NUCG_BOVIN
ID NUCG_BOVIN Reviewed; 299 AA.
AC P38447; A4IFL3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Endonuclease G, mitochondrial;
DE Short=Endo G;
DE EC=3.1.30.-;
DE Flags: Precursor;
GN Name=ENDOG;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=7688144; DOI=10.1126/science.7688144;
RA Cote J., Ruiz-Carrillo A.;
RT "Primers for mitochondrial DNA replication generated by endonuclease G.";
RL Science 261:765-769(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 49-75.
RC TISSUE=Liver, and Thymus;
RX PubMed=3360771; DOI=10.1016/s0021-9258(18)68738-1;
RA Moos M. Jr., Nguyen N.Y., Liu T.-Y.;
RT "Reproducible high yield sequencing of proteins electrophoretically
RT separated and transferred to an inert support.";
RL J. Biol. Chem. 263:6005-6008(1988).
RN [4]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RC TISSUE=Heart;
RX PubMed=7870594; DOI=10.1093/nar/23.1.88;
RA Gerschenson M., Houmiel K.L., Low R.L.;
RT "Endonuclease G from mammalian nuclei is identical to the major
RT endonuclease of mitochondria.";
RL Nucleic Acids Res. 23:88-97(1995).
CC -!- FUNCTION: Endonuclease that preferentially catalyzes the cleavage of
CC double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA (By
CC similarity). The 5hmC-modified nucleotide does not increase the binding
CC affinity, but instead increases the efficiency of cutting and specifies
CC the site of cleavage for the modified DNAs (By similarity). Shows
CC significantly higher affinity for four- stranded Holliday junction over
CC duplex and single-stranded DNAs (By similarity). Promotes conservative
CC recombination when the DNA is 5hmC-modified (By similarity). Promotes
CC autophagy through the suppression of mTOR by its phosphorylation-
CC mediated interaction with YWHAG and its endonuclease activity-mediated
CC DNA damage response (By similarity). GSK3-beta mediated phosphorylation
CC of ENDOG enhances its interaction with YWHAG, leading to the release of
CC TSC2 and PIK3C3 from YWHAG resulting in mTOR pathway suppression and
CC autophagy initiation (By similarity). Promotes cleavage of mtDNA in
CC response to oxidative and nitrosative stress, in turn inducing
CC compensatory mtDNA replication (By similarity).
CC {ECO:0000250|UniProtKB:O08600, ECO:0000250|UniProtKB:Q14249}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O08600};
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Homodimerization
CC is essential for its activity (By similarity). Interacts with YWHAG (By
CC similarity). {ECO:0000250|UniProtKB:Q14249}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q14249}.
CC -!- PTM: GSK3-beta-mediated dual phosphorylations at Thr-130 and Ser-290 is
CC necessary for its interaction with YWHAG and the induction of
CC autophagy. {ECO:0000250|UniProtKB:Q14249}.
CC -!- SIMILARITY: Belongs to the DNA/RNA non-specific endonuclease family.
CC {ECO:0000305}.
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DR EMBL; X72802; CAA51320.1; -; mRNA.
DR EMBL; BC134634; AAI34635.1; -; mRNA.
DR RefSeq; NP_787017.1; NM_175823.3.
DR AlphaFoldDB; P38447; -.
DR SMR; P38447; -.
DR STRING; 9913.ENSBTAP00000016564; -.
DR PaxDb; P38447; -.
DR PRIDE; P38447; -.
DR GeneID; 327707; -.
DR KEGG; bta:327707; -.
DR CTD; 2021; -.
DR eggNOG; KOG3721; Eukaryota.
DR HOGENOM; CLU_055174_0_1_1; -.
DR InParanoid; P38447; -.
DR OrthoDB; 933605at2759; -.
DR TreeFam; TF105386; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IBA:GO_Central.
DR GO; GO:0004521; F:endoribonuclease activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central.
DR GO; GO:0032043; P:mitochondrial DNA catabolic process; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0090297; P:positive regulation of mitochondrial DNA replication; ISS:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; ISS:UniProtKB.
DR Gene3D; 3.40.570.10; -; 1.
DR InterPro; IPR018524; DNA/RNA_endonuclease_AS.
DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR InterPro; IPR020821; Extracellular_endonuc_su_A.
DR InterPro; IPR044925; His-Me_finger_sf.
DR InterPro; IPR040255; Non-specific_endonuclease.
DR PANTHER; PTHR13966; PTHR13966; 1.
DR Pfam; PF01223; Endonuclease_NS; 1.
DR SMART; SM00892; Endonuclease_NS; 1.
DR SMART; SM00477; NUC; 1.
DR SUPFAM; SSF54060; SSF54060; 1.
DR PROSITE; PS01070; NUCLEASE_NON_SPEC; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Endonuclease; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Mitochondrion; Nuclease;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..48
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3360771"
FT CHAIN 49..299
FT /note="Endonuclease G, mitochondrial"
FT /id="PRO_0000019917"
FT REGION 288..298
FT /note="Essential for deoxyribonuclease activity"
FT /evidence="ECO:0000250|UniProtKB:O08600"
FT ACT_SITE 143
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10047"
FT BINDING 174
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O08600"
FT SITE 112
FT /note="Essential for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:O08600"
FT MOD_RES 130
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14249"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14249"
FT DISULFID 115
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O08600"
FT CONFLICT 172
FT /note="H -> S (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="H -> S (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 299 AA; 32262 MW; B28FAFF56F04CFC7 CRC64;
MQLLRAGLTL ALGAGLGAAA ESWWRQRADA RATPGLLSRL PVLPVAAAAG LPAVPGAPAG
GGPGELAKYG LPGVAQLKSR ASYVLCYDPR TRGALWVVEQ LRPEGLRGDG NRSSCDFHED
DSVHAYHRAT NADYRGSGFD RGHLAAAANH RWSQKAMDDT FYLSNVAPQV PHLNQNAWNN
LEKYSRSLTR TYQNVYVCTG PLFLPRTEAD GKSYVKYQVI GKNHVAVPTH FFKVLILEAA
GGQIELRSYV MPNAPVDEAI PLEHFLVPIE SIERASGLLF VPNILARAGS LKAITAGSK
