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Protein

Ubiquitin carboxyl-terminal hydrolase 46

Gene

USP46

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

Functioni

Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67 (By similarity). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014).By similarity1 Publication

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).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei44NucleophilePROSITE-ProRule annotation1 Publication1 Publication1
Active sitei313Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Behavior, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS03209-MONOMER.

Protein family/group databases

MEROPSiC19.052.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 46 (EC:3.4.19.123 Publications)
Alternative name(s):
Deubiquitinating enzyme 46
Ubiquitin thioesterase 46
Ubiquitin-specific-processing protease 46
Gene namesi
Name:USP46
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:20075. USP46.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44C → S: Abolishes enzyme activity. 2 Publications1

Organism-specific databases

DisGeNETi64854.
OpenTargetsiENSG00000109189.
PharmGKBiPA134922048.

Polymorphism and mutation databases

BioMutaiUSP46.
DMDMi49065850.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806741 – 366Ubiquitin carboxyl-terminal hydrolase 46Add BLAST366

Proteomic databases

EPDiP62068.
MaxQBiP62068.
PaxDbiP62068.
PeptideAtlasiP62068.
PRIDEiP62068.

PTM databases

PhosphoSitePlusiP62068.

Expressioni

Tissue specificityi

Broadly expressed.1 Publication

Gene expression databases

BgeeiENSG00000109189.
CleanExiHS_USP46.
ExpressionAtlasiP62068. baseline and differential.
GenevisibleiP62068. HS.

Organism-specific databases

HPAiCAB076369.
CAB076370.
HPA007288.

Interactioni

Subunit structurei

Interacts with WDR48.2 Publications

Protein-protein interaction databases

BioGridi122327. 36 interactors.
DIPiDIP-53590N.
IntActiP62068. 20 interactors.
STRINGi9606.ENSP00000407818.

Structurei

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 37Combined sources4
Beta strandi40 – 42Combined sources3
Helixi44 – 54Combined sources11
Helixi57 – 68Combined sources12
Helixi76 – 89Combined sources14
Beta strandi91 – 97Combined sources7
Helixi100 – 109Combined sources10
Helixi111 – 113Combined sources3
Beta strandi114 – 117Combined sources4
Helixi121 – 141Combined sources21
Helixi167 – 172Combined sources6
Beta strandi174 – 182Combined sources9
Turni183 – 185Combined sources3
Beta strandi188 – 200Combined sources13
Beta strandi204 – 207Combined sources4
Helixi208 – 215Combined sources8
Beta strandi219 – 221Combined sources3
Helixi223 – 225Combined sources3
Beta strandi227 – 229Combined sources3
Turni230 – 233Combined sources4
Beta strandi234 – 236Combined sources3
Beta strandi238 – 246Combined sources9
Beta strandi249 – 255Combined sources7
Beta strandi258 – 261Combined sources4
Turni262 – 265Combined sources4
Beta strandi266 – 269Combined sources4
Beta strandi278 – 283Combined sources6
Beta strandi286 – 290Combined sources5
Beta strandi293 – 311Combined sources19
Beta strandi313 – 320Combined sources8
Beta strandi323 – 328Combined sources6
Beta strandi331 – 335Combined sources5
Helixi337 – 344Combined sources8
Beta strandi354 – 364Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CVMX-ray1.90A25-366[»]
5CVNX-ray3.36B25-366[»]
5CVOX-ray3.88B/E25-366[»]
5L8HX-ray1.85A8-366[»]
ProteinModelPortaliP62068.
SMRiP62068.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 365USPAdd BLAST331

Sequence similaritiesi

Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1864. Eukaryota.
ENOG410XQ81. LUCA.
GeneTreeiENSGT00850000132276.
HOVERGENiHBG054038.
InParanoidiP62068.
KOiK11842.
OMAiNGNPKSN.
OrthoDBiEOG091G0FC5.
PhylomeDBiP62068.
TreeFamiTF314144.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P62068-1) [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
MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL
60 70 80 90 100
QALYFCRPFR ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK
110 120 130 140 150
KFISRLRKEN DLFDNYMQQD AHEFLNYLLN TIADILQEEK KQEKQNGKLK
160 170 180 190 200
NGNMNEPAEN NKPELTWVHE IFQGTLTNET RCLNCETVSS KDEDFLDLSV
210 220 230 240 250
DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK RMRVKKLPMI
260 270 280 290 300
LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA
310 320 330 340 350
VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI
360
SKNSESGYIL FYQSRE
Length:366
Mass (Da):42,442
Last modified:June 21, 2004 - v1
Checksum:i67BB113FC4081C46
GO
Isoform 2 (identifier: P62068-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-116: Missing.
     334-366: KIDAQAIEEFYGLTSDISKNSESGYILFYQSRE → VGLQIILQ

Note: No experimental confirmation available.
Show »
Length:225
Mass (Da):26,243
Checksum:i1460D49881E7AFBF
GO
Isoform 3 (identifier: P62068-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MTVRNIASICNM → MNCFQ

Note: No experimental confirmation available.
Show »
Length:359
Mass (Da):41,732
Checksum:i724DEC421BEC14AC
GO
Isoform 4 (identifier: P62068-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     40-51: Missing.

Note: No experimental confirmation available.
Show »
Length:354
Mass (Da):41,112
Checksum:i0018B82362D8A874
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti177T → A in BAH13161 (PubMed:14702039).Curated1
Sequence conflicti250I → V in BAB14133 (PubMed:14702039).Curated1
Sequence conflicti265H → R in BAB14133 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05154081A → V.Corresponds to variant rs17475800dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0376181 – 116Missing in isoform 2. 1 PublicationAdd BLAST116
Alternative sequenceiVSP_0376191 – 12MTVRN…SICNM → MNCFQ in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_03762040 – 51Missing in isoform 4. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_037621334 – 366KIDAQ…YQSRE → VGLQIILQ in isoform 2. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
GU455414 mRNA. Translation: ADV57651.1.
AK022614 mRNA. Translation: BAB14133.1.
AK024318 mRNA. Translation: BAB14881.1.
AK296493 mRNA. Translation: BAH12373.1.
AK299883 mRNA. Translation: BAH13161.1.
AK302438 mRNA. Translation: BAH13709.1.
CH471057 Genomic DNA. Translation: EAX05435.1.
BC037574 mRNA. Translation: AAH37574.1.
CCDSiCCDS47053.1. [P62068-1]
CCDS47054.1. [P62068-3]
RefSeqiNP_001127695.1. NM_001134223.1. [P62068-3]
NP_001273696.1. NM_001286767.1. [P62068-4]
NP_001273697.1. NM_001286768.1. [P62068-2]
NP_073743.2. NM_022832.3. [P62068-1]
UniGeneiHs.7966.

Genome annotation databases

EnsembliENST00000441222; ENSP00000407818; ENSG00000109189. [P62068-1]
ENST00000508499; ENSP00000423244; ENSG00000109189. [P62068-3]
GeneIDi64854.
KEGGihsa:64854.
UCSCiuc003gzm.5. human. [P62068-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
GU455414 mRNA. Translation: ADV57651.1.
AK022614 mRNA. Translation: BAB14133.1.
AK024318 mRNA. Translation: BAB14881.1.
AK296493 mRNA. Translation: BAH12373.1.
AK299883 mRNA. Translation: BAH13161.1.
AK302438 mRNA. Translation: BAH13709.1.
CH471057 Genomic DNA. Translation: EAX05435.1.
BC037574 mRNA. Translation: AAH37574.1.
CCDSiCCDS47053.1. [P62068-1]
CCDS47054.1. [P62068-3]
RefSeqiNP_001127695.1. NM_001134223.1. [P62068-3]
NP_001273696.1. NM_001286767.1. [P62068-4]
NP_001273697.1. NM_001286768.1. [P62068-2]
NP_073743.2. NM_022832.3. [P62068-1]
UniGeneiHs.7966.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CVMX-ray1.90A25-366[»]
5CVNX-ray3.36B25-366[»]
5CVOX-ray3.88B/E25-366[»]
5L8HX-ray1.85A8-366[»]
ProteinModelPortaliP62068.
SMRiP62068.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122327. 36 interactors.
DIPiDIP-53590N.
IntActiP62068. 20 interactors.
STRINGi9606.ENSP00000407818.

Protein family/group databases

MEROPSiC19.052.

PTM databases

PhosphoSitePlusiP62068.

Polymorphism and mutation databases

BioMutaiUSP46.
DMDMi49065850.

Proteomic databases

EPDiP62068.
MaxQBiP62068.
PaxDbiP62068.
PeptideAtlasiP62068.
PRIDEiP62068.

Protocols and materials databases

DNASUi64854.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000441222; ENSP00000407818; ENSG00000109189. [P62068-1]
ENST00000508499; ENSP00000423244; ENSG00000109189. [P62068-3]
GeneIDi64854.
KEGGihsa:64854.
UCSCiuc003gzm.5. human. [P62068-1]

Organism-specific databases

CTDi64854.
DisGeNETi64854.
GeneCardsiUSP46.
HGNCiHGNC:20075. USP46.
HPAiCAB076369.
CAB076370.
HPA007288.
MIMi612849. gene.
neXtProtiNX_P62068.
OpenTargetsiENSG00000109189.
PharmGKBiPA134922048.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1864. Eukaryota.
ENOG410XQ81. LUCA.
GeneTreeiENSGT00850000132276.
HOVERGENiHBG054038.
InParanoidiP62068.
KOiK11842.
OMAiNGNPKSN.
OrthoDBiEOG091G0FC5.
PhylomeDBiP62068.
TreeFamiTF314144.

Enzyme and pathway databases

BioCyciZFISH:HS03209-MONOMER.

Miscellaneous databases

GenomeRNAii64854.
PROiP62068.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109189.
CleanExiHS_USP46.
ExpressionAtlasiP62068. baseline and differential.
GenevisibleiP62068. HS.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP46_HUMAN
AccessioniPrimary (citable) accession number: P62068
Secondary accession number(s): B7Z3Y7
, B7Z675, B7Z7S3, G8ACC7, Q80V95, Q9H7U4, Q9H9T8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: June 21, 2004
Last modified: November 30, 2016
This is version 111 of the entry and version 1 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 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.