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P62068

- UBP46_HUMAN

UniProt

P62068 - UBP46_HUMAN

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
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    • History
      Entry version 89 (01 Oct 2014)
      Sequence version 1 (21 Jun 2004)
      Previous versions | rss
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    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. protein binding Source: UniProtKB
    2. ubiquitin-specific protease activity Source: UniProtKB
    3. ubiquitin thiolesterase 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

    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

    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.
    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.
    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

    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:
    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

    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 1, 2014
    This is version 89 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