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ALDH1A1

ALDH Gene Record


Summary for ALDH1A1
Trivial Names & Synonyms
Database Accession ID's
Molecular Features
Polymorphisms
Substrates and Kinetic Values
Tissue Expression & Cellular Localization
Reference List

ALDH1A1

Summary for ALDH1A1:

The ALDH1A1 gene product is a cytosolic homo-tetramer (~55 kDa subunits) expressed in a number of tissues including brain, cornea, lens, retina, liver, and gastrointestinal tract (9723161) (11744377) (9973596) . ALDH1A1 is one of four known vertebrate retinaldehyde dehydrogenases and is often referred to in the literature as RALDH1 (1292933) retaining a high affinity for all-trans and 9-cis-retinaldehyde (Km < 0.1 umol/L) and acetaldehyde (Km ~ 50-100 umol/L) (1292933) .

The retinaldehyde dehydrogenases play a significant role in vertebrate embryogenesis. Retinoic acid (RA) is a low molecular weight (300 Da), lipophilic, rapidly-diffusing signaling molecule essential for growth and developmental processes in the embryo. It is produced in vivo via a two-step enzymatic pathway oxidizing retinols such as vitamin A (all-trans-retinol) by specific cytosolic alcohol or microsomal retinol dehydrogenases to retinaldehyde and then to retinoic acid by one of several cytosolic retinaldehyde dehydrogenases. ALDH1A1 was first shown to catalyze the irreversible oxidation of retinaldehyde to its carboxylic acid, retinoic acid (10880953) . Studies have been conducted to address the role of ALDH1A1 genes during organogenesis and embryonic development using transgenic and knockout animals (11744377) . These studies have shown that the pups are viable and may demonstrate redundancies in retinoic acid synthesis during development.

ALDH1A1\'s abundant expression in the mammalian cornea and lens categorizes it as a corneal crystalline based on the similarity in the level of expression to lens enzyme crystallins (9695791) (9599288) . Although the exact function of this enzyme in the cornea and lens remains a matter of controversy there is evidence that it may play a role in the development and/or maintenance of tissue transparency through its affects on light-scattering and absorption (9973596) as well as a metabolic role in mitigating the effects of oxidative stress (12941160) .

ALDH1A1 has been linked to drug resistance against oxazaphosphorines, including cyclophosphamide in various tumor types (7484368) (8124665) . Its over-expression in a number of cell lines and normal hematopoietic progenitor cells results in a significant increase in resistance to the active metabolites of cyclophosphamide (10773007) .

ALDH1A1 has been implicated in several alcohol-related phenotypes including alcoholism, alcohol-induced flushing and alcohol sensitivity. Acetaldehyde formed during ethanol metabolism is efficiently metabolized by ALDH1A1 to non-toxic metabolites. Due to the role of ALDH1A1 in acetaldehyde metabolism, ALDH1A1 inhibition by the anti-alcoholic medication, disulfiram (>90%) or low ALDH1A1 activity due to polymorphisms contribute to alcohol sensitivity and alcohol-induced flushing.

 
 

Trivial Names and Synonyms for ALDH1A1:

Acetaldehyde dehydrogenase 1,    ALDC,    ALDH, Liver cytosolic,    ALDH-E1,    ALDH1,    ALDH11,    ALHDII,    MGC2318,    PUMB1,    RALDH1 (Raldh1),    Retinal dehydrogenase 1
 
 

Database Accession ID's for ALDH1A1:

Species Gene-related Accession ID's Transcript-related Accession ID's Protein-related Accession ID's
Bos taurus
(Domestic cow)
Institute Database Accession No.
NCBIEntrez Gene281615
NCBIGenBankNC_007306
NCBIUniGene4732
Institute Database Accession No.
NCBIGenBankNM_174239
Institute Database Accession No.
NCBIGenBankNP_776664
EBI, SIB, PIRUniProtP48644
 
Species Gene-related Accession ID's Transcript-related Accession ID's Protein-related Accession ID's
Homo sapiens
(Human)
Institute Database Accession No.
NCBICCDS6644.1
NCBIEntrez Gene216
NCBIGenBankNC_000009
NCBIOMIM100640
NCBIUniGene76392
HUGOHGNC402
EBI, WTSIEnsembl - GeneViewENSG00000165092
Institute Database Accession No.
NCBIGenBankNM_000689
EBI, WTSIEnsembl - TransViewENST00000376939, ENST00000297785
Institute Database Accession No.
NCBIAceViewALDH1A1.dApr07, ALDH1A1.aApr07
NCBIEntrez ProteinNP_000680
EBI, WTSIEnsembl - ProtViewENSP00000366138, ENSP00000297785
EBI, SIB, PIRUniProtP00352
 
Species Gene-related Accession ID's Transcript-related Accession ID's Protein-related Accession ID's
Mus musculus
(House mouse)
Institute Database Accession No.
NCBIEntrez Gene11668
NCBIGenBankNC_000085
NCBIUniGene250866
JLMGI1353450
EBI, WTSIEnsembl - GeneViewENSMUSG00000053279
Institute Database Accession No.
NCBIGenBankNM_013467
EBI, WTSIEnsembl - TransViewENSMUST00000087638
Institute Database Accession No.
NCBIEntrez ProteinNP_038495
EBI, WTSIEnsembl - ProtViewENSMUSP00000084918, ENSMUSP00000066820
EBI, SIB, PIRUniProtP24549
 
Species Gene-related Accession ID's Transcript-related Accession ID's Protein-related Accession ID's
Rattus norvegicus
(Norway rat)
Institute Database Accession No.
NCBIEntrez Gene24188
NCBIGenBankNC_005100
NCBIUniGene6132
MCWRGD2087
EBI, WTSIEnsembl - GeneViewENSRNOG00000017619
Institute Database Accession No.
NCBIGenBankNM_022407
EBI, WTSIEnsembl - TransViewENSRNOT00000046103, ENSRNOT00000054788, ENSRNOT00000024000, ENSRNOT00000054789
Institute Database Accession No.
NCBIEntrez ProteinNP_071852
EBI, WTSIEnsembl - ProtViewENSRNOP00000048171, ENSRNOP00000024000
EBI, WTSIEnsembl - TransViewENSRNOP00000051673, ENSRNOP00000051672
EBI, SIB, PIRUniProtP51647
 
 
 

Molecular Features for ALDH1A1:

Species  
Bos taurus
(Domestic cow)
Chromosome Locus : 8 (- strand)
 

 
ALDH1A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH1A1_v1 :   13 Click Here for Bos taurus Transcript Sequences for Alternative Splice Variant 1
Click Here for Bos taurus Peptide Sequences for Alternative Splice Variant 1
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
NM_174239 2071 NP_776664 501 54834 Click Here for Graphical and Tabular Details

Transcript : The first 13 bases of this transcript are likely from the vector sequence as 12 or 13 are mismatches (SNPs).

SNP's : 17 single nucleotide polymorphism(s) identified

 
Species  
Homo sapiens
(Human)
Chromosome Locus : 9 q 21.13 (- strand)
 

 
ALDH1A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH1A1_v1 :   13 Click Here for Homo sapiens Transcript Sequences for Alternative Splice Variant 1
Click Here for Homo sapiens Peptide Sequences for Alternative Splice Variant 1
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENST00000297785 2095 ENSP00000297785 501 54862 6.7 Click Here for Graphical and Tabular Details

NM_000689 2116 NP_000680 501 54862 6.30 Click Here for Graphical and Tabular Details

ALDH1A1.aApr07 2099 ALDH1A1.aApr07 501 54862 6.30 Click Here for Graphical and Tabular Details

 
 
ALDH1A1_v2     (Alternative Splice Variant 2) Number of Exons for ALDH1A1_v2 :   8 Click Here for Homo sapiens Transcript Sequences for Alternative Splice Variant 2
Click Here for Homo sapiens Peptide Sequences for Alternative Splice Variant 2
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENST00000376939 822 ENSP00000366138 230 25314 6.27 Click Here for Graphical and Tabular Details

 
 
ALDH1A1_v3     (Alternative Splice Variant 3) Number of Exons for ALDH1A1_v3 :   7 Click Here for Homo sapiens Transcript Sequences for Alternative Splice Variant 3
Click Here for Homo sapiens Peptide Sequences for Alternative Splice Variant 3
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ALDH1A1.dApr07 957 ALDH1A1.dApr07 258 28221 5.85 Click Here for Graphical and Tabular Details

SNP's : 1 single nucleotide polymorphism(s) identified

 
Species  
Mus musculus
(House mouse)
Chromosome Locus : 19 12.0 cM (+ strand)
 

 
ALDH1A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH1A1_v1 :   13 Click Here for Mus musculus Transcript Sequences for Alternative Splice Variant 1
Click Here for Mus musculus Peptide Sequences for Alternative Splice Variant 1
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENSMUST00000087638 2032 ENSMUSP00000084918 501 54468 7.89 Click Here for Graphical and Tabular Details

NM_013467 2032 NP_038495 501 54468 7.91 Click Here for Graphical and Tabular Details

 
Species  
Rattus norvegicus
(Norway rat)
Chromosome Locus : 1 q 51 (+ strand)
 

 
ALDH1A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH1A1_v1 :   13 Click Here for Rattus norvegicus Transcript Sequences for Alternative Splice Variant 1
Click Here for Rattus norvegicus Peptide Sequences for Alternative Splice Variant 1
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENSRNOT00000024000 2013 ENSRNOP00000024000 501 54459 7.93 Click Here for Graphical and Tabular Details

NM_022407 2095 NP_071852 501 54459 7.94 Click Here for Graphical and Tabular Details

SNP's : 1 single nucleotide polymorphism(s) identified

 
 
ALDH1A1_v2     (Alternative Splice Variant 2) Number of Exons for ALDH1A1_v2 :   13 Click Here for Rattus norvegicus Transcript Sequences for Alternative Splice Variant 2
Click Here for Rattus norvegicus Peptide Sequences for Alternative Splice Variant 2
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENSRNOT00000054789 1506 ENSRNOP00000051673 501 54416 8.10 Click Here for Graphical and Tabular Details

Transcript : Transcript utilizes an alternate splice site at the 3 prime end of Exon 9 relative to the primary variant. The primary variant uses a -GC intron boundary on Intron 9 and the variant 2 uses an intron splice site 4 bases downstream -GT. However this transcript sequence has a 4 base deletion relative to the genomic sequence at the 5 prime end on the subseqent exon.

Peptide : This transcript sequence is missing 4 bases at the 5 prime end of Exon 10 near the intron-exon boundary. The transcript if derived from the genomic sequence would indicate an early termination signal where these bases are deleted from the transcript sequence.

Deletions : 4 base deletion(s) identified

 
 
ALDH1A1_v3     (Alternative Splice Variant 3) Number of Exons for ALDH1A1_v3 :   13 Click Here for Rattus norvegicus Transcript Sequences for Alternative Splice Variant 3
Click Here for Rattus norvegicus Peptide Sequences for Alternative Splice Variant 3
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENSRNOT00000046103 2101 ENSRNOP00000048171 503 54658 8.10 Click Here for Graphical and Tabular Details

Transcript : The sequence surrounding Exon 9 and 10 required manual alignment. The SAST algorithm was unable to appropriately align the sequence because there is either a 2 base deletion at the end of Exon 9 prior to the Intron 9 -GT sequence or Intron 9 uses an alternate end sequence to the typical AG- prior.

 
 
ALDH1A1_v4     (Alternative Splice Variant 4) Number of Exons for ALDH1A1_v4 :   7 Click Here for Rattus norvegicus Transcript Sequences for Alternative Splice Variant 4
Click Here for Rattus norvegicus Peptide Sequences for Alternative Splice Variant 4
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
ENSRNOT00000054788 699 ENSRNOP00000051672 233 25353 7.99 Click Here for Graphical and Tabular Details

 
 
 

Polymorphisms for ALDH1A1:

Currently Under Development
 
 

Substrates, Inhibitors and Enzyme Kinetics for ALDH1A1:

Species  
Oryctolagus cuniculus
(Rabbit)
Substrate [Substrate] Experimental Design Activity Km Vmax Kcat ALDG.ORG Curator Comments Pubmed ID
4-hydroxy-2-nonenal
System :Purified Recombinant Protein
 
Cofactor : NAD+
 
2 μM 12941160
  
Species  
Homo sapiens
(Human)
Substrate [Substrate] Experimental Design Activity Km Vmax Kcat ALDG.ORG Curator Comments Pubmed ID
4-hydroxy-2-nonenal
System :Purified Recombinant Protein
 
Cofactor : NAD+
 
18 μM 12941160
acetaldehyde
System :Purified Protein
 
Tissue Type :Cornea
 
Cofactor : NAD+
 
117 μM 0.27 9723161
Inhibitor : Disulfuram
System :Purified Protein
 
Tissue Type :Cornea
 
Cofactor : NAD+
 
Fully inhibited at 4.2 μM 9723161
malondialdehyde
System :Purified Protein
 
Tissue Type :Cornea
 
Cofactor : NAD+
 
15 μM 0.13 9723161
trans-2-hexanal
System :Purified Protein
 
Tissue Type :Cornea
 
Cofactor : NAD+
 
0.2 μM 0.20 9723161
  
 
 

Tissue Expression & Cellular Localization for ALDH1A1:

Currently Under Development
 
 

Reference List for ALDH1A1:

ALDH1A1 Year Authors Title Journal Pubmed ID
2008 Lassen, Black, Estey, Vasiliou
The role of corneal crystallins in the cellular defense mechanisms against oxidative stress. Semin Cell Dev Biol 18077195
 
2007 Lassen, Bateman, Estey, Kuszak, Nees, Piatigorsky, Duester, Day, Huang, Hines, Vasiliou
Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in aldh3a1(-/-)/aldh1a1(-/-) knockout mice. J Biol Chem 17567582
 
2003 Manzer, Qamar, Estey, Pappa, Petersen, Vasiliou
Molecular cloning and baculovirus expression of the rabbit corneal aldehyde dehydrogenase (ALDH1A1) cDNA DNA Cell Biol 12941160
 
2003 Fan, Molotkov, Manabe, Donmoyer, Deltour, Foglio, Cuenca, Blaner, Lipton, Duester
Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina. Mol Cell Biol 12808103
 
2002 Sládek, Kollander, Sreerama, Kiang
Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer chemotherapeutic regimens Cancer Chemother Pharmacol 11914911
 
2002 Niederreither, Fraulob, Garnier, Chambon, Dollé
Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse. Mech Dev 11744377
 
2001 Pappa, Sophos, Vasiliou
Corneal and stomach expression of aldehyde dehydrogenases: from fish to mammals Chem Biol Interact 11306042
 
2000 Reichard, Vasiliou, Petersen
Characterization of 4-hydroxy-2-nonenal metabolism in stellate cell lines derived from normal and cirrhotic rat liver Biochim Biophys Acta 11018474
 
2000 Duester
Families of retinoid dehydrogenases regulating vitamin A function: production of visual pigment and retinoic acid. Eur J Biochem 10880953
 
2000 Moreb, Maccow, Schweder, Hecomovich
Expression of antisense RNA to aldehyde dehydrogenase class-1 sensitizes tumor cells to 4-hydroperoxycyclophosphamide in vitro. J Pharmacol Exp Ther 10773007
 
1999 Jester, Moller-Pedersen, Huang, Sax, Kays, Cavangh, Petroll, Piatigorsky
The cellular basis of corneal transparency: evidence for corneal crystallins. J Cell Sci 9973596
 
1999 Haselbeck, Hoffmann, Duester
Distinct functions for Aldh1 and Raldh2 in the control of ligand production for embryonic retinoid signaling pathways. Dev Genet 10570467
 
1999 Niederreither, Subbarayan, Dollé, Chambon
Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet 10192400
 
1998 King, Holmes
Human ocular aldehyde dehydrogenase isozymes: distribution and properties as major soluble proteins in cornea and lens. J Exp Zool 9723161
 
1998 Piatigorsky
Gene sharing in lens and cornea: facts and implications. Prog Retin Eye Res 9695791
 
1998 Piatigorsky
Multifunctional lens crystallins and corneal enzymes. More than meets the eye. Ann N Y Acad Sci 9599288
 
1996 Stewart, Malek, Crabb
Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues. J Investig Med 8689400
 
1995 Agarwal, von Eitzen, Meier-Tackmann, Goedde
Metabolism of cyclophosphamide by aldehyde dehydrogenases. Adv Exp Med Biol 7484368
 
1994 von Eitzen, Meier-Tackmann, Agarwal, Goedde
Detoxification of cyclophosphamide by human aldehyde dehydrogenase isozymes. Cancer Lett 8124665
 
1992 Yoshida, Hsu, Davé
Retinal oxidation activity and biological role of human cytosolic aldehyde dehydrogenase. Enzyme 1292933
 
 
 

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