RDH11 (retinol dehydrogenase 11; also PSDR1/ARSDR1/RalR1/SDR7C1) is a microsomal, membrane-bound NADPH-dependent retinaldehyde reductase / retinol dehydrogenase of the short-chain dehydrogenase/reductase (SDR) family. It catalyzes the interconversion of retinols and retinaldehydes (EC 1.1.1.300), with a clear preference for NADP(H) over NAD(H) and dual stereo-specificity: it acts on all-trans-, 9-cis-, 11-cis- and (more weakly) 13-cis-retinoids. Under physiological conditions the reductive direction (retinaldehyde to retinol) dominates. RDH11 is anchored in the endoplasmic reticulum membrane as a single-pass type II membrane protein with an N-terminal signal-anchor and a cytoplasmically oriented catalytic Rossmann-fold domain. It contributes to retinoid homeostasis broadly (including the retinal pigment epithelium of the visual cycle, where it participates in reduction of all-trans-retinal and can substitute for RDH5 in 11-cis retinol/retinal interconversion) and to vitamin A metabolism. It has no steroid dehydrogenase activity. Its activity is inhibited by physical interaction with selenoprotein F (SELENOF). Biallelic loss-of-function variants cause retinal dystrophy, juvenile cataracts and short stature syndrome (RDJCSS).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ER membrane localization by UniProt SubCell keyword mapping. Correct and well-supported: RDH11 is an ER-membrane single-pass type II membrane protein, shown experimentally (PMID:12036956). This IEA is redundant with the experimental IDA/EXP annotations to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Endoplasmic reticulum membrane |
| GO:0008106 alcohol dehydrogenase (NADP+) activity | IEA GO_REF:0000116 | MARK AS OVER ANNOTATED | Summary: Rhea-mapped generic parent term (alcohol + NADP+ = aldehyde/ketone + NADPH), derived from the 9-cis- and 13-cis-retinol reactions (RHEA:54916, RHEA:54920). The chemistry is correct for RDH11 (an NADP-dependent retinol dehydrogenase), but this is a broad grouping term; the specific retinol dehydrogenase (NADP+) child term captures the function more precisely. Reason: Correct chemistry but overly general; the specific all-trans-retinol dehydrogenase (NADP+) term (GO:0052650) is the informative function. Proposed replacements: all-trans-retinol dehydrogenase (NADP+) activity Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Retinol dehydrogenase with a clear preference for NADP. |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function of RDH11 (EC 1.1.1.300; RHEA:25033), assigned by combined IEA methods. Strongly supported experimentally and captures the NADP-dependent all-trans-retinol/retinal interconversion. Redundant with the EXP/IDA annotations to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Displays high activity towards 9-cis, 11-cis and all-trans-retinol, and |
| GO:0102354 11-cis-retinol dehydrogenase (NADP+) activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-mapped 11-cis-retinol/retinal NADP-dependent activity (RHEA:54912). Correct and experimentally supported; the 11-cis activity is biologically significant because RDH11 can partly substitute for RDH5 in the RPE. Redundant with the EXP annotations to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Displays high activity towards 9-cis, 11-cis and all-trans-retinol, and |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale AP-MS interactome study (BioPlex 2.0), in which RDH11 is one of thousands of baits/preys (WITH/FROM UBAC1, Q9BSL1). This is uninformative about RDH11 molecular function and not a core annotation; retained as an IPI per policy but marked over-annotated. Reason: High-throughput interactome hit; bare protein binding conveys no specific molecular function. Supporting Evidence: PMID:28514442 the largest such network so far |
| GO:0005515 protein binding | IPI PMID:29410696 The interaction of selenoprotein F (SELENOF) with retinol de... | MARK AS OVER ANNOTATED | Summary: "Protein binding" from a targeted study demonstrating physical interaction of RDH11 with selenoprotein F (SELENOF, O60613) by Y2H, FRET, co-IP and pull-down. The interaction is biologically meaningful (SELENOF inhibits RDH11 activity), but the GO term itself is uninformative bare protein binding. Kept as IPI (non-removable) but not a core molecular function; the regulatory significance is captured in the notes. Reason: Meaningful regulatory interaction (SELENOF inhibits RDH11), but GO:0005515 is uninformative as a molecular function annotation. Supporting Evidence: PMID:29410696 SELENOF interacts with RDH11 and blocks its enzyme activity to reduce all-trans-retinaldehyde. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale AP-MS interactome study (BioPlex 3.0), WITH/FROM UBAC1 (Q9BSL1). Uninformative about molecular function; retained as IPI but marked over-annotated. Reason: High-throughput interactome hit; bare protein binding conveys no specific function. Supporting Evidence: PMID:33961781 118,162 interactions among 14,586 proteins |
| GO:0007601 visual perception | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from the mouse ortholog (Q9QYF1) via Ensembl Compara. Biologically plausible and consistent with RDH11's role in the retinal pigment epithelium of the visual cycle and with the human retinal-dystrophy disease phenotype, but for the human gene this is an ortholog-based inference rather than a direct visual-perception assay. RDH11 contributes to visual-cycle retinoid processing but is not required for normal dark adaptation in mouse knockouts, so this is a contributory/non-core process. Supporting Evidence: PMID:12226107 RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). |
| GO:0033721 aldehyde dehydrogenase (NADP+) activity | IEA GO_REF:0000107 | REMOVE | Summary: Electronic transfer from the mouse ortholog (Q9QYF1) via Ensembl. This term is defined as the OXIDATION of an aldehyde to a carboxylic acid (aldehyde + NADP+ + H2O = acid + NADPH), which is not the chemistry RDH11 performs: RDH11 is a REDUCTASE that converts aldehydes (retinaldehyde) to alcohols (retinol). Even the mouse SCALD ortholog is described as reducing aldehydes to alcohols, not oxidizing them to acids. This is a wrong-reaction electronic over-annotation and should be removed. Reason: Wrong-reaction IEA: GO:0033721 is aldehyde-to-acid oxidation, whereas RDH11 (and its mouse ortholog) reduce aldehydes to alcohols. The ortholog-transferred term misrepresents the enzyme's reaction. Supporting Evidence: PMID:12807874 The enzyme specifically uses NADPH to reduce a variety of short-chain aldehydes, including nonanal and 4-hydroxy-2-nonenal. |
| GO:0042572 retinol metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Retinol metabolic process assigned by combined IEA methods (with UniPathway UPA00912, retinol metabolism). Correct: RDH11 is a retinol dehydrogenase acting in retinol/vitamin A metabolism. This is a core biological process for the gene. Redundant with the ISS annotation to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Cofactor metabolism; retinol metabolism. |
| GO:0110095 cellular detoxification of aldehyde | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from the mouse ortholog (Q9QYF1) via Ensembl. Aldehyde detoxification was demonstrated for the MOUSE ortholog SCALD (reduces nonanal / 4-hydroxy-2-nonenal), but UniProt explicitly cautions that human RDH11 "exhibits little or no activity towards toxic lipid peroxidation products, such as nonanal or 4-hydroxy-nonenal." This species difference makes the detoxification role poorly supported for the human protein; keep as non-core rather than a core function. Reason: Detoxification of toxic aldehydes is a property of the mouse ortholog; human RDH11 has little/no activity toward these substrates (UniProt CAUTION), so it is non-core here. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt In contrast to mouse, human RDH11 exhibits little or no |
| GO:0001523 retinoid metabolic process | TAS Reactome:R-HSA-2453902 | ACCEPT | Summary: Retinoid metabolic process, Reactome TAS (canonical retinoid cycle in rods). Correct and core: RDH11 acts in retinoid metabolism / the visual retinoid cycle. This general BP term is appropriate for a retinaldehyde reductase. Supporting Evidence: PMID:12226107 display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C(15) pro-R specificity |
| GO:0001523 retinoid metabolic process | TAS Reactome:R-HSA-975634 | ACCEPT | Summary: Duplicate retinoid metabolic process annotation from a second Reactome pathway (Retinoid metabolism and transport). Same correct, core BP as above. Supporting Evidence: PMID:12226107 display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C(15) pro-R specificity |
| GO:0004745 all-trans-retinol dehydrogenase (NAD+) activity | TAS Reactome:R-HSA-5362721 | MODIFY | Summary: NAD+-dependent all-trans-retinol dehydrogenase, Reactome TAS. RDH11 has a clear preference for NADP(H) (~800-fold lower Km for NADP+/NADPH than NAD+/NADH), so the NAD+-specific cofactor term misrepresents the physiological cofactor. The correct cofactor-specific term is the NADP+ form (GO:0052650). Reason: Wrong cofactor: RDH11 is NADP(H)-preferring; replace the NAD+ term with the NADP+ form. Proposed replacements: all-trans-retinol dehydrogenase (NADP+) activity Supporting Evidence: PMID:12036956 with at least an 800-fold lower apparent K(m) values for NADP+ and NADPH versus NAD+ and NADH as cofactors. |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | TAS Reactome:R-HSA-5419165 | ACCEPT | Summary: Core NADP-dependent all-trans-retinol dehydrogenase activity, Reactome TAS (RDH11 et al. reduce atRAL to atROL). Correct and well-supported; redundant with the EXP/IDA/IEA annotations to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Retinol dehydrogenase with a clear preference for NADP. |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | TAS Reactome:R-HSA-74872 | ACCEPT | Summary: Core NADP-dependent all-trans-retinol dehydrogenase activity, Reactome TAS. Correct; redundant with the other annotations to this term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Retinol dehydrogenase with a clear preference for NADP. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:12036956 Evidence that the human gene for prostate short-chain dehydr... | ACCEPT | Summary: Experimental (EXP) ER membrane localization. RDH11 localizes to the ER, shown by immunostaining of human prostate and LNCaP cells. Core cellular component; supported by the type II single-pass membrane topology. Supporting Evidence: PMID:12036956 localizes to the endoplasmic reticulum. |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | EXP PMID:12036956 Evidence that the human gene for prostate short-chain dehydr... | ACCEPT | Summary: Experimental characterization of the NADP-dependent all-trans-retinol/retinal oxidoreductase activity (RalR1). This is the defining core molecular function of RDH11. Supporting Evidence: PMID:12036956 RalR1 exhibits an oxidoreductive catalytic activity toward retinoids, but not steroids |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | EXP PMID:29410696 The interaction of selenoprotein F (SELENOF) with retinol de... | ACCEPT | Summary: Experimental confirmation (HPLC assay) that RDH11 reduces all-trans-retinaldehyde to all-trans-retinol using NADPH. Supports the core NADP-dependent retinol dehydrogenase activity. Supporting Evidence: PMID:29410696 RDH11 is an enzyme for the reduction of all-trans-retinaldehyde to all-trans-retinol (vitamin A). |
| GO:0102354 11-cis-retinol dehydrogenase (NADP+) activity | EXP PMID:12036956 Evidence that the human gene for prostate short-chain dehydr... | ACCEPT | Summary: Experimental NADP-dependent 11-cis-retinol/retinal activity. Correct and core; RDH11's 11-cis activity underlies its ability to partly compensate for RDH5 in the RPE. Supporting Evidence: PMID:12036956 RalR1 exhibits an oxidoreductive catalytic activity toward retinoids, but not steroids |
| GO:0102354 11-cis-retinol dehydrogenase (NADP+) activity | EXP PMID:12226107 Dual-substrate specificity short chain retinol dehydrogenase... | ACCEPT | Summary: Experimental dual-substrate-specificity characterization showing NADP-dependent metabolism of cis-retinols including 11-cis. Core molecular function. Supporting Evidence: PMID:12226107 display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C(15) pro-R specificity |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | TAS Reactome:R-HSA-975629 | MARK AS OVER ANNOTATED | Summary: High-level oxidoreductase grouping term (CH-OH donor, NAD/NADP acceptor), Reactome TAS. Chemically correct but far too general for a well-characterized retinol dehydrogenase; the specific NADP-dependent retinol dehydrogenase term is more informative. Reason: Correct but overly general grouping term; superseded by the specific all-trans-retinol dehydrogenase (NADP+) function. Proposed replacements: all-trans-retinol dehydrogenase (NADP+) activity Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Retinol dehydrogenase with a clear preference for NADP. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:12807874 Characterization of mouse short-chain aldehyde reductase (SC... | ACCEPT | Summary: IDA ER membrane localization (assigned via the mouse SCALD ortholog study, which characterizes a membrane-bound ER enzyme). Consistent with the human experimental ER localization; correct core component. Redundant with the human EXP annotation. Supporting Evidence: PMID:12807874 The gene encodes a membrane-bound enzyme that we designate SCALD |
| GO:0110095 cellular detoxification of aldehyde | IDA PMID:12807874 Characterization of mouse short-chain aldehyde reductase (SC... | KEEP AS NON CORE | Summary: IDA aldehyde-detoxification from the mouse SCALD ortholog paper, which shows reduction of toxic short-chain aldehydes (nonanal, 4-hydroxy-2-nonenal). This activity is a property of the mouse ortholog; UniProt cautions that human RDH11 has little or no activity toward these toxic aldehydes. As an experimental annotation it is not removed, but for the human protein it is a non-core / weakly-transferable role. Reason: Experimental detoxification shown for the mouse ortholog; species difference makes it non-core for human RDH11 (UniProt CAUTION). Not removed (experimental IDA). Supporting Evidence: PMID:12807874 The enzyme specifically uses NADPH to reduce a variety of short-chain aldehydes, including nonanal and 4-hydroxy-2-nonenal. file:human/RDH11/RDH11-uniprot.txt In contrast to mouse, human RDH11 exhibits little or no |
| GO:0001523 retinoid metabolic process | IDA PMID:12226107 Dual-substrate specificity short chain retinol dehydrogenase... | ACCEPT | Summary: IDA retinoid metabolic process based on direct enzymatic characterization of RDH11 as a dual-specificity retinol dehydrogenase. Correct and core biological process. Supporting Evidence: PMID:12226107 display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C(15) pro-R specificity |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | IDA PMID:12226107 Dual-substrate specificity short chain retinol dehydrogenase... | ACCEPT | Summary: IDA NADP-dependent all-trans-retinol dehydrogenase activity from direct enzymatic assays. Core molecular function. Supporting Evidence: PMID:12226107 Members of the short chain alcohol dehydrogenase/reductase superfamily catalyze the transformation of retinol to retinal. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5362721 | ACCEPT | Summary: ER membrane, Reactome TAS. Correct core component; redundant with the experimental annotations to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5419165 | ACCEPT | Summary: ER membrane, Reactome TAS. Correct core component; redundant. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-74872 | ACCEPT | Summary: ER membrane, Reactome TAS. Correct core component; redundant. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-975629 | ACCEPT | Summary: ER membrane, Reactome TAS. Correct core component; redundant. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Endoplasmic reticulum membrane |
| GO:0042574 retinal metabolic process | IDA PMID:12807874 Characterization of mouse short-chain aldehyde reductase (SC... | ACCEPT | Summary: IDA retinal (retinaldehyde) metabolic process from the mouse SCALD ortholog paper, which shows reduction of all-trans- and 9-cis-retinaldehyde. RDH11 acts on retinaldehyde (its preferred substrate direction), so participation in retinal metabolism is well-founded and a core biological process. The acts_upstream_of_or_within qualifier is appropriate for an ortholog-derived process annotation. Supporting Evidence: PMID:12807874 The enzyme also reduces retinaldehydes, showing equal activity for all-trans-retinal and 9-cis-retinal. |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | IDA PMID:12807874 Characterization of mouse short-chain aldehyde reductase (SC... | ACCEPT | Summary: IDA NADP-dependent all-trans-retinol/retinal activity assigned via the mouse SCALD ortholog, which reduces all-trans-retinaldehyde using NADPH. Consistent with the human experimental characterization; core molecular function. Supporting Evidence: PMID:12807874 The enzyme also reduces retinaldehydes, showing equal activity for all-trans-retinal and 9-cis-retinal. |
| GO:0004745 all-trans-retinol dehydrogenase (NAD+) activity | ISS GO_REF:0000024 | MODIFY | Summary: NAD+-dependent all-trans-retinol dehydrogenase, transferred by ISS from the paralog human RDH12 (WITH/FROM UniProtKB:Q96NR8). RDH11 has a clear preference for NADP(H) (~800-fold lower Km than for NAD(H)), so the NAD+-specific term mis-assigns the physiological cofactor. Modify to the NADP+ form. Reason: Wrong cofactor transferred from the RDH12 paralog; RDH11 is NADP(H)-preferring. Replace with the NADP+ form. Proposed replacements: all-trans-retinol dehydrogenase (NADP+) activity Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Retinol dehydrogenase with a clear preference for NADP. |
| GO:0042572 retinol metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Retinol metabolic process transferred by ISS from the paralog RDH12 (Q96NR8). The BP is correct for RDH11 independently of the sequence-similarity source: RDH11 is a retinol dehydrogenase in retinol/vitamin A metabolism. Core biological process; redundant with the IEA annotation to the same term. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Cofactor metabolism; retinol metabolism. |
| GO:0050661 NADP binding | IEA GO_REF:0000024 | NEW | Summary: Proposed new annotation (not in current GOA). RDH11 binds NADP(H) via a Rossmann-fold SDR NADP-binding motif (UniProt BINDING 48..54, ligand NADP(+)) and strongly prefers NADP(H) over NAD(H) as cofactor. Adding NADP binding makes the cofactor dependency of the core catalytic activity explicit. Supporting Evidence: file:human/RDH11/RDH11-uniprot.txt Retinol dehydrogenase with a clear preference for NADP. PMID:12036956 with at least an 800-fold lower apparent K(m) values for NADP+ and NADPH versus NAD+ and NADH as cofactors. |
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