Reviewed, UniProtKB/Swiss-Prot P05091 (ALDH2_HUMAN)

Names and origin

Protein names

Recommended name:
    Aldehyde dehydrogenase, mitochondrial
    EC=1.2.1.3
Alternative name(s):
    ALDH class 2
    ALDHI
    ALDH-E2

Gene names

Name:	ALDH2
Synonyms:	ALDM

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	517 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	An aldehyde + NAD+ + H2O = an acid + NADH.
Pathway	Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion matrix.
Polymorphism	Allele ALDH2*2 is associated with a very high incidence of acute alcohol intoxication in Orientals and South American Indians, as compared to Caucasians.
Involvement in disease	Defects in ALDH2 are a cause of acute alcohol sensitivity [MIM:610251]. There are wide individual differences in responses to drinking alcohol. Recent estimates claim that subjective effects (how people feel when they drink) vary from 200%-300% in the adult population, and ethanol metabolism (how quickly alcohol is absorbed into the bloodstream and metabolized by the liver) varies by approximately 200%. Unfortunately, alcohol researchers know very little about why such drastic differences occur between individuals and how individual differences in alcohol sensitivity might link drinking behavior with problematic alcohol-related outcomes.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.
Sequence caution	The sequence AAA62825.1 differs from that shown. Reason: Frameshift at positions 424, 444, 448 and 461. The sequence CAA68290.1 differs from that shown. Reason: Frameshift at several positions. The sequence CAA68290.1 differs from that shown. Reason: Miscellaneous discrepancy.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	alcohol metabolic process Traceable author statement. Source: ProtInc carbohydrate metabolic process Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aldehyde dehydrogenase (NAD) activity Traceable author statement. Source: ProtInc aldehyde dehydrogenase [NAD(P)+] activity Traceable author statement. Source: ProtInc electron carrier activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 17

17

Mitochondrion Ref.8

Chain

18 – 517

500

Aldehyde dehydrogenase, mitochondrial

PRO_0000007168

Regions

Nucleotide binding

262 – 267

6

NAD By similarity

Sites

Active site

285

1

Proton acceptor

Active site

319

1

Nucleophile

Site

186

1

Transition state stabilizer

Amino acid modifications

Modified residue

368

1

N6-acetyllysine By similarity

Natural variations

Natural variant

337

1

E → V: dbSNP rs1062136. Ref.13

VAR_011869

Natural variant

496

1

E → K in allele ALDH2*3. Ref.18

VAR_011302

Natural variant

504

1

E → K in allele ALDH2*2; drastic reduction of enzyme activity. dbSNP rs671. Ref.17

VAR_002248

Experimental info

Sequence conflict

7 – 12

6

RFGPRL → ARAPP in CAA28990. Ref.1

Sequence conflict

18

1

S → A AA sequence Ref.8

Sequence conflict

60

1

S → F in CAG33272. Ref.6

Sequence conflict

80 – 85

6

VKAARA → REGRPG in CAA28990. Ref.1

Sequence conflict

101

1

R → S in CAA28990. Ref.1

Sequence conflict

116

1

R → Q in AAT41621. Ref.5

Sequence conflict

216

1

L → S in AAA62825. Ref.13

Sequence conflict

218

1

A → R in AAA62825. Ref.13

Sequence conflict

247

1

A → P in AAA62825. Ref.13

Sequence conflict

362

1

V → L in CAG33272. Ref.6

Sequence conflict

380

1

E → Q in AAA51693. Ref.4

Secondary structure

1

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517

Helix Strand Turn

Details...

Beta strand

38 – 41

4

Beta strand

44 – 46

3

Beta strand

53 – 57

5

Turn

59 – 61

3

Beta strand

64 – 69

6

Helix

73 – 86

14

Helix

92 – 95

4

Helix

98 – 114

17

Helix

116 – 127

12

Helix

131 – 136

6

Helix

138 – 152

15

Turn

153 – 155

3

Beta strand

158 – 161

4

Beta strand

164 – 175

12

Beta strand

178 – 182

5

Beta strand

185 – 187

3

Helix

188 – 201

14

Beta strand

205 – 209

5

Helix

216 – 228

13

Beta strand

234 – 237

4

Turn

242 – 244

3

Helix

245 – 250

6

Beta strand

257 – 262

6

Helix

264 – 276

13

Beta strand

281 – 285

5

Beta strand

290 – 294

5

Helix

300 – 312

13

Helix

313 – 316

4

Beta strand

322 – 328

7

Helix

329 – 345

17

Helix

364 – 379

16

Beta strand

383 – 386

4

Beta strand

393 – 396

4

Beta strand

401 – 405

5

Helix

411 – 414

4

Beta strand

419 – 427

9

Helix

430 – 438

9

Beta strand

444 – 449

6

Helix

453 – 462

10

Beta strand

465 – 471

7

Helix

486 – 488

3

Beta strand

489 – 491

3

Helix

496 – 502

7

Beta strand

503 – 511

9

Sequences

	Sequence		Length	Mass (Da)
	P05091-1 [UniParc]. Last modified January 1, 1990. Version 2. Checksum: E8F74D44D285A00E	FASTA	517	56,381
	10 20 30 40 50 60 MLRAAARFGP RLGRRLLSAA ATQAVPAPNQ QPEVFCNQIF INNEWHDAVS RKTFPTVNPS 70 80 90 100 110 120 TGEVICQVAE GDKEDVDKAV KAARAAFQLG SPWRRMDASH RGRLLNRLAD LIERDRTYLA 130 140 150 160 170 180 ALETLDNGKP YVISYLVDLD MVLKCLRYYA GWADKYHGKT IPIDGDFFSY TRHEPVGVCG 190 200 210 220 230 240 QIIPWNFPLL MQAWKLGPAL ATGNVVVMKV AEQTPLTALY VANLIKEAGF PPGVVNIVPG 250 260 270 280 290 300 FGPTAGAAIA SHEDVDKVAF TGSTEIGRVI QVAAGSSNLK RVTLELGGKS PNIIMSDADM 310 320 330 340 350 360 DWAVEQAHFA LFFNQGQCCC AGSRTFVQED IYDEFVERSV ARAKSRVVGN PFDSKTEQGP 370 380 390 400 410 420 QVDETQFKKI LGYINTGKQE GAKLLCGGGI AADRGYFIQP TVFGDVQDGM TIAKEEIFGP 430 440 450 460 470 480 VMQILKFKTI EEVVGRANNS TYGLAAAVFT KDLDKANYLS QALQAGTVWV NCYDVFGAQS 490 500 510 PFGGYKMSGS GRELGEYGLQ AYTEVKTVTV KVPQKNS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evidence for a signal peptide at the amino-terminal end of human mitochondrial aldehyde dehydrogenase." Braun T., Bober E., Singh S., Agarwal D.P., Goedde H.W. FEBS Lett. 215:233-236(1987) [PubMed: 3582651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Muscle.
[2]	Erratum Braun T., Bober E., Singh S., Agarwal D.P., Goedde H.W. FEBS Lett. 233:440-440(1988) Cited for: SEQUENCE REVISION TO N-TERMINUS.
[3]	"Isolation and sequence analysis of a full length cDNA clone coding for human mitochondrial aldehyde dehydrogenase." Braun T., Bober E., Singh S., Agarwal D.P., Goedde H.W. Nucleic Acids Res. 15:3179-3179(1987) [PubMed: 3562250] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Muscle.
[4]	"Genomic structure of the human mitochondrial aldehyde dehydrogenase gene." Hsu L.C., Bendel R.E., Yoshida A. Genomics 2:57-65(1988) [PubMed: 2838413] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Lassen N., Estey T., Vasiliou V. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lymph.
[8]	"Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations." Hempel J., Kaiser R., Joernvall H. Eur. J. Biochem. 153:13-28(1985) [PubMed: 4065146] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-517. Tissue: Liver.
[9]	"Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2." Hsu L.C., Tani K., Fujiyoshi T., Kurachi K., Yoshida A. Proc. Natl. Acad. Sci. U.S.A. 82:3771-3775(1985) [PubMed: 2987944] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 119-517. Tissue: Liver.
[10]	"Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases." Yoshida A., Ikawa M., Hsu L.C., Tani K. Alcohol 2:103-106(1985) [PubMed: 4015823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 119-517.
[11]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 160-172 AND 325-338, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[12]	"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes." Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V. Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 196-226 AND 325-338. Tissue: Adipocyte.
[13]	"Human aldehyde dehydrogenase isozymes and alcohol sensitivity." Agarwal D.P., Goedde H.W. Isozymes Curr. Top. Biol. Med. Res. 16:21-48(1987) [PubMed: 3610592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 214-500, VARIANT VAL-337. Tissue: Liver.
[14]	"Mitochondrial aldehyde dehydrogenase. Homology of putative targeting sequence to that of carbamyl phosphate synthetase I revealed by correlation of cDNA and protein data." Hempel J., Hoeoeg J.-O., Joernvall H. FEBS Lett. 222:95-98(1987) [PubMed: 3653404] [Abstract] Cited for: DESCRIPTION OF ORIGIN OF CONFLICTS BETWEEN THE SEQUENCE DESCRIBED IN PUBMED:4065146 AND DNA SEQUENCES.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms." Ni L., Zhou J., Hurley T.D., Weiner H. Protein Sci. 8:2784-2790(1999) [PubMed: 10631996] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS).
[17]	"Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals." Yoshida A., Huang I.-Y., Ikawa M. Proc. Natl. Acad. Sci. U.S.A. 81:258-261(1984) [PubMed: 6582480] [Abstract] Cited for: VARIANT LYS-504.
[18]	"Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations: detection of new ALDH2 alleles." Novoradovsky A., Tsai S.J., Goldfarb L., Peterson R., Long J.C., Goldman D. Alcohol. Clin. Exp. Res. 19:1105-1110(1995) [PubMed: 8561277] [Abstract] Cited for: VARIANT LYS-496.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

X05409 mRNA. Translation: CAA28990.1.
Y00109 mRNA. Translation: CAA68290.1. Sequence problems.
M20456 , M20444, M20445, M20446, M20447, M20448, M20449, M20450, M20451, M20452, M20453, M20454 Genomic DNA. Translation: AAA51693.1.
AY621070 mRNA. Translation: AAT41621.1.
CR456991 mRNA. Translation: CAG33272.1.
BC002967 mRNA. Translation: AAH02967.1.
BC071839 mRNA. Translation: AAH71839.1.
K03001 mRNA. Translation: AAB59500.1.
M26760 mRNA. Translation: AAA51694.1.
M54931 mRNA. Translation: AAA62825.1. Frameshift.

IPI

IPI00006663.

PIR

DEHUE2. A29975.

RefSeq

NP_000681.2.

UniGene

Hs.632733

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CW3	X-ray	2.58	A/B/C/D/E/F/G/H	24-517	[»]
1NZW	X-ray	2.65	A/B/C/D/E/F/G/H	18-517	[»]
1NZX	X-ray	2.45	A/B/C/D/E/F/G/H	18-517	[»]
1NZZ	X-ray	2.45	A/B/C/D/E/F/G/H	18-517	[»]
1O00	X-ray	2.60	A/B/C/D/E/F/G/H	18-517	[»]
1O01	X-ray	2.15	A/B/C/D/E/F/G/H	18-517	[»]
1O02	X-ray	1.90	A/B/C/D/E/F/G/H	18-517	[»]
1O04	X-ray	1.42	A/B/C/D/E/F/G/H	18-517	[»]
1O05	X-ray	2.25	A/B/C/D/E/F/G/H	18-517	[»]
1ZUM	X-ray	2.10	A/B/C/D/E/F/G/H/I/J/K/L	18-517	[»]
2ONM	X-ray	2.50	A/B/C/D/E/F/G/H/I/J/K/L	18-517	[»]
2ONN	X-ray	2.75	A/B/C/D/E/F/G/H	18-517	[»]
2ONO	X-ray	2.15	A/B/C/D/E/F/G/H	18-517	[»]
2ONP	X-ray	2.00	A/B/C/D/E/F/G/H	18-517	[»]
2VLE	X-ray	2.40	A/B/C/D/E/F/G/H	24-517	[»]

DisProt

DP00383.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05091. 8 interactions.

STRING

P05091.

PTM databases

PhosphoSite

P05091.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00006663.
P05091.

Proteomic databases

PeptideAtlas

P05091.

PRIDE

P05091.

Genome annotation databases

Ensembl

ENST00000261733; ENSP00000261733; ENSG00000111275; Homo sapiens. [Genome view]
ENST00000416293; ENSP00000403349; ENSG00000111275; Homo sapiens. [Genome view]

GeneID

217.

KEGG

hsa:217.

NMPDR

fig|9606.3.peg.8268.

UCSC

uc001tst.1. human.

Organism-specific databases

CTD

217.

GeneCards

GC12P110667.

H-InvDB

HIX0011002.

HGNC

HGNC:404. ALDH2.

MIM

100650. gene+phenotype.
610251. phenotype.

PharmGKB

PA24696.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P05091.

HOVERGEN

P05091.

OMA

PFDSQTE.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-39.

BRENDA

1.2.1.3. 247.

Reactome

REACT_13433. Biological oxidations.
REACT_13685. Synaptic Transmission.

Gene expression databases

ArrayExpress

P05091.

Bgee

P05091.

CleanEx

HS_ALDH2.

Genevestigator

P05091.

GermOnline

ENSG00000111275. Homo sapiens.

Family and domain databases

InterPro

IPR016160. Ald_DH_CS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH.
[Graphical view]

Gene3D

G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.

PANTHER

PTHR11699. Aldehyde_dehyd. 1 hit.

Pfam

PF00171. Aldedh. 1 hit.
[Graphical view]

PROSITE

PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00822. Disulfiram.
DB00536. Guanidine.
DB00157. NADH.
DB00727. Nitroglycerin.

NextBio

878.

SOURCE

Search...

Entry information

Entry name

ALDH2_HUMAN

Accession

Primary (citable) accession number: P05091
Secondary accession number(s): Q03639, Q6IB13, Q6IV71

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 1, 1990
Last modified:	November 3, 2009
This is version 137 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.