P40925 (MDHC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	334 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro gluconeogenesis Traceable author statement. Source: Reactome malate metabolic process Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	centrosome Inferred from direct assay. Source: HPA cytosol Traceable author statement. Source: Reactome
Molecular_function	L-malate dehydrogenase activity Traceable author statement. Source: Reactome diiodophenylpyruvate reductase activity Inferred from electronic annotation. Source: EC malic enzyme activity Traceable author statement Ref.1. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 334	333	Malate dehydrogenase, cytoplasmic		PRO_0000113409
Regions
	Nucleotide binding	11 – 17	7	NAD By similarity
	Nucleotide binding	129 – 131	3	NAD By similarity
Sites
	Active site	187	1	Proton acceptor By similarity
	Binding site	92	1	Substrate By similarity
	Binding site	98	1	Substrate By similarity
	Binding site	105	1	NAD By similarity
	Binding site	112	1	NAD By similarity
	Binding site	131	1	Substrate By similarity
	Binding site	162	1	Substrate
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.8
	Modified residue	118	1	N6-acetyllysine Ref.13 Ref.16
	Modified residue	121	1	N6-acetyllysine Ref.16
	Modified residue	210	1	Phosphotyrosine By similarity
	Modified residue	241	1	Phosphoserine By similarity
	Modified residue	298	1	N6-acetyllysine Ref.13 Ref.16
	Modified residue	333	1	Phosphoserine Ref.14
Natural variations
	Alternative sequence	1 – 89	89	Missing in isoform 2.		VSP_042661
	Alternative sequence	1	1	M → MRRCSYFPKDVTVFDKDDK in isoform 3.		VSP_045847
Experimental info
	Sequence conflict	15	1	Q → R in BAH12223. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 5F7ED9789CA1DB55	FASTA	334	36,426
	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
	Isoform 2 [UniParc]. Checksum: DEBC412374575BD9	FASTA	245	27,025
	10 20 30 40 50 60 MPRREGMERK DLLKANVKIF KSQGAALDKY AKKSVKVIVV GNPANTNCLT ASKSAPSIPK 70 80 90 100 110 120 ENFSCLTRLD HNRAKAQIAL KLGVTANDVK NVIIWGNHSS TQYPDVNHAK VKLQGKEVGV 130 140 150 160 170 180 YEALKDDSWL KGEFVTTVQQ RGAAVIKARK LSSAMSAAKA ICDHVRDIWF GTPEGEFVSM 190 200 210 220 230 240 GVISDGNSYG VPDDLLYSFP VVIKNKTWKF VEGLPINDFS REKMDLTAKE LTEEKESAFE FLSSA
	Isoform 3 [UniParc]. Checksum: 058B25735B30BBC2	FASTA	352	38,628
	10 20 30 40 50 60 MRRCSYFPKD VTVFDKDDKS EPIRVLVTGA AGQIAYSLLY SIGNGSVFGK DQPIILVLLD 70 80 90 100 110 120 ITPMMGVLDG VLMELQDCAL PLLKDVIATD KEDVAFKDLD VAILVGSMPR REGMERKDLL 130 140 150 160 170 180 KANVKIFKSQ GAALDKYAKK SVKVIVVGNP ANTNCLTASK SAPSIPKENF SCLTRLDHNR 190 200 210 220 230 240 AKAQIALKLG VTANDVKNVI IWGNHSSTQY PDVNHAKVKL QGKEVGVYEA LKDDSWLKGE 250 260 270 280 290 300 FVTTVQQRGA AVIKARKLSS AMSAAKAICD HVRDIWFGTP EGEFVSMGVI SDGNSYGVPD 310 320 330 340 350 DLLYSFPVVI KNKTWKFVEG LPINDFSREK MDLTAKELTE EKESAFEFLS SA

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00916111. IPI00952583.
PIR	G01650.
RefSeq	NP_001186040.1. NM_001199111.1. NP_001186041.1. NM_001199112.1. NP_005908.1. NM_005917.3.
UniGene	Hs.526521.
3D structure databases
ProteinModelPortal	P40925.
ModBase	Search...
Protein-protein interaction databases
IntAct	P40925. 6 interactions.
MINT	MINT-4999585.
STRING	9606.ENSP00000233114.
PTM databases
PhosphoSite	P40925.
Polymorphism databases
DMDM	1708967.
2D gel databases
REPRODUCTION-2DPAGE	IPI00291005.
UCD-2DPAGE	P40925.
Proteomic databases
PaxDb	P40925.
PeptideAtlas	P40925.
PRIDE	P40925.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000233114; ENSP00000233114; ENSG00000014641. ENST00000394423; ENSP00000377945; ENSG00000014641. ENST00000539945; ENSP00000438144; ENSG00000014641. ENST00000544381; ENSP00000446395; ENSG00000014641.
GeneID	4190.
KEGG	hsa:4190.
UCSC	uc002scj.2. human.
Organism-specific databases
CTD	4190.
GeneCards	GC02P063727.
HGNC	HGNC:6970. MDH1.
HPA	CAB047333. HPA027296.
MIM	154200. gene.
neXtProt	NX_P40925.
PharmGKB	PA30714.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0039.
HOVERGEN	HBG006340.
InParanoid	P40925.
KO	K00025.
OrthoDB	EOG4CVG78.
PhylomeDB	P40925.
Enzyme and pathway databases
BioCyc	MetaCyc:HS00361-MONOMER.
Reactome	REACT_111217. Metabolism.
SABIO-RK	P40925.
Gene expression databases
ArrayExpress	P40925.
Bgee	P40925.
CleanEx	HS_MDH1.
Genevestigator	P40925.
GermOnline	ENSG00000014641. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 1 hit. 3.90.110.10. 1 hit.
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. IPR016040. NAD(P)-bd_dom. [Graphical view]
PANTHER	PTHR23382. PTHR23382. 1 hit.
Pfam	PF02866. Ldh_1_C. 1 hit. PF00056. Ldh_1_N. 1 hit. [Graphical view]
PIRSF	PIRSF000102. Lac_mal_DH. 1 hit.
SUPFAM	SSF56327. Lactate_DH/Glyco_hydro_4_C. 1 hit.
TIGRFAMs	TIGR01759. MalateDH-SF1. 1 hit. TIGR01758. MDH_euk_cyt. 1 hit.
PROSITE	PS00068. MDH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P40925.
ChEMBL	CHEMBL3560.
ChiTaRS	MDH1. human.
DrugBank	DB00157. NADH.
GenomeRNAi	4190.
NextBio	16510.
SOURCE	Search...

Entry information

Entry name

MDHC_HUMAN

Accession

Primary (citable) accession number: P40925
Secondary accession number(s): B2R5V5 , 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 status

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.