UniProt Accession

 UBP13_HUMAN; Q92995; A8K2S3; B4DYF3; D3DNS2; Q96B25 

Genbank Protein ID

 U75362; AK290338; AK302404; AC007687; AC125604; CH471052; CH471052; BC016146 

Genbank Nucleotide ID

 AAC63405.1; BAF83027.1; BAG63715.1; EAW78383.1; EAW78384.1; AAH16146.1 

Protein Name

 Ubiquitin carboxyl-terminal hydrolase 13 

Protein Synonyms/Alias

 Deubiquitinating enzyme 13; Isopeptidase T-3; ISOT-3; Ubiquitin thioesterase 13; Ubiquitin-specific-processing protease 13 

Gene Name

 USP13 

Gene Synonyms/Alias

 ISOT3 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
18	PGGSGGRKMAAGDIG	ubiquitination	[1, 2, 3, 4, 5, 6]
176	SSKSPYRKQDPDTWE	ubiquitination	[1, 6, 7]
190	ENELPVSKYANNLTQ	ubiquitination	[1, 2, 3, 5, 6, 7, 8, 9]
259	MGYPLAVKLGTITPD	ubiquitination	[1, 2, 3, 5, 6, 7]
326	VIQESGTKLKPMYGP	ubiquitination	[1, 2, 5, 7]
328	QESGTKLKPMYGPGY	ubiquitination	[1, 3, 4, 5, 6, 7, 8, 9]
389	DFNTQMTKLGHGLLS	ubiquitination	[5]
401	LLSGQYSKPPVKSEL	ubiquitination	[1, 5]
430	GISPRMFKAFVSKSH	ubiquitination	[1, 3, 4, 5]
435	MFKAFVSKSHPEFSS	ubiquitination	[1, 5]
511	AMEAATNKDELIAYE	ubiquitination	[1]
565	WSSALQAKSAGVKTS	ubiquitination	[5]
586	EYLVVQIKKFTFGLD	ubiquitination	[1, 7]
587	YLVVQIKKFTFGLDW	ubiquitination	[1, 4, 5]
597	FGLDWVPKKFDVSID	ubiquitination	[1, 8]
598	GLDWVPKKFDVSIDM	ubiquitination	[5]
640	IVIPDDSKDRLMNQL	ubiquitination	[1, 2, 5, 6, 7, 10, 11, 12]
841	WVIYNDHKVCASERP	ubiquitination	[5]
850	CASERPPKDLGYMYF	ubiquitination	[5]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [10] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [11] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [12] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum- associated degradation (ERAD). 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. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34- containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data. 

Sequence Annotation

 DOMAIN 652 693 UBA 1.
 DOMAIN 727 767 UBA 2.
 ZN_FING 209 281 UBP-type.
 ACT_SITE 345 345 Nucleophile (Probable).
 ACT_SITE 823 823 Proton acceptor (By similarity).
 MOD_RES 114 114 Phosphoserine.
 MOD_RES 122 122 Phosphothreonine.  

Keyword

 3D-structure; Alternative splicing; Autophagy; Complete proteome; Hydrolase; Metal-binding; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 863 AA 

Protein Sequence

Gene Ontology

 GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
 GO:0008242; F:omega peptidase activity; IEA:InterPro.
 GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0008283; P:cell proliferation; IMP:UniProtKB.
 GO:0030318; P:melanocyte differentiation; TAS:UniProtKB.
 GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
 GO:0050821; P:protein stabilization; IDA:UniProtKB.
 GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
 GO:0006355; P:regulation of transcription, DNA-dependent; IMP:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 

Interpro

 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR009060; UBA-like.
 IPR000449; UBA/transl_elong_EF1B_N.
 IPR015940; UBA/transl_elong_EF1B_N_euk.
 IPR016652; Ubiquitinyl_hydrolase.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR001607; Znf_UBP. 

Pfam

 PF00627; UBA
 PF00443; UCH
 PF02148; zf-UBP 

SMART

 SM00165; UBA
 SM00290; ZnF_UBP 

PROSITE

 PS50030; UBA
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3
 PS50271; ZF_UBP 

PRINTS