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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 – 441Nucleophile By similarity
Active sitei313 – 3131Proton acceptor By similarity

GO - Molecular functioni

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

GO - Biological processi

  1. behavioral fear response Source: Ensembl
  2. protein deubiquitination Source: UniProtKB
  3. regulation of synaptic transmission, GABAergic Source: UniProtKB
  4. 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 46
PRO_0000080674Add
BLAST

Proteomic databases

MaxQBiP62068.
PaxDbiP62068.
PRIDEiP62068.

Expressioni

Tissue specificityi

Broadly expressed.1 Publication

Gene expression databases

ArrayExpressiP62068.
BgeeiP62068.
CleanExiHS_USP46.
GenevestigatoriP62068.

Organism-specific databases

HPAiHPA007288.

Interactioni

Subunit structurei

Interacts with WDR48.1 Publication

Protein-protein interaction databases

BioGridi122327. 21 interactions.
IntActiP62068. 17 interactions.
STRINGi9606.ENSP00000407818.

Structurei

3D structure databases

ProteinModelPortaliP62068.
SMRiP62068. Positions 36-366.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Contains 1 USP domain.

Phylogenomic databases

eggNOGiCOG5077.
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

MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL    50
QALYFCRPFR ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK 100
KFISRLRKEN DLFDNYMQQD AHEFLNYLLN TIADILQEEK KQEKQNGKLK 150
NGNMNEPAEN NKPELTWVHE IFQGTLTNET RCLNCETVSS KDEDFLDLSV 200
DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK RMRVKKLPMI 250
LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA 300
VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI 350
SKNSESGYIL FYQSRE 366
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

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.
VSP_037618Add
BLAST
Alternative sequencei1 – 1212MTVRN…SICNM → MNCFQ in isoform 3.
VSP_037619Add
BLAST
Alternative sequencei40 – 5112Missing in isoform 4.
VSP_037620Add
BLAST
Alternative sequencei334 – 36633KIDAQ…YQSRE → VGLQIILQ in isoform 2.
VSP_037621Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti177 – 1771T → A in BAH13161. 1 Publication
Sequence conflicti250 – 2501I → V in BAB14133. 1 Publication
Sequence conflicti265 – 2651H → R in BAB14133. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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. 21 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.
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

ArrayExpressi P62068.
Bgeei P62068.
CleanExi HS_USP46.
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: July 9, 2014
This is version 88 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

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