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Protein

Dimethylglycine dehydrogenase, mitochondrial

Gene

DMGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the demethylation of N,N-dimethylglycine to sarcosine. Also has activity with sarcosine in vitro.1 Publication

Catalytic activityi

N,N-dimethylglycine + 5,6,7,8-tetrahydrofolate + electron-transfer flavoprotein = sarcosine + 5,10-methylenetetrahydrofolate + reduced electron-transfer flavoprotein.1 Publication

Cofactori

FAD1 PublicationNote: Binds 1 FAD covalently per monomer.1 Publication

Kineticsi

kcat is 213 min(-1) for N,N-dimethylglycine.1 Publication
  1. KM=1.4 mM for N,N-dimethylglycine1 Publication
  1. Vmax=22.1 µmol/min/mg enzyme

Pathwayi: betaine degradation

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:
  1. Betaine--homocysteine S-methyltransferase 1 (BHMT)
  2. Dimethylglycine dehydrogenase, mitochondrial (DMGDH)
This subpathway is part of the pathway betaine degradation, which is itself part of Amine and polyamine degradation.
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei219FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
Binding sitei251FADBy similarity1
Binding sitei676TetrahydrofolateBy similarity1
Binding sitei744TetrahydrofolateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi59 – 60FADCombined sources1 Publication2
Nucleotide bindingi80 – 81FADCombined sources1 Publication2
Nucleotide bindingi87 – 95FADCombined sources1 Publication9
Nucleotide bindingi397 – 402FADCombined sources1 Publication6

GO - Molecular functioni

  • dimethylglycine dehydrogenase activity Source: UniProtKB
  • electron transfer activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein

Enzyme and pathway databases

BioCyciMetaCyc:HS05695-MONOMER
ReactomeiR-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000132837.14
HGNCiHGNC:24475 DMGDH
MIMi605849 gene
neXtProtiNX_Q9UI17

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

DMGDH deficiency (DMGDHD)2 Publications
The disease is caused by mutations 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.
See also OMIM:605850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011505109H → 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 mutation

Organism-specific databases

DisGeNETi29958
MalaCardsiDMGDH
MIMi605850 phenotype
OpenTargetsiENSG00000132837
Orphaneti243343 Dimethylglycine dehydrogenase deficiency
PharmGKBiPA134947212

Polymorphism and mutation databases

BioMutaiDMGDH
DMDMi296434575

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 50MitochondrionSequence analysisAdd BLAST50
ChainiPRO_000001076751 – 866Dimethylglycine dehydrogenase, mitochondrialAdd BLAST816

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei91Tele-8alpha-FAD histidineCombined sources1 Publication1
Modified residuei114N6-acetyllysineBy similarity1
Modified residuei148N6-acetyllysine; alternateBy similarity1
Modified residuei148N6-succinyllysine; alternateBy similarity1
Modified residuei168N6-acetyllysineBy similarity1
Modified residuei223N6-acetyllysineBy similarity1
Modified residuei317N6-succinyllysineBy similarity1
Modified residuei319N6-succinyllysineBy similarity1
Modified residuei335N6-acetyllysineBy similarity1
Modified residuei360N6-acetyllysineBy similarity1
Modified residuei434N6-acetyllysine; alternateBy similarity1
Modified residuei434N6-succinyllysine; alternateBy similarity1
Modified residuei523N6-acetyllysine; alternateBy similarity1
Modified residuei523N6-succinyllysine; alternateBy similarity1
Modified residuei655N6-acetyllysine; alternateBy similarity1
Modified residuei655N6-succinyllysine; alternateBy similarity1
Modified residuei764N6-acetyllysineBy similarity1
Modified residuei795N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ9UI17
PeptideAtlasiQ9UI17
PRIDEiQ9UI17
ProteomicsDBi84455

PTM databases

CarbonylDBiQ9UI17
iPTMnetiQ9UI17
PhosphoSitePlusiQ9UI17

Expressioni

Gene expression databases

BgeeiENSG00000132837 Expressed in 138 organ(s), highest expression level in liver
CleanExiHS_DMGDH
ExpressionAtlasiQ9UI17 baseline and differential
GenevisibleiQ9UI17 HS

Organism-specific databases

HPAiHPA036441
HPA036442
HPA077849

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi118994, 1 interactor
STRINGi9606.ENSP00000255189

Structurei

Secondary structure

1866
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UI17
SMRiQ9UI17
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni580 – 582Tetrahydrofolate bindingBy similarity3
Regioni683 – 685Tetrahydrofolate bindingBy similarity3

Sequence similaritiesi

Belongs to the GcvT family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2844 Eukaryota
COG0404 LUCA
COG0665 LUCA
GeneTreeiENSGT00530000063120
HOGENOMiHOG000251716
HOVERGENiHBG081945
InParanoidiQ9UI17
KOiK00315
OMAiYESQEKM
OrthoDBiEOG091G01OO
PhylomeDBiQ9UI17
TreeFamiTF314735

Family and domain databases

Gene3Di3.30.1360.120, 2 hits
3.50.50.60, 3 hits
InterProiView 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
PfamiView protein in Pfam
PF01266 DAO, 1 hit
PF16350 FAO_M, 1 hit
PF01571 GCV_T, 1 hit
PF08669 GCV_T_C, 1 hit
SUPFAMiSSF101790 SSF101790, 1 hit
SSF51905 SSF51905, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9UI17-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:866
Mass (Da):96,811
Last modified:May 18, 2010 - v2
Checksum:i2EC1FA7DCB6C1F8C
GO
Isoform 2 (identifier: Q9UI17-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MLRPGAQLLRGLLLRSCP → MWSCWRNQSSRLDLPGTQ
     19-398: Missing.
     751-774: PADFIGKQALKQIKAKGLKRRLVC → DQNSCFAHFKEENGWVSRWAIRPY
     775-866: Missing.

Note: No experimental confirmation available.
Show »
Length:394
Mass (Da):45,079
Checksum:iCA6DCA6EA8F01BCF
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8TCC6Q8TCC6_HUMAN
DMGDH protein
DMGDH
613Annotation score:
E5RG50E5RG50_HUMAN
Dimethylglycine dehydrogenase, mito...
DMGDH
98Annotation score:
E5RK15E5RK15_HUMAN
Dimethylglycine dehydrogenase, mito...
DMGDH
106Annotation score:
E5RGI4E5RGI4_HUMAN
Dimethylglycine dehydrogenase, mito...
DMGDH
50Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti381M → I in BAG37277 (PubMed:14702039).Curated1
Sequence conflicti627L → F in BAG37277 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011505109H → 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_014950279S → P2 PublicationsCorresponds to variant dbSNP:rs532964Ensembl.1
Natural variantiVAR_014951530A → G1 PublicationCorresponds to variant dbSNP:rs1805073EnsemblClinVar.1
Natural variantiVAR_014952646S → PCombined sources1 PublicationCorresponds to variant dbSNP:rs1805074EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0569591 – 18MLRPG…LRSCP → MWSCWRNQSSRLDLPGTQ in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_05696019 – 398Missing in isoform 2. 1 PublicationAdd BLAST380
Alternative sequenceiVSP_056961751 – 774PADFI…RRLVC → DQNSCFAHFKEENGWVSRWA IRPY in isoform 2. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_056962775 – 866Missing in isoform 2. 1 PublicationAdd BLAST92

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.
CCDSiCCDS4044.1 [Q9UI17-1]
RefSeqiNP_037523.2, NM_013391.3 [Q9UI17-1]
UniGeneiHs.655653

Genome annotation databases

EnsembliENST00000255189; ENSP00000255189; ENSG00000132837 [Q9UI17-1]
GeneIDi29958
KEGGihsa:29958
UCSCiuc003kfs.5 human [Q9UI17-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiM2GD_HUMAN
AccessioniPrimary (citable) accession number: Q9UI17
Secondary accession number(s): B2RBN0, B4E1J9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 18, 2010
Last modified: September 12, 2018
This is version 160 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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