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P40925 (MDHC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 139. 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.

Post-translational modification

ISGylated. Ref.12

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

Sequence similarities

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

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
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 residue1181N6-acetyllysine Ref.13 Ref.16
Modified residue1211N6-acetyllysine Ref.16
Modified residue2101Phosphotyrosine By similarity
Modified residue2411Phosphoserine By similarity
Modified residue2981N6-acetyllysine Ref.13 Ref.16
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, 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, 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY.
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.
IPIIPI00916111.
IPI00952583.
PIRG01650.
RefSeqNP_001186040.1. NM_001199111.1.
NP_001186041.1. NM_001199112.1.
NP_005908.1. NM_005917.3.
UniGeneHs.526521.

3D structure databases

ProteinModelPortalP40925.
ModBaseSearch...

Protein-protein interaction databases

IntActP40925. 6 interactions.
MINTMINT-4999585.
STRING9606.ENSP00000233114.

PTM databases

PhosphoSiteP40925.

Polymorphism databases

DMDM1708967.

2D gel databases

REPRODUCTION-2DPAGEIPI00291005.
UCD-2DPAGEP40925.

Proteomic databases

PaxDbP40925.
PeptideAtlasP40925.
PRIDEP40925.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233114; ENSP00000233114; ENSG00000014641.
ENST00000394423; ENSP00000377945; ENSG00000014641.
ENST00000539945; ENSP00000438144; ENSG00000014641.
ENST00000544381; ENSP00000446395; ENSG00000014641.
GeneID4190.
KEGGhsa:4190.
UCSCuc002scj.2. human.

Organism-specific databases

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

Phylogenomic databases

eggNOGCOG0039.
HOVERGENHBG006340.
InParanoidP40925.
KOK00025.
OrthoDBEOG4CVG78.
PhylomeDBP40925.

Enzyme and pathway databases

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

Gene expression databases

ArrayExpressP40925.
BgeeP40925.
CleanExHS_MDH1.
GenevestigatorP40925.
GermOnlineENSG00000014641. Homo sapiens.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
3.90.110.10. 1 hit.
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. Lactate_DH/Glyco_hydro_4_C. 1 hit.
TIGRFAMsTIGR01759. MalateDH-SF1. 1 hit.
TIGR01758. MDH_euk_cyt. 1 hit.
PROSITEPS00068. MDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP40925.
ChEMBLCHEMBL3560.
ChiTaRSMDH1. human.
DrugBankDB00157. NADH.
GenomeRNAi4190.
NextBio16510.
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: May 1, 2013
This is version 139 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

Human chromosome 2

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

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families