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ALDH18A1

ALDH Gene Record


Summary for ALDH18A1
Trivial Names & Synonyms
Database Accession ID's
Molecular Features
Polymorphisms
Substrates and Kinetic Values
Tissue Expression & Cellular Localization
Reference List

ALDH18A1

Summary for ALDH18A1:

The ALDH18A1 gene encodes for a bifunctional ATP- and NAD(P)H-dependent mitochondrial inner membrane enzyme (~87.1 kDa subunits) with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities (6933554) .

Traditionally known as Δ1-pyrroline-5-carboxylate synthetase, ALDH18A1 catalyzes the reduction of L-glutamate to Δ1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine.

Alternative splicing of ALDH18A1 generates two isoforms, a short and a long isoform that differ by a 2-amino acid insert at the N terminus of the gamma-glutamyl kinase active site (10037775) . The short isoform of ALDH18A1 has a high activity in the gut and catalyzes the essential step in arginine biosynthesis. It is inhibited by ornithine thereby providing a mechanism for the regulation of arginine synthesis. The long isoform is expressed in multiple tissues and is necessary for the synthesis of proline from glutamate. It is insensitive to ornithine inhibition (10037775) .

Individuals with an allelic variant in the ALDH18A1 gene (a G-to-A transition at position 251) exhibit hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and associated neurodegeneration, cataracts and connective tissue diseases secondary to the impaired functions of the long and short isoforms of the enzyme (11092761) .

 
 

Trivial Names and Synonyms for ALDH18A1:

Delta1-pyrroline-5-carboxylate synthetase,    Glutamate gamma-semialdehyde synthetase,    GSAS,    LOC361755 (rat),    MGC117316,    P5CS,    PYCS,    Pyrroline-5-carboxylate synthetase (glutamate gamma-semialdehyde synthetase)
 
 

Database Accession ID's for ALDH18A1:

Species Gene-related Accession ID's Transcript-related Accession ID's Protein-related Accession ID's
Homo sapiens
(Human)
Institute Database Accession No.
NCBICCDS7443.1
NCBIEntrez Gene5832
NCBIGenBankNC_000010
NCBIOMIM138250
NCBIUniGene500645
HUGOHGNC9722
EBI, WTSIEnsembl - GeneViewENSG00000059573
Institute Database Accession No.
NCBIGenBankNM_002860, NM_001017423
EBI, WTSIEnsembl - TransViewENST00000371224, ENST00000371221
Institute Database Accession No.
NCBIAceViewALDH18A1.aApr07, ALDH18A1.bApr07
NCBIEntrez ProteinNP_002851, NP_001017423
EBI, WTSIEnsembl - ProtViewENSP00000360268, ENSP00000360265
EBI, SIB, PIRUniProtQ5T566, Q3KQU2, Q5T567, P54886
 
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 Gene56454
NCBIGenBankNC_000085
NCBIUniGene233117
JLMGI1888908
EBI, WTSIEnsembl - GeneViewENSMUSG00000025007
Institute Database Accession No.
NCBIGenBankNM_019698, NM_153554
EBI, WTSIEnsembl - TransViewENSMUST00000025979
Institute Database Accession No.
NCBIEntrez ProteinNP_062672, NP_705782
EBI, WTSIEnsembl - ProtViewENSMUSP00000025979
EBI, SIB, PIRUniProtQ9Z110
 
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 Gene361755
NCBIGenBankNC_005100
NCBIUniGene3148
MCWRGD1311431
Institute Database Accession No.
NCBIGenBankNM_001108524
EBI, WTSIEnsembl - TransViewENSRNOT00000020940
Institute Database Accession No.
NCBIGenBankNP_001101994, XP_342049
EBI, WTSIEnsembl - TransViewENSRNOP00000020940
 
 
 

Molecular Features for ALDH18A1:

Species  
Homo sapiens
(Human)
Chromosome Locus : 10 q 24.3 (- strand)
 

 
ALDH18A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH18A1_v1 :   18 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
ENST00000371224 3462 ENSP00000360268 795 87303 7.13 Click Here for Graphical and Tabular Details

NM_002860 3470 NP_002851 795 87303 6.66 Click Here for Graphical and Tabular Details

ALDH18A1.aApr07 3659 ALDH18A1.aApr07 795 87303 6.66 Click Here for Graphical and Tabular Details

 
 
ALDH18A1_v2     (Alternative Splice Variant 2) Number of Exons for ALDH18A1_v2 :   18 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
ENST00000371221 3456 ENSP00000360265 793 87089 7.13 Click Here for Graphical and Tabular Details

NM_001017423 3464 NP_001017423 793 87089 6.66 Click Here for Graphical and Tabular Details

ALDH18A1.bApr07 3462 ALDH18A1.bApr07 793 87089 6.66 Click Here for Graphical and Tabular Details

 
Species  
Mus musculus
(House mouse)
Chromosome Locus : 19 3 C (- strand)
 

 
ALDH18A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH18A1_v1 :   19 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
ENSMUST00000025979 3445 ENSMUSP00000025979 795 87267 7.59 Click Here for Graphical and Tabular Details

 
 
ALDH18A1_v?     (Alternative Splice Variant Unknown or To Be Determined) Number of Exons : N/A Click Here for Mus musculus Transcript Sequences for Unknown Variants
Click Here for Mus musculus Peptide Sequences for Unknown Variants
Transcript Length
(b.p.'s)
Peptide Translation Length
(a.a.'s)
M.W.
(Da)
Isoelectric Point Comments
NM_019698 3448 NP_062672 795 87297 Click Here for Graphical and Tabular Details

Transcript : The transcript sequence does not align with the genomic sequence due to numerous SNPs, Insertions and Deletions. Further analysis is required for exon structure and sequence integrity.

NM_153554 3442 NP_705782 793 87084 Click Here for Graphical and Tabular Details

Transcript : The transcript sequence does not align to the genomic sequence (NCBI Accession NC_000085) due to multiple SNPs, insertions and deletions. Further analysis is required for exon structure and sequence integrity.

 
Species  
Rattus norvegicus
(Norway rat)
Chromosome Locus : 1 q 54 (- strand)
 

 
ALDH18A1_v1     (Alternative Splice Variant 1) Number of Exons for ALDH18A1_v1 :   17 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
ENSRNOT00000020940 2388 ENSRNOP00000020940 795 87330 7.60 Click Here for Graphical and Tabular Details

 
 
ALDH18A1_v2     (Alternative Splice Variant 2) Number of Exons for ALDH18A1_v2 :   19 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
NM_001108524 3454 NP_001101994 795 87330 7.20 Click Here for Graphical and Tabular Details

Transcript : Intron 2 begins with an -ATCAT rather then the usual -GT that most introns begin with. The segment require manual alignment due to this anomaly.

 
 
 

Polymorphisms for ALDH18A1:

Currently Under Development
 
 

Substrates, Inhibitors and Enzyme Kinetics for ALDH18A1:

 
 

Tissue Expression & Cellular Localization for ALDH18A1:

Currently Under Development
 
 

Reference List for ALDH18A1:

ALDH18A1 Year Authors Title Journal Pubmed ID
2000 Baumgartner, Hu, Almashanu, Steel, Obie, Aral, Rabier, Kamoun, Saudubray, Valle
Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Hum Mol Genet 11092761
 
1999 Hu, Lin, Obie, Valle
Molecular enzymology of mammalian Delta1-pyrroline-5-carboxylate synthase. Alternative splice donor utilization generates isoforms with different sensitivity to ornithine inhibition. J Biol Chem 10037775
 
1980 Smith, Downing, Phang, Lodato, Aoki
Pyrroline-5-carboxylate synthase activity in mammalian cells. Proc Natl Acad Sci U S A 6933554
 
 
 

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