ID   UBP46_PONAB             Reviewed;         366 AA.
AC   Q5RBQ4; Q5RBN2;
DT   11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   24-JAN-2024, entry version 82.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 46;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:P62068};
DE   AltName: Full=Deubiquitinating enzyme 46;
DE   AltName: Full=Ubiquitin thioesterase 46;
DE   AltName: Full=Ubiquitin-specific-processing protease 46;
GN   Name=USP46;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Deubiquitinating enzyme that plays a role in behavior,
CC       possibly by regulating GABA action. May act by mediating the
CC       deubiquitination of GAD1/GAD67 (By similarity). Has almost no
CC       deubiquitinating activity by itself and requires the interaction with
CC       WDR48 to have a high activity. Not involved in deubiquitination of
CC       monoubiquitinated FANCD2 (By similarity).
CC       {ECO:0000250|UniProtKB:P62068, ECO:0000250|UniProtKB:P62069}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:P62068};
CC   -!- SUBUNIT: Interacts with WDR48. Interacts with WDR20. Interacts with
CC       DMWD. Component of the USP46/WDR20/WDR48 deubiquitinating complex.
CC       {ECO:0000250|UniProtKB:P62068}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P62068}.
CC       Note=USP46/WDR48/WDR20 complex is predominantly cytoplasmic.
CC       {ECO:0000250|UniProtKB:P62068}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q5RBQ4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5RBQ4-2; Sequence=VSP_037622;
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. USP12/USP46 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; CR858584; CAH90806.1; -; mRNA.
DR   EMBL; CR858606; CAH90828.1; -; mRNA.
DR   RefSeq; NP_001127337.1; NM_001133865.1. [Q5RBQ4-1]
DR   RefSeq; NP_001128936.1; NM_001135464.1. [Q5RBQ4-2]
DR   AlphaFoldDB; Q5RBQ4; -.
DR   SMR; Q5RBQ4; -.
DR   STRING; 9601.ENSPPYP00000016505; -.
DR   Ensembl; ENSPPYT00000040326.1; ENSPPYP00000032861.1; ENSPPYG00000014777.2. [Q5RBQ4-2]
DR   Ensembl; ENSPPYT00000046675.1; ENSPPYP00000029459.1; ENSPPYG00000014777.2. [Q5RBQ4-1]
DR   GeneID; 100174399; -.
DR   GeneID; 100189895; -.
DR   KEGG; pon:100189895; -.
DR   CTD; 64854; -.
DR   eggNOG; KOG1864; Eukaryota.
DR   GeneTree; ENSGT00940000153284; -.
DR   HOGENOM; CLU_008279_2_0_1; -.
DR   InParanoid; Q5RBQ4; -.
DR   OrthoDB; 227085at2759; -.
DR   Proteomes; UP000001595; Chromosome 4.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007610; P:behavior; IEA:UniProtKB-KW.
DR   GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISS:UniProtKB.
DR   CDD; cd02663; Peptidase_C19G; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF714; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 46; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Behavior; Cytoplasm; Hydrolase; Metal-binding;
KW   Protease; Reference proteome; Thiol protease; Ubl conjugation pathway;
KW   Zinc.
FT   CHAIN           1..366
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 46"
FT                   /id="PRO_0000304740"
FT   DOMAIN          35..365
FT                   /note="USP"
FT   ACT_SITE        44
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        313
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   BINDING         182
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P62068"
FT   BINDING         185
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P62068"
FT   BINDING         229
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P62068"
FT   BINDING         232
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P62068"
FT   VAR_SEQ         13..39
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_037622"
SQ   SEQUENCE   366 AA;  42442 MW;  67BB113FC4081C46 CRC64;
     MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL QALYFCRPFR
     ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK KFISRLRKEN DLFDNYMQQD
     AHEFLNYLLN TIADILQEEK KQEKQNGKLK NGNMNEPAEN NKPELTWVHE IFQGTLTNET
     RCLNCETVSS KDEDFLDLSV DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK
     RMRVKKLPMI LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA
     VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI SKNSESGYIL
     FYQSRE
//