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P40926 (MDHM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Malate dehydrogenase, mitochondrial

EC=1.1.1.37
Gene names
Name:MDH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length338 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

(S)-malate + NAD+ = oxaloacetate + NADH.

Enzyme regulation

Enzyme activity is enhanced by acetylation. Ref.9

Subunit structure

Homodimer. Ref.12

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. Ref.9

Sequence similarities

Belongs to the LDH/MDH superfamily. MDH type 1 family.

Ontologies

Keywords
   Biological processTricarboxylic acid cycle
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADH metabolic process

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular carbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

cellular metabolic process

Traceable author statement. Source: Reactome

gluconeogenesis

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

internal protein amino acid acetylation

Inferred from direct assay Ref.9. Source: UniProtKB

malate metabolic process

Inferred from direct assay PubMed 16740313. Source: UniProtKB

oxaloacetate metabolic process

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

tricarboxylic acid cycle

Traceable author statement. Source: Reactome

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337PubMed 23376485. Source: UniProt

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 16740313. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functionL-malate dehydrogenase activity

Inferred from direct assay PubMed 16740313. Source: UniProtKB

malate dehydrogenase (NADP+) activity

Inferred from electronic annotation. Source: Ensembl

poly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P40926-1)

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.
Isoform 2 (identifier: P40926-2)

The sequence of this isoform differs from the canonical sequence as follows:
     144-185: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2424Mitochondrion By similarity
Chain25 – 338314Malate dehydrogenase, mitochondrial
PRO_0000018628

Regions

Nucleotide binding31 – 377NAD
Nucleotide binding140 – 1423NAD

Sites

Active site2001Proton acceptor By similarity
Binding site571NAD
Binding site1041Substrate
Binding site1101Substrate
Binding site1171NAD
Binding site1421Substrate
Binding site1761Substrate
Binding site2511NAD

Amino acid modifications

Modified residue781N6-acetyllysine; alternate By similarity
Modified residue781N6-succinyllysine; alternate By similarity
Modified residue911N6-acetyllysine; alternate By similarity
Modified residue911N6-succinyllysine; alternate By similarity
Modified residue1651N6-acetyllysine Ref.8
Modified residue1851N6-acetyllysine; alternate Ref.8 Ref.9
Modified residue1851N6-succinyllysine; alternate By similarity
Modified residue2031N6-succinyllysine By similarity
Modified residue2151N6-acetyllysine; alternate By similarity
Modified residue2151N6-succinyllysine; alternate By similarity
Modified residue2391N6-acetyllysine; alternate By similarity
Modified residue2391N6-malonyllysine; alternate By similarity
Modified residue2391N6-succinyllysine; alternate By similarity
Modified residue2691N6-succinyllysine By similarity
Modified residue2961N6-acetyllysine; alternate By similarity
Modified residue2961N6-succinyllysine; alternate By similarity
Modified residue3011N6-acetyllysine; alternate Ref.8 Ref.9
Modified residue3011N6-succinyllysine; alternate By similarity
Modified residue3071N6-acetyllysine; alternate Ref.9
Modified residue3071N6-malonyllysine; alternate Ref.11
Modified residue3071N6-succinyllysine; alternate By similarity
Modified residue3141N6-acetyllysine; alternate Ref.8 Ref.9
Modified residue3141N6-succinyllysine; alternate By similarity
Modified residue3241N6-acetyllysine; alternate By similarity
Modified residue3241N6-succinyllysine; alternate By similarity
Modified residue3281N6-acetyllysine; alternate By similarity
Modified residue3281N6-succinyllysine; alternate By similarity
Modified residue3291N6-acetyllysine; alternate Ref.8
Modified residue3291N6-malonyllysine; alternate By similarity
Modified residue3351N6-acetyllysine; alternate Ref.8
Modified residue3351N6-succinyllysine; alternate By similarity

Natural variations

Alternative sequence144 – 18542Missing in isoform 2.
VSP_055312
Natural variant91A → V. Ref.5 Ref.12
Corresponds to variant rs17849553 [ dbSNP | Ensembl ].
VAR_047787

Experimental info

Mutagenesis1851K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-301; R-307 and R-314. Ref.9
Mutagenesis3011K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-307 and R-314. Ref.9
Mutagenesis3071K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-314. Ref.9
Mutagenesis3141K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-307. Ref.9
Sequence conflict3011K → R in BAG56955. Ref.2

Secondary structure

................................................. 338
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 25, 2008. Version 3.
Checksum: AAB9F5E5B2FBC8CA

FASTA33835,503
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 309B55235F0097F7
Show »

FASTA29630,875

References

« Hide '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] (ISOFORM 1), 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. expand/collapse author list , 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] (ISOFORMS 1 AND 2).
Tissue: Kidney and Tongue.
[3]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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. expand/collapse author list , 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].
[5]"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] (ISOFORM 1), VARIANT VAL-9.
Tissue: Lung.
[6]"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].
[7]"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.
[8]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF LYS-185; LYS-301; LYS-307 AND LYS-314.
[10]"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].
[11]"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.
[12]"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.
AK293460 mRNA. Translation: BAG56955.1.
AK316587 mRNA. Translation: BAG38175.1.
AC005077 Genomic DNA. No translation available.
AC006330 Genomic DNA. No translation available.
CH471220 Genomic DNA. Translation: EAW71796.1.
BC001917 mRNA. Translation: AAH01917.1.
CCDSCCDS5581.1.
RefSeqNP_001269332.1. NM_001282403.1.
NP_001269333.1. NM_001282404.1.
NP_005909.2. NM_005918.3.
UniGeneHs.520967.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DFDX-ray1.90A/B/C/D20-338[»]
ProteinModelPortalP40926.
SMRP40926. Positions 24-337.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110356. 27 interactions.
IntActP40926. 12 interactions.
MINTMINT-1408946.
STRING9606.ENSP00000327070.

Chemistry

BindingDBP40926.
ChEMBLCHEMBL5917.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP40926.

Polymorphism databases

DMDM215274114.

2D gel databases

DOSAC-COBS-2DPAGEP40926.
REPRODUCTION-2DPAGEIPI00291006.
P40926.
UCD-2DPAGEP40926.

Proteomic databases

MaxQBP40926.
PaxDbP40926.
PRIDEP40926.

Protocols and materials databases

DNASU4191.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315758; ENSP00000327070; ENSG00000146701.
ENST00000432020; ENSP00000408649; ENSG00000146701.
ENST00000573193; ENSP00000459911; ENSG00000262847.
GeneID4191.
KEGGhsa:4191.
UCSCuc003ueo.3. human.

Organism-specific databases

CTD4191.
GeneCardsGC07P075677.
HGNCHGNC:6971. MDH2.
HPAHPA019714.
HPA019716.
HPA019848.
HPA026720.
MIM154100. gene.
neXtProtNX_P40926.
PharmGKBPA30716.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0039.
HOGENOMHOG000213792.
HOVERGENHBG001662.
InParanoidP40926.
KOK00026.
OMAMVAEAMS.
OrthoDBEOG74R1R7.
PhylomeDBP40926.
TreeFamTF300834.

Enzyme and pathway databases

BioCycMetaCyc:HS07366-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP40926.
BgeeP40926.
CleanExHS_MDH2.
GenevestigatorP40926.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
InterProIPR001557. 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]
PANTHERPTHR11540. PTHR11540. 1 hit.
PfamPF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]
PIRSFPIRSF000102. Lac_mal_DH. 1 hit.
SUPFAMSSF56327. SSF56327. 1 hit.
TIGRFAMsTIGR01772. MDH_euk_gproteo. 1 hit.
PROSITEPS00068. MDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMdh2. human.
EvolutionaryTraceP40926.
GeneWikiMalate_dehydrogenase_2.
GenomeRNAi4191.
NextBio16514.
PROP40926.
SOURCESearch...

Entry information

Entry nameMDHM_HUMAN
AccessionPrimary (citable) accession number: P40926
Secondary accession number(s): A8K414 expand/collapse secondary AC list , B2RE78, B4DE44, E9PDB2, O43682
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM