Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Malate dehydrogenase, mitochondrial

Gene

MDH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalytic activityi

(S)-malate + NAD+ = oxaloacetate + NADH.1 Publication

Enzyme regulationi

Enzyme activity is enhanced by acetylation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei57NAD1 Publication1
Binding sitei104SubstratePROSITE-ProRule annotation1 Publication1
Binding sitei110SubstratePROSITE-ProRule annotation1 Publication1
Binding sitei117NAD1 Publication1
Binding sitei142SubstratePROSITE-ProRule annotation1 Publication1
Binding sitei176SubstratePROSITE-ProRule annotation1 Publication1
Active sitei200Proton acceptorBy similarity1
Binding sitei251NAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 37NAD1 Publication7
Nucleotide bindingi140 – 142NAD1 Publication3

GO - Molecular functioni

GO - Biological processi

  • aerobic respiration Source: UniProtKB
  • gluconeogenesis Source: Reactome
  • internal protein amino acid acetylation Source: UniProtKB
  • malate metabolic process Source: UniProtKB
  • NADH metabolic process Source: Ensembl
  • oxaloacetate metabolic process Source: Ensembl
  • tricarboxylic acid cycle Source: Reactome

Keywordsi

Molecular functionOxidoreductase
Biological processTricarboxylic acid cycle
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS07366-MONOMER
ReactomeiR-HSA-70263 Gluconeogenesis
R-HSA-71403 Citric acid cycle (TCA cycle)

Names & Taxonomyi

Protein namesi
Recommended name:
Malate dehydrogenase, mitochondrial (EC:1.1.1.371 Publication)
Gene namesi
Name:MDH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000146701.11
HGNCiHGNC:6971 MDH2
MIMi154100 gene
neXtProtiNX_P40926

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Epileptic encephalopathy, early infantile, 51 (EIEE51)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE51 is an autosomal recessive form characterized by onset of intractable seizures and hypotonia in the first days or weeks of life, and severely delayed psychomotor development.
See also OMIM:617339
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07800137G → R in EIEE51; severe defects in aerobic respiration, when assayed in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs782308462EnsemblClinVar.1
Natural variantiVAR_078002133P → L in EIEE51; decreased protein abundance; strong decrease in malate dehydrogenase activity; severe defects in aerobic respiration, when assayed in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs375002796EnsemblClinVar.1
Natural variantiVAR_078003207P → L in EIEE51; decreased protein abundance; strong decrease in malate dehydrogenase activity; severe defects in aerobic respiration, when assayed in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs1057519566Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi185K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-301; R-307 and R-314. 1 Publication1
Mutagenesisi301K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-307 and R-314. 1 Publication1
Mutagenesisi307K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-314. 1 Publication1
Mutagenesisi314K → R: No activation of enzyme activity on treatment with TSA or NAM; when associated with R-185; R-301 and R-307. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi4191
MalaCardsiMDH2
MIMi617339 phenotype
OpenTargetsiENSG00000146701
PharmGKBiPA30716

Chemistry databases

ChEMBLiCHEMBL5917
DrugBankiDB04272 Citric Acid
DB00157 NADH

Polymorphism and mutation databases

BioMutaiMDH2
DMDMi215274114

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 24MitochondrionBy similarityAdd BLAST24
ChainiPRO_000001862825 – 338Malate dehydrogenase, mitochondrialAdd BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi33O-linked (GlcNAc) serineBy similarity1
Modified residuei78N6-acetyllysine; alternateBy similarity1
Modified residuei78N6-succinyllysine; alternateBy similarity1
Modified residuei91N6-acetyllysine; alternateBy similarity1
Modified residuei91N6-succinyllysine; alternateBy similarity1
Modified residuei165N6-acetyllysineCombined sources1
Modified residuei185N6-acetyllysine; alternateCombined sources1 Publication1
Modified residuei185N6-succinyllysine; alternateBy similarity1
Modified residuei203N6-succinyllysineBy similarity1
Modified residuei215N6-acetyllysine; alternateBy similarity1
Modified residuei215N6-succinyllysine; alternateBy similarity1
Modified residuei239N6-acetyllysine; alternateBy similarity1
Modified residuei239N6-malonyllysine; alternateBy similarity1
Modified residuei239N6-succinyllysine; alternateBy similarity1
Modified residuei246PhosphoserineCombined sources1
Modified residuei269N6-succinyllysineBy similarity1
Modified residuei296N6-acetyllysine; alternateBy similarity1
Modified residuei296N6-succinyllysine; alternateBy similarity1
Modified residuei301N6-acetyllysine; alternateCombined sources1 Publication1
Modified residuei301N6-succinyllysine; alternateBy similarity1
Modified residuei307N6-acetyllysine; alternate1 Publication1
Modified residuei307N6-malonyllysine; alternate1 Publication1
Modified residuei307N6-succinyllysine; alternateBy similarity1
Modified residuei314N6-acetyllysine; alternateCombined sources1 Publication1
Modified residuei314N6-succinyllysine; alternateBy similarity1
Modified residuei324N6-acetyllysine; alternateBy similarity1
Modified residuei324N6-succinyllysine; alternateBy similarity1
Modified residuei326PhosphoserineCombined sources1
Modified residuei328N6-acetyllysine; alternateBy similarity1
Modified residuei328N6-succinyllysine; alternateBy similarity1
Modified residuei329N6-acetyllysine; alternateCombined sources1
Modified residuei329N6-malonyllysine; alternateBy similarity1
Modified residuei335N6-acetyllysine; alternateCombined sources1
Modified residuei335N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

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%.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP40926
MaxQBiP40926
PaxDbiP40926
PeptideAtlasiP40926
PRIDEiP40926
ProteomicsDBi55386
TopDownProteomicsiP40926-1 [P40926-1]

2D gel databases

DOSAC-COBS-2DPAGEiP40926
REPRODUCTION-2DPAGEiIPI00291006
P40926
UCD-2DPAGEiP40926

PTM databases

iPTMnetiP40926
PhosphoSitePlusiP40926
SwissPalmiP40926

Expressioni

Gene expression databases

BgeeiENSG00000146701
CleanExiHS_MDH2
ExpressionAtlasiP40926 baseline and differential
GenevisibleiP40926 HS

Organism-specific databases

HPAiHPA019714
HPA019716
HPA019848
HPA026720

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110356, 62 interactors
IntActiP40926, 16 interactors
MINTiP40926
STRINGi9606.ENSP00000327070

Chemistry databases

BindingDBiP40926

Structurei

Secondary structure

1338
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 30Combined sources6
Turni31 – 33Combined sources3
Helixi37 – 45Combined sources9
Beta strandi50 – 60Combined sources11
Helixi61 – 69Combined sources9
Beta strandi71 – 74Combined sources4
Beta strandi76 – 82Combined sources7
Turni83 – 85Combined sources3
Helixi86 – 90Combined sources5
Beta strandi94 – 98Combined sources5
Helixi110 – 113Combined sources4
Helixi114 – 131Combined sources18
Beta strandi135 – 139Combined sources5
Helixi144 – 157Combined sources14
Beta strandi165 – 168Combined sources4
Helixi171 – 185Combined sources15
Helixi189 – 191Combined sources3
Beta strandi196 – 198Combined sources3
Helixi202 – 204Combined sources3
Beta strandi205 – 207Combined sources3
Helixi209 – 211Combined sources3
Helixi220 – 241Combined sources22
Helixi249 – 266Combined sources18
Beta strandi273 – 279Combined sources7
Beta strandi282 – 295Combined sources14
Beta strandi298 – 302Combined sources5
Helixi310 – 335Combined sources26

3D structure databases

ProteinModelPortaliP40926
SMRiP40926
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40926

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1494 Eukaryota
COG0039 LUCA
GeneTreeiENSGT00390000016686
HOGENOMiHOG000213792
HOVERGENiHBG001662
InParanoidiP40926
KOiK00026
OMAiQCTPKVE
OrthoDBiEOG091G0AVO
PhylomeDBiP40926
TreeFamiTF300834

Family and domain databases

Gene3Di3.90.110.10, 1 hit
InterProiView protein in 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
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF02866 Ldh_1_C, 1 hit
PF00056 Ldh_1_N, 1 hit
PIRSFiPIRSF000102 Lac_mal_DH, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit
SSF56327 SSF56327, 1 hit
TIGRFAMsiTIGR01772 MDH_euk_gproteo, 1 hit
PROSITEiView protein in PROSITE
PS00068 MDH, 1 hit

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: P40926-1) [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
MLSALARPAS AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV
60 70 80 90 100
SRLTLYDIAH TPGVAADLSH IETKAAVKGY LGPEQLPDCL KGCDVVVIPA
110 120 130 140 150
GVPRKPGMTR DDLFNTNATI VATLTAACAQ HCPEAMICVI ANPVNSTIPI
160 170 180 190 200
TAEVFKKHGV YNPNKIFGVT TLDIVRANTF VAELKGLDPA RVNVPVIGGH
210 220 230 240 250
AGKTIIPLIS QCTPKVDFPQ DQLTALTGRI QEAGTEVVKA KAGAGSATLS
260 270 280 290 300
MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETECTYFST PLLLGKKGIE
310 320 330
KNLGIGKVSS FEEKMISDAI PELKASIKKG EDFVKTLK
Length:338
Mass (Da):35,503
Last modified:November 25, 2008 - v3
Checksum:iAAB9F5E5B2FBC8CA
GO
Isoform 2 (identifier: P40926-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     144-185: Missing.

Note: No experimental confirmation available.
Show »
Length:296
Mass (Da):30,875
Checksum:i309B55235F0097F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti301K → R in BAG56955 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0477879A → V2 PublicationsCorresponds to variant dbSNP:rs6720Ensembl.1
Natural variantiVAR_07800137G → R in EIEE51; severe defects in aerobic respiration, when assayed in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs782308462EnsemblClinVar.1
Natural variantiVAR_078002133P → L in EIEE51; decreased protein abundance; strong decrease in malate dehydrogenase activity; severe defects in aerobic respiration, when assayed in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs375002796EnsemblClinVar.1
Natural variantiVAR_078003207P → L in EIEE51; decreased protein abundance; strong decrease in malate dehydrogenase activity; severe defects in aerobic respiration, when assayed in a heterologous system. 1 PublicationCorresponds to variant dbSNP:rs1057519566Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055312144 – 185Missing in isoform 2. 1 PublicationAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS5581.1 [P40926-1]
CCDS64691.1 [P40926-2]
RefSeqiNP_001269332.1, NM_001282403.1 [P40926-2]
NP_001269333.1, NM_001282404.1
NP_005909.2, NM_005918.3 [P40926-1]
UniGeneiHs.520967

Genome annotation databases

EnsembliENST00000315758; ENSP00000327070; ENSG00000146701 [P40926-1]
ENST00000432020; ENSP00000408649; ENSG00000146701 [P40926-2]
GeneIDi4191
KEGGihsa:4191
UCSCiuc003ueo.5 human [P40926-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMDHM_HUMAN
AccessioniPrimary (citable) accession number: P40926
Secondary accession number(s): A8K414
, B2RE78, B4DE44, E9PDB2, O43682
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2008
Last modified: June 20, 2018
This is version 191 of the entry and version 3 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 7
    Human chromosome 7: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health