ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)

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ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)

Identity

HGNC (Hugo)	ALDH2
Location	12q24.2
Location_base_pair	Starts at 110688729 and ends at 110732167 bp from pter ( according to hg18-Mar_2006) [Mapping]

DNA/RNA

Description	ALDH2 gene spans 46031 base pairs (bp), consists of 13 exons and 12 introns and is located on the (+) DNA strand.
Transcription	The ALDH2 mRNA consists of 1989 base

Protein

Description	The ALDH2 protein is 517 amino acid long, has a molecular weight of 56 Kd, and forms a homotetramer.
Expression	ALDH2 is expressed in several human tissues with the highest levels found in liver. Screening of human cDNA libraries has revealed that ALDH2 transcripts are present in human liver, kidney, heart, stomach, colon, muscle, ovary, pancreas, lung, prostate, ear, eye, marrow, gall bladder, testis, thyroid, retina, adipose, adrenal gland, blood, brain, breast, placenta, uterus, B-cells, fetal brain, tonsil, foreskin, nervous normal and also in lung tumor, bladder tumor, nervous tumor.
Localisation	Mitochondrial matrix
Function	Conversion of aldehydes to acids via the reaction: ALDEHYDE + NAD + H2O = ACID + NADH
Homology	ALDH2 belongs to the aldehyde dehydrogenase gene superfamily .

Mutations

Germinal

One of the most studied polymorphism is a single base-pair mutation (1510 GÆA) in exon 12 of ALDH2 gene that causes an E487K substitution (ALDH2*2 allele), which results in catalytic inactivation of the enzyme. The ALDH2*2 allele is dominant negative and is responsible for acute alcohol intoxication due to accumulation of acetaldehyde. Facial flushing, nausea, dizziness and tachycardia characterize this alcohol intoxication. The ALDH2*2 allele is frequent in, but confined to Asian individuals, and it appears to be a determinant against alcoholism. On the other hand, alcohol-drinking individuals having the ALDH2*2 genotype are at substantially high risk of developing esophageal and upper aerodigestive tract cancers, head and neck cancers, colorectal cancer.

Implicated in

Entity	Uterine leiomyoma (uterine fibroids) --> HMGIC-ALDH2
Disease	Benign mesenchymal tumors
Prognosis	Good
Hybrid/Mutated Gene	The HMGIC-ALDH2 aberrant transcript contains complete exons 1-3 of HMGI-C and the epitopic sequence that includes complete exon 13 of the ALDH2 gene and part of the 3' untrasnlated region of this gene.
Abnormal Protein	The ALDH2 contributes 10 amino acids to the fusion HMGIC-ALDH2 protein.
Oncogenesis	HMGIC-ALDH2: it has been suggested that the truncation of HMGIC, rather than fusion may be responsible for tumorigenesis. The fusion of the 3' untranslated region of the ALDH2 may contribute to the stabilization of HMGIC mRNA.

External links

	Nomenclature
HGNC (Hugo)	ALDH2 404
Entrez_Gene (NCBI)	ALDH2 217 aldehyde dehydrogenase 2 family (mitochondrial)
	Cards
Atlas	ALDH2ID250
GeneCards (Weizmann)	ALDH2
Ensembl (Hinxton)	ENSG00000111275 [Gene_View] ALDH2 [Vega]
AceView (NCBI)	ALDH2
Genatlas (Paris)	ALDH2
euGene (Indiana)	217
SOURCE (Stanford)	NM_000690
Gene Expression (Array Express)	ENSG00000111275
	Genomic and cartography
GoldenPath (UCSC)	ALDH2 - 12q24.2 chr12:110688729-110732167 + 12q24.2 [Description] (hg18-Mar_2006)
Ensembl	ALDH2 - 12q24.2 [CytoView]
Mapping of homologs : NCBI	ALDH2 [Mapview]
OMIM	100650 610251
	Gene and transcription
Gene : Genbank (Entrez)	AK223373 AK301375 AK314856 AY621070 BC002967
Reference sequence (RefSeq transcript) :SRS	NM_000690
Reference transcript : Entrez	NM_000690
RefSeq genomic : SRS	AC_000055 AC_000144 NC_000012 NG_012250 NT_009775 NW_001838063 NW_925395
RefSeq genomic : Entrez	AC_000055 AC_000144 NC_000012 NG_012250 NT_009775 NW_001838063 NW_925395
Consensus coding sequences : CCDS NCBI	ALDH2
Cluster EST : Unigene	Hs.632733 [ SRS ] Hs.632733 [ NCBI ]
Alternative Splicing : Fast-db (Paris)	13453
	Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProt	P05091 (SRS) P05091 (Expasy) P05091 (Uniprot)
With graphics : InterPro	P05091
Splice isoforms : VarSplice FASTA	P05091(VarSplice FASTA)
Domaine pattern : Prosite (SRS)	ALDEHYDE_DEHYDR_CYS (PS00070) ALDEHYDE_DEHYDR_GLU (PS00687)
Domain pattern : Prosite (Expaxy)	ALDEHYDE_DEHYDR_CYS (PS00070) ALDEHYDE_DEHYDR_GLU (PS00687)
Domains : Interpro (SRS)	Ald_DH/histidinol_DH Ald_DH_CS Ald_DH_N Aldehyde_DH
Domains : Interpro (EBI)	Ald_DH/histidinol_DH Ald_DH_CS Ald_DH_N Aldehyde_DH
Related proteins : CluSTr	P05091
Domain families : Pfam SRS	Aldedh (PF00171)
Domain families : Pfam Sanger	Aldedh (PF00171)
Domain families : Pfam NCBI	pfam00171
Blocks (Seattle)	P05091
Crystal structure of protein : PDB SRS	1CW3 1NZW 1NZX 1NZZ 1O00 1O01 1O02 1O04 1O05 1ZUM 2ONM 2ONN 2ONO 2ONP 2VLE
Crystal structure of protein : PDBSum	1CW3 1NZW 1NZX 1NZZ 1O00 1O01 1O02 1O04 1O05 1ZUM 2ONM 2ONN 2ONO 2ONP 2VLE
Crystal structure of protein : IMB	1CW3 1NZW 1NZX 1NZZ 1O00 1O01 1O02 1O04 1O05 1ZUM 2ONM 2ONN 2ONO 2ONP 2VLE
Crystal structure of protein : PDB RSDB	1CW3 1NZW 1NZX 1NZZ 1O00 1O01 1O02 1O04 1O05 1ZUM 2ONM 2ONN 2ONO 2ONP 2VLE
HPRD	00003
	Protein Interaction databases
DIP (DOE-UCLA)	P05091
IntAct (EBI)	P05091
	Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBI	ALDH2
SNP : GeneSNP Utah	ALDH2
SNP : HGBase	ALDH2
Genetic variants : HAPMAP	ALDH2
Somatic Mutations in Cancer : COSMIC	ALDH2
Mutations and Diseases : HGMD	ALDH2
Hereditary diseases : OMIM	100650 610251
Hereditary diseases : GENETests	100650 610251
Diseases : Genetic Association	ALDH2
	General knowledge
Homologs : HomoloGene	ALDH2
Homology/Alignments : Family Browser UCSC	ALDH2
Phylogenetic Trees/Animal Genes : TreeFam	ALDH2
Catalytic activity : Enzyme	1.2.1.3 [ Enzyme-Expasy ] 1.2.1.3 [ Enzyme-SRS ] 1.2.1.3 [ IntEnz-EBI ] 1.2.1.3 [ BRENDA ] 1.2.1.3 [ KEGG ]
Chemical/Protein Interactions : CTD	217
Keywords Ontology : AmiGO	liver development aldehyde dehydrogenase (NAD) activity aldehyde dehydrogenase [NAD(P)+] activity mitochondrion mitochondrial matrix carbohydrate metabolic process alcohol metabolic process electron carrier activity oxidoreductase activity response to progesterone stimulus cellular response to hormone stimulus response to testosterone stimulus response to nicotine identical protein binding response to hyperoxia oxidation reduction
Keywords Ontology : EGO-EBI	liver development aldehyde dehydrogenase (NAD) activity aldehyde dehydrogenase [NAD(P)+] activity mitochondrion mitochondrial matrix carbohydrate metabolic process alcohol metabolic process electron carrier activity oxidoreductase activity response to progesterone stimulus cellular response to hormone stimulus response to testosterone stimulus response to nicotine identical protein binding response to hyperoxia oxidation reduction
Pathways : BIOCARTA
Pathways : KEGG	Glycolysis / Gluconeogenesis Ascorbate and aldarate metabolism Fatty acid metabolism Bile acid biosynthesis Valine, leucine and isoleucine degradation Lysine degradation Arginine and proline metabolism Histidine metabolism Tryptophan metabolism beta-Alanine metabolism Glycerolipid metabolism Pyruvate metabolism Propanoate metabolism Butanoate metabolism Limonene and pinene degradation
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probes : Imagenes	ALDH2 Related clones (RZPD - Berlin)
	Literature
PubMed	303 Pubmed reference(s) in Entrez
PubGene	ALDH2

Bibliography

Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.

Yoshida A, Ikawa M, Hsu LC, Tani K

Alcohol (Fayetteville, N.Y.). 1985 ; 2 (1) : 103-106.

PMID 4015823

Description of a novel fusion transcript between HMGI-C, a gene encoding for a member of the high mobility group proteins, and the mitochondrial aldehyde dehydrogenase gene.

Kazmierczak B, Hennig Y, Wanschura S, Rogalla P, Bartnitzke S, Van de Ven W, Bullerdiek J

Cancer research. 1995 ; 55 (24) : 6038-6039.

PMID 8521389

Investigation of genetic risk factors associated with alcoholism.

Harada S, Okubo T, Tsutsumi M, Takase S, Muramatsu T

Alcoholism, clinical and experimental research. 1996 ; 20 (9 Suppl) : 293A-296A.

PMID 8986225

Description of a novel fusion transcript between HMGI-C, a gene encoding for a member of the high mobility group proteins, and the mitochondrial aldehyde dehydrogenase gene.

Kazmierczak B, Hennig Y, Wanschura S, Rogalla P, Bartnitzke S, Van de Ven W, Bullerdiek J

Cancer research. 1995 ; 55 (24) : 6038-6039.

PMID 8521389

Effects of worldwide population subdivision on ALDH2 linkage disequilibrium.

Peterson RJ, Goldman D, Long JC

Genome research. 1999 ; 9 (9) : 844-852.

PMID 10508843

Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.

Murata M, Tagawa M, Watanabe S, Kimura H, Takeshita T, Morimoto K

Japanese journal of cancer research : Gann. 1999 ; 90 (7) : 711-719.

PMID 10470282

Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.

Muto M, Hitomi Y, Ohtsu A, Ebihara S, Yoshida S, Esumi H

Gut. 2000 ; 47 (2) : 256-261.

PMID 10896918

Polymorphisms of human aldehyde dehydrogenases. Consequences for drug metabolism and disease.

Vasiliou V, Pappa A

Pharmacology. 2000 ; 61 (3) : 192-198.

PMID 10971205

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	09-2001	Vasilis Vasiliou, Nickolas Sophos
		Molecular Toxicology University of Colorado Health Sciences Center (UCHSC) Dept. of Pharmaceutical Sciences, C-238 4200 East Ninth Avenue Denver, CO 80262, USA

Citation
This paper should be referenced as such :
Vasiliou V, Sophos N . ALDH2 aldehyde dehydrogenase 2 family (mitochondrial). Atlas Genet Cytogenet Oncol Haematol. September 2001 .
URL : http://AtlasGeneticsOncology.org/Genes/ALDH2ID250.html

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indexed on : Sat Feb 27 10:51:12 CET 2010

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