[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1006/abbi.1993.1032; PubMed=8424657 [NCBI, ExPASy, EBI, Israel, Japan] Kulkarni G., Cook P.F., Harris B.G.; "Cloning and nucleotide sequence of a full-length cDNA encoding Ascaris suum malic enzyme."; Arch. Biochem. Biophys. 300:231-237(1993).
[2]	MUTAGENESIS OF GLU-96; ASP-216; ASP-310; ASP-332; ASP-333; ASP-399 AND GLU-478. DOI=10.1021/bi9906165; PubMed=10441149 [NCBI, ExPASy, EBI, Israel, Japan] Karsten W.E., Chooback L., Liu D., Hwang C.-C., Lynch C., Cook P.F.; "Mapping the active site topography of the NAD-malic enzyme via alanine-scanning site-directed mutagenesis."; Biochemistry 38:10527-10532(1999).
[3]	MUTAGENESIS OF TYR-164 AND LYS-237. DOI=10.1021/bi000790p; PubMed=11009609 [NCBI, ExPASy, EBI, Israel, Japan] Liu D., Karsten W.E., Cook P.F.; "Lysine 199 is the general acid in the NAD-malic enzyme reaction."; Biochemistry 39:11955-11960(2000).
[4]	MECHANISM, AND PH-DEPENDENCE OF ACTIVITY OF MUTANTS PHE-164; ARG-237 AND ALA-332. DOI=10.1021/bi047826o; PubMed=15736972 [NCBI, ExPASy, EBI, Israel, Japan] Karsten W.E., Liu D., Rao G.S., Harris B.G., Cook P.F.; "A catalytic triad is responsible for acid-base chemistry in the Ascaris suum NAD-malic enzyme."; Biochemistry 44:3626-3635(2005).
[5]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 39-643 IN COMPLEX WITH NAD. DOI=10.1021/bi0255120; PubMed=12033925 [NCBI, ExPASy, EBI, Israel, Japan] Coleman D.E., Rao G.S.J., Goldsmith E.J., Cook P.F., Harris B.G.; "Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 A resolution."; Biochemistry 41:6928-6938(2002).
[6]	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 39-643 IN COMPLEX WITH NAD; MAGNESIUM AND INHIBITOR. DOI=10.1074/jbc.M305145200; PubMed=12853453 [NCBI, ExPASy, EBI, Israel, Japan] Rao G.S.J., Coleman D.E., Karsten W.E., Cook P.F., Harris B.G.; "Crystallographic studies on Ascaris suum NAD-malic enzyme bound to reduced cofactor and identification of an effector site."; J. Biol. Chem. 278:38051-38058(2003).

Comments

CATALYTIC ACTIVITY: (S)-malate + NAD⁺ = pyruvate + CO₂ + NADH.
COFACTOR: Divalent metal cations. Prefers magnesium or manganese.
ENZYME REGULATION: Subject to allosteric activation by fumarate.
SUBUNIT: Homotetramer (By similarity).
SUBCELLULAR LOCATION: Mitochondrion matrix.
MISCELLANEOUS: This isoenzyme can also use NADP(+) but is more effective with NAD(+).
SIMILARITY: Belongs to the malic enzymes family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M81055; -; NOT_ANNOTATED_CDS; mRNA.

[EMBL / GenBank / DDBJ]

PIR

S29742; S29742.

3D structure databases

PDB

1LLQ; X-ray; 2.30 A; A/B=39-643.	[ExPASy / RCSB / EBI]
1O0S; X-ray; 2.00 A; A/B=39-643.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1LLQ; -.
1O0S; -.

ModBase

P27443.

Ontologies

GO:0005759;	Cellular component: mitochondrial matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0016619;	Molecular function: malate dehydrogenase (oxaloacetate-decarboxylating) activity (inferred from electronic annotation from EC).
GO:0046872;	Molecular function: metal ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR015884; Malic_enzyme_CS.
IPR012301; Malic_N.
IPR012302; Malic_NAD_bd.
IPR001891; Malic_OxRdtase.
IPR016040; NAD(P)-bd.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.50.720; NAD(P)-bd; 1.

Pfam

PF00390; malic; 1.
PF03949; Malic_M; 1.
Pfam graphical view of domain structure.

PRINTS

PR00072; MALOXRDTASE.

PROSITE

PS00331; MALIC_ENZYMES; 1.

Other

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Allosteric enzyme; Metal-binding; Mitochondrion; NAD; Oxidoreductase; Transit peptide.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`TRANSIT`	`<1 38`	`>38`	`Mitochondrion.`
`CHAIN`	`39 643`	`605`	`NAD-dependent malic enzyme, mitochondrial.`	`PRO_0000018541`
`NP_BIND`	`219 227`	`9`	`NAD.`
`NP_BIND`	`365 382`	`18`	`NAD.`
`ACT_SITE`	`164 164`		`Proton donor.`
`ACT_SITE`	`237 237`		`Proton acceptor.`
`METAL`	`309 309`		`Divalent metal cation.`
`METAL`	`310 310`		`Divalent metal cation.`
`METAL`	`333 333`		`Divalent metal cation (Probable).`
`BINDING`	`78 78`		`Allosteric activator.`
`BINDING`	`81 81`		`Allosteric activator.`
`BINDING`	`105 105`		`Allosteric activator.`
`BINDING`	`333 333`		`NAD.`
`BINDING`	`472 472`		`NAD.`
`SITE`	`333 333`	`1`	`Important for activity.`
`MUTAGEN`	`96 96`		`E->A: Reduces activity over 1000-fold.`
`MUTAGEN`	`164 164`		`Y->F: Reduces activity over 60000-fold.`
`MUTAGEN`	`216 216`		`D->A: Reduces activity over 50-fold.`
`MUTAGEN`	`237 237`		`K->A: Reduces activity over 100000-fold.`
`MUTAGEN`	`237 237`		`K->R: Reduces activity over 10-fold.`
`MUTAGEN`	`310 310`		`D->A: Reduces activity over 800-fold.`
`MUTAGEN`	`332 332`		`D->A: Reduces activity over 13000-fold.`
`MUTAGEN`	`333 333`		`D->A: Reduces activity over 100000-fold.`
`MUTAGEN`	`399 399`		`D->A: Reduces activity 10-fold.`
`MUTAGEN`	`478 478`		`E->A: Reduces activity over 1000-fold.`
`NON_TER`	`1 1`
`HELIX`	`57 66`	`10`
`HELIX`	`77 81`	`5`
`TURN`	`84 86`	`3`
`HELIX`	`89 91`	`3`
`HELIX`	`94 99`	`6`
`HELIX`	`113 125`	`13`
`STRAND`	`127 129`	`3`
`HELIX`	`130 141`	`12`
`HELIX`	`145 154`	`10`
`HELIX`	`156 163`	`8`
`HELIX`	`167 175`	`9`
`STRAND`	`184 188`	`5`
`HELIX`	`189 191`	`3`
`HELIX`	`194 202`	`9`
`STRAND`	`211 215`	`5`
`STRAND`	`217 220`	`4`
`TURN`	`221 223`	`3`
`HELIX`	`227 231`	`5`
`HELIX`	`232 245`	`14`
`HELIX`	`249 251`	`3`
`STRAND`	`252 259`	`8`
`HELIX`	`264 268`	`5`
`HELIX`	`283 300`	`18`
`STRAND`	`305 308`	`4`
`HELIX`	`313 323`	`11`
`TURN`	`324 326`	`3`
`STRAND`	`327 331`	`5`
`HELIX`	`332 352`	`21`
`HELIX`	`356 358`	`3`
`STRAND`	`361 364`	`4`
`HELIX`	`368 382`	`15`
`TURN`	`383 385`	`3`
`TURN`	`388 391`	`4`
`HELIX`	`392 394`	`3`
`STRAND`	`395 399`	`5`
`STRAND`	`405 407`	`3`
`HELIX`	`413 416`	`4`
`STRAND`	`420 422`	`3`
`HELIX`	`428 435`	`8`
`STRAND`	`438 442`	`5`
`HELIX`	`452 461`	`10`
`STRAND`	`466 469`	`4`
`HELIX`	`474 476`	`3`
`HELIX`	`481 486`	`6`
`TURN`	`487 490`	`4`
`STRAND`	`493 498`	`6`
`STRAND`	`503 505`	`3`
`STRAND`	`508 510`	`3`
`HELIX`	`517 519`	`3`
`HELIX`	`521 530`	`10`
`HELIX`	`538 550`	`13`
`HELIX`	`554 557`	`4`
`TURN`	`558 560`	`3`
`HELIX`	`566 568`	`3`
`HELIX`	`569 586`	`18`
`STRAND`	`592 594`	`3`
`HELIX`	`599 604`	`6`
`HELIX`	`624 627`	`4`

Sequence information

Length: 643 AA [This is the length of the partial sequence of the unprocessed precursor]

Molecular weight: 72757 Da [This is the MW of the partial sequence of the unprocessed precursor]

CRC64: 7B1A480F086FE267 [This is a checksum on the sequence]

        10         20         30         40         50         60 
PRVRSFIAHQ SGITSVIRRS PDIAHRMVRS LSVSSQRNKS VAHHEDVYSH NLPPMDEKEM 

        70         80         90        100        110        120 
ALYKLYRPER VTPKKRSAEL LKEPRLNKGM GFSLYERQYL GLHGLLPPAF MTQEQQAYRV 

       130        140        150        160        170        180 
ITKLREQPND LARYIQLDGL QDRNEKLFYR VVCDHVKELM PIVYTPTVGL ACQNFGYIYR 

       190        200        210        220        230        240 
KPKGLYITIN DNSVSKIYQI LSNWHEEDVR AIVVTDGERI LGLGDLGAYG IGIPVGKLAL 

       250        260        270        280        290        300 
YVALGGVQPK WCLPVLLDVG TNNMDLLNDP FYIGLRHKRV RGKDYDTLLD NFMKACTKKY 

       310        320        330        340        350        360 
GQKTLIQFED FANPNAFRLL DKYQDKYTMF NDDIQGTASV IVAGLLTCTR VTKKLVSQEK 

       370        380        390        400        410        420 
YLFFGAGAAS TGIAEMIVHQ MQNEGISKEE ACNRIYLMDI DGLVTKNRKE MNPRHVQFAK 

       430        440        450        460        470        480 
DMPETTSILE VIRAARPGAL IGASTVRGAF NEEVIRAMAE INERPIIFAL SNPTSKAECT 

       490        500        510        520        530        540 
AEEAYTFTNG AALYASGSPF PNFELNGHTY KPGQGNNAYI FPGVALGTIL FQIRHVDNDL 

       550        560        570        580        590        600 
FLLAAKKVAS CVTEDSLKVG RVYPQLKEIR EISIQIAVEM AKYCYKNGTA NLYPQPEDLE 

       610        620        630        640 
KYVRAQVYNT EYEELINATY DWPEQDMRHG FPVPVVRHDS MDG

P27443 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools