UniProtKB - Q9UI17 (M2GD_HUMAN)
Protein
Dimethylglycine dehydrogenase, mitochondrial
Gene
DMGDH
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the demethylation of N,N-dimethylglycine to sarcosine. Also has activity with sarcosine in vitro.1 Publication
Catalytic activityi
- (6S)-5,6,7,8-tetrahydrofolyl-(γ-L-Glu)n + H+ + N,N-dimethylglycine + oxidized [electron-transfer flavoprotein] = (6R)-5,10-methylenetetrahydrofolyl-(γ-L-Glu)(n) + reduced [electron-transfer flavoprotein] + sarcosine1 PublicationEC:1.5.8.41 Publication
Cofactori
FAD1 PublicationNote: Binds 1 FAD covalently per monomer.1 Publication
Kineticsi
kcat is 213 min(-1) for N,N-dimethylglycine.1 Publication
- KM=1.4 mM for N,N-dimethylglycine1 Publication
- Vmax=22.1 µmol/min/mg enzyme
: betaine degradation Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes sarcosine from betaine.Proteins known to be involved in the 2 steps of the subpathway in this organism are:
- Betaine--homocysteine S-methyltransferase 1 (BHMT)
- Dimethylglycine dehydrogenase, mitochondrial (DMGDH)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes sarcosine from betaine, the pathway betaine degradation and in Amine and polyamine degradation.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 219 | FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication | 1 | |
Binding sitei | 251 | FADBy similarity | 1 | |
Binding sitei | 676 | TetrahydrofolateBy similarity | 1 | |
Binding sitei | 744 | TetrahydrofolateBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 59 – 60 | FADCombined sources1 Publication | 2 | |
Nucleotide bindingi | 80 – 81 | FADCombined sources1 Publication | 2 | |
Nucleotide bindingi | 87 – 95 | FADCombined sources1 Publication | 9 | |
Nucleotide bindingi | 397 – 402 | FADCombined sources1 Publication | 6 |
GO - Molecular functioni
- dimethylglycine dehydrogenase activity Source: UniProtKB
- electron transfer activity Source: UniProtKB
- oxidoreductase activity Source: GO_Central
- RNA binding Source: UniProtKB
GO - Biological processi
- amino-acid betaine catabolic process Source: UniProtKB-UniPathway
- choline catabolic process Source: UniProtKB
- choline metabolic process Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Ligand | FAD, Flavoprotein |
Enzyme and pathway databases
BioCyci | MetaCyc:HS05695-MONOMER |
PathwayCommonsi | Q9UI17 |
Reactomei | R-HSA-6798163, Choline catabolism |
UniPathwayi | UPA00291;UER00433 |
Names & Taxonomyi
Protein namesi | Recommended name: Dimethylglycine dehydrogenase, mitochondrial (EC:1.5.8.41 Publication)Alternative name(s): ME2GLYDH |
Gene namesi | Name:DMGDH |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:24475, DMGDH |
MIMi | 605849, gene |
neXtProti | NX_Q9UI17 |
VEuPathDBi | HostDB:ENSG00000132837.14 |
Subcellular locationi
Mitochondrion
Mitochondrion
- mitochondrial matrix Source: GO_Central
- mitochondrion Source: HPA
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Involvement in diseasei
DMGDH deficiency (DMGDHD)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionDisorder characterized by fish odor, muscle fatigue with increased serum creatine kinase. Biochemically it is characterized by an increase of N,N-dimethylglycine (DMG) in serum and urine.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_011505 | 109 | H → R in DMGDHD; shows 10 fold lower catalytic efficiency due to lower cofactor saturation and reduced thermal stability. 2 PublicationsCorresponds to variant dbSNP:rs121908331EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 29958 |
MalaCardsi | DMGDH |
MIMi | 605850, phenotype |
OpenTargetsi | ENSG00000132837 |
Orphaneti | 243343, Dimethylglycine dehydrogenase deficiency |
PharmGKBi | PA134947212 |
Miscellaneous databases
Pharosi | Q9UI17, Tbio |
Genetic variation databases
BioMutai | DMGDH |
DMDMi | 296434575 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 50 | MitochondrionSequence analysisAdd BLAST | 50 | |
ChainiPRO_0000010767 | 51 – 866 | Dimethylglycine dehydrogenase, mitochondrialAdd BLAST | 816 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 91 | Tele-8alpha-FAD histidineCombined sources1 Publication | 1 | |
Modified residuei | 114 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 148 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 148 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 168 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 223 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 317 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 319 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 335 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 360 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 434 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 434 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 523 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 523 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 655 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 655 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 764 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 795 | N6-succinyllysineBy similarity | 1 |
Keywords - PTMi
AcetylationProteomic databases
MassIVEi | Q9UI17 |
PaxDbi | Q9UI17 |
PeptideAtlasi | Q9UI17 |
PRIDEi | Q9UI17 |
ProteomicsDBi | 5764 84455 [Q9UI17-1] |
PTM databases
CarbonylDBi | Q9UI17 |
iPTMneti | Q9UI17 |
PhosphoSitePlusi | Q9UI17 |
Expressioni
Gene expression databases
Bgeei | ENSG00000132837, Expressed in adult mammalian kidney and 162 other tissues |
ExpressionAtlasi | Q9UI17, baseline and differential |
Genevisiblei | Q9UI17, HS |
Organism-specific databases
HPAi | ENSG00000132837, Group enriched (kidney, liver) |
Interactioni
Subunit structurei
Monomer.
Protein-protein interaction databases
BioGRIDi | 118994, 2 interactors |
IntActi | Q9UI17, 2 interactors |
STRINGi | 9606.ENSP00000255189 |
Miscellaneous databases
RNActi | Q9UI17, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9UI17 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 580 – 582 | Tetrahydrofolate bindingBy similarity | 3 | |
Regioni | 683 – 685 | Tetrahydrofolate bindingBy similarity | 3 |
Sequence similaritiesi
Belongs to the GcvT family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG2844, Eukaryota |
GeneTreei | ENSGT00940000158176 |
HOGENOMi | CLU_007884_11_1_1 |
InParanoidi | Q9UI17 |
OMAi | PAIPVEH |
PhylomeDBi | Q9UI17 |
TreeFami | TF314735 |
Family and domain databases
Gene3Di | 3.30.1360.120, 1 hit 3.50.50.60, 1 hit |
InterProi | View protein in InterPro IPR006076, FAD-dep_OxRdtase IPR036188, FAD/NAD-bd_sf IPR032503, FAO_M IPR013977, GCV_T_C IPR006222, GCV_T_N IPR029043, GcvT/YgfZ_C IPR027266, TrmE/GcvT_dom1 |
Pfami | View protein in Pfam PF01266, DAO, 1 hit PF16350, FAO_M, 1 hit PF01571, GCV_T, 1 hit PF08669, GCV_T_C, 1 hit |
SUPFAMi | SSF101790, SSF101790, 1 hit SSF51905, SSF51905, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9UI17-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLRPGAQLLR GLLLRSCPLQ GSPGRPRSVC GREGEEKPPL SAETQWKDRA
60 70 80 90 100
ETVIIGGGCV GVSLAYHLAK AGMKDVVLLE KSELTAGSTW HAAGLTTYFH
110 120 130 140 150
PGINLKKIHY DSIKLYEKLE EETGQVVGFH QPGSIRLATT PVRVDEFKYQ
160 170 180 190 200
MTRTGWHATE QYLIEPEKIQ EMFPLLNMNK VLAGLYNPGD GHIDPYSLTM
210 220 230 240 250
ALAAGARKCG ALLKYPAPVT SLKARSDGTW DVETPQGSMR ANRIVNAAGF
260 270 280 290 300
WAREVGKMIG LEHPLIPVQH QYVVTSTISE VKALKRELPV LRDLEGSYYL
310 320 330 340 350
RQERDGLLFG PYESQEKMKV QDSWVTNGVP PGFGKELFES DLDRIMEHIK
360 370 380 390 400
AAMEMVPVLK KADIINVVNG PITYSPDILP MVGPHQGVRN YWVAIGFGYG
410 420 430 440 450
IIHAGGVGKY LSDWILHGEP PFDLIELDPN RYGKWTTTQY TEAKARESYG
460 470 480 490 500
FNNIVGYPKE ERFAGRPTQR VSGLYQRLES KCSMGFHAGW EQPHWFYKPG
510 520 530 540 550
QDTQYRPSFR RTNWFEPVGS EYKQVMQRVA VTDLSPFGKF NIKGQDSIRL
560 570 580 590 600
LDHLFANVIP KVGFTNISHM LTPKGRVYAE LTVSHQSPGE FLLITGSGSE
610 620 630 640 650
LHDLRWIEEE AVKGGYDVEI KNITDELGVL GVAGPQARKV LQKLTSEDLS
660 670 680 690 700
DDVFKFLQTK SLKVSNIPVT AIRISYTGEL GWELYHRRED SVALYDAIMN
710 720 730 740 750
AGQEEGIDNF GTYAMNALRL EKAFRAWGLE MNCDTNPLEA GLEYFVKLNK
760 770 780 790 800
PADFIGKQAL KQIKAKGLKR RLVCLTLATD DVDPEGNESI WYNGKVVGNT
810 820 830 840 850
TSGSYSYSIQ KSLAFAYVPV QLSEVGQQVE VELLGKNYPA VIIQEPLVLT
860
EPTRNRLQKK GGKDKT
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RK15 | E5RK15_HUMAN | Dimethylglycine dehydrogenase, mito... | DMGDH | 106 | Annotation score: | ||
Q8TCC6 | Q8TCC6_HUMAN | DMGDH protein | DMGDH | 613 | Annotation score: | ||
E5RG50 | E5RG50_HUMAN | Dimethylglycine dehydrogenase, mito... | DMGDH | 98 | Annotation score: | ||
E5RGI4 | E5RGI4_HUMAN | Dimethylglycine dehydrogenase, mito... | DMGDH | 50 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 381 | M → I in BAG37277 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 627 | L → F in BAG37277 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_011505 | 109 | H → R in DMGDHD; shows 10 fold lower catalytic efficiency due to lower cofactor saturation and reduced thermal stability. 2 PublicationsCorresponds to variant dbSNP:rs121908331EnsemblClinVar. | 1 | |
Natural variantiVAR_014950 | 279 | S → P2 PublicationsCorresponds to variant dbSNP:rs532964Ensembl. | 1 | |
Natural variantiVAR_014951 | 530 | A → G1 PublicationCorresponds to variant dbSNP:rs1805073EnsemblClinVar. | 1 | |
Natural variantiVAR_014952 | 646 | S → PCombined sources1 PublicationCorresponds to variant dbSNP:rs1805074EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056959 | 1 – 18 | MLRPG…LRSCP → MWSCWRNQSSRLDLPGTQ in isoform 2. 1 PublicationAdd BLAST | 18 | |
Alternative sequenceiVSP_056960 | 19 – 398 | Missing in isoform 2. 1 PublicationAdd BLAST | 380 | |
Alternative sequenceiVSP_056961 | 751 – 774 | PADFI…RRLVC → DQNSCFAHFKEENGWVSRWA IRPY in isoform 2. 1 PublicationAdd BLAST | 24 | |
Alternative sequenceiVSP_056962 | 775 – 866 | Missing in isoform 2. 1 PublicationAdd BLAST | 92 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF111858 mRNA Translation: AAF21941.1 AK303873 mRNA Translation: BAG64811.1 AK314736 mRNA Translation: BAG37277.1 AC008502 Genomic DNA No translation available. AC016559 Genomic DNA No translation available. AC020937 Genomic DNA No translation available. |
CCDSi | CCDS4044.1 [Q9UI17-1] |
RefSeqi | NP_037523.2, NM_013391.3 [Q9UI17-1] |
Genome annotation databases
Ensembli | ENST00000255189; ENSP00000255189; ENSG00000132837 [Q9UI17-1] |
GeneIDi | 29958 |
KEGGi | hsa:29958 |
UCSCi | uc003kfs.5, human [Q9UI17-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF111858 mRNA Translation: AAF21941.1 AK303873 mRNA Translation: BAG64811.1 AK314736 mRNA Translation: BAG37277.1 AC008502 Genomic DNA No translation available. AC016559 Genomic DNA No translation available. AC020937 Genomic DNA No translation available. |
CCDSi | CCDS4044.1 [Q9UI17-1] |
RefSeqi | NP_037523.2, NM_013391.3 [Q9UI17-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5L46 | X-ray | 3.09 | A/B | 29-866 | [»] | |
SMRi | Q9UI17 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 118994, 2 interactors |
IntActi | Q9UI17, 2 interactors |
STRINGi | 9606.ENSP00000255189 |
PTM databases
CarbonylDBi | Q9UI17 |
iPTMneti | Q9UI17 |
PhosphoSitePlusi | Q9UI17 |
Genetic variation databases
BioMutai | DMGDH |
DMDMi | 296434575 |
Proteomic databases
MassIVEi | Q9UI17 |
PaxDbi | Q9UI17 |
PeptideAtlasi | Q9UI17 |
PRIDEi | Q9UI17 |
ProteomicsDBi | 5764 84455 [Q9UI17-1] |
Protocols and materials databases
Antibodypediai | 48453, 183 antibodies |
DNASUi | 29958 |
Genome annotation databases
Ensembli | ENST00000255189; ENSP00000255189; ENSG00000132837 [Q9UI17-1] |
GeneIDi | 29958 |
KEGGi | hsa:29958 |
UCSCi | uc003kfs.5, human [Q9UI17-1] |
Organism-specific databases
CTDi | 29958 |
DisGeNETi | 29958 |
GeneCardsi | DMGDH |
HGNCi | HGNC:24475, DMGDH |
HPAi | ENSG00000132837, Group enriched (kidney, liver) |
MalaCardsi | DMGDH |
MIMi | 605849, gene 605850, phenotype |
neXtProti | NX_Q9UI17 |
OpenTargetsi | ENSG00000132837 |
Orphaneti | 243343, Dimethylglycine dehydrogenase deficiency |
PharmGKBi | PA134947212 |
VEuPathDBi | HostDB:ENSG00000132837.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2844, Eukaryota |
GeneTreei | ENSGT00940000158176 |
HOGENOMi | CLU_007884_11_1_1 |
InParanoidi | Q9UI17 |
OMAi | PAIPVEH |
PhylomeDBi | Q9UI17 |
TreeFami | TF314735 |
Enzyme and pathway databases
UniPathwayi | UPA00291;UER00433 |
BioCyci | MetaCyc:HS05695-MONOMER |
PathwayCommonsi | Q9UI17 |
Reactomei | R-HSA-6798163, Choline catabolism |
Miscellaneous databases
BioGRID-ORCSi | 29958, 1 hit in 988 CRISPR screens |
ChiTaRSi | DMGDH, human |
GenomeRNAii | 29958 |
Pharosi | Q9UI17, Tbio |
PROi | PR:Q9UI17 |
RNActi | Q9UI17, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000132837, Expressed in adult mammalian kidney and 162 other tissues |
ExpressionAtlasi | Q9UI17, baseline and differential |
Genevisiblei | Q9UI17, HS |
Family and domain databases
Gene3Di | 3.30.1360.120, 1 hit 3.50.50.60, 1 hit |
InterProi | View protein in InterPro IPR006076, FAD-dep_OxRdtase IPR036188, FAD/NAD-bd_sf IPR032503, FAO_M IPR013977, GCV_T_C IPR006222, GCV_T_N IPR029043, GcvT/YgfZ_C IPR027266, TrmE/GcvT_dom1 |
Pfami | View protein in Pfam PF01266, DAO, 1 hit PF16350, FAO_M, 1 hit PF01571, GCV_T, 1 hit PF08669, GCV_T_C, 1 hit |
SUPFAMi | SSF101790, SSF101790, 1 hit SSF51905, SSF51905, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | M2GD_HUMAN | |
Accessioni | Q9UI17Primary (citable) accession number: Q9UI17 Secondary accession number(s): B2RBN0, B4E1J9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | May 18, 2010 | |
Last modified: | April 7, 2021 | |
This is version 176 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families