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P62068

- UBP46_HUMAN

UniProt

P62068 - UBP46_HUMAN

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Protein

Ubiquitin carboxyl-terminal hydrolase 46

Gene

USP46

Organism
Homo sapiens (Human)
Status
Reviewed - 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. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.1 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).2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei44 – 441NucleophilePROSITE-ProRule annotation
Active sitei313 – 3131Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. ubiquitin-specific protease activity Source: UniProtKB
  2. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. adult feeding behavior Source: Ensembl
  2. behavioral fear response Source: Ensembl
  3. behavioral response to ethanol Source: Ensembl
  4. protein deubiquitination Source: UniProtKB
  5. regulation of synaptic transmission, GABAergic Source: UniProtKB
  6. righting reflex Source: Ensembl
  7. ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Behavior, Ubl conjugation pathway

Protein family/group databases

MEROPSiC19.052.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 46 (EC:3.4.19.12)
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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:20075. USP46.

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134922048.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 366366Ubiquitin carboxyl-terminal hydrolase 46PRO_0000080674Add
BLAST

Proteomic databases

MaxQBiP62068.
PaxDbiP62068.
PRIDEiP62068.

Expressioni

Tissue specificityi

Broadly expressed.1 Publication

Gene expression databases

BgeeiP62068.
CleanExiHS_USP46.
ExpressionAtlasiP62068. baseline and differential.
GenevestigatoriP62068.

Organism-specific databases

HPAiHPA007288.

Interactioni

Subunit structurei

Interacts with WDR48.1 Publication

Protein-protein interaction databases

BioGridi122327. 27 interactions.
IntActiP62068. 17 interactions.
STRINGi9606.ENSP00000407818.

Structurei

3D structure databases

ProteinModelPortaliP62068.
SMRiP62068. Positions 36-366.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 365331USPAdd
BLAST

Sequence similaritiesi

Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiCOG5077.
GeneTreeiENSGT00650000093027.
HOVERGENiHBG054038.
InParanoidiP62068.
KOiK11842.
OMAiAPKKFIT.
OrthoDBiEOG7RBZ8G.
PhylomeDBiP62068.
TreeFamiTF314144.

Family and domain databases

InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti177 – 1771T → A in BAH13161. (PubMed:14702039)Curated
Sequence conflicti250 – 2501I → V in BAB14133. (PubMed:14702039)Curated
Sequence conflicti265 – 2651H → R in BAB14133. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti81 – 811A → V.
Corresponds to variant rs17475800 [ dbSNP | Ensembl ].
VAR_051540

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 116116Missing in isoform 2. 1 PublicationVSP_037618Add
BLAST
Alternative sequencei1 – 1212MTVRN…SICNM → MNCFQ in isoform 3. 1 PublicationVSP_037619Add
BLAST
Alternative sequencei40 – 5112Missing in isoform 4. 1 PublicationVSP_037620Add
BLAST
Alternative sequencei334 – 36633KIDAQ…YQSRE → VGLQIILQ in isoform 2. 1 PublicationVSP_037621Add
BLAST

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.4. human. [P62068-3]
uc003gzn.3. human. [P62068-1]
uc011bzr.2. human. [P62068-4]
uc011bzs.2. human. [P62068-2]

Polymorphism databases

DMDMi49065850.

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 .
CCDSi CCDS47053.1. [P62068-1 ]
CCDS47054.1. [P62068-3 ]
RefSeqi NP_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 ]
UniGenei Hs.7966.

3D structure databases

ProteinModelPortali P62068.
SMRi P62068. Positions 36-366.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 122327. 27 interactions.
IntActi P62068. 17 interactions.
STRINGi 9606.ENSP00000407818.

Protein family/group databases

MEROPSi C19.052.

Polymorphism databases

DMDMi 49065850.

Proteomic databases

MaxQBi P62068.
PaxDbi P62068.
PRIDEi P62068.

Protocols and materials databases

DNASUi 64854.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000441222 ; ENSP00000407818 ; ENSG00000109189 . [P62068-1 ]
ENST00000508499 ; ENSP00000423244 ; ENSG00000109189 . [P62068-3 ]
GeneIDi 64854.
KEGGi hsa:64854.
UCSCi uc003gzm.4. human. [P62068-3 ]
uc003gzn.3. human. [P62068-1 ]
uc011bzr.2. human. [P62068-4 ]
uc011bzs.2. human. [P62068-2 ]

Organism-specific databases

CTDi 64854.
GeneCardsi GC04M053376.
HGNCi HGNC:20075. USP46.
HPAi HPA007288.
MIMi 612849. gene.
neXtProti NX_P62068.
PharmGKBi PA134922048.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5077.
GeneTreei ENSGT00650000093027.
HOVERGENi HBG054038.
InParanoidi P62068.
KOi K11842.
OMAi APKKFIT.
OrthoDBi EOG7RBZ8G.
PhylomeDBi P62068.
TreeFami TF314144.

Miscellaneous databases

GenomeRNAii 64854.
NextBioi 66987.
PROi P62068.
SOURCEi Search...

Gene expression databases

Bgeei P62068.
CleanExi HS_USP46.
ExpressionAtlasi P62068. baseline and differential.
Genevestigatori P62068.

Family and domain databases

InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view ]
Pfami PF00443. UCH. 1 hit.
[Graphical view ]
PROSITEi PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral despair' in mice, influences the deubiquitinating enzyme activity."
    Zhang W., Tian Q.B., Li Q.K., Wang J.M., Wang C.N., Liu T., Liu D.W., Wang M.W.
    PLoS ONE 6:E26297-E26297(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
    Tissue: Brain, Placenta, Teratocarcinoma, Testis and Thalamus.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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: Uterus.
  5. "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases."
    Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C.
    Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ENZYME ACTIVITY.
  6. "UAF1 is a subunit of multiple deubiquitinating enzyme complexes."
    Cohn M.A., Kee Y., Haas W., Gygi S.P., D'Andrea A.D.
    J. Biol. Chem. 284:5343-5351(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH WDR48.

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: October 29, 2014
This is version 90 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

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. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3