EXOG_HUMAN
ID EXOG_HUMAN Reviewed; 368 AA.
AC Q9Y2C4; A8K242; B4DVG2; Q3SXM9; Q9Y2C8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Nuclease EXOG, mitochondrial;
DE EC=3.1.30.-;
DE AltName: Full=Endonuclease G-like 1;
DE Short=Endo G-like 1;
DE Flags: Precursor;
GN Name=EXOG; Synonyms=ENDOGL1, ENDOGL2, ENGL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT VAL-277.
RX PubMed=10231028; DOI=10.1093/dnares/6.1.37;
RA Daigo Y., Isomura M., Nishiwaki T., Tamari M., Ishikawa S., Kai M.,
RA Takeuchi K., Yamane Y., Hayashi R., Minami M., Fujino M.A., Hojo Y.,
RA Uchiyama I., Takagi T., Nakamura Y.;
RT "Characterization of a 1200-kb genomic segment of chromosome 3p22-p21.3.";
RL DNA Res. 6:37-44(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Spleen, and Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, COFACTOR, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-137
RP AND HIS-140, AND CHARACTERIZATION OF VARIANT VAL-277.
RX PubMed=18187503; DOI=10.1093/nar/gkm1169;
RA Cymerman I.A., Chung I., Beckmann B.M., Bujnicki J.M., Meiss G.;
RT "EXOG, a novel paralog of endonuclease G in higher eukaryotes.";
RL Nucleic Acids Res. 36:1369-1379(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Endo/exonuclease with nicking activity towards supercoiled
CC DNA, a preference for single-stranded DNA and 5'-3' exonuclease
CC activity. {ECO:0000269|PubMed:18187503}.
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:18187503};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18187503}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:18187503}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=ENGL-a;
CC IsoId=Q9Y2C4-1; Sequence=Displayed;
CC Name=2; Synonyms=ENDOGL2, ENGL-b;
CC IsoId=Q9Y2C4-2; Sequence=VSP_034506, VSP_034507, VSP_034508;
CC Name=3;
CC IsoId=Q9Y2C4-3; Sequence=VSP_034506;
CC Name=4;
CC IsoId=Q9Y2C4-4; Sequence=VSP_041214;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- MISCELLANEOUS: The active site contains 1 hydrated divalent metal
CC cation that has only 1 direct interaction with the protein; all other
CC interactions are via water molecules. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: Probably inactive since it lacks the active
CC site. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Probably inactive since it lacks the active
CC site. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the DNA/RNA non-specific endonuclease family.
CC {ECO:0000305}.
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DR EMBL; AB020523; BAA76752.1; -; mRNA.
DR EMBL; AB020735; BAA76753.1; -; mRNA.
DR EMBL; AK289602; BAF82291.1; -; mRNA.
DR EMBL; AK290107; BAF82796.1; -; mRNA.
DR EMBL; AK301067; BAG62674.1; -; mRNA.
DR EMBL; AK315814; BAF98705.1; -; mRNA.
DR EMBL; CH471055; EAW64538.1; -; Genomic_DNA.
DR EMBL; BC104212; AAI04213.1; -; mRNA.
DR EMBL; BC104213; AAI04214.1; -; mRNA.
DR CCDS; CCDS2680.1; -. [Q9Y2C4-1]
DR CCDS; CCDS46795.1; -. [Q9Y2C4-4]
DR RefSeq; NP_001138936.1; NM_001145464.1. [Q9Y2C4-4]
DR RefSeq; NP_001305883.1; NM_001318954.1.
DR RefSeq; NP_001305884.1; NM_001318955.1.
DR RefSeq; NP_001305885.1; NM_001318956.1.
DR RefSeq; NP_001305886.1; NM_001318957.1.
DR RefSeq; NP_001305887.1; NM_001318958.1.
DR RefSeq; NP_001305888.1; NM_001318959.1.
DR RefSeq; NP_005098.2; NM_005107.3. [Q9Y2C4-1]
DR RefSeq; XP_005265690.1; XM_005265633.3.
DR RefSeq; XP_006713507.1; XM_006713444.3.
DR RefSeq; XP_016863073.1; XM_017007584.1. [Q9Y2C4-3]
DR RefSeq; XP_016863074.1; XM_017007585.1. [Q9Y2C4-3]
DR RefSeq; XP_016863075.1; XM_017007586.1. [Q9Y2C4-3]
DR RefSeq; XP_016863076.1; XM_017007587.1. [Q9Y2C4-3]
DR RefSeq; XP_016863077.1; XM_017007588.1. [Q9Y2C4-3]
DR RefSeq; XP_016863078.1; XM_017007589.1. [Q9Y2C4-3]
DR RefSeq; XP_016863079.1; XM_017007590.1. [Q9Y2C4-3]
DR RefSeq; XP_016863080.1; XM_017007591.1. [Q9Y2C4-3]
DR RefSeq; XP_016863081.1; XM_017007592.1. [Q9Y2C4-3]
DR RefSeq; XP_016863082.1; XM_017007593.1. [Q9Y2C4-3]
DR PDB; 4A1N; X-ray; 2.80 A; A=42-368.
DR PDB; 5T3V; X-ray; 2.60 A; A/B=59-368.
DR PDB; 5T40; X-ray; 1.81 A; A/B=59-368.
DR PDB; 5T4I; X-ray; 2.39 A; A/B=59-368.
DR PDB; 5T5C; X-ray; 1.85 A; A/B=59-368.
DR PDB; 5ZKI; X-ray; 2.32 A; A/B=42-368.
DR PDB; 5ZKJ; X-ray; 2.80 A; A/B=42-368.
DR PDB; 6IID; X-ray; 2.99 A; A/B/C/D=42-368.
DR PDBsum; 4A1N; -.
DR PDBsum; 5T3V; -.
DR PDBsum; 5T40; -.
DR PDBsum; 5T4I; -.
DR PDBsum; 5T5C; -.
DR PDBsum; 5ZKI; -.
DR PDBsum; 5ZKJ; -.
DR PDBsum; 6IID; -.
DR AlphaFoldDB; Q9Y2C4; -.
DR SMR; Q9Y2C4; -.
DR BioGRID; 115267; 52.
DR IntAct; Q9Y2C4; 18.
DR MINT; Q9Y2C4; -.
DR STRING; 9606.ENSP00000287675; -.
DR iPTMnet; Q9Y2C4; -.
DR PhosphoSitePlus; Q9Y2C4; -.
DR BioMuta; EXOG; -.
DR DMDM; 193806336; -.
DR EPD; Q9Y2C4; -.
DR jPOST; Q9Y2C4; -.
DR MassIVE; Q9Y2C4; -.
DR MaxQB; Q9Y2C4; -.
DR PaxDb; Q9Y2C4; -.
DR PeptideAtlas; Q9Y2C4; -.
DR PRIDE; Q9Y2C4; -.
DR ProteomicsDB; 85725; -. [Q9Y2C4-1]
DR ProteomicsDB; 85726; -. [Q9Y2C4-2]
DR ProteomicsDB; 85727; -. [Q9Y2C4-3]
DR ProteomicsDB; 85728; -. [Q9Y2C4-4]
DR Antibodypedia; 2527; 161 antibodies from 31 providers.
DR DNASU; 9941; -.
DR Ensembl; ENST00000287675.10; ENSP00000287675.5; ENSG00000157036.13. [Q9Y2C4-1]
DR Ensembl; ENST00000422077.6; ENSP00000404305.2; ENSG00000157036.13. [Q9Y2C4-4]
DR GeneID; 9941; -.
DR KEGG; hsa:9941; -.
DR MANE-Select; ENST00000287675.10; ENSP00000287675.5; NM_005107.4; NP_005098.2.
DR UCSC; uc003cih.3; human. [Q9Y2C4-1]
DR CTD; 9941; -.
DR DisGeNET; 9941; -.
DR GeneCards; EXOG; -.
DR HGNC; HGNC:3347; EXOG.
DR HPA; ENSG00000157036; Low tissue specificity.
DR MIM; 604051; gene.
DR neXtProt; NX_Q9Y2C4; -.
DR OpenTargets; ENSG00000157036; -.
DR PharmGKB; PA27784; -.
DR VEuPathDB; HostDB:ENSG00000157036; -.
DR eggNOG; KOG3721; Eukaryota.
DR GeneTree; ENSGT00940000160677; -.
DR HOGENOM; CLU_055174_3_0_1; -.
DR InParanoid; Q9Y2C4; -.
DR OMA; CKFRPDP; -.
DR OrthoDB; 933605at2759; -.
DR PhylomeDB; Q9Y2C4; -.
DR TreeFam; TF105386; -.
DR PathwayCommons; Q9Y2C4; -.
DR SignaLink; Q9Y2C4; -.
DR BioGRID-ORCS; 9941; 15 hits in 1079 CRISPR screens.
DR ChiTaRS; EXOG; human.
DR GenomeRNAi; 9941; -.
DR Pharos; Q9Y2C4; Tbio.
DR PRO; PR:Q9Y2C4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y2C4; protein.
DR Bgee; ENSG00000157036; Expressed in buccal mucosa cell and 163 other tissues.
DR ExpressionAtlas; Q9Y2C4; baseline and differential.
DR Genevisible; Q9Y2C4; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:HGNC.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:HGNC.
DR GO; GO:0004519; F:endonuclease activity; IDA:HGNC.
DR GO; GO:0004521; F:endoribonuclease activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
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 Gene3D; 3.40.570.10; -; 1.
DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR InterPro; IPR041003; Exog_C.
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 Pfam; PF18026; Exog_C; 1.
DR SMART; SM00892; Endonuclease_NS; 1.
DR SMART; SM00477; NUC; 1.
DR SUPFAM; SSF54060; SSF54060; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Endonuclease; Hydrolase; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane; Nuclease;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..41
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 42..368
FT /note="Nuclease EXOG, mitochondrial"
FT /id="PRO_0000178669"
FT ACT_SITE 140
FT /note="Proton acceptor"
FT BINDING 171
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..140
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10231028,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_034506"
FT VAR_SEQ 55..104
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_041214"
FT VAR_SEQ 231..289
FT /note="VILARRSSVSTEPLALGAFVVPNEAIGFQPQLTEFQVSLQDLEKLSGLVFFP
FT HLDRTSD -> DHAGCCVESPLGTRTSEEATARIQERDDGGSDQRSGLVELGIYFEGRA
FT NRISGRIGCRV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10231028"
FT /id="VSP_034507"
FT VAR_SEQ 290..368
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10231028"
FT /id="VSP_034508"
FT VARIANT 277
FT /note="G -> V (abolishes catalytic activity;
FT dbSNP:rs1141223)"
FT /evidence="ECO:0000269|PubMed:10231028,
FT ECO:0000269|PubMed:18187503"
FT /id="VAR_044320"
FT MUTAGEN 137
FT /note="S->D: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:18187503"
FT MUTAGEN 140
FT /note="H->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:18187503"
FT CONFLICT 309
FT /note="L -> S (in Ref. 2; BAF82796)"
FT /evidence="ECO:0000305"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:5ZKJ"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:5T40"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 90..98
FT /evidence="ECO:0007829|PDB:5T40"
FT TURN 100..103
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:5T40"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 151..157
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 168..172
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 174..185
FT /evidence="ECO:0007829|PDB:5T40"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 190..199
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:6IID"
FT STRAND 210..217
FT /evidence="ECO:0007829|PDB:5T40"
FT TURN 218..221
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:6IID"
FT STRAND 226..236
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 245..254
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 269..276
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:6IID"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:5T40"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:5T5C"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 304..318
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 322..334
FT /evidence="ECO:0007829|PDB:5T40"
FT HELIX 341..355
FT /evidence="ECO:0007829|PDB:5T40"
SQ SEQUENCE 368 AA; 41085 MW; 432E046A6F4ADF0E CRC64;
MAIKSIASRL RGSRRFLSGF VAGAVVGAAG AGLAALQFFR SQGAEGALTG KQPDGSAEKA
VLEQFGFPLT GTEARCYTNH ALSYDQAKRV PRWVLEHISK SKIMGDADRK HCKFKPDPNI
PPTFSAFNED YVGSGWSRGH MAPAGNNKFS SKAMAETFYL SNIVPQDFDN NSGYWNRIEM
YCRELTERFE DVWVVSGPLT LPQTRGDGKK IVSYQVIGED NVAVPSHLYK VILARRSSVS
TEPLALGAFV VPNEAIGFQP QLTEFQVSLQ DLEKLSGLVF FPHLDRTSDI RNICSVDTCK
LLDFQEFTLY LSTRKIEGAR SVLRLEKIME NLKNAEIEPD DYFMSRYEKK LEELKAKEQS
GTQIRKPS
