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Protein

Malate dehydrogenase, cytoplasmic

Gene

MDH1

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.1 Publication
3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD+ = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + NADH.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei92SubstrateBy similarity1
Binding sitei98SubstrateBy similarity1
Binding sitei105NADBy similarity1
Binding sitei112NADBy similarity1
Binding sitei131SubstrateBy similarity1
Binding sitei162Substrate1
Active sitei187Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi11 – 17NADBy similarity7
Nucleotide bindingi129 – 131NADBy similarity3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Tricarboxylic acid cycle

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciMetaCyc:HS00361-MONOMER.
ZFISH:HS00361-MONOMER.
ReactomeiR-HSA-70263. Gluconeogenesis.
SABIO-RKP40925.

Names & Taxonomyi

Protein namesi
Recommended name:
Malate dehydrogenase, cytoplasmic (EC:1.1.1.37)
Alternative name(s):
Cytosolic malate dehydrogenase
Diiodophenylpyruvate reductase (EC:1.1.1.96)
Gene namesi
Name:MDH1
Synonyms:MDHA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:6970. MDH1.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: HPA
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • mitochondrion Source: GO_Central
  • myelin sheath Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi4190.
OpenTargetsiENSG00000014641.
PharmGKBiPA30714.

Chemistry databases

ChEMBLiCHEMBL3560.

Polymorphism and mutation databases

BioMutaiMDH1.
DMDMi1708967.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001134092 – 334Malate dehydrogenase, cytoplasmicAdd BLAST333

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei110N6-succinyllysineBy similarity1
Modified residuei118N6-acetyllysineCombined sources1 Publication1
Modified residuei121N6-acetyllysine1 Publication1
Modified residuei214N6-succinyllysineBy similarity1
Modified residuei217PhosphoserineBy similarity1
Modified residuei230Omega-N-methylarginineBy similarity1
Modified residuei241PhosphoserineCombined sources1
Modified residuei298N6-acetyllysine; alternateCombined sources1 Publication1
Modified residuei298N6-succinyllysine; alternateBy similarity1
Modified residuei309PhosphoserineBy similarity1
Modified residuei318N6-succinyllysineBy similarity1
Modified residuei332PhosphoserineBy similarity1
Modified residuei333PhosphoserineCombined sources1

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 conjugation

Proteomic databases

EPDiP40925.
PaxDbiP40925.
PeptideAtlasiP40925.
PRIDEiP40925.
TopDownProteomicsiP40925-1. [P40925-1]

2D gel databases

REPRODUCTION-2DPAGEIPI00291005.
UCD-2DPAGEP40925.

PTM databases

iPTMnetiP40925.
PhosphoSitePlusiP40925.
SwissPalmiP40925.

Expressioni

Gene expression databases

BgeeiENSG00000014641.
CleanExiHS_MDH1.
ExpressionAtlasiP40925. baseline and differential.
GenevisibleiP40925. HS.

Organism-specific databases

HPAiCAB047333.
HPA027296.
HPA054276.

Interactioni

Subunit structurei

Homodimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF1P542742EBI-709625,EBI-710997

Protein-protein interaction databases

BioGridi110355. 38 interactors.
IntActiP40925. 8 interactors.
MINTiMINT-4999585.
STRINGi9606.ENSP00000438144.

Chemistry databases

BindingDBiP40925.

Structurei

3D structure databases

ProteinModelPortaliP40925.
SMRiP40925.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the LDH/MDH superfamily. MDH type 2 family.Curated

Phylogenomic databases

eggNOGiKOG1496. Eukaryota.
COG0039. LUCA.
GeneTreeiENSGT00530000063410.
HOGENOMiHOG000220953.
HOVERGENiHBG006340.
InParanoidiP40925.
KOiK00025.
OMAiQYPDAGQ.
OrthoDBiEOG091G0BLA.
PhylomeDBiP40925.
TreeFamiTF105826.

Family and domain databases

CDDicd01336. MDH_cytoplasmic_cytosolic. 1 hit.
Gene3Di3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
HAMAPiMF_01517. Malate_dehydrog_2. 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.
IPR011274. Malate_DH_NAD-dep_euk.
IPR010945. Malate_DH_type2.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR23382. PTHR23382. 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.
TIGRFAMsiTIGR01759. MalateDH-SF1. 1 hit.
TIGR01758. MDH_euk_cyt. 1 hit.
PROSITEiPS00068. MDH. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P40925-1) [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
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
Length:334
Mass (Da):36,426
Last modified:January 23, 2007 - v4
Checksum:i5F7ED9789CA1DB55
GO
Isoform 2 (identifier: P40925-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: Missing.

Show »
Length:245
Mass (Da):27,025
Checksum:iDEBC412374575BD9
GO
Isoform 3 (identifier: P40925-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRRCSYFPKDVTVFDKDDK

Note: No experimental confirmation available.
Show »
Length:352
Mass (Da):38,628
Checksum:i058B25735B30BBC2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15Q → R in BAH12223 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0426611 – 89Missing in isoform 2. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_0458471M → MRRCSYFPKDVTVFDKDDK in isoform 3. 1 Publication1

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.
CCDSiCCDS1874.1. [P40925-1]
CCDS56121.1. [P40925-3]
CCDS56122.1. [P40925-2]
PIRiG01650.
RefSeqiNP_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]
UniGeneiHs.526521.

Genome annotation databases

EnsembliENST00000233114; ENSP00000233114; ENSG00000014641. [P40925-1]
ENST00000539945; ENSP00000438144; ENSG00000014641. [P40925-3]
ENST00000544381; ENSP00000446395; ENSG00000014641. [P40925-2]
GeneIDi4190.
KEGGihsa:4190.
UCSCiuc010ypv.3. human. [P40925-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS1874.1. [P40925-1]
CCDS56121.1. [P40925-3]
CCDS56122.1. [P40925-2]
PIRiG01650.
RefSeqiNP_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]
UniGeneiHs.526521.

3D structure databases

ProteinModelPortaliP40925.
SMRiP40925.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110355. 38 interactors.
IntActiP40925. 8 interactors.
MINTiMINT-4999585.
STRINGi9606.ENSP00000438144.

Chemistry databases

BindingDBiP40925.
ChEMBLiCHEMBL3560.

PTM databases

iPTMnetiP40925.
PhosphoSitePlusiP40925.
SwissPalmiP40925.

Polymorphism and mutation databases

BioMutaiMDH1.
DMDMi1708967.

2D gel databases

REPRODUCTION-2DPAGEIPI00291005.
UCD-2DPAGEP40925.

Proteomic databases

EPDiP40925.
PaxDbiP40925.
PeptideAtlasiP40925.
PRIDEiP40925.
TopDownProteomicsiP40925-1. [P40925-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233114; ENSP00000233114; ENSG00000014641. [P40925-1]
ENST00000539945; ENSP00000438144; ENSG00000014641. [P40925-3]
ENST00000544381; ENSP00000446395; ENSG00000014641. [P40925-2]
GeneIDi4190.
KEGGihsa:4190.
UCSCiuc010ypv.3. human. [P40925-1]

Organism-specific databases

CTDi4190.
DisGeNETi4190.
GeneCardsiMDH1.
HGNCiHGNC:6970. MDH1.
HPAiCAB047333.
HPA027296.
HPA054276.
MIMi154200. gene.
neXtProtiNX_P40925.
OpenTargetsiENSG00000014641.
PharmGKBiPA30714.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1496. Eukaryota.
COG0039. LUCA.
GeneTreeiENSGT00530000063410.
HOGENOMiHOG000220953.
HOVERGENiHBG006340.
InParanoidiP40925.
KOiK00025.
OMAiQYPDAGQ.
OrthoDBiEOG091G0BLA.
PhylomeDBiP40925.
TreeFamiTF105826.

Enzyme and pathway databases

BioCyciMetaCyc:HS00361-MONOMER.
ZFISH:HS00361-MONOMER.
ReactomeiR-HSA-70263. Gluconeogenesis.
SABIO-RKP40925.

Miscellaneous databases

ChiTaRSiMDH1. human.
GenomeRNAii4190.
PROiP40925.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000014641.
CleanExiHS_MDH1.
ExpressionAtlasiP40925. baseline and differential.
GenevisibleiP40925. HS.

Family and domain databases

CDDicd01336. MDH_cytoplasmic_cytosolic. 1 hit.
Gene3Di3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
HAMAPiMF_01517. Malate_dehydrog_2. 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.
IPR011274. Malate_DH_NAD-dep_euk.
IPR010945. Malate_DH_type2.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR23382. PTHR23382. 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.
TIGRFAMsiTIGR01759. MalateDH-SF1. 1 hit.
TIGR01758. MDH_euk_cyt. 1 hit.
PROSITEiPS00068. MDH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDHC_HUMAN
AccessioniPrimary (citable) accession number: P40925
Secondary accession number(s): B2R5V5
, B4DUN2, B7Z3I7, F5H098, Q6I9V0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 176 of the entry and version 4 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.