UBP10_RAT
ID UBP10_RAT Reviewed; 794 AA.
AC Q3KR59;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 111.
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 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=Spleen;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-568 AND SER-572, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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; BC105892; AAI05893.1; -; mRNA.
DR RefSeq; NP_001029318.1; NM_001034146.1.
DR AlphaFoldDB; Q3KR59; -.
DR SMR; Q3KR59; -.
DR STRING; 10116.ENSRNOP00000022432; -.
DR MEROPS; C19.018; -.
DR iPTMnet; Q3KR59; -.
DR PhosphoSitePlus; Q3KR59; -.
DR jPOST; Q3KR59; -.
DR PaxDb; Q3KR59; -.
DR PRIDE; Q3KR59; -.
DR GeneID; 307905; -.
DR KEGG; rno:307905; -.
DR UCSC; RGD:1561965; rat.
DR CTD; 9100; -.
DR RGD; 1561965; Usp10.
DR VEuPathDB; HostDB:ENSRNOG00000016509; -.
DR eggNOG; KOG1871; Eukaryota.
DR HOGENOM; CLU_008279_4_1_1; -.
DR InParanoid; Q3KR59; -.
DR OMA; TPRTCDS; -.
DR OrthoDB; 1078977at2759; -.
DR PhylomeDB; Q3KR59; -.
DR TreeFam; TF323203; -.
DR Reactome; R-RNO-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:Q3KR59; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000016509; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q3KR59; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
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: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 1: Evidence at protein 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..794
FT /note="Ubiquitin carboxyl-terminal hydrolase 10"
FT /id="PRO_0000393000"
FT DOMAIN 411..791
FT /note="USP"
FT REGION 2..99
FT /note="Interaction with p53/TP53"
FT /evidence="ECO:0000250"
FT REGION 123..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 546..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 420
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 745
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 99
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P52479"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 332
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14694"
FT MOD_RES 568
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 794 AA; 87311 MW; F8D1A3D6C66D0926 CRC64;
MALHNPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTQCG IQAEEELLDG QEHQRIEFGV
DEVIEPSDGL QRAPSYSISS TLNPQAPEFI LGCPTSKKTP DDIEKDETYS SIDQYPASAL
ALESSSNAEA ETLENDSGAG GLGQRERKKK KKRPPGYYSY LKDGSEEGAS PAALVNGHAT
SVGTNSEGVE DPEFMVDMLP SVMPRTCDSP QNPMDLISDP VPDSPFPRTL GGDARTAGLP
EGCRETDFEQ PCLPTDNLLR TAVTQPNAGA DTTENLAVAN GKILESLGEG TAAANGVELH
TDESADLDPA KPESQSPPAE SALSVSGAIS ISQPAKSWAS LFHDSKPSSS SPVAYVETKC
SPPVPSPLAS EKQMEVKEGL VPVSEDPVAI KIAELLETVT LVHKPVSLQP RGLINKGNWC
YINATLQALV ACPPMYHLMK FIPLYSKVQR PCTSTPMIDS FVRLMNEFTN MPVPPKPRQA
LGDKIVRDIR PGAAFEPTYI YRLLTVIKSS LSEKGRQEDA EEYLGFILNG LHEEMLSLKK
LLSPTHEKHS VSNGPGSHLI EDEELEDTGE GSEDEWEQVG PKNKTSVTRQ ADFVQTPITG
IFGGHIRSVV YQQSSKESAT LQPFFTLQLD IQSDKIRTVQ DALESLVARE SVQGYTTKTK
QEVEVSRRVT LEKLPPVLVL HLKRFVYEKT GGCQKLVKNI EYPVDLEISR ELLSPGVKNK
NFKCHRTYRL FAVVYHHGNS ATGGHYTTDV FQIGLNGWLR IDDQTVKVIN QYQVVRPSAD
RTAYLLYYRR VDLL
