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Protein

Ubiquitin carboxyl-terminal hydrolase 13

Gene

USP13

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.6 Publications

Catalytic activityi

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 regulationi

Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei345NucleophileCurated1
Active sitei823Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri209 – 281UBP-typePROSITE-ProRule annotationAdd BLAST73

GO - Molecular functioni

  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • chaperone binding Source: ParkinsonsUK-UCL
  • cysteine-type endopeptidase activity Source: UniProtKB
  • proteasome binding Source: ParkinsonsUK-UCL
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-specific protease activity involved in positive regulation of ERAD pathway Source: ParkinsonsUK-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • cell proliferation Source: UniProtKB
  • maintenance of unfolded protein involved in ERAD pathway Source: ParkinsonsUK-UCL
  • melanocyte differentiation Source: UniProtKB
  • positive regulation of ERAD pathway Source: ParkinsonsUK-UCL
  • protein K63-linked deubiquitination Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of autophagy Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Autophagy, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS00715-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.012.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 13 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 13
Isopeptidase T-3
Short name:
ISOT-3
Ubiquitin thioesterase 13
Ubiquitin-specific-processing protease 13
Gene namesi
Name:USP13
Synonyms:ISOT3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:12611. USP13.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi221W → A: Does not abolish ability to stabilize SIAH2. 1 Publication1
Mutagenesisi233K → A: Does not abolish ability to stabilize SIAH2. 1 Publication1
Mutagenesisi273F → A: Impairs ability to stabilize SIAH2. 1 Publication1
Mutagenesisi345C → A: Abolishes deubiquitinating activity. Does not abolish ability to stabilize SIAH2. Does not abolish ability to stabilize SIAH2; when associated with A-814 and A-823. 2 Publications1
Mutagenesisi664M → E: Impairs ability to stabilize SIAH2. Abolishes ability to stabilize SIAH2; when associated with E-739. 1 Publication1
Mutagenesisi739M → E: Impairs ability to stabilize SIAH2. Abolishes ability to stabilize SIAH2; when associated with E-664. 1 Publication1
Mutagenesisi814H → A: Does not abolish ability to stabilize SIAH2; when associated with A-345 and A-823. 1 Publication1
Mutagenesisi823H → A: Does not abolish ability to stabilize SIAH2; when associated with A-345 and A-814. 1 Publication1

Organism-specific databases

DisGeNETi8975.
OpenTargetsiENSG00000058056.
PharmGKBiPA37237.

Chemistry databases

ChEMBLiCHEMBL3407324.

Polymorphism and mutation databases

BioMutaiUSP13.
DMDMi209572692.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806351 – 863Ubiquitin carboxyl-terminal hydrolase 13Add BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei114PhosphoserineCombined sources1
Modified residuei122PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92995.
MaxQBiQ92995.
PaxDbiQ92995.
PeptideAtlasiQ92995.
PRIDEiQ92995.

PTM databases

iPTMnetiQ92995.
PhosphoSitePlusiQ92995.

Expressioni

Tissue specificityi

Highly expressed in ovary and testes.

Gene expression databases

BgeeiENSG00000058056.
CleanExiHS_USP13.
ExpressionAtlasiQ92995. baseline and differential.
GenevisibleiQ92995. HS.

Organism-specific databases

HPAiHPA004827.

Interactioni

Subunit structurei

Interacts with UFD1. Interacts (via UBA domains) with SIAH2 (when ubiquitinated).2 Publications

GO - Molecular functioni

  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • chaperone binding Source: ParkinsonsUK-UCL
  • proteasome binding Source: ParkinsonsUK-UCL
  • ubiquitin binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114465. 49 interactors.
DIPiDIP-53511N.
IntActiQ92995. 31 interactors.
MINTiMINT-1195142.
STRINGi9606.ENSP00000263966.

Chemistry databases

BindingDBiQ92995.

Structurei

Secondary structure

1863
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni191 – 194Combined sources4
Beta strandi212 – 214Combined sources3
Beta strandi217 – 223Combined sources7
Turni224 – 226Combined sources3
Beta strandi229 – 231Combined sources3
Helixi244 – 251Combined sources8
Beta strandi256 – 260Combined sources5
Beta strandi269 – 272Combined sources4
Turni273 – 275Combined sources3
Beta strandi277 – 279Combined sources3
Helixi284 – 290Combined sources7
Helixi296 – 299Combined sources4
Helixi656 – 662Combined sources7
Helixi669 – 678Combined sources10
Helixi683 – 692Combined sources10
Helixi693 – 695Combined sources3
Beta strandi697 – 700Combined sources4
Beta strandi710 – 714Combined sources5
Helixi730 – 739Combined sources10
Helixi743 – 753Combined sources11
Helixi757 – 765Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L80NMR-A188-301[»]
2LBCNMR-A652-777[»]
ProteinModelPortaliQ92995.
SMRiQ92995.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini336 – 861USPAdd BLAST526
Domaini652 – 693UBA 1PROSITE-ProRule annotationAdd BLAST42
Domaini727 – 767UBA 2PROSITE-ProRule annotationAdd BLAST41

Domaini

The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin. Swapping with the UBP-type zinc finger from USP5 restores ability to bind unanchored ubiquitin and subsequent activation of the protein (PubMed:22216260).1 Publication
The UBA domains mediate binding to ubiquitin.1 Publication

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 2 UBA domains.PROSITE-ProRule annotation
Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri209 – 281UBP-typePROSITE-ProRule annotationAdd BLAST73

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0944. Eukaryota.
COG5207. LUCA.
GeneTreeiENSGT00390000000874.
HOGENOMiHOG000162311.
HOVERGENiHBG002833.
InParanoidiQ92995.
KOiK11836.
OMAiMKEEHKP.
OrthoDBiEOG091G01W3.
PhylomeDBiQ92995.
TreeFamiTF300576.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR015940. UBA.
IPR009060. UBA-like.
IPR016652. Ubiquitinyl_hydrolase.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF00627. UBA. 2 hits.
PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PIRSFiPIRSF016308. UBP. 1 hit.
SMARTiSM00165. UBA. 2 hits.
SM00290. ZnF_UBP. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiPS50030. UBA. 2 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92995-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQRRGALFGM PGGSGGRKMA AGDIGELLVP HMPTIRVPRS GDRVYKNECA
60 70 80 90 100
FSYDSPNSEG GLYVCMNTFL AFGREHVERH FRKTGQSVYM HLKRHVREKV
110 120 130 140 150
RGASGGALPK RRNSKIFLDL DTDDDLNSDD YEYEDEAKLV IFPDHYEIAL
160 170 180 190 200
PNIEELPALV TIACDAVLSS KSPYRKQDPD TWENELPVSK YANNLTQLDN
210 220 230 240 250
GVRIPPSGWK CARCDLRENL WLNLTDGSVL CGKWFFDSSG GNGHALEHYR
260 270 280 290 300
DMGYPLAVKL GTITPDGADV YSFQEEEPVL DPHLAKHLAH FGIDMLHMHG
310 320 330 340 350
TENGLQDNDI KLRVSEWEVI QESGTKLKPM YGPGYTGLKN LGNSCYLSSV
360 370 380 390 400
MQAIFSIPEF QRAYVGNLPR IFDYSPLDPT QDFNTQMTKL GHGLLSGQYS
410 420 430 440 450
KPPVKSELIE QVMKEEHKPQ QNGISPRMFK AFVSKSHPEF SSNRQQDAQE
460 470 480 490 500
FFLHLVNLVE RNRIGSENPS DVFRFLVEER IQCCQTRKVR YTERVDYLMQ
510 520 530 540 550
LPVAMEAATN KDELIAYELT RREAEANRRP LPELVRAKIP FSACLQAFSE
560 570 580 590 600
PENVDDFWSS ALQAKSAGVK TSRFASFPEY LVVQIKKFTF GLDWVPKKFD
610 620 630 640 650
VSIDMPDLLD INHLRARGLQ PGEEELPDIS PPIVIPDDSK DRLMNQLIDP
660 670 680 690 700
SDIDESSVMQ LAEMGFPLEA CRKAVYFTGN MGAEVAFNWI IVHMEEPDFA
710 720 730 740 750
EPLTMPGYGG AASAGASVFG ASGLDNQPPE EIVAIITSMG FQRNQAIQAL
760 770 780 790 800
RATNNNLERA LDWIFSHPEF EEDSDFVIEM ENNANANIIS EAKPEGPRVK
810 820 830 840 850
DGSGTYELFA FISHMGTSTM SGHYICHIKK EGRWVIYNDH KVCASERPPK
860
DLGYMYFYRR IPS
Length:863
Mass (Da):97,327
Last modified:October 14, 2008 - v2
Checksum:i988713ADF8C0B938
GO
Isoform 2 (identifier: Q92995-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Note: No experimental confirmation available.
Show »
Length:798
Mass (Da):90,383
Checksum:i5F9943C19D16FE4F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96V → A in AAC63405 (PubMed:9841226).Curated1
Sequence conflicti293I → V in BAF83027 (PubMed:14702039).Curated1
Sequence conflicti305L → F in BAF83027 (PubMed:14702039).Curated1
Sequence conflicti325T → A in BAF83027 (PubMed:14702039).Curated1
Sequence conflicti338L → P in BAF83027 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0439541 – 65Missing in isoform 2. 1 PublicationAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75362 mRNA. Translation: AAC63405.1.
AK290338 mRNA. Translation: BAF83027.1.
AK302404 mRNA. Translation: BAG63715.1.
AC007687 Genomic DNA. No translation available.
AC125604 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78383.1.
CH471052 Genomic DNA. Translation: EAW78384.1.
BC016146 mRNA. Translation: AAH16146.1.
CCDSiCCDS3235.1. [Q92995-1]
RefSeqiNP_003931.2. NM_003940.2. [Q92995-1]
UniGeneiHs.175322.

Genome annotation databases

EnsembliENST00000263966; ENSP00000263966; ENSG00000058056. [Q92995-1]
ENST00000496897; ENSP00000417146; ENSG00000058056. [Q92995-2]
GeneIDi8975.
KEGGihsa:8975.
UCSCiuc003fkh.4. human. [Q92995-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75362 mRNA. Translation: AAC63405.1.
AK290338 mRNA. Translation: BAF83027.1.
AK302404 mRNA. Translation: BAG63715.1.
AC007687 Genomic DNA. No translation available.
AC125604 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78383.1.
CH471052 Genomic DNA. Translation: EAW78384.1.
BC016146 mRNA. Translation: AAH16146.1.
CCDSiCCDS3235.1. [Q92995-1]
RefSeqiNP_003931.2. NM_003940.2. [Q92995-1]
UniGeneiHs.175322.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L80NMR-A188-301[»]
2LBCNMR-A652-777[»]
ProteinModelPortaliQ92995.
SMRiQ92995.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114465. 49 interactors.
DIPiDIP-53511N.
IntActiQ92995. 31 interactors.
MINTiMINT-1195142.
STRINGi9606.ENSP00000263966.

Chemistry databases

BindingDBiQ92995.
ChEMBLiCHEMBL3407324.

Protein family/group databases

MEROPSiC19.012.

PTM databases

iPTMnetiQ92995.
PhosphoSitePlusiQ92995.

Polymorphism and mutation databases

BioMutaiUSP13.
DMDMi209572692.

Proteomic databases

EPDiQ92995.
MaxQBiQ92995.
PaxDbiQ92995.
PeptideAtlasiQ92995.
PRIDEiQ92995.

Protocols and materials databases

DNASUi8975.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263966; ENSP00000263966; ENSG00000058056. [Q92995-1]
ENST00000496897; ENSP00000417146; ENSG00000058056. [Q92995-2]
GeneIDi8975.
KEGGihsa:8975.
UCSCiuc003fkh.4. human. [Q92995-1]

Organism-specific databases

CTDi8975.
DisGeNETi8975.
GeneCardsiUSP13.
H-InvDBHIX0003883.
HGNCiHGNC:12611. USP13.
HPAiHPA004827.
MIMi603591. gene.
neXtProtiNX_Q92995.
OpenTargetsiENSG00000058056.
PharmGKBiPA37237.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0944. Eukaryota.
COG5207. LUCA.
GeneTreeiENSGT00390000000874.
HOGENOMiHOG000162311.
HOVERGENiHBG002833.
InParanoidiQ92995.
KOiK11836.
OMAiMKEEHKP.
OrthoDBiEOG091G01W3.
PhylomeDBiQ92995.
TreeFamiTF300576.

Enzyme and pathway databases

BioCyciZFISH:HS00715-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiUSP13. human.
GeneWikiiUSP13.
GenomeRNAii8975.
PROiQ92995.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000058056.
CleanExiHS_USP13.
ExpressionAtlasiQ92995. baseline and differential.
GenevisibleiQ92995. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR015940. UBA.
IPR009060. UBA-like.
IPR016652. Ubiquitinyl_hydrolase.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF00627. UBA. 2 hits.
PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PIRSFiPIRSF016308. UBP. 1 hit.
SMARTiSM00165. UBA. 2 hits.
SM00290. ZnF_UBP. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiPS50030. UBA. 2 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP13_HUMAN
AccessioniPrimary (citable) accession number: Q92995
Secondary accession number(s): A8K2S3
, B4DYF3, D3DNS2, Q96B25
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 14, 2008
Last modified: November 30, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.