P49419 · AL7A1_HUMAN
- ProteinAlpha-aminoadipic semialdehyde dehydrogenase
- GeneALDH7A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids539 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
Catalytic activity
- H2O + NAD+ + nonanal = 2 H+ + NADH + nonanoateThis reaction proceeds in the forward direction.
- H2O + hexanal + NAD+ = 2 H+ + hexanoate + NADHThis reaction proceeds in the forward direction.
- H2O + NAD+ + octanal = 2 H+ + NADH + octanoateThis reaction proceeds in the forward direction.
- (E)-non-2-enal + H2O + NAD+ = (E)-non-2-enoate + 2 H+ + NADHThis reaction proceeds in the forward direction.
- (E)-4-hydroxynon-2-enal + H2O + NAD+ = (E)-4-hydroxynon-2-enoate + 2 H+ + NADHThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
28.5 μM | nonanal | |||||
5.3 μM | trans-2-nonenal | |||||
39.1 μM | hexanal | |||||
17.5 μM | octanal | |||||
41.1 μM | betaine aldehyde | |||||
169 μM | L-2-aminoadipate 6-semialdehyde | |||||
530.2 μM | benzaldehyde | |||||
647.4 μM | propanal | |||||
7374.3 μM | glyceraldehyde | |||||
119.5 μM | (E)-4-hydroxynon-2-enal |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
364.9 nmol/min/mg | toward nonanal | ||||
323.5 nM/min/mg | toward (E)-4-hydroxynon-2-enal | ||||
34.9 nmol/min/mg | toward trans-2-nonenal | ||||
243.3 nmol/min/mg | toward hexanal | ||||
72.3 nmol/min/mg | toward octanal | ||||
101.4 nmol/min/mg | toward betaine aldehyde | ||||
276.2 nmol/min/mg | toward L-2-aminoadipate 6-semialdehyde | ||||
125.2 nmol/min/mg | toward benzaldehyde | ||||
69.9 nmol/min/mg | toward propanal | ||||
174 nmol/min/mg | toward glyceraldehyde |
Pathway
Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine from betaine aldehyde: step 1/1.
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 192-194 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: TAF | ||||||
Site | 195 | Transition state stabilizer | ||||
Sequence: N | ||||||
Binding site | 218 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 258-259 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: GT | ||||||
Binding site | 274-275 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: GS | ||||||
Active site | 296 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 296-297 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: EL | ||||||
Active site | 330 | Nucleophile | ||||
Sequence: C | ||||||
Binding site | 331 | (S)-2-amino-6-oxohexanoate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 427 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 489 | (S)-2-amino-6-oxohexanoate (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 490 | (S)-2-amino-6-oxohexanoate (UniProtKB | ChEBI) | ||||
Sequence: A |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Cellular Component | nucleus | |
Molecular Function | aldehyde dehydrogenase (NAD+) activity | |
Molecular Function | betaine-aldehyde dehydrogenase activity | |
Molecular Function | glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity | |
Molecular Function | identical protein binding | |
Molecular Function | L-aminoadipate-semialdehyde dehydrogenase activity | |
Biological Process | cellular aldehyde metabolic process | |
Biological Process | choline catabolic process | |
Biological Process | glycine betaine biosynthetic process from choline | |
Biological Process | sensory perception of sound |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAlpha-aminoadipic semialdehyde dehydrogenase
- EC number
- Short namesAlpha-AASA dehydrogenase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP49419
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 2
Isoform 1
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Epilepsy, early-onset, 4, vitamin B6-dependent (EPEO4)
- Note
- DescriptionAn autosomal recessive neurologic disorder ocharacterized 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.
- See alsoMIM:266100
Natural variants in EPEO4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085776 | 110-539 | missing | in EPEO4; loss of alpha-AASA dehydrogenase activity | |
VAR_031718 | 199 | A>V | in EPEO4; loss of alpha-AASA dehydrogenase activity; dbSNP:rs121912709 | |
VAR_069184 | 202 | G>V | in EPEO4 | |
VAR_069185 | 291 | G>E | in EPEO4 | |
VAR_069186 | 301 | N>I | in EPEO4; dbSNP:rs121912711 | |
VAR_069187 | 335 | R>Q | in EPEO4; dbSNP:rs754449549 | |
VAR_069188 | 395 | V>G | in EPEO4 | |
VAR_031719 | 427 | E>Q | in EPEO4; loss of alpha-AASA dehydrogenase activity; dbSNP:rs121912707 | |
VAR_069189 | 458 | S>N | in EPEO4 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_085776 | 110-539 | in EPEO4; loss of alpha-AASA dehydrogenase activity | |||
Sequence: Missing | ||||||
Natural variant | VAR_031718 | 199 | in EPEO4; loss of alpha-AASA dehydrogenase activity; dbSNP:rs121912709 | |||
Sequence: A → V | ||||||
Natural variant | VAR_069184 | 202 | in EPEO4 | |||
Sequence: G → V | ||||||
Natural variant | VAR_069185 | 291 | in EPEO4 | |||
Sequence: G → E | ||||||
Natural variant | VAR_069186 | 301 | in EPEO4; dbSNP:rs121912711 | |||
Sequence: N → I | ||||||
Natural variant | VAR_069187 | 335 | in EPEO4; dbSNP:rs754449549 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_069188 | 395 | in EPEO4 | |||
Sequence: V → G | ||||||
Natural variant | VAR_028202 | 412 | in dbSNP:rs2306618 | |||
Sequence: T → A | ||||||
Natural variant | VAR_031719 | 427 | in EPEO4; loss of alpha-AASA dehydrogenase activity; dbSNP:rs121912707 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_028203 | 439 | in dbSNP:rs12514417 | |||
Sequence: K → Q | ||||||
Natural variant | VAR_069189 | 458 | in EPEO4 | |||
Sequence: S → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 704 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, transit peptide, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | In isoform P49419-2; Removed | ||||
Sequence: M | |||||||
Transit peptide | 1-26 | UniProt | Mitochondrion | ||||
Sequence: MWRLPRALCVHAAKTSKLSGPWSRPA | |||||||
Modified residue | 2 | UniProt | In isoform P49419-2; N-acetylserine | ||||
Sequence: W | |||||||
Chain | PRO_0000056490 | 27-539 | UniProt | Alpha-aminoadipic semialdehyde dehydrogenase | |||
Sequence: AFMSTLLINQPQYAWLKELGLREENEGVYNGSWGGRGEVITTYCPANNEPIARVRQASVADYEETVKKAREAWKIWADIPAPKRGEIVRQIGDALREKIQVLGSLVSLEMGKILVEGVGEVQEYVDICDYAVGLSRMIGGPILPSERSGHALIEQWNPVGLVGIITAFNFPVAVYGWNNAIAMICGNVCLWKGAPTTSLISVAVTKIIAKVLEDNKLPGAICSLTCGGADIGTAMAKDERVNLLSFTGSTQVGKQVGLMVQERFGRSLLELGGNNAIIAFEDADLSLVVPSALFAAVGTAGQRCTTARRLFIHESIHDEVVNRLKKAYAQIRVGNPWDPNVLYGPLHTKQAVSMFLGAVEEAKKEGGTVVYGGKVMDRPGNYVEPTIVTGLGHDASIAHTETFAPILYVFKFKNEEEVFAWNNEVKQGLSSSIFTKDLGRIFRWLGPKGSDCGIVNVNIPTSGAEIGGAFGGEKHTGGGRESGSDAWKQYMRRSTCTINYSKDLPLAQGIKFQ | |||||||
Modified residue (large scale data) | 84 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 94 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 94 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 462 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 500 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 516 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 520 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 526 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 537 | UniProt | N6-succinyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homotetramer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P49419 | EPS8 Q12929 | 2 | EBI-726842, EBI-375576 | |
BINARY | P49419-2 | ALDH7A1 P49419-2 | 3 | EBI-11107920, EBI-11107920 | |
BINARY | P49419-2 | LCN2 P80188 | 3 | EBI-11107920, EBI-11911016 | |
BINARY | P49419-2 | MYG1 Q9HB07 | 3 | EBI-11107920, EBI-709754 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
P49419-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymshALDH7A1_v1
- Length539
- Mass (Da)58,487
- Last updated2010-04-20 v5
- Checksum05385562F71312B6
P49419-2
- Name2
- SynonymshALDH7A1_v2
- Differences from canonical
- 1-28: Missing
P49419-4
- Name4
- Differences from canonical
- 337-400: Missing
Computationally mapped potential isoform sequences
There are 17 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F8WD33 | F8WD33_HUMAN | ALDH7A1 | 97 | ||
F8WDY6 | F8WDY6_HUMAN | ALDH7A1 | 136 | ||
H0YHM6 | H0YHM6_HUMAN | ALDH7A1 | 239 | ||
F8VVF2 | F8VVF2_HUMAN | ALDH7A1 | 193 | ||
A0A1B0GV49 | A0A1B0GV49_HUMAN | ALDH7A1 | 472 | ||
A0A1B0GUY0 | A0A1B0GUY0_HUMAN | ALDH7A1 | 348 | ||
A0A1B0GUA1 | A0A1B0GUA1_HUMAN | ALDH7A1 | 521 | ||
A0A1B0GTY9 | A0A1B0GTY9_HUMAN | ALDH7A1 | 479 | ||
A0A1B0GTJ4 | A0A1B0GTJ4_HUMAN | ALDH7A1 | 499 | ||
A0A1B0GTG2 | A0A1B0GTG2_HUMAN | ALDH7A1 | 536 | ||
A0A1B0GW77 | A0A1B0GW77_HUMAN | ALDH7A1 | 554 | ||
A0A1B0GW82 | A0A1B0GW82_HUMAN | ALDH7A1 | 545 | ||
A0A1B0GW65 | A0A1B0GW65_HUMAN | ALDH7A1 | 77 | ||
A0A1B0GVU0 | A0A1B0GVU0_HUMAN | ALDH7A1 | 164 | ||
A0A0J9YWF7 | A0A0J9YWF7_HUMAN | ALDH7A1 | 294 | ||
A0A0J9YWK1 | A0A0J9YWK1_HUMAN | ALDH7A1 | 27 | ||
A0A0J9YWM6 | A0A0J9YWM6_HUMAN | ALDH7A1 | 41 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S74728 EMBL· GenBank· DDBJ | AAB31966.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312459 EMBL· GenBank· DDBJ | BAG35366.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK295526 EMBL· GenBank· DDBJ | BAG58439.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AK297365 EMBL· GenBank· DDBJ | BAG59812.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AC093535 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC099513 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC002515 EMBL· GenBank· DDBJ | AAH02515.3 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC071712 EMBL· GenBank· DDBJ | AAH71712.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC073174 EMBL· GenBank· DDBJ | AAH73174.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF002696 EMBL· GenBank· DDBJ | AAC51935.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. |