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Reviewed, UniProtKB/Swiss-Prot P05091 (ALDH2_HUMAN)

Last modified July 22, 2008. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Aldehyde dehydrogenase, mitochondrial
    EC=1.2.1.3
Alternative name(s):
    ALDH class 2
    ALDHI
    ALDH-E2
Gene names
Name: ALDH2
Synonyms: ALDM
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length517 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Catalytic activity

An aldehyde + NAD(+) + H(2)O = 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.

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.

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Ontologies

Keywords

   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DomainTransit peptide
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processalcohol metabolic process

Traceable author statement. Source: ProtInc

carbohydrate metabolic process

Traceable author statement. Source: ProtInc

   Molecular functionaldehyde 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...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Transit peptide1 – 1717Mitochondrion
Chain18 – 517500Aldehyde dehydrogenase, mitochondrial

Regions

Nucleotide binding262 – 2676NAD By similarity

Sites

Active site2851Proton acceptor
Active site3191Nucleophile
Site1861Transition state stabilizer

Amino acid modifications

Modified residue3681N6-acetyllysine By similarity

Natural variations

Natural variant3371E → V: dbSNP rs1062136.
Natural variant4961E → K in allele ALDH2*3.
Natural variant5041E → K in allele ALDH2*2; drastic reduction of enzyme activity. dbSNP rs671.

Experimental info

Sequence conflict7 – 126RFGPRL → ARAPP in CAA28990. Ref.1
Sequence conflict181S → A AA sequence Ref.8
Sequence conflict601S → F in CAG33272. Ref.6
Sequence conflict80 – 856VKAARA → REGRPG in CAA28990. Ref.1
Sequence conflict1011R → S in CAA28990. Ref.1
Sequence conflict1161R → Q in AAT41621. Ref.5
Sequence conflict2161L → S in AAA62825. Ref.13
Sequence conflict2181A → R in AAA62825. Ref.13
Sequence conflict2471A → P in AAA62825. Ref.13
Sequence conflict3621V → L in CAG33272. Ref.6
Sequence conflict3801E → Q in AAA51693. Ref.4

Secondary structure

1 .................................................................................. 517
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P05091-1 [UniParc].

Last modified January 1, 1990. Version 2.
Checksum: E8F74D44D285A00E

FASTA51756,381
        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

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References

« Hide '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 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]"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).
[16]"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.
[17]"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] [