Q96NR8 · RDH12_HUMAN
- ProteinRetinol dehydrogenase 12
- GeneRDH12
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids316 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Retinoids dehydrogenase/reductase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinal. Shows very weak activity towards 13-cis-retinol (PubMed:12226107, PubMed:15865448).
Also exhibits activity, albeit with lower affinity than for retinaldehydes, towards lipid peroxidation products (C9 aldehydes) such as 4-hydroxynonenal and trans-2-nonenal (PubMed:15865448, PubMed:19686838).
May play an important function in photoreceptor cells to detoxify 4-hydroxynonenal and potentially other toxic aldehyde products resulting from lipid peroxidation (PubMed:19686838).
Has no dehydrogenase activity towards steroids (PubMed:12226107, PubMed:15865448).
Also exhibits activity, albeit with lower affinity than for retinaldehydes, towards lipid peroxidation products (C9 aldehydes) such as 4-hydroxynonenal and trans-2-nonenal (PubMed:15865448, PubMed:19686838).
May play an important function in photoreceptor cells to detoxify 4-hydroxynonenal and potentially other toxic aldehyde products resulting from lipid peroxidation (PubMed:19686838).
Has no dehydrogenase activity towards steroids (PubMed:12226107, PubMed:15865448).
Miscellaneous
Shows clear specificity for the pro-S hydrogen on C4 of NADPH and the pro-R hydrogen on C15 of retinols.
Catalytic activity
- all-trans-retinol + NADP+ = all-trans-retinal + H+ + NADPH
- 11-cis-retinol + NADP+ = 11-cis-retinal + H+ + NADPH
- 9-cis-retinol + NADP+ = 9-cis-retinal + H+ + NADPH
- a 4-hydroxynonen-1-ol + NADP+ = a 4-hydroxynonenal + H+ + NADPH
- (E)-non-2-en-1-ol + NADP+ = (E)-non-2-enal + H+ + NADPH
- (Z)-non-6-en-1-ol + NADP+ = (Z)-non-6-enal + H+ + NADPH
- NADP+ + nonan-1-ol = H+ + NADPH + nonanal
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
1.2 μM | NADPH | |||||
2200 μM | NADH | |||||
0.04 μM | all-trans-retinal | |||||
0.1 μM | 11-cis-retinal | |||||
0.14 μM | 9-cis-retinal | |||||
0.16 μM | 11-cis-retinol | |||||
0.16 μM | 9-cis-retinol | |||||
0.4 μM | all-trans-retinol | |||||
3.1 μM | nonanal | |||||
20 μM | (E)-non-2-enal | |||||
1 μM | (Z)-non-6-enal |
kcat is 36 min-1 for all-trans-retinal as substrate. kcat is 45 min-1 for 11-cis-retinal as substrate. kcat is 14 min-1 for 9-cis-retinal as substrate. kcat is 27 min-1 for all-trans-retinol as substrate. kcat is 7 min-1 for 11-cis-retinol as substrate. kcat is 7 min-1 for 9-cis-retinol as substrate. kcat is 56 min-1 for nonanal as substrate. kcat is 45 min-1 for (Z)-non-6-enal as substrate. kcat is 28 min-1 for (E)-non-2-enal.
Pathway
Cofactor metabolism; retinol metabolism.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | photoreceptor inner segment | |
Cellular Component | photoreceptor inner segment membrane | |
Molecular Function | 11-cis-retinol dehydrogenase activity | |
Molecular Function | all-trans-retinol dehydrogenase (NAD+) activity | |
Molecular Function | all-trans-retinol dehydrogenase (NADP+) activity | |
Biological Process | cellular detoxification of aldehyde | |
Biological Process | photoreceptor cell maintenance | |
Biological Process | retinoid metabolic process | |
Biological Process | retinol metabolic process | |
Biological Process | visual perception |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameRetinol dehydrogenase 12
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96NR8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Leber congenital amaurosis 13 (LCA13)
- Note
- DescriptionA severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
- See alsoMIM:612712
Natural variants in LCA13
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_020858 | 49 | T>M | in LCA13; abolishes protection against the toxicity of 4-hydroxynonenal in the retina; results in aberrant activity in interconverting isomers of retinol and retinal; the activity profiles depend on presence or absence of variant Q-161; genetic background may act as a modifier of variant effect; dbSNP:rs28940314 | |
VAR_020859 | 51 | I>N | in LCA13; dbSNP:rs104894473 | |
VAR_020860 | 99 | L>I | in LCA13; exhibits a profound loss of catalytic activity; dbSNP:rs28940315 | |
VAR_020861 | 151 | H>D | in LCA13; exhibits a profound loss of catalytic activity; dbSNP:rs104894475 | |
VAR_020862 | 151 | H>N | in LCA13; dbSNP:rs104894475 | |
VAR_020863 | 175 | S>P | in LCA13; dbSNP:rs104894472 | |
VAR_020864 | 226 | Y>C | in LCA13; diminished activity in interconverting isomers of retinol and retinal; dbSNP:rs28940313 | |
VAR_020865 | 230 | P>A | in LCA13; dbSNP:rs104894476 |
Retinitis pigmentosa 53 (RP53)
- Note
- DescriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP53 inheritance is autosomal dominant or autosomal recessive.
- See alsoMIM:612712
Natural variants in RP53
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064166 | 76 | G>R | in RP53; dbSNP:rs368489658 | |
VAR_064169 | 126 | A>V | in RP53; dbSNP:rs202126574 | |
VAR_081222 | 146 | V>D | in RP53; uncertain significance; dbSNP:rs116649873 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_064163 | 47 | in retinal dystrophy; exhibits a profound loss of catalytic activity; dbSNP:rs761231974 | |||
Sequence: A → T | ||||||
Natural variant | VAR_020858 | 49 | in LCA13; abolishes protection against the toxicity of 4-hydroxynonenal in the retina; results in aberrant activity in interconverting isomers of retinol and retinal; the activity profiles depend on presence or absence of variant Q-161; genetic background may act as a modifier of variant effect; dbSNP:rs28940314 | |||
Sequence: T → M | ||||||
Natural variant | VAR_020859 | 51 | in LCA13; dbSNP:rs104894473 | |||
Sequence: I → N | ||||||
Natural variant | VAR_064164 | 55 | in retinal dystrophy; exhibits a profound loss of catalytic activity; dbSNP:rs766631462 | |||
Sequence: T → M | ||||||
Natural variant | VAR_064165 | 65 | in dbSNP:rs745471670 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_064166 | 76 | in RP53; dbSNP:rs368489658 | |||
Sequence: G → R | ||||||
Natural variant | VAR_067193 | 79 | found in a patient with LCA13; dbSNP:rs763414313 | |||
Sequence: A → V | ||||||
Natural variant | VAR_020860 | 99 | in LCA13; exhibits a profound loss of catalytic activity; dbSNP:rs28940315 | |||
Sequence: L → I | ||||||
Natural variant | VAR_064167 | 101 | in dbSNP:rs148334092 | |||
Sequence: D → N | ||||||
Natural variant | VAR_064168 | 125 | in retinal dystrophy; exhibits a profound loss of catalytic activity | |||
Sequence: N → K | ||||||
Natural variant | VAR_064169 | 126 | in RP53; dbSNP:rs202126574 | |||
Sequence: A → V | ||||||
Natural variant | VAR_064170 | 145 | in retinal dystrophy; exhibits a profound loss of catalytic activity; dbSNP:rs907600014 | |||
Sequence: G → E | ||||||
Natural variant | VAR_081222 | 146 | in RP53; uncertain significance; dbSNP:rs116649873 | |||
Sequence: V → D | ||||||
Natural variant | VAR_020861 | 151 | in LCA13; exhibits a profound loss of catalytic activity; dbSNP:rs104894475 | |||
Sequence: H → D | ||||||
Natural variant | VAR_020862 | 151 | in LCA13; dbSNP:rs104894475 | |||
Sequence: H → N | ||||||
Natural variant | VAR_064171 | 155 | in retinal dystrophy; exhibits a profound loss of catalytic activity; dbSNP:rs121434337 | |||
Sequence: T → I | ||||||
Natural variant | VAR_028281 | 161 | does not affect the protection against the toxicity of 4-hydroxynonenal in the retina; dbSNP:rs17852293 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_020863 | 175 | in LCA13; dbSNP:rs104894472 | |||
Sequence: S → P | ||||||
Natural variant | VAR_064172 | 193 | in retinal dystrophy; uncertain significance; dbSNP:rs148629905 | |||
Sequence: R → C | ||||||
Natural variant | VAR_064173 | 206 | in retinal dystrophy; exhibits a profound loss of catalytic activity | |||
Sequence: A → D | ||||||
Natural variant | VAR_064174 | 206 | in retinal dystrophy; uncertain significance; dbSNP:rs1254096311 | |||
Sequence: A → V | ||||||
Natural variant | VAR_020864 | 226 | in LCA13; diminished activity in interconverting isomers of retinol and retinal; dbSNP:rs28940313 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_020865 | 230 | in LCA13; dbSNP:rs104894476 | |||
Sequence: P → A | ||||||
Natural variant | VAR_064175 | 230 | in retinal dystrophy; uncertain significance | |||
Sequence: P → L | ||||||
Natural variant | VAR_064176 | 234 | in retinal dystrophy; uncertain significance; exhibits a loss of catalytic activity; dbSNP:rs750636662 | |||
Sequence: R → H | ||||||
Natural variant | VAR_064177 | 239 | in retinal dystrophy; exhibits a profound loss of catalytic activity; dbSNP:rs751589863 | |||
Sequence: R → W | ||||||
Natural variant | VAR_064178 | 274 | in retinal dystrophy; exhibits a profound loss of catalytic activity | |||
Sequence: L → P | ||||||
Natural variant | VAR_064179 | 285 | in retinal dystrophy; exhibits a profound loss of catalytic activity; dbSNP:rs973306929 | |||
Sequence: C → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 469 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 chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000054766 | 1-316 | UniProt | Retinol dehydrogenase 12 | |||
Sequence: MLVTLGLLTSFFSFLYMVAPSIRKFFAGGVCRTNVQLPGKVVVITGANTGIGKETARELASRGARVYIACRDVLKGESAASEIRVDTKNSQVLVRKLDLSDTKSIRAFAEGFLAEEKQLHILINNAGVMMCPYSKTADGFETHLGVNHLGHFLLTYLLLERLKVSAPARVVNVSSVAHHIGKIPFHDLQSEKRYSRGFAYCHSKLANVLFTRELAKRLQGTGVTTYAVHPGVVRSELVRHSSLLCLLWRLFSPFVKTAREGAQTSLHCALAEGLEPLSGKYFSDCKRTWVSPRARNNKTAERLWNVSCELLGIRWE | |||||||
Modified residue (large scale data) | 174 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 175 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, mostly in retina, kidney, brain, skeletal muscle, pancreas and stomach.
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96NR8 | PLEKHA7 Q6IQ23-2 | 3 | EBI-3916363, EBI-12069346 | |
BINARY | Q96NR8 | RBPMS Q93062 | 3 | EBI-3916363, EBI-740322 | |
BINARY | Q96NR8 | RBPMS Q93062-3 | 3 | EBI-3916363, EBI-740343 | |
BINARY | Q96NR8 | UBC P0CG48 | 2 | EBI-3916363, EBI-3390054 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length316
- Mass (Da)35,094
- Last updated2006-10-17 v3
- ChecksumEA0915E1E484879B
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK054835 EMBL· GenBank· DDBJ | BAB70811.1 EMBL· GenBank· DDBJ | mRNA | ||
AK315462 EMBL· GenBank· DDBJ | BAG37849.1 EMBL· GenBank· DDBJ | mRNA | ||
AL049779 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471061 EMBL· GenBank· DDBJ | EAW80951.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC025724 EMBL· GenBank· DDBJ | AAH25724.1 EMBL· GenBank· DDBJ | mRNA |