A5PJS6 (UBP10_BOVIN) 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

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	800 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.

Ontologies

Keywords
Biological process	Autophagy DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm Endosome Nucleus
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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 800	799	Ubiquitin carboxyl-terminal hydrolase 10		PRO_0000392999
Regions
	Region	2 – 100	99	Interaction with p53/TP53 By similarity
Sites
	Active site	426	1	Nucleophile By similarity
	Active site	751	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	208	1	Phosphothreonine By similarity
	Modified residue	337	1	Phosphoserine; by ATM By similarity
	Modified residue	367	1	Phosphoserine By similarity
	Modified residue	372	1	Phosphoserine By similarity
	Modified residue	565	1	Phosphoserine By similarity
	Modified residue	578	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	A5PJS6 [UniParc]. Last modified July 10, 2007. Version 1. Checksum: 16B8045CABAE6AED	FASTA	800	86,532
	10 20 30 40 50 60 MALRSPQYIF GDFSPDEFNQ FFVTPRASVE LPPYGGTVLC GAQAADDLPD GHDYQRIEFG 70 80 90 100 110 120 VNEVIEPSDT LPRTPNYSIS STLNPQAPEF ILSCTTSKKL PDDIDKEVNY SSANCQYPGP 130 140 150 160 170 180 ALALDGGSPA EAEALENDGV SGGLGQRERK KKKKRPPGYY SYLKDGGEGG PSAEALVNGH 190 200 210 220 230 240 AGPAVSNSVG AEDTDLMGDV PTAGTPRTWG SPQDATDFVS DAGPAGAFPG ALDGGARTAG 250 260 270 280 290 300 QLEGCPGADS EASCLPAEAG RDTLLRTAVA QPSVGTDTTE NLGVTNGQIL ESLGEGTAAN 310 320 330 340 350 360 GVELHTVESS DSDPAKAESA PPPADAPASA AGTVPASQPA KSWASLFHDS KPSSSSLPVV 370 380 390 400 410 420 SVETKYSPPA TSPLVSEKQA EVKEGLVPVS EDPVAIKIAE LLENVTLIHK PVSLQPRGLI 430 440 450 460 470 480 NKGNWCYINA TLQALVACPP MYHLMKLIPL YSKVQRPCTS TPMIDSFVRL MNEFTNMPVP 490 500 510 520 530 540 PKPRQALGDK IVRDIRPGAA FEPTYIYRLL TVIKSSLSEK GRQEDAEEYL GFILNGLHEE 550 560 570 580 590 600 MLNLKKLLSP NNDKLTISNG PKSHSVNEDE QEEPGEGSED EWEQVGPRNK TSVTRQADFV 610 620 630 640 650 660 QTPITGIFGG HIRSVVYQQS SKESATLQPF FTLQLDIQSD KIRTVQDALE SLVARESVQG 670 680 690 700 710 720 YTTKTRQEVE ISRRVTLEKL PPVLVLHLKR FVYEKTGGCQ KLIKNIEYPV DLEISKELLS 730 740 750 760 770 780 PGVKNKNFKC HRTYRLFAVV YHHGSSATGG HYTTDVFQIG LNGWLRIDDQ TVKVVSQQQV 790 800 VRPAAERTAY LLYYRRVDLL

References

[1]	NIH - Mammalian Gene Collection (MGC) project Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Hereford. Tissue: Fetal skin.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC142223 mRNA. Translation: AAI42224.1.
IPI	IPI00714006.
RefSeq	NP_001092394.1. NM_001098924.1.
UniGene	Bt.27346.
3D structure databases
ProteinModelPortal	A5PJS6.
ModBase	Search...
Protein-protein interaction databases
STRING	9913.ENSBTAP00000012432.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000012432; ENSBTAP00000012432; ENSBTAG00000009446.
GeneID	510164.
KEGG	bta:510164.
Organism-specific databases
CTD	9100.
Phylogenomic databases
eggNOG	COG5533.
GeneTree	ENSGT00550000074994.
HOGENOM	HOG000285959.
HOVERGEN	HBG059823.
InParanoid	A5PJS6.
KO	K11841.
OMA	GQEYQRI.
OrthoDB	EOG4FN4H7.
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
NextBio	20869309.

Entry information

Entry name

UBP10_BOVIN

Accession

Primary (citable) accession number: A5PJS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 23, 2010
Last sequence update:	July 10, 2007
Last modified:	April 3, 2013
This is version 41 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program