M2GD_MOUSE
ID M2GD_MOUSE Reviewed; 869 AA.
AC Q9DBT9; B1B1D0; Q8R1S7;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Dimethylglycine dehydrogenase, mitochondrial;
DE EC=1.5.8.4 {ECO:0000250|UniProtKB:Q63342};
DE AltName: Full=ME2GLYDH;
DE Flags: Precursor;
GN Name=Dmgdh;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 237-869.
RC TISSUE=Liver;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-141; LYS-310; LYS-312; LYS-427;
RP LYS-469; LYS-516; LYS-648; LYS-786 AND LYS-788, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-107; LYS-141; LYS-161; LYS-216;
RP LYS-328; LYS-353; LYS-427; LYS-469; LYS-516; LYS-648; LYS-757 AND LYS-786,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Catalyzes the demethylation of N,N-dimethylglycine to
CC sarcosine. Also has activity with sarcosine in vitro.
CC {ECO:0000250|UniProtKB:Q63342}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + H(+) + N,N-
CC dimethylglycine + oxidized [electron-transfer flavoprotein] = (6R)-
CC 5,10-methylenetetrahydrofolyl-(gamma-L-Glu)(n) + reduced [electron-
CC transfer flavoprotein] + sarcosine; Xref=Rhea:RHEA:52856, Rhea:RHEA-
CC COMP:10685, Rhea:RHEA-COMP:10686, Rhea:RHEA-COMP:13257, Rhea:RHEA-
CC COMP:14738, ChEBI:CHEBI:15378, ChEBI:CHEBI:57433, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58251, ChEBI:CHEBI:58307, ChEBI:CHEBI:136572,
CC ChEBI:CHEBI:141005; EC=1.5.8.4;
CC Evidence={ECO:0000250|UniProtKB:Q63342};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q63342};
CC Note=Binds 1 FAD covalently per monomer.
CC {ECO:0000250|UniProtKB:Q63342};
CC -!- PATHWAY: Amine and polyamine degradation; betaine degradation;
CC sarcosine from betaine: step 2/2.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q63342}.
CC -!- SIMILARITY: Belongs to the GcvT family. {ECO:0000305}.
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DR EMBL; AK004755; BAB23536.1; -; mRNA.
DR EMBL; AC131739; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT030023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024126; AAH24126.1; -; mRNA.
DR CCDS; CCDS26690.1; -.
DR RefSeq; NP_083048.1; NM_028772.3.
DR AlphaFoldDB; Q9DBT9; -.
DR SMR; Q9DBT9; -.
DR STRING; 10090.ENSMUSP00000039663; -.
DR iPTMnet; Q9DBT9; -.
DR PhosphoSitePlus; Q9DBT9; -.
DR SwissPalm; Q9DBT9; -.
DR jPOST; Q9DBT9; -.
DR MaxQB; Q9DBT9; -.
DR PaxDb; Q9DBT9; -.
DR PeptideAtlas; Q9DBT9; -.
DR PRIDE; Q9DBT9; -.
DR ProteomicsDB; 252697; -.
DR Antibodypedia; 48453; 194 antibodies from 26 providers.
DR DNASU; 74129; -.
DR Ensembl; ENSMUST00000048001; ENSMUSP00000039663; ENSMUSG00000042102.
DR GeneID; 74129; -.
DR KEGG; mmu:74129; -.
DR UCSC; uc007rll.1; mouse.
DR CTD; 29958; -.
DR MGI; MGI:1921379; Dmgdh.
DR VEuPathDB; HostDB:ENSMUSG00000042102; -.
DR eggNOG; KOG2844; Eukaryota.
DR GeneTree; ENSGT00940000158176; -.
DR HOGENOM; CLU_007884_11_1_1; -.
DR InParanoid; Q9DBT9; -.
DR OMA; PAIPVEH; -.
DR OrthoDB; 752680at2759; -.
DR PhylomeDB; Q9DBT9; -.
DR TreeFam; TF314735; -.
DR BRENDA; 1.5.8.4; 3474.
DR Reactome; R-MMU-6798163; Choline catabolism.
DR UniPathway; UPA00291; UER00433.
DR BioGRID-ORCS; 74129; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Dmgdh; mouse.
DR PRO; PR:Q9DBT9; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9DBT9; protein.
DR Bgee; ENSMUSG00000042102; Expressed in left lobe of liver and 52 other tissues.
DR Genevisible; Q9DBT9; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047865; F:dimethylglycine dehydrogenase activity; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0005542; F:folic acid binding; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006579; P:amino-acid betaine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042426; P:choline catabolic process; ISO:MGI.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; ISO:MGI.
DR Gene3D; 3.30.1360.120; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR032503; FAO_M.
DR InterPro; IPR013977; GCV_T_C.
DR InterPro; IPR006222; GCV_T_N.
DR InterPro; IPR029043; GcvT/YgfZ_C.
DR InterPro; IPR027266; TrmE/GcvT_dom1.
DR Pfam; PF01266; DAO; 1.
DR Pfam; PF16350; FAO_M; 1.
DR Pfam; PF01571; GCV_T; 1.
DR Pfam; PF08669; GCV_T_C; 1.
DR SUPFAM; SSF101790; SSF101790; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Acetylation; FAD; Flavoprotein; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 44..869
FT /note="Dimethylglycine dehydrogenase, mitochondrial"
FT /id="PRO_0000010768"
FT REGION 14..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 52..53
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 73..74
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 80..88
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 212
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 244
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 390..395
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 573..575
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 669
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 676..678
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT BINDING 737
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT MOD_RES 84
FT /note="Tele-8alpha-FAD histidine"
FT /evidence="ECO:0000250|UniProtKB:Q63342"
FT MOD_RES 107
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 141
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 141
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 161
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 216
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 310
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 312
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 328
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 427
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 427
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 469
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 469
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 516
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 516
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 648
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 648
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 757
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 786
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 786
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 788
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 758
FT /note="T -> A (in Ref. 3; AAH24126)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 869 AA; 97255 MW; D415C743105A0547 CRC64;
MLRPGALRLR GLALRGSPRR PSSAGLREGQ ESPASPPEWK DRAETVIIGG GCVGVSLAYH
LAKAGMRDVV LMEKSELTAG STWHAAGLTT YFHPGINLKK IHYDSIKLYE RLEEETGQVV
GFHQPGSIRL ATTPVRVDEF KYQMTRTNWH ATEQYIIEPE KIHELFPLLN MNKILAGLYN
PGDGHIDPYS LTMALAAGAR KYGALLKYPA PVTSLKPRPD GTWDVETPQG SVRANRIVNA
AGFWAREVGK MIGLDHPLIP VQHQYVVTST IPEVKALKRE LPVLRDLEGS YYLRQERDGL
LFGPYESQEK MKLQASWVTH GVPPGFGKEL FESDLDRISD HLEAAMEMIP VLKKADIINV
VNGPITYSPD ILPMVGPHQG VRNYWVATGF GYGIIHAGGV GKFLSDWILH GEPPFDLIEL
DPNRYGKWTT TQYTEAKARE SYGFNNIVGY PKEERFAGRP TQRVSGLYKT LKSKCSMGFH
AGWEQPHWFY KPGQDTQYRP SFRRTNWFEP VGSEYKQVMQ RVGVIDLSPF GKFNIKGRDS
TQLLDHLFAN VIPKVGFTNI SHMLTPRGRV YAELTVSQQS PGEFLLITGS GSELHDLRWI
EEAAFRGGYD VEIQNITDEF GVLGVAGPYA RRVLQKLTSE DLSDDAFKFL QTKSFNISDI
PVTAIRISYT GELGWELYHR REDSATLYER IMSAGQEEGI GDFGTYALNA LRLEKAFRAW
GSEMNCDTNP LEAGLEYFVK LNKPADFIGK QALKQIKTEG LKRRLVCLTV ATDDVDPEGN
ESIWYKGKVV GNTTSGSYSY SIQKSLAFAY VPVQLSEVGQ QVEVELLGKN YPATIIQEPL
VLTEPARARL QKDGKKTNLE KGPSRTTKL
