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Protein

Malate dehydrogenase, mitochondrial

Gene

MDH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

(S)-malate + NAD+ = oxaloacetate + NADH.PROSITE-ProRule annotation

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

  • L-malate dehydrogenase activity Source: UniProtKB
  • malate dehydrogenase (NADP+) activity Source: Ensembl
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • 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
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Tricarboxylic acid cycle

Keywords - Ligandi

NAD

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Malate dehydrogenase, mitochondrial (EC:1.1.1.37)
Gene namesi
Name:MDH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:6971. MDH2.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial inner membrane Source: Ensembl
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
  • myelin sheath Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

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

Organism-specific databases

DisGeNETi4191.
OpenTargetsiENSG00000146701.
PharmGKBiPA30716.

Chemistry databases

ChEMBLiCHEMBL5917.

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)By 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% (By similarity).By similarity

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

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

2D gel databases

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

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

Protein-protein interaction databases

BioGridi110356. 49 interactors.
IntActiP40926. 13 interactors.
MINTiMINT-1408946.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DFDX-ray1.90A/B/C/D20-338[»]
4WLEX-ray1.90A/B/C/D20-338[»]
4WLFX-ray2.20A/B/C/D20-338[»]
4WLNX-ray2.28A/B/C/D20-338[»]
4WLOX-ray2.50A/B/C/D20-338[»]
4WLUX-ray2.14A/B/C/D20-338[»]
4WLVX-ray2.40A/B/C/D20-338[»]
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.
OMAiVEVKGFA.
OrthoDBiEOG091G0AVO.
PhylomeDBiP40926.
TreeFamiTF300834.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
InterProiIPR001557. 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]
PANTHERiPTHR11540. PTHR11540. 1 hit.
PfamiPF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000102. Lac_mal_DH. 1 hit.
SUPFAMiSSF51735. SSF51735. 1 hit.
SSF56327. SSF56327. 1 hit.
TIGRFAMsiTIGR01772. MDH_euk_gproteo. 1 hit.
PROSITEiPS00068. MDH. 1 hit.
[Graphical view]

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 → V.2 PublicationsCorresponds to variant rs17849553dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Wikipedia

Malate dehydrogenase entry

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DFDX-ray1.90A/B/C/D20-338[»]
4WLEX-ray1.90A/B/C/D20-338[»]
4WLFX-ray2.20A/B/C/D20-338[»]
4WLNX-ray2.28A/B/C/D20-338[»]
4WLOX-ray2.50A/B/C/D20-338[»]
4WLUX-ray2.14A/B/C/D20-338[»]
4WLVX-ray2.40A/B/C/D20-338[»]
ProteinModelPortaliP40926.
SMRiP40926.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110356. 49 interactors.
IntActiP40926. 13 interactors.
MINTiMINT-1408946.
STRINGi9606.ENSP00000327070.

Chemistry databases

BindingDBiP40926.
ChEMBLiCHEMBL5917.

PTM databases

iPTMnetiP40926.
PhosphoSitePlusiP40926.
SwissPalmiP40926.

Polymorphism and mutation databases

BioMutaiMDH2.
DMDMi215274114.

2D gel databases

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

Proteomic databases

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

Protocols and materials databases

DNASUi4191.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4191.
DisGeNETi4191.
GeneCardsiMDH2.
HGNCiHGNC:6971. MDH2.
HPAiHPA019714.
HPA019716.
HPA019848.
HPA026720.
MIMi154100. gene.
neXtProtiNX_P40926.
OpenTargetsiENSG00000146701.
PharmGKBiPA30716.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiMDH2. human.
EvolutionaryTraceiP40926.
GeneWikiiMalate_dehydrogenase_2.
GenomeRNAii4191.
PROiP40926.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000146701.
CleanExiHS_MDH2.
ExpressionAtlasiP40926. baseline and differential.
GenevisibleiP40926. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
InterProiIPR001557. 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]
PANTHERiPTHR11540. PTHR11540. 1 hit.
PfamiPF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000102. Lac_mal_DH. 1 hit.
SUPFAMiSSF51735. SSF51735. 1 hit.
SSF56327. SSF56327. 1 hit.
TIGRFAMsiTIGR01772. MDH_euk_gproteo. 1 hit.
PROSITEiPS00068. MDH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDHM_HUMAN
AccessioniPrimary (citable) accession number: P40926
Secondary accession number(s): A8K414
, B2RE78, B4DE44, E9PDB2, O43682
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2008
Last modified: November 2, 2016
This is version 176 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.