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Protein

Dimethylglycine dehydrogenase, mitochondrial

Gene

DMGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 + electron-transfer flavoprotein + H2O = sarcosine + formaldehyde + 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 carrier activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • amino-acid betaine catabolic process Source: UniProtKB-UniPathway
  • choline catabolic process Source: Reactome
  • choline metabolic process Source: UniProtKB
  • glycine metabolic process Source: UniProtKB

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein

Enzyme and pathway databases

BioCyciMetaCyc:HS05695-MONOMER.
ReactomeiR-HSA-6798163. Choline catabolism.
UniPathwayiUPA00291; 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

HGNCiHGNC:24475. DMGDH.

Subcellular locationi

GO - Cellular componenti

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:rs121908331Ensembl.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

EPDiQ9UI17.
PaxDbiQ9UI17.
PeptideAtlasiQ9UI17.
PRIDEiQ9UI17.

PTM databases

iPTMnetiQ9UI17.
PhosphoSitePlusiQ9UI17.

Expressioni

Gene expression databases

BgeeiENSG00000132837.
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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi48 – 55Combined sources8
Helixi59 – 70Combined sources12
Beta strandi74 – 79Combined sources6
Beta strandi81 – 83Combined sources3
Turni84 – 88Combined sources5
Helixi89 – 91Combined sources3
Beta strandi101 – 103Combined sources3
Helixi105 – 123Combined sources19
Beta strandi134 – 138Combined sources5
Helixi141 – 154Combined sources14
Beta strandi157 – 159Combined sources3
Beta strandi162 – 164Combined sources3
Helixi166 – 170Combined sources5
Beta strandi183 – 187Combined sources5
Helixi195 – 208Combined sources14
Beta strandi212 – 214Combined sources3
Beta strandi221 – 224Combined sources4
Beta strandi230 – 233Combined sources4
Beta strandi238 – 246Combined sources9
Helixi249 – 251Combined sources3
Helixi252 – 256Combined sources5
Helixi257 – 259Combined sources3
Beta strandi266 – 275Combined sources10
Helixi279 – 283Combined sources5
Beta strandi290 – 293Combined sources4
Turni294 – 296Combined sources3
Beta strandi298 – 303Combined sources6
Beta strandi306 – 311Combined sources6
Turni315 – 317Combined sources3
Helixi323 – 326Combined sources4
Helixi342 – 344Combined sources3
Helixi346 – 355Combined sources10
Helixi357 – 360Combined sources4
Beta strandi364 – 374Combined sources11
Beta strandi381 – 384Combined sources4
Beta strandi391 – 395Combined sources5
Helixi400 – 415Combined sources16
Turni425 – 427Combined sources3
Helixi438 – 450Combined sources13
Helixi451 – 453Combined sources3
Helixi474 – 478Combined sources5
Helixi479 – 481Combined sources3
Beta strandi482 – 487Combined sources6
Beta strandi490 – 496Combined sources7
Helixi515 – 527Combined sources13
Beta strandi530 – 533Combined sources4
Beta strandi537 – 544Combined sources8
Helixi547 – 554Combined sources8
Beta strandi564 – 571Combined sources8
Beta strandi577 – 585Combined sources9
Beta strandi591 – 595Combined sources5
Helixi597 – 599Combined sources3
Helixi600 – 613Combined sources14
Beta strandi619 – 622Combined sources4
Turni624 – 626Combined sources3
Beta strandi630 – 634Combined sources5
Helixi637 – 642Combined sources6
Turni651 – 653Combined sources3
Beta strandi658 – 664Combined sources7
Beta strandi667 – 673Combined sources7
Beta strandi678 – 687Combined sources10
Helixi690 – 702Combined sources13
Turni703 – 706Combined sources4
Helixi712 – 722Combined sources11
Turni727 – 729Combined sources3
Turni737 – 741Combined sources5
Helixi743 – 745Combined sources3
Beta strandi750 – 752Combined sources3
Helixi757 – 766Combined sources10
Beta strandi769 – 777Combined sources9
Beta strandi789 – 792Combined sources4
Beta strandi795 – 806Combined sources12
Turni807 – 810Combined sources4
Beta strandi811 – 819Combined sources9
Helixi820 – 822Combined sources3
Beta strandi828 – 833Combined sources6
Beta strandi836 – 842Combined sources7
Turni851 – 853Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L46X-ray3.09A/B29-866[»]
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

Gene3Di2.40.30.110. 1 hit.
InterProiView protein in InterPro
IPR006076. FAD-dep_OxRdtase.
IPR023753. FAD/NAD-binding_dom.
IPR032503. FAO_M.
IPR013977. GCV_T_C.
IPR006222. GCV_T_N.
IPR029043. GcvT/YgfZ_C.
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

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

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:rs121908331Ensembl.1
Natural variantiVAR_014950279S → P2 PublicationsCorresponds to variant dbSNP:rs532964Ensembl.1
Natural variantiVAR_014951530A → G1 PublicationCorresponds to variant dbSNP:rs1805073Ensembl.1
Natural variantiVAR_014952646S → PCombined sources1 PublicationCorresponds to variant dbSNP:rs1805074Ensembl.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

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L46X-ray3.09A/B29-866[»]
ProteinModelPortaliQ9UI17.
SMRiQ9UI17.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118994. 1 interactor.
STRINGi9606.ENSP00000255189.

PTM databases

iPTMnetiQ9UI17.
PhosphoSitePlusiQ9UI17.

Polymorphism and mutation databases

BioMutaiDMGDH.
DMDMi296434575.

Proteomic databases

EPDiQ9UI17.
PaxDbiQ9UI17.
PeptideAtlasiQ9UI17.
PRIDEiQ9UI17.

Protocols and materials databases

DNASUi29958.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi29958.
DisGeNETi29958.
GeneCardsiDMGDH.
H-InvDBiHIX0200737.
HGNCiHGNC:24475. DMGDH.
HPAiHPA036441.
HPA036442.
HPA077849.
MalaCardsiDMGDH.
MIMi605849. gene.
605850. phenotype.
neXtProtiNX_Q9UI17.
OpenTargetsiENSG00000132837.
Orphaneti243343. Dimethylglycine dehydrogenase deficiency.
PharmGKBiPA134947212.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00291; UER00433.
BioCyciMetaCyc:HS05695-MONOMER.
ReactomeiR-HSA-6798163. Choline catabolism.

Miscellaneous databases

GenomeRNAii29958.
PROiPR:Q9UI17.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132837.
CleanExiHS_DMGDH.
ExpressionAtlasiQ9UI17. baseline and differential.
GenevisibleiQ9UI17. HS.

Family and domain databases

Gene3Di2.40.30.110. 1 hit.
InterProiView protein in InterPro
IPR006076. FAD-dep_OxRdtase.
IPR023753. FAD/NAD-binding_dom.
IPR032503. FAO_M.
IPR013977. GCV_T_C.
IPR006222. GCV_T_N.
IPR029043. GcvT/YgfZ_C.
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.
ProtoNetiSearch...

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: May 10, 2017
This is version 151 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

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.