UniProt functional annotation for P49419



	UniProt functional annotation for P49419

UniProt code: P49419.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:20207735}.

Catalytic activity: Reaction=(S)-2-amino-6-oxohexanoate + H2O + NADP(+) = 2 H(+) + L-2- aminoadipate + NADPH; Xref=Rhea:RHEA:12304, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58321, ChEBI:CHEBI:58349, ChEBI:CHEBI:58672; EC=1.2.1.31;

Catalytic activity: Reaction=(S)-2-amino-6-oxohexanoate + H2O + NAD(+) = 2 H(+) + L-2- aminoadipate + NADH; Xref=Rhea:RHEA:12308, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58321, ChEBI:CHEBI:58672; EC=1.2.1.31;

Catalytic activity: Reaction=betaine aldehyde + H2O + NAD(+) = glycine betaine + 2 H(+) + NADH; Xref=Rhea:RHEA:15305, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15710, ChEBI:CHEBI:17750, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.8;

Catalytic activity: Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH; Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.3;

Biophysicochemical properties: Kinetic parameters: KM=28.5 uM for nonanal {ECO:0000269|PubMed:20207735}; KM=5.3 uM for trans-2-nonenal {ECO:0000269|PubMed:20207735}; KM=39.1 uM for hexanal {ECO:0000269|PubMed:20207735}; KM=17.5 uM for octanal {ECO:0000269|PubMed:20207735}; KM=41.1 uM for betaine aldehyde {ECO:0000269|PubMed:20207735}; KM=169 uM for L-2-aminoadipate 6-semialdehyde {ECO:0000269|PubMed:20207735}; KM=530.2 uM for benzaldehyde {ECO:0000269|PubMed:20207735}; KM=647.4 uM for propanal {ECO:0000269|PubMed:20207735}; KM=7374.3 uM for glyceraldehyde {ECO:0000269|PubMed:20207735}; Vmax=364.9 nmol/min/mg enzyme toward nonanal {ECO:0000269|PubMed:20207735}; Vmax=34.9 nmol/min/mg enzyme toward trans-2-nonenal {ECO:0000269|PubMed:20207735}; Vmax=243.3 nmol/min/mg enzyme toward hexanal {ECO:0000269|PubMed:20207735}; Vmax=72.3 nmol/min/mg enzyme toward octanal {ECO:0000269|PubMed:20207735}; Vmax=101.4 nmol/min/mg enzyme toward betaine aldehyde {ECO:0000269|PubMed:20207735}; Vmax=276.2 nmol/min/mg enzyme toward L-2-aminoadipate 6-semialdehyde {ECO:0000269|PubMed:20207735}; Vmax=125.2 nmol/min/mg enzyme toward benzaldehyde {ECO:0000269|PubMed:20207735}; Vmax=69.9 nmol/min/mg enzyme toward propanal {ECO:0000269|PubMed:20207735}; Vmax=174 nmol/min/mg enzyme toward glyceraldehyde {ECO:0000269|PubMed:20207735};

Pathway: Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine from betaine aldehyde: step 1/1.

Subunit: Homotetramer. {ECO:0000250}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:20207735}. Nucleus {ECO:0000269|PubMed:20207735}.

Subcellular location: [Isoform 1]: Mitochondrion {ECO:0000269|PubMed:20207735}.

Tissue specificity: Abundant in hepatoma cells and fetal cochlea, ovary, eye, heart, adrenal gland, liver and kidney. Low levels present in adult peripheral blood leukocytes and fetal brain, thymus, spleen, skeletal muscle, lung and tongue. {ECO:0000269|PubMed:8088832, ECO:0000269|PubMed:9417906}.

Disease: Pyridoxine-dependent epilepsy (PDE) [MIM:266100]: Characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:17068770}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the aldehyde dehydrogenase family. {ECO:0000305}.

Sequence caution: Sequence=AAC51935.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAH02515.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH71712.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH73174.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG35366.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG58439.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; Sequence=BAG59812.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269\|PubMed:16491085, ECO:0000269\|PubMed:20207735}.


Catalytic activity:		Reaction=(S)-2-amino-6-oxohexanoate + H2O + NADP(+) = 2 H(+) + L-2- aminoadipate + NADPH; Xref=Rhea:RHEA:12304, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58321, ChEBI:CHEBI:58349, ChEBI:CHEBI:58672; EC=1.2.1.31;
Catalytic activity:		Reaction=(S)-2-amino-6-oxohexanoate + H2O + NAD(+) = 2 H(+) + L-2- aminoadipate + NADH; Xref=Rhea:RHEA:12308, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58321, ChEBI:CHEBI:58672; EC=1.2.1.31;
Catalytic activity:		Reaction=betaine aldehyde + H2O + NAD(+) = glycine betaine + 2 H(+) + NADH; Xref=Rhea:RHEA:15305, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15710, ChEBI:CHEBI:17750, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.8;
Catalytic activity:		Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH; Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.3;
Biophysicochemical properties:		Kinetic parameters: KM=28.5 uM for nonanal {ECO:0000269\|PubMed:20207735}; KM=5.3 uM for trans-2-nonenal {ECO:0000269\|PubMed:20207735}; KM=39.1 uM for hexanal {ECO:0000269\|PubMed:20207735}; KM=17.5 uM for octanal {ECO:0000269\|PubMed:20207735}; KM=41.1 uM for betaine aldehyde {ECO:0000269\|PubMed:20207735}; KM=169 uM for L-2-aminoadipate 6-semialdehyde {ECO:0000269\|PubMed:20207735}; KM=530.2 uM for benzaldehyde {ECO:0000269\|PubMed:20207735}; KM=647.4 uM for propanal {ECO:0000269\|PubMed:20207735}; KM=7374.3 uM for glyceraldehyde {ECO:0000269\|PubMed:20207735}; Vmax=364.9 nmol/min/mg enzyme toward nonanal {ECO:0000269\|PubMed:20207735}; Vmax=34.9 nmol/min/mg enzyme toward trans-2-nonenal {ECO:0000269\|PubMed:20207735}; Vmax=243.3 nmol/min/mg enzyme toward hexanal {ECO:0000269\|PubMed:20207735}; Vmax=72.3 nmol/min/mg enzyme toward octanal {ECO:0000269\|PubMed:20207735}; Vmax=101.4 nmol/min/mg enzyme toward betaine aldehyde {ECO:0000269\|PubMed:20207735}; Vmax=276.2 nmol/min/mg enzyme toward L-2-aminoadipate 6-semialdehyde {ECO:0000269\|PubMed:20207735}; Vmax=125.2 nmol/min/mg enzyme toward benzaldehyde {ECO:0000269\|PubMed:20207735}; Vmax=69.9 nmol/min/mg enzyme toward propanal {ECO:0000269\|PubMed:20207735}; Vmax=174 nmol/min/mg enzyme toward glyceraldehyde {ECO:0000269\|PubMed:20207735};
Pathway:		Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine from betaine aldehyde: step 1/1.
Subunit:		Homotetramer. {ECO:0000250}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:20207735}. Nucleus {ECO:0000269\|PubMed:20207735}.
Subcellular location:		[Isoform 1]: Mitochondrion {ECO:0000269\|PubMed:20207735}.
Tissue specificity:		Abundant in hepatoma cells and fetal cochlea, ovary, eye, heart, adrenal gland, liver and kidney. Low levels present in adult peripheral blood leukocytes and fetal brain, thymus, spleen, skeletal muscle, lung and tongue. {ECO:0000269\|PubMed:8088832, ECO:0000269\|PubMed:9417906}.
Disease:		Pyridoxine-dependent epilepsy (PDE) [MIM:266100]: Characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride. {ECO:0000269\|PubMed:16491085, ECO:0000269\|PubMed:17068770}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the aldehyde dehydrogenase family. {ECO:0000305}.
Sequence caution:		Sequence=AAC51935.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAH02515.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH71712.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH73174.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG35366.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG58439.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; Sequence=BAG59812.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};