P52479 (UBP10_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 10
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 10
Ubiquitin thioesterase 10
Ubiquitin-specific-processing protease 10

Gene names

Name:	Usp10
Synonyms:	Kiaa0190, Ode-1, Uchrp

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	792 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling By similarity.
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Enzyme regulation	Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes By similarity.
Subunit structure	Interacts with G3BP, which may regulate its function. Interacts with p53/TP53, SNX3 and CFTR By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Early endosome By similarity. Note: Cytoplasmic in normal conditions. After DNA damage, translocates to the nucleus following phosphorylation by ATM By similarity.
Post-translational modification	Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus By similarity. Ubiquitinated. Deubiquitinated by USP13 By similarity.
Sequence similarities	Belongs to the peptidase C19 family. USP10 subfamily.
Sequence caution	The sequence BAC97893.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Autophagy DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm Endosome Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator Inferred from sequence or structural similarity. Source: UniProtKB DNA repair Inferred from electronic annotation. Source: UniProtKB-KW autophagy Inferred from electronic annotation. Source: UniProtKB-KW protein deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB regulation of autophagy Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	early endosome Inferred from sequence or structural similarity. Source: UniProtKB intermediate filament cytoskeleton Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	cysteine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB ion channel binding Inferred from sequence or structural similarity. Source: UniProtKB p53 binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin thiolesterase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P52479-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P52479-2)

The sequence of this isoform differs from the canonical sequence as follows:
     49-49: D → DA

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 792	791	Ubiquitin carboxyl-terminal hydrolase 10		PRO_0000080630
Regions
	Region	2 – 99	98	Interaction with p53/TP53 By similarity
Sites
	Active site	418	1	Nucleophile By similarity
	Active site	743	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	24	1	Phosphothreonine By similarity
	Modified residue	205	1	Phosphothreonine Ref.7
	Modified residue	223	1	Phosphoserine By similarity
	Modified residue	330	1	Phosphoserine; by ATM By similarity
	Modified residue	359	1	Phosphoserine By similarity
	Modified residue	364	1	Phosphoserine By similarity
	Modified residue	570	1	Phosphoserine Ref.6 Ref.7 Ref.8 Ref.9
Natural variations
	Alternative sequence	49	1	D → DA in isoform 2.		VSP_038870
Experimental info
	Sequence conflict	72	1	P → R in AAH07134. Ref.5
	Sequence conflict	101	1	E → D in AAH07134. Ref.5
	Sequence conflict	293	1	N → S in AAH07134. Ref.5
	Sequence conflict	347	1	A → S in AAH07134. Ref.5
	Sequence conflict	448	1	R → G in BAE34291. Ref.3
	Sequence conflict	472	1	P → T in BAE32139. Ref.3
	Sequence conflict	528	1	G → R in BAE38053. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 23, 2010. Version 3. Checksum: 02D07A8194215D09	FASTA	792	87,022
	10 20 30 40 50 60 MALHNPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTLCS IQAEDELPDG QEHQRIEFGV 70 80 90 100 110 120 DEVIEPSEGL PPTPSYSISS TLNPQAPEFI LGCTTSKKIP EAVEKDETYS SIDQYPASAL 130 140 150 160 170 180 ALESNSNAEA ETLENDSGAG GLGQRERKKK KKRPPGYYSY LKDGGEDSAS PATLVNGHAT 190 200 210 220 230 240 SVGTSGEAVE DAEFMDVLPP VMPRTCDSPQ NPVDFISGPV PDSPFPRTLG GDARTAGLCE 250 260 270 280 290 300 GCHEADFEQP CLPADSLLRT AGTQPYVGTD TTENFAVANG KILESPGEDT AANGAELHTD 310 320 330 340 350 360 EGADLDPAKP ESQSPPAESA LSASGAIPIS QPAKSWASLF HDSKPSASSP MAYVETKCSP 370 380 390 400 410 420 PVPSPLASEK QMEVKEGLVP VSEDPVAIKI AELLETVTLI HKPVSLQPRG LINKGNWCYI 430 440 450 460 470 480 NATLQALVAC PPMYHLMKFI PLYSKVQRPC TSTPMIDSFV RLMNEFTNMP VPPKPRQALG 490 500 510 520 530 540 DKIVRDIRPG AAFEPTYIYR LLTVIKSSLS EKGRQEDAEE YLGFILNGLH EEMLSLKKLL 550 560 570 580 590 600 SPTHEKHSVS NGPRSDLIED EELEDTGKGS EDEWEQVGPK NKTSITRQAD FVQTPITGIF 610 620 630 640 650 660 GGHIRSVVYQ QSSKESATLQ LFFTLQLDIQ SDKIRTVQDA LESLVARESV QGYTTKTKQE 670 680 690 700 710 720 VEVSRRVTLE KLPPVLVLHL KRFVYEKTGG CQKLVKNIDY PVDLEISREL LSPGIKNKNF 730 740 750 760 770 780 KCQRTYRLFA VVYHHGNSAT GGHYTTDVFQ IGLNGWLRID DQTVKVINQY QVVKPPADRT 790 AYLLYYRRVD LL
	Isoform 2 [UniParc]. Checksum: AC67428E5DBC3D9F	FASTA	793	87,093
	10 20 30 40 50 60 MALHNPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTLCS IQAEDELPDA GQEHQRIEFG 70 80 90 100 110 120 VDEVIEPSEG LPPTPSYSIS STLNPQAPEF ILGCTTSKKI PEAVEKDETY SSIDQYPASA 130 140 150 160 170 180 LALESNSNAE AETLENDSGA GGLGQRERKK KKKRPPGYYS YLKDGGEDSA SPATLVNGHA 190 200 210 220 230 240 TSVGTSGEAV EDAEFMDVLP PVMPRTCDSP QNPVDFISGP VPDSPFPRTL GGDARTAGLC 250 260 270 280 290 300 EGCHEADFEQ PCLPADSLLR TAGTQPYVGT DTTENFAVAN GKILESPGED TAANGAELHT 310 320 330 340 350 360 DEGADLDPAK PESQSPPAES ALSASGAIPI SQPAKSWASL FHDSKPSASS PMAYVETKCS 370 380 390 400 410 420 PPVPSPLASE KQMEVKEGLV PVSEDPVAIK IAELLETVTL IHKPVSLQPR GLINKGNWCY 430 440 450 460 470 480 INATLQALVA CPPMYHLMKF IPLYSKVQRP CTSTPMIDSF VRLMNEFTNM PVPPKPRQAL 490 500 510 520 530 540 GDKIVRDIRP GAAFEPTYIY RLLTVIKSSL SEKGRQEDAE EYLGFILNGL HEEMLSLKKL 550 560 570 580 590 600 LSPTHEKHSV SNGPRSDLIE DEELEDTGKG SEDEWEQVGP KNKTSITRQA DFVQTPITGI 610 620 630 640 650 660 FGGHIRSVVY QQSSKESATL QLFFTLQLDI QSDKIRTVQD ALESLVARES VQGYTTKTKQ 670 680 690 700 710 720 EVEVSRRVTL EKLPPVLVLH LKRFVYEKTG GCQKLVKNID YPVDLEISRE LLSPGIKNKN 730 740 750 760 770 780 FKCQRTYRLF AVVYHHGNSA TGGHYTTDVF QIGLNGWLRI DDQTVKVINQ YQVVKPPADR 790 TAYLLYYRRV DLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning from a mouse osteoblastic cell line of a gene, encoding a ubiquitin carboxyl-terminal hydrolase related polypeptide, down regulated during ascorbic acid dependent differentiation." Ito M., Hitomi K., Tsukagoshi N. Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Embryonic tail.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J and NOD. Tissue: Inner ear, Spleen and Thymus.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary tumor.
[6]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-205 AND SER-570, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570, MASS SPECTROMETRY. Tissue: Liver.
[9]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D84096 mRNA. Translation: BAA12220.1. AK129083 mRNA. Translation: BAC97893.1. Different initiation. AK153675 mRNA. Translation: BAE32139.1. AK157970 mRNA. Translation: BAE34291.1. AK165156 mRNA. Translation: BAE38053.1. AK172443 mRNA. Translation: BAE43006.1. CH466525 Genomic DNA. Translation: EDL11620.1. BC007134 mRNA. Translation: AAH07134.1.
IPI	IPI00420601. IPI00955687.
RefSeq	NP_033488.1. NM_009462.1.
UniGene	Mm.256910. Mm.421337.
3D structure databases
ProteinModelPortal	P52479.
SMR	P52479. Positions 410-790.
ModBase	Search...
Protein family/group databases
MEROPS	C19.018.
PTM databases
PhosphoSite	P52479.
Proteomic databases
PRIDE	P52479.
Protocols and materials databases
DNASU	22224.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000108988; ENSMUSP00000104616; ENSMUSG00000031826. ENSMUST00000144458; ENSMUSP00000123590; ENSMUSG00000031826.
GeneID	22224.
KEGG	mmu:22224.
UCSC	uc009nqn.1. mouse. uc009nqo.1. mouse.
Organism-specific databases
CTD	9100.
MGI	MGI:894652. Usp10.
Rouge	Search...
Phylogenomic databases
GeneTree	ENSGT00550000074994.
HOVERGEN	HBG059823.
InParanoid	Q6ZQG9.
KO	K11841.
OMA	GQEYQRI.
Gene expression databases
ArrayExpress	P52479.
Bgee	P52479.
CleanEx	MM_USP10.
Genevestigator	P52479.
GermOnline	ENSMUSG00000031826. Mus musculus.
Family and domain databases
InterPro	IPR009818. Ataxin-2_C. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
Pfam	PF07145. PAM2. 1 hit. PF00443. UCH. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	USP10. mouse.
NextBio	302247.
SOURCE	Search...

Entry information

Entry name

UBP10_MOUSE

Accession

Primary (citable) accession number: P52479
Secondary accession number(s): Q3T9L4 , Q3TNN5, Q3TZB8, Q3U5E0, Q6ZQG9, Q91VY7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	March 23, 2010
Last modified:	May 1, 2013
This is version 108 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program