Reviewed, UniProtKB/Swiss-Prot P48163 (MAOX_HUMAN)

Names and origin

Protein names

Recommended name:
    NADP-dependent malic enzyme
      Short name=NADP-ME
    EC=1.1.1.40
Alternative name(s):
    Malic enzyme 1

Gene names

Name:

ME1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	572 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	(S)-malate + NADP+ = pyruvate + CO2 + NADPH.
Cofactor	Divalent metal cations. Prefers magnesium or manganese By similarity.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm. Ref.1
Tissue specificity	Expressed in all tissues tested including liver, placenta and white adipose tissue. Ref.1 Ref.2
Sequence similarities	Belongs to the malic enzymes family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Metal-binding NADP
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	NADP biosynthetic process Ref.1 Traceable author statement. Source: UniProtKB carbohydrate metabolic process Ref.1 Non-traceable author statement. Source: ProtInc malate metabolic process Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to carbohydrate stimulus Ref.1 Traceable author statement. Source: UniProtKB response to hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	ADP binding Ref.2 Traceable author statement. Source: UniProtKB NAD or NADH binding Ref.2 Traceable author statement. Source: UniProtKB NADP or NADPH binding Ref.2 Traceable author statement. Source: UniProtKB electron carrier activity Ref.2 Traceable author statement. Source: UniProtKB malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) activity Ref.1 Inferred from direct assay. Source: UniProtKB manganese ion binding Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 572

572

NADP-dependent malic enzyme

PRO_0000160192

Regions

Nucleotide binding

301 – 318

18

NADP By similarity

Sites

Active site

102

1

Proton donor By similarity

Active site

173

1

Proton acceptor By similarity

Metal binding

245

1

Divalent metal cation By similarity

Metal binding

246

1

Divalent metal cation By similarity

Metal binding

269

1

Divalent metal cation By similarity

Binding site

155

1

NADP By similarity

Binding site

269

1

NADP By similarity

Binding site

408

1

NADP By similarity

Site

269

1

Important for activity By similarity

Experimental info

Sequence conflict

266

1

F → S in BAD97137. Ref.3

Sequence conflict

438

1

P → S in AAC50613. Ref.6

Sequence conflict

443 – 448

6

NGQTLY → DGRTLF in AAB01380. Ref.2

Sequence conflict

472 – 477

6

QITDNI → HIDDKV in AAB01380. Ref.2

Sequence conflict

486

1

A → S in AAB01380. Ref.2

Sequence conflict

495

1

E → Q in AAB01380. Ref.2

Sequence conflict

515

1

E → V in AAB01380. Ref.2

Sequence conflict

519

1

K → Q in AAB01380. Ref.2

Sequence conflict

523

1

Q → K in AAB01380. Ref.2

Sequence conflict

526

1

T → M in AAB01380. Ref.2

Sequence conflict

538

1

A → E in AAB01380. Ref.2

Sequence conflict

541

1

R → S in AAB01380. Ref.2

Sequence conflict

548

1

D → N in AAB01380. Ref.2

Sequence conflict

558

1

S → P in AAB01380. Ref.2

Sequence conflict

561

1

E → A in AAB01380. Ref.2

Sequence conflict

571

1

D → N in AAB01380. Ref.2

Secondary structure

1

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572

Helix Strand Turn

Details...

Helix

16 – 20

5

Turn

22 – 24

3

Helix

27 – 29

3

Helix

32 – 37

6

Turn

41 – 43

3

Helix

51 – 64

14

Helix

68 – 81

14

Helix

83 – 91

9

Turn

95 – 97

3

Helix

98 – 101

4

Helix

105 – 111

7

Helix

113 – 116

4

Beta strand

122 – 126

5

Helix

127 – 129

3

Helix

133 – 137

5

Beta strand

147 – 151

5

Turn

157 – 159

3

Helix

163 – 167

5

Helix

168 – 181

14

Helix

185 – 187

3

Beta strand

188 – 194

7

Helix

200 – 204

5

Helix

218 – 236

19

Beta strand

241 – 244

4

Helix

249 – 259

11

Turn

260 – 262

3

Beta strand

263 – 267

5

Turn

268 – 270

3

Helix

271 – 288

18

Helix

292 – 294

3

Beta strand

297 – 301

5

Helix

304 – 320

17

Helix

324 – 328

5

Beta strand

331 – 335

5

Helix

351 – 354

4

Helix

364 – 371

8

Beta strand

374 – 378

5

Helix

388 – 397

10

Beta strand

402 – 405

4

Helix

410 – 412

3

Helix

417 – 423

7

Turn

424 – 426

3

Beta strand

429 – 434

6

Helix

454 – 456

3

Helix

458 – 468

11

Helix

475 – 487

13

Helix

491 – 495

5

Helix

503 – 505

3

Helix

506 – 523

18

Helix

536 – 542

7

Sequences

	Sequence		Length	Mass (Da)
	P48163-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: EA4C8CB36F6C619C	FASTA	572	64,150
	10 20 30 40 50 60 MEPEAPRRRH THQRGYLLTR NPHLNKDLAF TLEERQQLNI HGLLPPSFNS QEIQVLRVVK 70 80 90 100 110 120 NFEHLNSDFD RYLLLMDLQD RNEKLFYRVL TSDIEKFMPI VYTPTVGLAC QQYSLVFRKP 130 140 150 160 170 180 RGLFITIHDR GHIASVLNAW PEDVIKAIVV TDGERILGLG DLGCNGMGIP VGKLALYTAC 190 200 210 220 230 240 GGMNPQECLP VILDVGTENE ELLKDPLYIG LRQRRVRGSE YDDFLDEFME AVSSKYGMNC 250 260 270 280 290 300 LIQFEDFANV NAFRLLNKYR NQYCTFNDDI QGTASVAVAG LLAALRITKN KLSDQTILFQ 310 320 330 340 350 360 GAGEAALGIA HLIVMALEKE GLPKEKAIKK IWLVDSKGLI VKGRASLTQE KEKFAHEHEE 370 380 390 400 410 420 MKNLEAIVQE IKPTALIGVA AIGGAFSEQI LKDMAAFNER PIIFALSNPT SKAECSAEQC 430 440 450 460 470 480 YKITKGRAIF ASGSPFDPVT LPNGQTLYPG QGNNSYVFPG VALGVVACGL RQITDNIFLT 490 500 510 520 530 540 TAEVIAQQVS DKHLEEGRLY PPLNTIRDVS LKIAEKIVKD AYQEKTATVY PEPQNKEAFV 550 560 570 RSQMYSTDYD QILPDCYSWP EEVQKIQTKV DQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of cytosolic malic enzyme in human tumor cells." Loeber G., Dworkin M.B., Infante A., Ahorn H. FEBS Lett. 344:181-186(1994) [PubMed: 8187880] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: White adipose tissue.
[2]	"Cloning, sequencing and functional expression of a cDNA encoding a NADP-dependent malic enzyme from human liver." Gonzalez-Manchon C., Ferrer M., Ayuso M.S., Parrilla R. Gene 159:255-260(1995) [PubMed: 7622060] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Skin.
[6]	"Nonidentity of the cDNA sequence of human breast cancer cell malic enzyme to that from the normal human cell." Chou W.Y., Huang S.M., Chang G.G. J. Protein Chem. 15:273-279(1996) [PubMed: 8804575] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-572.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Crystal structure of a human malic enzyme." Structural genomics consortium (SGC) Submitted (MAR-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 15-555.
+	Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBLGenBankDDBJ

X77244 mRNA. Translation: CAA54460.1.
L34035 mRNA. Translation: AAB01380.1.
AK223417 mRNA. Translation: BAD97137.1.
AL391416, AL049699, AL136970 Genomic DNA. Translation: CAH73129.1.
AL049699, AL136970, AL391416 Genomic DNA. Translation: CAI22634.1.
AL136970, AL049699, AL391416 Genomic DNA. Translation: CAC19505.2.
BC025246 mRNA. Translation: AAH25246.1.
U43944 mRNA. Translation: AAC50613.1.

IPI

IPI00008215.

PIR

JC4160.
S44415.

RefSeq

NP_002386.1.

UniGene

Hs.21160

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AW5	X-ray	2.50	A/B/C	13-564	[»]

ModBase

Search...

2-D gel databases

REPRODUCTION-2DPAGE

IPI00008215.

Proteomic databases

PeptideAtlas

P48163.

PRIDE

P48163.

Genome annotation databases

Ensembl

ENSG00000065833. Homo sapiens. [Contig view]

GeneID

4199.

KEGG

hsa:4199.

Organism-specific databases

GeneCards

GC06M083977.

H-InvDB

HIX0019232.

HGNC

HGNC:6983. ME1.

HPA

HPA006493.

MIM

154250. gene.

PharmGKB

PA134904115.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P48163.

OMA

P48163. MEPEAPR.

Enzyme and pathway databases

BRENDA

1.1.1.40. 247.

Gene expression databases

ArrayExpress

P48163.

Bgee

P48163.

CleanEx

HS_ME1.

GermOnline

ENSG00000065833. Homo sapiens.

Family and domain databases

InterPro

IPR015884. Malic_enzyme_CS.
IPR012301. Malic_N.
IPR012302. Malic_NAD_bd.
IPR001891. Malic_OxRdtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Gene3D

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

Pfam

PF00390. malic. 1 hit.
PF03949. Malic_M. 1 hit.
[Graphical view]

PRINTS

PR00072. MALOXRDTASE.

PROSITE

PS00331. MALIC_ENZYMES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

16550.

SOURCE

Search...

Entry information

Entry name

MAOX_HUMAN

Accession

Primary (citable) accession number: P48163
Secondary accession number(s): Q16797 , Q16855, Q53F72, Q5VWA2, Q9BWX8, Q9H1W3, Q9UIY4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	June 16, 2009
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)