DR ExpressionAtlas; A5PJS6; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0032021; C:NELF complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; 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; ISS:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR009818; Ataxin-2_C.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR028767; USP10.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR PANTHER; PTHR13328:SF5; PTHR13328:SF5; 1.
DR Pfam; PF07145; PAM2; 1.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Autophagy; Cytoplasm; DNA damage; DNA repair; Endosome;
KW Hydrolase; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT CHAIN 2..800
FT /note="Ubiquitin carboxyl-terminal hydrolase 10"
FT /id="PRO_0000392999"
FT DOMAIN 417..797
FT /note="USP"
FT REGION 2..100
FT /note="Interaction with p53/TP53"
FT /evidence="ECO:0000250"
FT REGION 132..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 306..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 426
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 751
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 24
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P52479"
FT MOD_RES 337
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 565
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
SQ SEQUENCE 800 AA; 86532 MW; 16B8045CABAE6AED CRC64;
MALRSPQYIF GDFSPDEFNQ FFVTPRASVE LPPYGGTVLC GAQAADDLPD GHDYQRIEFG
VNEVIEPSDT LPRTPNYSIS STLNPQAPEF ILSCTTSKKL PDDIDKEVNY SSANCQYPGP
ALALDGGSPA EAEALENDGV SGGLGQRERK KKKKRPPGYY SYLKDGGEGG PSAEALVNGH
AGPAVSNSVG AEDTDLMGDV PTAGTPRTWG SPQDATDFVS DAGPAGAFPG ALDGGARTAG
QLEGCPGADS EASCLPAEAG RDTLLRTAVA QPSVGTDTTE NLGVTNGQIL ESLGEGTAAN
GVELHTVESS DSDPAKAESA PPPADAPASA AGTVPASQPA KSWASLFHDS KPSSSSLPVV
SVETKYSPPA TSPLVSEKQA EVKEGLVPVS EDPVAIKIAE LLENVTLIHK PVSLQPRGLI
NKGNWCYINA TLQALVACPP MYHLMKLIPL YSKVQRPCTS TPMIDSFVRL MNEFTNMPVP
PKPRQALGDK IVRDIRPGAA FEPTYIYRLL TVIKSSLSEK GRQEDAEEYL GFILNGLHEE
MLNLKKLLSP NNDKLTISNG PKSHSVNEDE QEEPGEGSED EWEQVGPRNK TSVTRQADFV
QTPITGIFGG HIRSVVYQQS SKESATLQPF FTLQLDIQSD KIRTVQDALE SLVARESVQG
YTTKTRQEVE ISRRVTLEKL PPVLVLHLKR FVYEKTGGCQ KLIKNIEYPV DLEISKELLS
PGVKNKNFKC HRTYRLFAVV YHHGSSATGG HYTTDVFQIG LNGWLRIDDQ TVKVVSQQQV
VRPAAERTAY LLYYRRVDLL
