P08249 (MDHM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Malate dehydrogenase, mitochondrial
EC=1.1.1.37

Gene names

Name:	Mdh2
Synonyms:	Mor1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	338 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.
Enzyme regulation	Enzyme activity is enhanced by acetylation By similarity.
Subunit structure	Homodimer.
Subcellular location	Mitochondrion matrix.
Post-translational modification	Acetylation is enhanced by up to 67% after treatment either with trichostin A (TCA) or with nicotinamide (NAM) with the appearance of tri-and tetraacetylations. Glucose also increases acetylation by about 60% By similarity. Acetylation of Lys-239 and Lys-314 is observed in liver mitochondria from fasted mice but not from fed mice.
Sequence similarities	Belongs to the LDH/MDH superfamily. MDH type 1 family.
Sequence caution	The sequence BAC24986.1 differs from that shown. Reason: Frameshift at position 39.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cellular carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro internal protein amino acid acetylation Inferred from sequence or structural similarity. Source: UniProtKB tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial inner membrane Inferred from direct assay. Source: MGI mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	L-malate dehydrogenase activity Inferred from direct assay. Source: MGI nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 24	24	Mitochondrion
	Chain	25 – 338	314	Malate dehydrogenase, mitochondrial		PRO_0000018629
Regions
	Nucleotide binding	31 – 37	7	NAD By similarity
	Nucleotide binding	140 – 142	3	NAD By similarity
Sites
	Active site	200	1	Proton acceptor By similarity
	Binding site	57	1	NAD By similarity
	Binding site	104	1	Substrate
	Binding site	110	1	Substrate
	Binding site	117	1	NAD By similarity
	Binding site	142	1	Substrate
	Binding site	176	1	Substrate
	Binding site	251	1	NAD By similarity
Amino acid modifications
	Modified residue	56	1	Phosphotyrosine By similarity
	Modified residue	157	1	N6-acetyllysine Ref.7
	Modified residue	165	1	N6-acetyllysine By similarity
	Modified residue	185	1	N6-acetyllysine By similarity
	Modified residue	239	1	N6-acetyllysine Ref.7
	Modified residue	301	1	N6-acetyllysine By similarity
	Modified residue	314	1	N6-acetyllysine Ref.7
	Modified residue	329	1	N6-acetyllysine By similarity
	Modified residue	335	1	N6-acetyllysine By similarity
Experimental info
	Sequence conflict	76	1	N → K in AAA39509. Ref.1
	Sequence conflict	269	1	K → L in AAA39509. Ref.1
	Sequence conflict	269	1	K → L in CAA30274. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P08249 [UniParc]. Last modified May 1, 2007. Version 3. Checksum: 99D13BB2099C19F1	FASTA	338	35,611
	10 20 30 40 50 60 MLSALARPAG AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH 70 80 90 100 110 120 TPGVAADLSH IETRANVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI 130 140 150 160 170 180 VATLTAACAQ HCPEAMVCII ANPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF 190 200 210 220 230 240 VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLATLTGRI QEAGTEVVKA 250 260 270 280 290 300 KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVQS KETECTYFST PLLLGKKGLE 310 320 330 KNLGIGKITP FEEKMIAEAI PELKASIKKG EDFVKNMK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of cDNAs encoding mammalian mitochondrial malate dehydrogenase." Joh T., Takeshima H., Tsuzuki T., Shimada K., Tanase S., Morino Y. Biochemistry 26:2515-2520(1987) [PubMed: 3038184] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structural organization of the mouse mitochondrial malate dehydrogenase gene." Takeshima H., Joh T., Tsuzuki T., Shimada K., Matsukado Y. J. Mol. Biol. 200:1-11(1988) [PubMed: 3379635] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: BALB/c and C57BL/6J. Tissue: Cerebellum and Kidney.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary tumor.
[5]	"Housekeeping genes for phylogenetic analysis of eutherian relationships." Kullberg M., Nilsson M.A., Arnason U., Harley E.H., Janke A. Mol. Biol. Evol. 23:1493-1503(2006) [PubMed: 16751257] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-322. Tissue: Liver.
[6]	Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 27-45; 53-74; 79-104; 166-185; 192-239; 242-257; 282-296 AND 308-324, MASS SPECTROMETRY. Strain: C57BL/6 and OF1. Tissue: Brain and Hippocampus.
[7]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-157; LYS-239 AND LYS-314, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M16229 mRNA. Translation: AAA39509.1. X07295 , X07296, X07297, X07298, X07299, X07300, X07301 Genomic DNA. Translation: CAA30274.1. AK002305 mRNA. Translation: BAC24986.1. Frameshift. AK167809 mRNA. Translation: BAE39836.1. AK160553 mRNA. Translation: BAE35869.1. AK135162 mRNA. Translation: BAE22447.1. BC023482 mRNA. Translation: AAH23482.1. DQ402950 mRNA. Translation: ABD77283.1.
IPI	IPI00323592.
PIR	DEMSMM. S01350.
RefSeq	NP_032643.2. NM_008617.2.
UniGene	Mm.297096.
3D structure databases
ProteinModelPortal	P08249.
SMR	P08249. Positions 25-337.
ModBase	Search...
Protein-protein interaction databases
IntAct	P08249. 3 interactions.
STRING	P08249.
PTM databases
PhosphoSite	P08249.
2D gel databases
SWISS-2DPAGE	P08249.
REPRODUCTION-2DPAGE	P08249.
UCD-2DPAGE	P08249.
Proteomic databases
PRIDE	P08249.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000019323; ENSMUSP00000019323; ENSMUSG00000019179.
GeneID	17448.
KEGG	mmu:17448.
NMPDR	fig|10090.3.peg.12582.
UCSC	uc008zyz.1. mouse.
Organism-specific databases
CTD	4191.
MGI	MGI:97050. Mdh2.
Phylogenomic databases
eggNOG	roNOG11242.
GeneTree	ENSGT00390000016686.
HOGENOM	HBG566126.
HOVERGEN	HBG001662.
InParanoid	P08249.
OMA	LVEKCAA.
OrthoDB	EOG4MKNGM.
PhylomeDB	P08249.
Gene expression databases
ArrayExpress	P08249.
Bgee	P08249.
CleanEx	MM_MDH2.
Genevestigator	P08249.
GermOnline	ENSMUSG00000019179. Mus musculus.
Family and domain databases
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. IPR010097. Malate_DH_type1. IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.90.110.10. lact_mal_DH. 1 hit. G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
KO	K00026.
PANTHER	PTHR11540:SF1. MDH_euk_g_bac. 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	TIGR01772. MDH_euk_gproteo. 1 hit.
PROSITE	PS00068. MDH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	292084.
SOURCE	Search...

Entry information

Entry name

MDHM_MOUSE

Accession

Primary (citable) accession number: P08249
Secondary accession number(s): Q0QF44, Q8CF79, Q8R1P0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	May 1, 2007
Last modified:	December 14, 2011
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program