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P40925 (MDHC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Malate dehydrogenase, cytoplasmic

EC=1.1.1.37
Alternative name(s):
Cytosolic malate dehydrogenase
Diiodophenylpyruvate reductase
EC=1.1.1.96
Gene names
Name:MDH1
Synonyms:MDHA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length334 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. Ref.11

3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD+ = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + NADH. Ref.11

Subunit structure

Homodimer.

Subcellular location

Cytoplasm HAMAP-Rule MF_01517.

Post-translational modification

ISGylated. Ref.12

Acetylation at Lys-118 dramatically enhances enzymatic activity and promotes adipogenic differentiation. Ref.8 Ref.16

Sequence similarities

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

Ontologies

Keywords
   Biological processTricarboxylic acid cycle
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processNADH metabolic process

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular carbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

gluconeogenesis

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

malate metabolic process

Inferred from electronic annotation. Source: Ensembl

oxaloacetate metabolic process

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

tricarboxylic acid cycle

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcentrosome

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 22664934. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionL-malate dehydrogenase activity

Traceable author statement. Source: Reactome

NAD binding

Inferred from electronic annotation. Source: Ensembl

diiodophenylpyruvate reductase activity

Inferred from electronic annotation. Source: UniProtKB-EC

malic enzyme activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P40925-1)

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.
Isoform 2 (identifier: P40925-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: Missing.
Isoform 3 (identifier: P40925-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRRCSYFPKDVTVFDKDDK
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 334333Malate dehydrogenase, cytoplasmic HAMAP-Rule MF_01517
PRO_0000113409

Regions

Nucleotide binding11 – 177NAD By similarity
Nucleotide binding129 – 1313NAD By similarity

Sites

Active site1871Proton acceptor By similarity
Binding site921Substrate By similarity
Binding site981Substrate By similarity
Binding site1051NAD By similarity
Binding site1121NAD By similarity
Binding site1311Substrate By similarity
Binding site1621Substrate

Amino acid modifications

Modified residue21N-acetylserine Ref.8
Modified residue1101N6-succinyllysine By similarity
Modified residue1181N6-acetyllysine Ref.13 Ref.16
Modified residue1211N6-acetyllysine Ref.16
Modified residue2141N6-succinyllysine By similarity
Modified residue2981N6-acetyllysine; alternate Ref.13 Ref.16
Modified residue2981N6-succinyllysine; alternate By similarity
Modified residue3181N6-succinyllysine By similarity
Modified residue3331Phosphoserine Ref.14

Natural variations

Alternative sequence1 – 8989Missing in isoform 2.
VSP_042661
Alternative sequence11M → MRRCSYFPKDVTVFDKDDK in isoform 3.
VSP_045847

Experimental info

Sequence conflict151Q → R in BAH12223. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 5F7ED9789CA1DB55

FASTA33436,426
        10         20         30         40         50         60 
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC 

        70         80         90        100        110        120 
ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALDKYA 

       130        140        150        160        170        180 
KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTANDVKN 

       190        200        210        220        230        240 
VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFVTTVQQR GAAVIKARKL 

       250        260        270        280        290        300 
SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV 

       310        320        330 
EGLPINDFSR EKMDLTAKEL TEEKESAFEF LSSA 

« Hide

Isoform 2 [UniParc].

Checksum: DEBC412374575BD9
Show »

FASTA24527,025
Isoform 3 [UniParc].

Checksum: 058B25735B30BBC2
Show »

FASTA35238,628

References

« Hide 'large scale' references
[1]"Molecular cloning and mapping of a human cDNA for cytosolic malate dehydrogenase (MDH1)."
Tanaka T., Inazawa J., Nakamura Y.
Genomics 32:128-130(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[2]Lo A.S.Y., Waye M.M.Y.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"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] (ISOFORMS 1; 2 AND 3).
Tissue: Cerebellum and Substantia nigra.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 1).
Tissue: Placenta.
[8]Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.
Submitted (MAY-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-18; 205-213 AND 324-334, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: T-cell.
[9]"The human myocardial two-dimensional gel protein database: update 1994."
Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.
Electrophoresis 15:1459-1465(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 168-181.
Tissue: Heart.
[10]Lubec G., Vishwanath V.
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 180-201 AND 299-310, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain and Cajal-Retzius cell.
[11]"Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes."
Friedrich C.A., Ferrell R.E., Siciliano M.J., Kitto G.B.
Ann. Hum. Genet. 52:25-37(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[12]"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells."
Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.
Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
[13]"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-118 AND LYS-298, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"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].
[16]"Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity."
Kim E.Y., Kim W.K., Kang H.J., Kim J.H., Chung S.J., Seo Y.S., Park S.G., Lee S.C., Bae K.H.
J. Lipid Res. 53:1864-1876(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-118; LYS-121 AND LYS-298.
+Additional computationally mapped references.

Web resources

Wikipedia

Malate dehydrogenase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS1874.1. [P40925-1]
CCDS56121.1. [P40925-3]
CCDS56122.1. [P40925-2]
PIRG01650.
RefSeqNP_001186040.1. NM_001199111.1. [P40925-3]
NP_001186041.1. NM_001199112.1. [P40925-2]
NP_005908.1. NM_005917.3. [P40925-1]
XP_005264377.1. XM_005264320.1. [P40925-2]
UniGeneHs.526521.

3D structure databases

ProteinModelPortalP40925.
SMRP40925. Positions 2-334.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110355. 20 interactions.
IntActP40925. 5 interactions.
MINTMINT-4999585.
STRING9606.ENSP00000233114.

Chemistry

BindingDBP40925.
ChEMBLCHEMBL3560.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP40925.

Polymorphism databases

DMDM1708967.

2D gel databases

REPRODUCTION-2DPAGEIPI00291005.
UCD-2DPAGEP40925.

Proteomic databases

MaxQBP40925.
PaxDbP40925.
PeptideAtlasP40925.
PRIDEP40925.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233114; ENSP00000233114; ENSG00000014641. [P40925-1]
ENST00000394423; ENSP00000377945; ENSG00000014641. [P40925-1]
ENST00000539945; ENSP00000438144; ENSG00000014641. [P40925-3]
ENST00000544381; ENSP00000446395; ENSG00000014641. [P40925-2]
GeneID4190.
KEGGhsa:4190.
UCSCuc002scj.2. human. [P40925-1]

Organism-specific databases

CTD4190.
GeneCardsGC02P063727.
HGNCHGNC:6970. MDH1.
HPACAB047333.
HPA027296.
HPA054276.
MIM154200. gene.
neXtProtNX_P40925.
PharmGKBPA30714.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0039.
HOVERGENHBG006340.
InParanoidP40925.
KOK00025.
OMANCLIASK.
OrthoDBEOG78H3TM.
PhylomeDBP40925.
TreeFamTF105826.

Enzyme and pathway databases

BioCycMetaCyc:HS00361-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP40925.

Gene expression databases

ArrayExpressP40925.
BgeeP40925.
CleanExHS_MDH1.
GenevestigatorP40925.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
HAMAPMF_01517. Malate_dehydrog_2.
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.
IPR011274. Malate_DH_NAD-dep_euk.
IPR010945. Malate_DH_type2.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERPTHR23382. PTHR23382. 1 hit.
PfamPF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]
PIRSFPIRSF000102. Lac_mal_DH. 1 hit.
SUPFAMSSF56327. SSF56327. 1 hit.
TIGRFAMsTIGR01759. MalateDH-SF1. 1 hit.
TIGR01758. MDH_euk_cyt. 1 hit.
PROSITEPS00068. MDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMDH1. human.
GenomeRNAi4190.
NextBio16510.
PROP40925.
SOURCESearch...

Entry information

Entry nameMDHC_HUMAN
AccessionPrimary (citable) accession number: P40925
Secondary accession number(s): B2R5V5 expand/collapse secondary AC list , B4DUN2, B7Z3I7, F5H098, Q6I9V0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 152 of the entry and version 4 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM