MGME1_HUMAN
ID MGME1_HUMAN Reviewed; 344 AA.
AC Q9BQP7; B2RDG5; D3DW29; Q96SW3;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Mitochondrial genome maintenance exonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03030};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03030};
GN Name=MGME1 {ECO:0000255|HAMAP-Rule:MF_03030}; Synonyms=C20orf72, DDK1;
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 [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT MTDPS11 CYS-233, CHARACTERIZATION
RP OF VARIANT MTDPS11 CYS-233, AND MUTAGENESIS OF LYS-253.
RX PubMed=23313956; DOI=10.1038/ng.2501;
RA Kornblum C., Nicholls T.J., Haack T.B., Scholer S., Peeva V., Danhauser K.,
RA Hallmann K., Zsurka G., Rorbach J., Iuso A., Wieland T., Sciacco M.,
RA Ronchi D., Comi G.P., Moggio M., Quinzii C.M., Dimauro S., Calvo S.E.,
RA Mootha V.K., Klopstock T., Strom T.M., Meitinger T., Minczuk M., Kunz W.S.,
RA Prokisch H.;
RT "Loss-of-function mutations in MGME1 impair mtDNA replication and cause
RT multisystemic mitochondrial disease.";
RL Nat. Genet. 45:214-219(2013).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, METAL-DEPENDENCY, SUBCELLULAR LOCATION,
RP ACTIVE SITE, AND MUTAGENESIS OF ASP-251 AND LYS-253.
RX PubMed=23358826; DOI=10.1093/nar/gkt029;
RA Szczesny R.J., Hejnowicz M.S., Steczkiewicz K., Muszewska A.,
RA Borowski L.S., Ginalski K., Dziembowski A.;
RT "Identification of a novel human mitochondrial endo-/exonuclease
RT Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels.";
RL Nucleic Acids Res. 41:3144-3161(2013).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Metal-dependent single-stranded DNA (ssDNA) exonuclease
CC involved in mitochondrial genome maintenance. Has preference for 5'-3'
CC exonuclease activity but is also capable of endoduclease activity on
CC linear substrates. Necessary for maintenance of proper 7S DNA levels.
CC Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the
CC processing of displaced DNA containing Okazaki fragments during RNA-
CC primed DNA synthesis on the lagging strand or via processing of DNA
CC flaps during long-patch base excision repair. Specifically binds 5-
CC hydroxymethylcytosine (5hmC)-containing DNA in stem cells.
CC {ECO:0000255|HAMAP-Rule:MF_03030, ECO:0000269|PubMed:23313956,
CC ECO:0000269|PubMed:23358826}.
CC -!- INTERACTION:
CC Q9BQP7; Q9UHG0: DCDC2; NbExp=3; IntAct=EBI-739561, EBI-10303987;
CC Q9BQP7; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-739561, EBI-79165;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03030,
CC ECO:0000269|PubMed:23313956, ECO:0000269|PubMed:23358826}.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 11 (MTDPS11)
CC [MIM:615084]: An autosomal recessive mitochondrial disorder
CC characterized by onset in childhood or adulthood of progressive
CC external ophthalmoplegia, muscle weakness and atrophy, exercise
CC intolerance, and respiratory insufficiency due to muscle weakness. More
CC variable features include spinal deformity, emaciation, and cardiac
CC abnormalities. Skeletal muscle biopsies show deletion and depletion of
CC mitochondrial DNA (mtDNA) with variable defects in respiratory chain
CC enzyme activities. {ECO:0000269|PubMed:23313956}. Note=The disease may
CC be caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: This protein may be expected to contain an N-terminal
CC transit peptide but none has been predicted. {ECO:0000255|HAMAP-
CC Rule:MF_03030}.
CC -!- SIMILARITY: Belongs to the MGME1 family. {ECO:0000255|HAMAP-
CC Rule:MF_03030}.
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DR EMBL; AK027503; BAB55160.1; -; mRNA.
DR EMBL; AK315532; BAG37912.1; -; mRNA.
DR EMBL; AL121585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10260.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10261.1; -; Genomic_DNA.
DR EMBL; BC016869; AAH16869.1; -; mRNA.
DR CCDS; CCDS13131.1; -.
DR RefSeq; NP_001297267.1; NM_001310338.1.
DR RefSeq; NP_001297268.1; NM_001310339.1.
DR RefSeq; NP_443097.1; NM_052865.3.
DR RefSeq; XP_016883616.1; XM_017028127.1.
DR RefSeq; XP_016883617.1; XM_017028128.1.
DR PDB; 5ZYT; X-ray; 2.70 A; A/B/C/D=21-344.
DR PDB; 5ZYU; X-ray; 1.75 A; A/B=91-344.
DR PDB; 5ZYV; X-ray; 2.72 A; A=91-344.
DR PDB; 5ZYW; X-ray; 2.20 A; A=91-344.
DR PDBsum; 5ZYT; -.
DR PDBsum; 5ZYU; -.
DR PDBsum; 5ZYV; -.
DR PDBsum; 5ZYW; -.
DR AlphaFoldDB; Q9BQP7; -.
DR SMR; Q9BQP7; -.
DR BioGRID; 124964; 127.
DR IntAct; Q9BQP7; 25.
DR MINT; Q9BQP7; -.
DR STRING; 9606.ENSP00000366939; -.
DR iPTMnet; Q9BQP7; -.
DR PhosphoSitePlus; Q9BQP7; -.
DR BioMuta; MGME1; -.
DR DMDM; 25452901; -.
DR EPD; Q9BQP7; -.
DR jPOST; Q9BQP7; -.
DR MassIVE; Q9BQP7; -.
DR MaxQB; Q9BQP7; -.
DR PaxDb; Q9BQP7; -.
DR PeptideAtlas; Q9BQP7; -.
DR PRIDE; Q9BQP7; -.
DR ProteomicsDB; 78703; -.
DR Antibodypedia; 48613; 81 antibodies from 18 providers.
DR DNASU; 92667; -.
DR Ensembl; ENST00000377710.10; ENSP00000366939.5; ENSG00000125871.14.
DR GeneID; 92667; -.
DR KEGG; hsa:92667; -.
DR MANE-Select; ENST00000377710.10; ENSP00000366939.5; NM_052865.4; NP_443097.1.
DR UCSC; uc002wqh.5; human.
DR CTD; 92667; -.
DR DisGeNET; 92667; -.
DR GeneCards; MGME1; -.
DR HGNC; HGNC:16205; MGME1.
DR HPA; ENSG00000125871; Low tissue specificity.
DR MalaCards; MGME1; -.
DR MIM; 615076; gene.
DR MIM; 615084; phenotype.
DR neXtProt; NX_Q9BQP7; -.
DR OpenTargets; ENSG00000125871; -.
DR Orphanet; 352447; Progressive external ophthalmoplegia-myopathy-emaciation syndrome.
DR PharmGKB; PA25783; -.
DR VEuPathDB; HostDB:ENSG00000125871; -.
DR eggNOG; ENOG502QVKE; Eukaryota.
DR GeneTree; ENSGT00390000003349; -.
DR InParanoid; Q9BQP7; -.
DR OMA; QLFYLER; -.
DR OrthoDB; 1513785at2759; -.
DR PhylomeDB; Q9BQP7; -.
DR TreeFam; TF320375; -.
DR PathwayCommons; Q9BQP7; -.
DR SignaLink; Q9BQP7; -.
DR BioGRID-ORCS; 92667; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; MGME1; human.
DR GenomeRNAi; 92667; -.
DR Pharos; Q9BQP7; Tbio.
DR PRO; PR:Q9BQP7; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BQP7; protein.
DR Bgee; ENSG00000125871; Expressed in upper arm skin and 180 other tissues.
DR ExpressionAtlas; Q9BQP7; baseline and differential.
DR Genevisible; Q9BQP7; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008297; F:single-stranded DNA exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0043504; P:mitochondrial DNA repair; TAS:UniProtKB.
DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:UniProtKB.
DR Gene3D; 3.90.320.10; -; 1.
DR HAMAP; MF_03030; MGME1; 1.
DR InterPro; IPR011604; PDDEXK-like_dom_sf.
DR InterPro; IPR038726; PDDEXK_AddAB-type.
DR InterPro; IPR011335; Restrct_endonuc-II-like.
DR Pfam; PF12705; PDDEXK_1; 1.
DR SUPFAM; SSF52980; SSF52980; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; DNA damage; DNA repair; Exonuclease;
KW Hydrolase; Mitochondrion; Nuclease; Phosphoprotein;
KW Primary mitochondrial disease; Progressive external ophthalmoplegia;
KW Reference proteome.
FT CHAIN 1..344
FT /note="Mitochondrial genome maintenance exonuclease 1"
FT /id="PRO_0000079439"
FT ACT_SITE 238
FT /evidence="ECO:0000269|PubMed:23358826"
FT ACT_SITE 251
FT /evidence="ECO:0000269|PubMed:23358826"
FT ACT_SITE 253
FT /evidence="ECO:0000269|PubMed:23358826"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 15
FT /note="S -> C (in dbSNP:rs11551768)"
FT /id="VAR_033758"
FT VARIANT 233
FT /note="Y -> C (in MTDPS11; impaired exonuclease activity;
FT dbSNP:rs587776944)"
FT /evidence="ECO:0000269|PubMed:23313956"
FT /id="VAR_069102"
FT MUTAGEN 251
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:23358826"
FT MUTAGEN 253
FT /note="K->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:23313956,
FT ECO:0000269|PubMed:23358826"
FT MUTAGEN 253
FT /note="K->A: Abolishes exonuclease activity."
FT /evidence="ECO:0000269|PubMed:23313956,
FT ECO:0000269|PubMed:23358826"
FT CONFLICT 308
FT /note="F -> L (in Ref. 1; BAB55160)"
FT /evidence="ECO:0000305"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:5ZYW"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 143..160
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 162..187
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 204..208
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:5ZYU"
FT STRAND 216..228
FT /evidence="ECO:0007829|PDB:5ZYU"
FT TURN 229..232
FT /evidence="ECO:0007829|PDB:5ZYU"
FT STRAND 233..243
FT /evidence="ECO:0007829|PDB:5ZYU"
FT STRAND 246..254
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:5ZYU"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:5ZYU"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:5ZYU"
FT HELIX 311..333
FT /evidence="ECO:0007829|PDB:5ZYU"
SQ SEQUENCE 344 AA; 39421 MW; 923DEE90FCFED6C6 CRC64;
MKMKLFQTIC RQLRSSKFSV ESAALVAFST SSYSCGRKKK VNPYEEVDQE KYSNLVQSVL
SSRGVAQTPG SVEEDALLCG PVSKHKLPNQ GEDRRVPQNW FPIFNPERSD KPNASDPSVP
LKIPLQRNVI PSVTRVLQQT MTKQQVFLLE RWKQRMILEL GEDGFKEYTS NVFLQGKRFH
EALESILSPQ ETLKERDENL LKSGYIESVQ HILKDVSGVR ALESAVQHET LNYIGLLDCV
AEYQGKLCVI DWKTSEKPKP FIQSTFDNPL QVVAYMGAMN HDTNYSFQVQ CGLIVVAYKD
GSPAHPHFMD AELCSQYWTK WLLRLEEYTE KKKNQNIQKP EYSE
