Human Gene ALDH18A1 (ENST00000371224.7) from GENCODE V44
Description: Homo sapiens aldehyde dehydrogenase 18 family member A1 (ALDH18A1), transcript variant 1, mRNA. (from RefSeq NM_002860) RefSeq Summary (NM_002860): This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000371224.7 Gencode Gene: ENSG00000059573.9 Transcript (Including UTRs) Position: hg38 chr10:95,605,941-95,656,711 Size: 50,771 Total Exon Count: 18 Strand: - Coding Region Position: hg38 chr10:95,606,762-95,653,377 Size: 46,616 Coding Exon Count: 17
ID:P5CS_HUMAN DESCRIPTION: RecName: Full=Delta-1-pyrroline-5-carboxylate synthase; Short=P5CS; AltName: Full=Aldehyde dehydrogenase family 18 member A1; Includes: RecName: Full=Glutamate 5-kinase; Short=GK; EC=2.7.2.11; AltName: Full=Gamma-glutamyl kinase; Includes: RecName: Full=Gamma-glutamyl phosphate reductase; Short=GPR; EC=1.2.1.41; AltName: Full=Glutamate-5-semialdehyde dehydrogenase; AltName: Full=Glutamyl-gamma-semialdehyde dehydrogenase; FUNCTION: Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine. CATALYTIC ACTIVITY: ATP + L-glutamate = ADP + L-glutamate 5- phosphate. CATALYTIC ACTIVITY: L-glutamate 5-semialdehyde + phosphate + NADP(+) = L-glutamyl 5-phosphate + NADPH. ENZYME REGULATION: Isoform Short is inhibited by L-ornithine with a Ki of approximately 0.25 mm. Isoform Long is insensitive to ornithine inhibition. This is due to the two amino acid insert which abolishes feedback inhibition of P5CS activity by L- ornithine. PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L- glutamate 5-semialdehyde from L-glutamate: step 1/2. PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L- glutamate 5-semialdehyde from L-glutamate: step 2/2. SUBCELLULAR LOCATION: Mitochondrion inner membrane. DISEASE: Defects in ALDH18A1 are the cause of cutis laxa, autosomal recessive, type 3A (ARCL3A) [MIM:219150]. A syndrome characterized by facial dysmorphism with a progeroid appearance, large and late-closing fontanel, cutis laxa, joint hyperlaxity, athetoid movements and hyperreflexia, pre- and postnatal growth retardation, intellectual deficit, developmental delay, and ophthalmologic abnormalities. SIMILARITY: In the N-terminal section; belongs to the glutamate 5- kinase family. SIMILARITY: In the C-terminal section; belongs to the gamma- glutamyl phosphate reductase family. SEQUENCE CAUTION: Sequence=BAH12086.1; Type=Erroneous initiation; Sequence=BAH13064.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P54886
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0003723 RNA binding GO:0003824 catalytic activity GO:0004349 glutamate 5-kinase activity GO:0004350 glutamate-5-semialdehyde dehydrogenase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0016301 kinase activity GO:0016491 oxidoreductase activity GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor GO:0016740 transferase activity GO:0017084 delta1-pyrroline-5-carboxylate synthetase activity GO:0042802 identical protein binding
Biological Process: GO:0006536 glutamate metabolic process GO:0006561 proline biosynthetic process GO:0006592 ornithine biosynthetic process GO:0008152 metabolic process GO:0008652 cellular amino acid biosynthetic process GO:0016310 phosphorylation GO:0019240 citrulline biosynthetic process GO:0055114 oxidation-reduction process GO:0055129 L-proline biosynthetic process
US Server
