RN146_PONAB
ID RN146_PONAB Reviewed; 358 AA.
AC Q5REL3;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=E3 ubiquitin-protein ligase RNF146;
DE EC=2.3.2.27;
DE AltName: Full=Iduna;
DE AltName: Full=RING finger protein 146;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF146 {ECO:0000305};
GN Name=RNF146;
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].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically binds poly-ADP-
CC ribosylated (PARsylated) proteins and mediates their ubiquitination and
CC subsequent degradation. May regulate many important biological
CC processes, such as cell survival and DNA damage response. Acts as an
CC activator of the Wnt signaling pathway by mediating the ubiquitination
CC of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin
CC destruction complex. Acts in cooperation with tankyrase proteins (TNKS
CC and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2,
CC BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent
CC PARsylated proteins via its WWE domain and mediates their
CC ubiquitination. May regulate TNKS and TNKS2 subcellular location,
CC preventing aggregation at a centrosomal location. Neuroprotective
CC protein. Protects the brain against N-methyl-D-aspartate (NMDA)
CC receptor-mediated glutamate excitotoxicity and ischemia, by interfering
CC with PAR-induced cell death, called parthanatos. Prevents nuclear
CC translocation of AIFM1 in a PAR-binding dependent manner. Does not
CC affect PARP1 activation. Protects against cell death induced by DNA
CC damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and
CC rescues cells from G1 arrest. Promotes cell survival after gamma-
CC irradiation. Facilitates DNA repair. Neuroprotective protein. Protects
CC the brain against N-methyl-D-aspartate (NMDA) receptor-mediated
CC glutamate excitotoxicity and ischemia, by interfering with PAR-induced
CC cell death, called parthanatos. Prevents nuclear translocation of AIFM1
CC in a PAR-binding dependent manner. Does not affect PARP1 activation (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Can form homooligomers. Interacts with PARsylated AXIN1,
CC AXIN2, BLZF1, CASC3, H1-2, IPO7, LIG3, NCL, PARP1, XRCC1, XRCC5 and
CC XRCC6. Interacts with DDB1, DHX15, IQGAP1, LRPPRC, PARP2, PRKDC,
CC RUVBL2, TNKS1 and TNKS2. Binding often leads to interactor
CC ubiquitination, in the presence of the appropriate E1 and E2 enzymes,
CC and proteasomal degradation (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Translocates to the nucleus after DNA damage, such
CC as laser-induced DNA breaks, and concentrates at DNA breaks. This
CC translocation requires PARP1 activation and PAR-binding (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The WWE domain mediates non-covalent poly(ADP-ribose)-binding.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated; autoubiquitinated. Autoubiquitination is enhanced
CC upon poly(ADP-ribose)-binding (By similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR857511; CAH89794.1; -; mRNA.
DR RefSeq; NP_001128751.1; NM_001135279.1.
DR AlphaFoldDB; Q5REL3; -.
DR BMRB; Q5REL3; -.
DR SMR; Q5REL3; -.
DR STRING; 9601.ENSPPYP00000019028; -.
DR GeneID; 100189646; -.
DR eggNOG; KOG0824; Eukaryota.
DR InParanoid; Q5REL3; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0072572; F:poly-ADP-D-ribose binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd16546; RING-HC_RNF146; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.720.50; -; 1.
DR InterPro; IPR044110; RING-HC_RNF146.
DR InterPro; IPR033509; RNF146.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR018123; WWE-dom_subgr.
DR InterPro; IPR037197; WWE_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13417:SF2; PTHR13417:SF2; 1.
DR Pfam; PF02825; WWE; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00678; WWE; 1.
DR SUPFAM; SSF117839; SSF117839; 1.
DR PROSITE; PS50918; WWE; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..358
FT /note="E3 ubiquitin-protein ligase RNF146"
FT /id="PRO_0000056109"
FT DOMAIN 91..167
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 36..74
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 253..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..274
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..324
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..358
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 107
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT BINDING 110
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT BINDING 144
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT BINDING 153
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000250"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XIK5"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XIK5"
FT CROSSLNK 84
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9NTX7"
FT CROSSLNK 94
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9NTX7"
FT CROSSLNK 130
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9NTX7"
FT CROSSLNK 175
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9NTX7"
SQ SEQUENCE 358 AA; 38761 MW; 446A3F76BFE0B93D CRC64;
MAGCGEIDHS INMLPTNRKA NESCSNTAPS LTVPECAICL QTCVHPVSLP CKHVFCYLCV
KGASWLGKRC ALCRQEIPED FLDKPTLLSP EELKAASRGN GEYAWYYEGR NGWWQYGERT
SRELEDAFSK GKKNTEMLIA GFLYVADLEN MVQYRRNEHG RRRKIKRDII DIPKKGVAGL
RLDCDANTVN LARESSADGA DSVSAQSGAS VQPLVSSVRP LTSVDGQLTS PATPSPDAST
SLEDSFAHLQ LSGDNTAERS HRGEGEEDHE SPSSGRVPAP DTSIEETESD ASSDSEDVSA
VVAQHSLTQQ RLLVSNANQT VPDRSDRSGT DRSVAGGGTV SVSVRSRRPD GQCTVTEV
