RN146_AILME
ID RN146_AILME Reviewed; 359 AA.
AC D2H0Y8;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 1.
DT 03-AUG-2022, entry version 72.
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; ORFNames=PANDA_003130;
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
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. {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. {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. {ECO:0000250}.
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DR EMBL; GL192419; EFB13674.1; -; Genomic_DNA.
DR AlphaFoldDB; D2H0Y8; -.
DR BMRB; D2H0Y8; -.
DR SMR; D2H0Y8; -.
DR STRING; 9646.ENSAMEP00000021212; -.
DR eggNOG; KOG0824; Eukaryota.
DR HOGENOM; CLU_067425_0_0_1; -.
DR InParanoid; D2H0Y8; -.
DR OMA; KTNESCA; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000008912; Unassembled WGS sequence.
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 3: Inferred from homology;
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..359
FT /note="E3 ubiquitin-protein ligase RNF146"
FT /id="PRO_0000409501"
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 259..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..275
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..325
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 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XIK5"
FT MOD_RES 294
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 359 AA; 38839 MW; DFE28DC43E92D4CD CRC64;
MAGCGEIDHS VNMLPTNRKA NESCANPAPS LTVPECAICL QTCVHPVSLP CKHVFCYLCV
KGASWLGKRC ALCRQEIPED FLDKPTLLSP EELKAASRGN GEYAWYYEGR NGWWQYDERT
SRELEDAFSK GKKSTEMLIA GFLYVADLEN MVQYRRNEHG RRRKIKRDII DIPKKGVAGL
RLDCEANTVN LARESSADGA DSVSAQSGAS SVQPLVSSLR PLTSVDGQLT SPATPSPDAS
TSLEDSFAHL QLSGDSIAER SHRGEGEEDH ESPSSGRVPA PDTSVEETES DASSDSEDVS
ALVAQHSLTQ QRLLVPNANQ TVSDRSDRSG IDRSVAGGGT VNAGVRSRRP DGQCTVTEV
