Skip Header

Contribute Send feedback
Read comments (?) or add your own

P40926 (MDHM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 141. 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·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.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.

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 residue1571N6-acetyllysine By similarity
Modified residue1651N6-acetyllysine Ref.7
Modified residue1851N6-acetyllysine Ref.7 Ref.8
Modified residue2391N6-malonyllysine; alternate By similarity
Modified residue2391N6-succinyllysine; alternate By similarity
Modified residue3011N6-acetyllysine Ref.7 Ref.8
Modified residue3011N6-succinyllysine; alternate By similarity
Modified residue3071N6-acetyllysine; alternate Ref.8
Modified residue3071N6-malonyllysine; alternate Ref.10
Modified residue3141N6-acetyllysine Ref.7 Ref.8
Modified residue3281N6-acetyllysine; alternate By similarity
Modified residue3281N6-succinyllysine; alternate By similarity
Modified residue3291N6-acetyllysine Ref.7
Modified residue3291N6-malonyllysine; alternate By similarity
Modified residue3351N6-acetyllysine Ref.7

Natural variations

Natural variant91A → V. Ref.4 Ref.11
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.8
Mutagenesis3011K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-307 and R-314. Ref.8
Mutagenesis3071K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-314. Ref.8
Mutagenesis3141K → 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

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P40926 [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

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], 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].
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. 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].
[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. 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, 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.
IPIIPI00291006.
RefSeqNP_005909.2. NM_005918.2.
UniGeneHs.520967.

3D structure databases

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

Protein-protein interaction databases

IntActP40926. 11 interactions.
MINTMINT-1408946.
STRING9606.ENSP00000327070.

PTM databases

PhosphoSiteP40926.

Polymorphism databases

DMDM215274114.

2D gel databases

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

Proteomic databases

PaxDbP40926.
PRIDEP40926.

Protocols and materials databases

DNASU4191.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315758; ENSP00000327070; 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.
OMAVEVKGFA.
OrthoDBEOG4MKNGM.
PhylomeDBP40926.

Enzyme and pathway databases

BioCycMetaCyc:HS07366-MONOMER.
ReactomeREACT_111217. Metabolism.

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.
PTHR11540:SF1. PTHR11540:SF1. 1 hit.
PfamPF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]
PIRSFPIRSF000102. Lac_mal_DH. 1 hit.
SUPFAMSSF56327. Lactate_DH/Glyco_hydro_4_C. 1 hit.
TIGRFAMsTIGR01772. MDH_euk_gproteo. 1 hit.
PROSITEPS00068. MDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP40926.
ChEMBLCHEMBL5917.
ChiTaRSMdh2. human.
DrugBankDB00157. NADH.
EvolutionaryTraceP40926.
GenomeRNAi4191.
NextBio16514.
SOURCESearch...

Entry information

Entry nameMDHM_HUMAN
AccessionPrimary (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 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

Human chromosome 7

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families