P40926 (MDHM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Malate dehydrogenase, mitochondrial
EC=1.1.1.37

Gene names

Name:

MDH2

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	338 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	(S)-malate + NAD+ = oxaloacetate + NADH.
Enzyme regulation	Enzyme activity is enhanced by acetylation. Ref.8
Subunit structure	Homodimer. Ref.11
Subcellular location	Mitochondrion matrix.
Post-translational modification	Acetylation is enhanced by up to 67% after treatment either with trichostin A (TSA) or with nicotinamide (NAM) with the appearance of tri-and tetraacetylations. Glucose also increases acetylation by about 60% By similarity.
Sequence similarities	Belongs to the LDH/MDH superfamily. MDH type 1 family.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NADH metabolic process Inferred from electronic annotation. Source: Compara cellular carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro gluconeogenesis Traceable author statement. Source: Reactome internal protein amino acid acetylation Inferred from direct assay Ref.8. Source: UniProtKB malate metabolic process Inferred from direct assay PubMed 16740313. Source: UniProtKB oxaloacetate metabolic process Inferred from electronic annotation. Source: Compara tricarboxylic acid cycle Traceable author statement. Source: Reactome
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	L-malate dehydrogenase activity Inferred from direct assay PubMed 16740313. Source: UniProtKB malate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: Compara nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 24

24

Mitochondrion By similarity

Chain

25 – 338

314

Malate dehydrogenase, mitochondrial

PRO_0000018628

Regions

Nucleotide binding

31 – 37

7

NAD

Nucleotide binding

140 – 142

3

NAD

Sites

Active site

200

1

Proton acceptor By similarity

Binding site

57

1

NAD

Binding site

104

1

Substrate

Binding site

110

1

Substrate

Binding site

117

1

NAD

Binding site

142

1

Substrate

Binding site

176

1

Substrate

Binding site

251

1

NAD

Amino acid modifications

Modified residue

157

1

N6-acetyllysine By similarity

Modified residue

165

1

N6-acetyllysine Ref.7

Modified residue

185

1

N6-acetyllysine Ref.7 Ref.8

Modified residue

239

1

N6-malonyllysine; alternate By similarity

Modified residue

239

1

N6-succinyllysine; alternate By similarity

Modified residue

301

1

N6-acetyllysine Ref.7 Ref.8

Modified residue

301

1

N6-succinyllysine; alternate By similarity

Modified residue

307

1

N6-acetyllysine; alternate Ref.8

Modified residue

307

1

N6-malonyllysine; alternate Ref.10

Modified residue

314

1

N6-acetyllysine Ref.7 Ref.8

Modified residue

328

1

N6-acetyllysine; alternate By similarity

Modified residue

328

1

N6-succinyllysine; alternate By similarity

Modified residue

329

1

N6-acetyllysine Ref.7

Modified residue

329

1

N6-malonyllysine; alternate By similarity

Modified residue

335

1

N6-acetyllysine Ref.7

Natural variations

Natural variant

9

1

A → V. Ref.4 Ref.11
Corresponds to variant rs17849553 [ dbSNP | Ensembl ].

VAR_047787

Experimental info

Mutagenesis

185

1

K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-301; R-307 and R-314. Ref.8

Mutagenesis

301

1

K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-307 and R-314. Ref.8

Mutagenesis

307

1

K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-314. Ref.8

Mutagenesis

314

1

K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-307. Ref.8

Secondary structure

1

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338

Helix Strand Turn

Details...

Beta strand

25 – 30

6

Turn

31 – 33

3

Helix

37 – 45

9

Beta strand

50 – 60

11

Helix

61 – 69

9

Beta strand

71 – 74

4

Beta strand

76 – 82

7

Turn

83 – 85

3

Helix

86 – 90

5

Beta strand

94 – 98

5

Helix

110 – 113

4

Helix

114 – 131

18

Beta strand

135 – 139

5

Helix

144 – 157

14

Beta strand

165 – 168

4

Helix

171 – 185

15

Helix

189 – 191

3

Beta strand

196 – 198

3

Helix

202 – 204

3

Beta strand

205 – 207

3

Helix

209 – 211

3

Helix

220 – 241

22

Helix

249 – 266

18

Beta strand

273 – 279

7

Beta strand

282 – 295

14

Beta strand

298 – 302

5

Helix

310 – 335

26

Sequences

	Sequence		Length	Mass (Da)
	P40926 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: AAB9F5E5B2FBC8CA	FASTA	338	35,503
	10 20 30 40 50 60 MLSALARPAS AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH 70 80 90 100 110 120 TPGVAADLSH IETKAAVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI 130 140 150 160 170 180 VATLTAACAQ HCPEAMICVI ANPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF 190 200 210 220 230 240 VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLTALTGRI QEAGTEVVKA 250 260 270 280 290 300 KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETECTYFST PLLLGKKGIE 310 320 330 KNLGIGKVSS FEEKMISDAI PELKASIKKG EDFVKTLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human homolog of mouse and pig MDH mRNA." Hu G. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-9.
[2]	"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]. Tissue: Kidney and Tongue.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-9. Tissue: Lung.
[5]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165; LYS-185; LYS-301; LYS-314; LYS-329 AND LYS-335, MASS SPECTROMETRY.
[8]	"Regulation of cellular metabolism by protein lysine acetylation." Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L., Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L., Chin J., Yang P. , Chen X., Lei Q., Xiong Y., Guan K.L. Science 327:1000-1004(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-185; LYS-301; LYS-307 AND LYS-314, ENZYME REGULATION, MASS SPECTROMETRY, MUTAGENESIS OF LYS-185; LYS-301; LYS-307 AND LYS-314.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"The first identification of lysine malonylation substrates and its regulatory enzyme." Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., Verdin E., Ye Y., Zhao Y. Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011) [PubMed] [Europe PMC] [Abstract] Cited for: MALONYLATION AT LYS-307.
[11]	"Crystal structure of human malate dehydrogenase type 2." Structural genomics consortium (SGC) Submitted (MAR-2006) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 20-338 IN COMPLEX WITH NAD AND SUBSTRATE, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Wikipedia

Malate dehydrogenase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF047470 mRNA. Translation: AAC03787.1.
AK290779 mRNA. Translation: BAF83468.1.
AK316587 mRNA. Translation: BAG38175.1.
CH471220 Genomic DNA. Translation: EAW71796.1.
BC001917 mRNA. Translation: AAH01917.1.

IPI

IPI00291006.

RefSeq

NP_005909.2. NM_005918.2.

UniGene

Hs.520967.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DFD	X-ray	1.90	A/B/C/D	20-338	[»]

ProteinModelPortal

P40926.

ModBase

Search...

Protein-protein interaction databases

IntAct

P40926. 11 interactions.

MINT

MINT-1408946.

STRING

9606.ENSP00000327070.

PTM databases

PhosphoSite

P40926.

Polymorphism databases

DMDM

215274114.

2D gel databases

DOSAC-COBS-2DPAGE

P40926.

REPRODUCTION-2DPAGE

IPI00291006.
P40926.

UCD-2DPAGE

P40926.

Proteomic databases

PaxDb

P40926.

PRIDE

P40926.

Protocols and materials databases

DNASU

4191.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000315758; ENSP00000327070; ENSG00000146701.
ENST00000573193; ENSP00000459911; ENSG00000262847.

GeneID

4191.

KEGG

hsa:4191.

UCSC

uc003ueo.3. human.

Organism-specific databases

CTD

4191.

GeneCards

GC07P075677.

HGNC

HGNC:6971. MDH2.

HPA

HPA019714.
HPA019716.
HPA019848.
HPA026720.

MIM

154100. gene.

neXtProt

NX_P40926.

PharmGKB

PA30716.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0039.

HOGENOM

HOG000213792.

HOVERGEN

HBG001662.

InParanoid

P40926.

KO

K00026.

OMA

VEVKGFA.

OrthoDB

EOG4MKNGM.

PhylomeDB

P40926.

Enzyme and pathway databases

BioCyc

MetaCyc:HS07366-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P40926.

Bgee

P40926.

CleanEx

HS_MDH2.

Genevestigator

P40926.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.
3.90.110.10. 1 hit.

InterPro

IPR001557. L-lactate/malate_DH.
IPR022383. Lactate/malate_DH_C.
IPR001236. Lactate/malate_DH_N.
IPR015955. Lactate_DH/Glyco_Ohase_4_C.
IPR001252. Malate_DH_AS.
IPR010097. Malate_DH_type1.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR11540. PTHR11540. 1 hit.
PTHR11540:SF1. PTHR11540:SF1. 1 hit.

Pfam

PF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000102. Lac_mal_DH. 1 hit.

SUPFAM

SSF56327. Lactate_DH/Glyco_hydro_4_C. 1 hit.

TIGRFAMs

TIGR01772. MDH_euk_gproteo. 1 hit.

PROSITE

PS00068. MDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P40926.

ChEMBL

CHEMBL5917.

ChiTaRS

Mdh2. human.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P40926.

GenomeRNAi

4191.

NextBio

16514.

SOURCE

Search...

Entry information

Entry name

MDHM_HUMAN

Accession

Primary (citable) accession number: P40926
Secondary accession number(s): A8K414, B2RE78, O43682

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 141 of the entry and version 3 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.