Q9UI17 (M2GD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dimethylglycine dehydrogenase, mitochondrial
EC=1.5.8.4

Alternative name(s):
ME2GLYDH

Gene names

Name:

DMGDH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	866 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	N,N-dimethylglycine + electron-transfer flavoprotein + H2O = sarcosine + formaldehyde + reduced electron-transfer flavoprotein.
Cofactor	Binds 1 FAD covalently per monomer.
Pathway	Amine and polyamine degradation; betaine degradation; sarcosine from betaine: step 2/2.
Subunit structure	Monomer.
Subcellular location	Mitochondrion.
Involvement in disease	DMGDH deficiency (DMGDHD) [MIM:605850]: Disorder 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.5
Sequence similarities	Belongs to the GcvT family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amino-acid betaine catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway choline metabolic process Non-traceable author statement Ref.1. Source: UniProtKB glycine catabolic process Inferred from electronic annotation. Source: InterPro glycine metabolic process Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	mitochondrial matrix Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	aminomethyltransferase activity Inferred from electronic annotation. Source: InterPro dimethylglycine dehydrogenase activity Inferred from mutant phenotype Ref.2. Source: UniProtKB electron carrier activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 50	50	Mitochondrion Potential
	Chain	51 – 866	816	Dimethylglycine dehydrogenase, mitochondrial		PRO_0000010767
Amino acid modifications
	Modified residue	91	1	Tele-8alpha-FAD histidine By similarity
Natural variations
	Natural variant	109	1	H → R in DMGDHD. Ref.2		VAR_011505
	Natural variant	279	1	S → P. Ref.1 Ref.3 Corresponds to variant rs532964 [ dbSNP | Ensembl ].		VAR_014950
	Natural variant	530	1	A → G. Ref.2 Corresponds to variant rs1805073 [ dbSNP | Ensembl ].		VAR_014951
	Natural variant	646	1	S → P. Ref.2 Corresponds to variant rs1805074 [ dbSNP | Ensembl ].		VAR_014952
Experimental info
	Sequence conflict	381	1	M → I in BAG37277. Ref.3
	Sequence conflict	627	1	L → F in BAG37277. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9UI17 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 2EC1FA7DCB6C1F8C	FASTA	866	96,811
	10 20 30 40 50 60 MLRPGAQLLR GLLLRSCPLQ GSPGRPRSVC GREGEEKPPL SAETQWKDRA ETVIIGGGCV 70 80 90 100 110 120 GVSLAYHLAK AGMKDVVLLE KSELTAGSTW HAAGLTTYFH PGINLKKIHY DSIKLYEKLE 130 140 150 160 170 180 EETGQVVGFH QPGSIRLATT PVRVDEFKYQ MTRTGWHATE QYLIEPEKIQ EMFPLLNMNK 190 200 210 220 230 240 VLAGLYNPGD GHIDPYSLTM ALAAGARKCG ALLKYPAPVT SLKARSDGTW DVETPQGSMR 250 260 270 280 290 300 ANRIVNAAGF WAREVGKMIG LEHPLIPVQH QYVVTSTISE VKALKRELPV LRDLEGSYYL 310 320 330 340 350 360 RQERDGLLFG PYESQEKMKV QDSWVTNGVP PGFGKELFES DLDRIMEHIK AAMEMVPVLK 370 380 390 400 410 420 KADIINVVNG PITYSPDILP MVGPHQGVRN YWVAIGFGYG IIHAGGVGKY LSDWILHGEP 430 440 450 460 470 480 PFDLIELDPN RYGKWTTTQY TEAKARESYG FNNIVGYPKE ERFAGRPTQR VSGLYQRLES 490 500 510 520 530 540 KCSMGFHAGW EQPHWFYKPG QDTQYRPSFR RTNWFEPVGS EYKQVMQRVA VTDLSPFGKF 550 560 570 580 590 600 NIKGQDSIRL LDHLFANVIP KVGFTNISHM LTPKGRVYAE LTVSHQSPGE FLLITGSGSE 610 620 630 640 650 660 LHDLRWIEEE AVKGGYDVEI KNITDELGVL GVAGPQARKV LQKLTSEDLS DDVFKFLQTK 670 680 690 700 710 720 SLKVSNIPVT AIRISYTGEL GWELYHRRED SVALYDAIMN AGQEEGIDNF GTYAMNALRL 730 740 750 760 770 780 EKAFRAWGLE MNCDTNPLEA GLEYFVKLNK PADFIGKQAL KQIKAKGLKR RLVCLTLATD 790 800 810 820 830 840 DVDPEGNESI WYNGKVVGNT TSGSYSYSIQ KSLAFAYVPV QLSEVGQQVE VELLGKNYPA 850 860 VIIQEPLVLT EPTRNRLQKK GGKDKT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and analysis of the human dimethylglycine dehydrogenase gene." Binzak B.A., Vockley J.G., Jenkins R.B., Vockley J. Mol. Genet. Metab. 69:181-187(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-279.
[2]	"Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency." Binzak B.A., Wevers R.A., Moolenaar S.H., Lee Y.-M., Hwu W.-L., Poggi-Bach J., Engelke U.F.H., Hoard H.M., Vockley J.G., Vockley J. Am. J. Hum. Genet. 68:839-847(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLY-530 AND PRO-646, VARIANT DMGDHD ARG-109.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-279. Tissue: Synovial cell.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study." Moolenaar S.H., Poggi-Bach J., Engelke U.F.H., Corstiaensen J.M.B., Heerschap A., de Jong J.G.N., Binzak B.A., Vockley J., Wevers R.A. Clin. Chem. 45:459-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: DISEASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF111858 mRNA. Translation: AAF21941.1. AK314736 mRNA. Translation: BAG37277.1. AC008502 Genomic DNA. No translation available. AC020937 Genomic DNA. No translation available.
IPI	IPI00296196.
RefSeq	NP_037523.2. NM_013391.2.
UniGene	Hs.655653.
3D structure databases
ProteinModelPortal	Q9UI17.
SMR	Q9UI17. Positions 49-856.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000255189.
PTM databases
PhosphoSite	Q9UI17.
Polymorphism databases
DMDM	296434575.
Proteomic databases
PaxDb	Q9UI17.
PRIDE	Q9UI17.
Protocols and materials databases
DNASU	29958.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000255189; ENSP00000255189; ENSG00000132837.
GeneID	29958.
KEGG	hsa:29958.
UCSC	uc003kfs.3. human.
Organism-specific databases
CTD	29958.
GeneCards	GC05M078293.
H-InvDB	HIX0200737.
HGNC	HGNC:24475. DMGDH.
HPA	HPA036442.
MIM	605849. gene. 605850. phenotype.
neXtProt	NX_Q9UI17.
Orphanet	243343. Dimethylglycine dehydrogenase deficiency.
PharmGKB	PA134947212.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0665.
HOGENOM	HOG000251716.
HOVERGEN	HBG081945.
InParanoid	Q9UI17.
KO	K00315.
OMA	REVGKMI.
OrthoDB	EOG466VK7.
PhylomeDB	Q9UI17.
Enzyme and pathway databases
UniPathway	UPA00291; UER00433.
Gene expression databases
ArrayExpress	Q9UI17.
Bgee	Q9UI17.
CleanEx	HS_DMGDH.
Genevestigator	Q9UI17.
GermOnline	ENSG00000132837. Homo sapiens.
Family and domain databases
Gene3D	3.30.1360.120. 2 hits.
InterPro	IPR006076. FAD-dep_OxRdtase. IPR013977. GCV_T_C. IPR006222. GCV_T_N. IPR027266. TrmE/GcvT_dom1. [Graphical view]
Pfam	PF01266. DAO. 1 hit. PF01571. GCV_T. 1 hit. PF08669. GCV_T_C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	29958.
NextBio	52675.
SOURCE	Search...

Entry information

Entry name

M2GD_HUMAN

Accession

Primary (citable) accession number: Q9UI17
Secondary accession number(s): B2RBN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.