UniProtKB - P40925 (MDHC_HUMAN)
Protein
Malate dehydrogenase, cytoplasmic
Gene
MDH1
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237).2 Publications
Catalytic activityi
- EC:1.1.1.371 Publication
- 3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD+ = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + H+ + NADH1 PublicationEC:1.1.1.961 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 42 | NADBy similarity | 1 | |
Binding sitei | 92 | SubstrateBy similarity | 1 | |
Binding sitei | 98 | SubstrateBy similarity | 1 | |
Binding sitei | 105 | NADBy similarity | 1 | |
Binding sitei | 112 | NADBy similarity | 1 | |
Binding sitei | 131 | SubstrateBy similarity | 1 | |
Binding sitei | 162 | Substrate | 1 | |
Active sitei | 187 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 11 – 17 | NADBy similarity | 7 | |
Nucleotide bindingi | 129 – 131 | NADBy similarity | 3 |
GO - Molecular functioni
- diiodophenylpyruvate reductase activity Source: UniProtKB-EC
- L-malate dehydrogenase activity Source: GO_Central
- malic enzyme activity Source: ProtInc
GO - Biological processi
- gluconeogenesis Source: Reactome
- malate metabolic process Source: GO_Central
- NADH metabolic process Source: GO_Central
- oxaloacetate metabolic process Source: GO_Central
- tricarboxylic acid cycle Source: GO_Central
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Tricarboxylic acid cycle |
Ligand | NAD |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00361-MONOMER |
PathwayCommonsi | P40925 |
Reactomei | R-HSA-70263, Gluconeogenesis |
SABIO-RKi | P40925 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000014641.17 |
HGNCi | HGNC:6970, MDH1 |
MIMi | 154200, gene |
neXtProti | NX_P40925 |
Subcellular locationi
Other locations
Cytosol
- cytosol Source: GO_Central
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Epileptic encephalopathy, early infantile, 88 (EIEE88)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 early-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. EIEE88 is an autosomal recessive severe form characterized by global developmental delay, epilepsy, and progressive microcephaly.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083894 | 120 | A → V in EIEE88; decreased protein expression; increased levels of glutamate and glycerol-3-phosphate. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, EpilepsyOrganism-specific databases
DisGeNETi | 4190 |
MIMi | 618959, phenotype |
OpenTargetsi | ENSG00000014641 |
PharmGKBi | PA30714 |
Miscellaneous databases
Pharosi | P40925, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3560 |
DrugBanki | DB11638, Artenimol DB00157, NADH DB03461, Nicotinamide adenine dinucleotide phosphate |
DrugCentrali | P40925 |
Polymorphism and mutation databases
BioMutai | MDH1 |
DMDMi | 1708967 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources1 Publication | |||
ChainiPRO_0000113409 | 2 – 334 | Malate dehydrogenase, cytoplasmicAdd BLAST | 333 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources1 Publication | 1 | |
Modified residuei | 110 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 118 | N6-acetyllysineCombined sources1 Publication | 1 | |
Modified residuei | 121 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 214 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 217 | PhosphoserineBy similarity | 1 | |
Modified residuei | 230 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 241 | PhosphoserineCombined sources | 1 | |
Modified residuei | 298 | N6-acetyllysine; alternateCombined sources1 Publication | 1 | |
Modified residuei | 298 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 309 | PhosphoserineBy similarity | 1 | |
Modified residuei | 318 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 332 | PhosphoserineBy similarity | 1 | |
Modified residuei | 333 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
ISGylated.1 Publication
Acetylation at Lys-118 dramatically enhances enzymatic activity and promotes adipogenic differentiation.2 Publications
Keywords - PTMi
Acetylation, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-236 CPTAC-237 |
EPDi | P40925 |
jPOSTi | P40925 |
MassIVEi | P40925 |
PaxDbi | P40925 |
PeptideAtlasi | P40925 |
PRIDEi | P40925 |
ProteomicsDBi | 25276 55384 [P40925-1] 55385 [P40925-2] |
TopDownProteomicsi | P40925-1 [P40925-1] |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00291005 |
UCD-2DPAGEi | P40925 |
PTM databases
iPTMneti | P40925 |
MetOSitei | P40925 |
PhosphoSitePlusi | P40925 |
SwissPalmi | P40925 |
Expressioni
Gene expression databases
Bgeei | ENSG00000014641, Expressed in superior frontal gyrus and 249 other tissues |
ExpressionAtlasi | P40925, baseline and differential |
Genevisiblei | P40925, HS |
Organism-specific databases
HPAi | ENSG00000014641, Tissue enhanced (heart) |
Interactioni
Subunit structurei
Homodimer.
Binary interactionsi
P40925
With | #Exp. | IntAct |
---|---|---|
TERF1 [P54274] | 2 | EBI-709625,EBI-710997 |
Protein-protein interaction databases
BioGRIDi | 110355, 73 interactors |
IntActi | P40925, 20 interactors |
MINTi | P40925 |
STRINGi | 9606.ENSP00000438144 |
Chemistry databases
BindingDBi | P40925 |
Miscellaneous databases
RNActi | P40925, protein |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1496, Eukaryota |
GeneTreei | ENSGT00530000063410 |
HOGENOMi | CLU_040727_2_0_1 |
InParanoidi | P40925 |
OMAi | TKGMERG |
OrthoDBi | 1118998at2759 |
PhylomeDBi | P40925 |
TreeFami | TF105826 |
Family and domain databases
CDDi | cd01336, MDH_cytoplasmic_cytosolic, 1 hit |
Gene3Di | 3.90.110.10, 1 hit |
HAMAPi | MF_01517, Malate_dehydrog_2, 1 hit |
InterProi | View 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 IPR011274, Malate_DH_NAD-dep_euk IPR010945, Malate_DH_type2 IPR036291, NAD(P)-bd_dom_sf |
PANTHERi | PTHR23382, PTHR23382, 1 hit |
Pfami | View protein in Pfam PF02866, Ldh_1_C, 1 hit PF00056, Ldh_1_N, 1 hit |
PIRSFi | PIRSF000102, Lac_mal_DH, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit SSF56327, SSF56327, 1 hit |
TIGRFAMsi | TIGR01759, MalateDH-SF1, 1 hit TIGR01758, MDH_euk_cyt, 1 hit |
PROSITEi | View protein in PROSITE PS00068, MDH, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P40925-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL
60 70 80 90 100
DGVLMELQDC ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD
110 120 130 140 150
LLKANVKIFK SQGAALDKYA KKSVKVIVVG NPANTNCLTA SKSAPSIPKE
160 170 180 190 200
NFSCLTRLDH NRAKAQIALK LGVTANDVKN VIIWGNHSST QYPDVNHAKV
210 220 230 240 250
KLQGKEVGVY EALKDDSWLK GEFVTTVQQR GAAVIKARKL SSAMSAAKAI
260 270 280 290 300
CDHVRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV
310 320 330
EGLPINDFSR EKMDLTAKEL TEEKESAFEF LSSA
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A5K1VW95 | A0A5K1VW95_HUMAN | Malate dehydrogenase | MDH1 | 353 | Annotation score: | ||
C9JF79 | C9JF79_HUMAN | Malate dehydrogenase | MDH1 | 222 | Annotation score: | ||
C9JLV6 | C9JLV6_HUMAN | Cytosolic malate dehydrogenase | MDH1 | 114 | Annotation score: | ||
C9IZI0 | C9IZI0_HUMAN | Cytosolic malate dehydrogenase | MDH1 | 67 | Annotation score: | ||
C9JRL4 | C9JRL4_HUMAN | Cytosolic malate dehydrogenase | MDH1 | 119 | Annotation score: | ||
B9A041 | B9A041_HUMAN | Malate dehydrogenase, cytoplasmic | MDH1 | 210 | Annotation score: | ||
B8ZZ51 | B8ZZ51_HUMAN | Malate dehydrogenase, cytoplasmic | MDH1 | 169 | Annotation score: | ||
F8WFC2 | F8WFC2_HUMAN | Malate dehydrogenase, cytoplasmic | MDH1 | 87 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 15 | Q → R in BAH12223 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083894 | 120 | A → V in EIEE88; decreased protein expression; increased levels of glutamate and glycerol-3-phosphate. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042661 | 1 – 89 | Missing in isoform 2. 1 PublicationAdd BLAST | 89 | |
Alternative sequenceiVSP_045847 | 1 | M → MRRCSYFPKDVTVFDKDDK in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D55654 mRNA Translation: BAA09513.1 U20352 mRNA Translation: AAC16436.1 CR457405 mRNA Translation: CAG33686.1 AK295931 mRNA Translation: BAH12223.1 AK300719 mRNA Translation: BAG62394.1 AK312331 mRNA Translation: BAG35252.1 AC016734 Genomic DNA Translation: AAY14893.1 CH471053 Genomic DNA Translation: EAW99959.1 BC001484 mRNA Translation: AAH01484.1 |
CCDSi | CCDS1874.1 [P40925-1] CCDS56121.1 [P40925-3] CCDS56122.1 [P40925-2] |
PIRi | G01650 |
RefSeqi | NP_001186040.1, NM_001199111.1 [P40925-3] NP_001186041.1, NM_001199112.1 [P40925-2] NP_001303303.1, NM_001316374.1 NP_005908.1, NM_005917.3 [P40925-1] |
Genome annotation databases
Ensembli | ENST00000233114; ENSP00000233114; ENSG00000014641 [P40925-1] ENST00000544381; ENSP00000446395; ENSG00000014641 [P40925-1] |
GeneIDi | 4190 |
KEGGi | hsa:4190 |
UCSCi | uc010ypv.3, human [P40925-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Malate dehydrogenase entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D55654 mRNA Translation: BAA09513.1 U20352 mRNA Translation: AAC16436.1 CR457405 mRNA Translation: CAG33686.1 AK295931 mRNA Translation: BAH12223.1 AK300719 mRNA Translation: BAG62394.1 AK312331 mRNA Translation: BAG35252.1 AC016734 Genomic DNA Translation: AAY14893.1 CH471053 Genomic DNA Translation: EAW99959.1 BC001484 mRNA Translation: AAH01484.1 |
CCDSi | CCDS1874.1 [P40925-1] CCDS56121.1 [P40925-3] CCDS56122.1 [P40925-2] |
PIRi | G01650 |
RefSeqi | NP_001186040.1, NM_001199111.1 [P40925-3] NP_001186041.1, NM_001199112.1 [P40925-2] NP_001303303.1, NM_001316374.1 NP_005908.1, NM_005917.3 [P40925-1] |
3D structure databases
SMRi | P40925 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 110355, 73 interactors |
IntActi | P40925, 20 interactors |
MINTi | P40925 |
STRINGi | 9606.ENSP00000438144 |
Chemistry databases
BindingDBi | P40925 |
ChEMBLi | CHEMBL3560 |
DrugBanki | DB11638, Artenimol DB00157, NADH DB03461, Nicotinamide adenine dinucleotide phosphate |
DrugCentrali | P40925 |
PTM databases
iPTMneti | P40925 |
MetOSitei | P40925 |
PhosphoSitePlusi | P40925 |
SwissPalmi | P40925 |
Polymorphism and mutation databases
BioMutai | MDH1 |
DMDMi | 1708967 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00291005 |
UCD-2DPAGEi | P40925 |
Proteomic databases
CPTACi | CPTAC-236 CPTAC-237 |
EPDi | P40925 |
jPOSTi | P40925 |
MassIVEi | P40925 |
PaxDbi | P40925 |
PeptideAtlasi | P40925 |
PRIDEi | P40925 |
ProteomicsDBi | 25276 55384 [P40925-1] 55385 [P40925-2] |
TopDownProteomicsi | P40925-1 [P40925-1] |
Protocols and materials databases
Antibodypediai | 15986, 396 antibodies |
CPTCi | P40925, 3 antibodies |
Genome annotation databases
Ensembli | ENST00000233114; ENSP00000233114; ENSG00000014641 [P40925-1] ENST00000544381; ENSP00000446395; ENSG00000014641 [P40925-1] |
GeneIDi | 4190 |
KEGGi | hsa:4190 |
UCSCi | uc010ypv.3, human [P40925-1] |
Organism-specific databases
CTDi | 4190 |
DisGeNETi | 4190 |
EuPathDBi | HostDB:ENSG00000014641.17 |
GeneCardsi | MDH1 |
HGNCi | HGNC:6970, MDH1 |
HPAi | ENSG00000014641, Tissue enhanced (heart) |
MIMi | 154200, gene 618959, phenotype |
neXtProti | NX_P40925 |
OpenTargetsi | ENSG00000014641 |
PharmGKBi | PA30714 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1496, Eukaryota |
GeneTreei | ENSGT00530000063410 |
HOGENOMi | CLU_040727_2_0_1 |
InParanoidi | P40925 |
OMAi | TKGMERG |
OrthoDBi | 1118998at2759 |
PhylomeDBi | P40925 |
TreeFami | TF105826 |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00361-MONOMER |
PathwayCommonsi | P40925 |
Reactomei | R-HSA-70263, Gluconeogenesis |
SABIO-RKi | P40925 |
Miscellaneous databases
BioGRID-ORCSi | 4190, 6 hits in 845 CRISPR screens |
ChiTaRSi | MDH1, human |
GenomeRNAii | 4190 |
Pharosi | P40925, Tbio |
PROi | PR:P40925 |
RNActi | P40925, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000014641, Expressed in superior frontal gyrus and 249 other tissues |
ExpressionAtlasi | P40925, baseline and differential |
Genevisiblei | P40925, HS |
Family and domain databases
CDDi | cd01336, MDH_cytoplasmic_cytosolic, 1 hit |
Gene3Di | 3.90.110.10, 1 hit |
HAMAPi | MF_01517, Malate_dehydrog_2, 1 hit |
InterProi | View 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 IPR011274, Malate_DH_NAD-dep_euk IPR010945, Malate_DH_type2 IPR036291, NAD(P)-bd_dom_sf |
PANTHERi | PTHR23382, PTHR23382, 1 hit |
Pfami | View protein in Pfam PF02866, Ldh_1_C, 1 hit PF00056, Ldh_1_N, 1 hit |
PIRSFi | PIRSF000102, Lac_mal_DH, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit SSF56327, SSF56327, 1 hit |
TIGRFAMsi | TIGR01759, MalateDH-SF1, 1 hit TIGR01758, MDH_euk_cyt, 1 hit |
PROSITEi | View protein in PROSITE PS00068, MDH, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MDHC_HUMAN | |
Accessioni | P40925Primary (citable) accession number: P40925 Secondary accession number(s): B2R5V5 Q6I9V0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 207 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- 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 - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations