Hsd11b2 encodes NAD-dependent 11beta-hydroxysteroid dehydrogenase type 2, a microsomal/endoplasmic-reticulum short-chain dehydrogenase that oxidizes active 11beta-hydroxyglucocorticoids such as corticosterone to inactive 11-keto forms such as 11-dehydrocorticosterone. The oxidation is high-affinity (KM about 10 nM for corticosterone) and essentially unidirectional, so the enzyme acts as a pre-receptor gatekeeper. By locally depleting active glucocorticoids in aldosterone-sensitive epithelia (distal nephron, distal colon, salivary and sweat glands) it confers aldosterone specificity on the otherwise non-selective mineralocorticoid receptor, and in placenta and fetal tissues it limits fetal exposure to maternal corticosterone. It is the inactivating member of the 11beta-HSD pair, distinct from the reductive, NADPH-dependent Hsd11b1. Loss of activity produces apparent mineralocorticoid excess, with sodium and water retention, hypokalaemia and salt-sensitive hypertension. Secondary activities of the mammalian enzyme include oxidation of 11beta-hydroxyandrogens to bioactive 11-ketoandrogens, and oxidation of 7beta-hydroxycholesterol to 7-ketocholesterol, the precursor of oxysterols that bind and activate Smoothened; through the latter the enzyme can potentiate Hedgehog signalling in cell types where it is expressed in domains of active Hedgehog activity, including cerebellar granule cell precursors and Hedgehog-driven tumours.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity is retained for Hsd11b2 because it matches the documented core enzymatic role or its direct pathway consequence (IBA, GO_REF:0000033). Reason: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity is directly supported by the curated function of Hsd11b2 and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P50233 CATALYTIC ACTIVITY: Reaction=an 11beta-hydroxysteroid + NAD(+) = an 11-oxosteroid + NADH + H(+) file:rat/Hsd11b2/Hsd11b2-deep-research-falcon.md 11β‑HSD2 is described as **NAD-dependent/NAD+-dependent**, consistent with SDR-family dehydrogenase directionality in epithelia. |
| GO:0008211 glucocorticoid metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: glucocorticoid metabolic process is retained for Hsd11b2 because it matches the documented core enzymatic role or its direct pathway consequence (IBA, GO_REF:0000033). Reason: glucocorticoid metabolic process is directly supported by the curated function of Hsd11b2 and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P50233 Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids (PubMed:34028587, PubMed:7649078). file:rat/Hsd11b2/Hsd11b2-deep-research-falcon.md 11β‑HSD2 catalyzes oxidation/inactivation of glucocorticoids: **cortisol→cortisone** and **corticosterone→11‑dehydrocorticosterone**. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Hsd11b2 is a microsomal/endoplasmic-reticulum enzyme, so the localization is correct; it is contextual rather than the defining activity (IEA, GO_REF:0000044). Reason: The subcellular location is recorded on the UniProt record (microsome, endoplasmic reticulum), consistent with an ER-membrane-anchored SDR whose catalytic domain faces the ER lumen. The term is retained as supporting context for where the enzyme acts rather than as a statement of its molecular function. Supporting Evidence: UniProtKB:P50233 SUBCELLULAR LOCATION: Microsome |
| GO:0034650 cortisol metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: cortisol metabolic process is an over-annotation for the rat enzyme; it is an electronic ortholog transfer from human, where cortisol is the primary substrate (IEA, GO_REF:0000107). Reason: Rats are a corticosterone-dominated glucocorticoid species, and rat 11beta-HSD2 acts principally on corticosterone, not cortisol. GO:0034650 is specific to cortisol (11-beta-17,21-trihydroxypregn-4-ene-3,20-dione). This electronic annotation derives from ortholog transfer out of the human context, where cortisol is the primary substrate; in the rat the relevant glucocorticoid metabolic process is the corticosterone-directed activity captured by GO:0008211, so the cortisol-specific term over-annotates the rat gene. UniProt makes the species point explicitly in a CAUTION note on the rat record. Supporting Evidence: UniProtKB:P50233 CATALYTIC ACTIVITY: Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone + NADH + H(+) UniProtKB:P50233 Rats and mice do not produce appreciable cortisol, because they do not express the 17-alpha hydroxylase (Cyp17a1) enzyme in the adrenals. |
| GO:0045880 positive regulation of smoothened signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Hsd11b2 contributes to smoothened pathway activation through its oxysterol-synthase side activity, oxidizing 7beta-hydroxycholesterol to 7-ketocholesterol, the precursor of the SMO-binding oxysterols 7-keto,27-hydroxycholesterol and 7beta,27-dihydroxycholesterol (IEA ortholog transfer from mouse Hsd11b2/UniProtKB:P51661, where the role was shown directly). Reason: The donor evidence is direct, not inferential. In mouse, depletion or pharmacologic inhibition of HSD11beta2 attenuated Hedgehog signalling in Ptch1-null MEFs but not Sufu-null MEFs, reduced ciliary SMO accumulation, and lowered 7-ketocholesterol in cells and cilia, with the downstream oxysterols restoring pathway activity (PMID:30340023). UniProt records the same 7beta-hydroxycholesterol to 7-ketocholesterol conversion for the rat enzyme, so the term transfers. It is kept as non-core because the enzyme catalyses a biosynthetic step upstream of the SMO ligand rather than acting within the pathway, and because the effect is restricted to cell types that express the enzyme in domains of active Hedgehog signalling (cerebellar external granule layer, Hedgehog-associated medulloblastoma) rather than to the glucocorticoid-barrier epithelia that define its main role. An earlier rationale that any smoothened effect must be an indirect consequence of glucocorticoid inactivation does not hold, because cerebellar deletion of the enzyme left glucocorticoid target gene expression unchanged while still impairing Hedgehog-driven growth. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P51661 SUPPORTS TRANSFER Mouse donor record carries the directly demonstrated oxysterol-synthase role (PMID:30340023); rat is the one-to-one ortholog and its UniProt record carries the same reaction, so the transfer is sound, but the role is secondary to glucocorticoid inactivation and confined to Hedgehog-active tissues. Supporting Evidence: PMID:30340023 Either genetic or pharmacologic inhibition of HSD11β2, an oxysterol synthase, attenuates HH signal transduction and the growth of HH pathway-associated medulloblastoma. PMID:30340023 However, deletion of HSD11β2 in the cerebellum did not affect glucocorticoid target gene expression (Figures S5A and S5B), suggesting that HSD11β2 may not be critical for restraining physiological levels of glucocorticoids in the cerebellum. UniProtKB:P50233 a precursor of 7-keto,27-hydroxycholesterol, which activates smoothened (SMO) and the smoothened signaling pathway |
| GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: 7-beta-hydroxysteroid dehydrogenase activity is a genuine secondary activity of 11beta-HSD2, which oxidizes 7beta-hydroxycholesterol to 7-ketocholesterol; the rat record carries the corresponding reaction (RHEA:68656) and the activity was shown directly for the mouse ortholog. Reason: This is not a family-level guess. Mouse HSD11beta2 oxidizes 7beta-hydroxycholesterol to 7-ketocholesterol - overexpression increased 7-ketocholesterol production from 7beta-hydroxycholesterol but not from the 7alpha isomer, and inhibition reduced 7-ketocholesterol in cells and cilia (PMID:30340023). UniProt records the 7-oxocholesterol/7beta-hydroxycholesterol reaction (RHEA:68656) and the 7beta-hydroxycholesterol to 7-ketocholesterol conversion for the rat enzyme. It is kept as non-core because the defining, high-affinity activity is NAD(+)-dependent oxidation of 11beta-hydroxyglucocorticoids, and with one caveat - the GO term specifies NADP(+) as cofactor, and while the UniProt reaction is written with NADP(H), the cofactor actually used for the 7beta-oxidation by the rat enzyme has not been established experimentally; that cofactor clause, not the 7beta-oxidation chemistry, is the part of the term that remains unverified for rat. Supporting Evidence: PMID:30340023 HSD11β2 increased 7k-C production in 7β-OHC-treated cells, but not in 7a-OHC-treated cells (Figure 4B). PMID:30340023 Pharmacologic inhibition of HSD11β2 reduced 7k-C in LLC-PK1 cells and cilia (Figure 4E), further indicating that HSD11β2 generates 7k-C. UniProtKB:P50233 Catalyzes the conversion of 7-beta-hydroxycholesterol into 7-ketocholesterol |
| GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity is retained for Hsd11b2 because it matches the documented core enzymatic role or its direct pathway consequence (IEA, GO_REF:0000120). Reason: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity is directly supported by the curated function of Hsd11b2 and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P50233 CATALYTIC ACTIVITY: Reaction=an 11beta-hydroxysteroid + NAD(+) = an 11-oxosteroid + NADH + H(+) |
| GO:0045880 positive regulation of smoothened signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ortholog transfer of the mouse annotation that HSD11beta2 is the oxysterol synthase producing 7-ketocholesterol, precursor of SMO-activating oxysterols, and thereby promotes Hedgehog pathway activity (ISO from mouse Hsd11b2, GO_REF:0000121). Reason: The mouse donor annotation rests on direct experiments rather than inference, including shRNA depletion and pharmacologic inhibition that attenuated Hedgehog signalling downstream of PTCH1 and upstream of SUFU, and rescue of pathway activity by the oxysterols made downstream of the enzyme (PMID:30340023). Rat Hsd11b2 is the one-to-one ortholog and its UniProt record carries the same 7beta-hydroxycholesterol to 7-ketocholesterol conversion, so the transfer is appropriate. It is non-core rather than core because the enzyme supplies a ligand precursor upstream of the pathway rather than acting in it, and because only cell types expressing the enzyme in Hedgehog-active domains are affected; the defining role of the rat enzyme remains NAD(+)-dependent glucocorticoid inactivation. The earlier reading of this row as an indirect glucocorticoid effect is contradicted by the donor paper, in which cerebellar deletion of the enzyme did not alter glucocorticoid target gene expression. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:104720 · mouse Hsd11b2 SUPPORTS TRANSFER Mouse donor annotation is experimentally grounded (IDA from PMID:30340023, oxysterol-synthase step upstream of SMO activation) and the activity is recorded for the rat enzyme in UniProt, so the transfer is sound; it is kept as non-core because it is a secondary, tissue-restricted role. Supporting Evidence: PMID:30340023 Like sterol depletion, depleting HSD11β2 attenuated HH signaling in Ptch1−/− MEFs, but not Sufu−/− MEFs, suggesting that HSD11β2 modulates HH signaling downstream of PTCH1 and upstream of SUFU PMID:30340023 Following genetic or pharmacologic inhibition of HSD11β2, the addition of 7k-C, 7β,27-DHC, and 7k,27-OHC restored HH pathway activity UniProtKB:P50233 a precursor of 7-keto,27-hydroxycholesterol, which activates smoothened (SMO) and the smoothened signaling pathway |
| GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity assertion of the same secondary 7beta-hydroxysteroid oxidation, based on mouse HSD11beta2 (UniProtKB:P51661), for which the conversion of 7beta-hydroxycholesterol to 7-ketocholesterol was demonstrated directly. Reason: The ISS source is the mouse ortholog, where the activity is experimentally established rather than assumed from the SDR fold (PMID:30340023), and the rat UniProt record carries the corresponding reaction. The activity is therefore retained, but as a secondary function - the rat enzyme's characterized and physiologically dominant activity is NAD(+)-dependent oxidation of 11beta-hydroxyglucocorticoids, and the NADP(+) cofactor written into the GO term has not been verified for the rat enzyme's 7beta-oxidation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P51661 SUPPORTS TRANSFER Mouse ortholog record is the ISS anchor and the 7beta-hydroxycholesterol to 7-ketocholesterol oxidation was shown directly for it; the transfer is sound, with the NADP(+) cofactor clause of the term the only unverified element for rat. Supporting Evidence: PMID:30340023 7k-C production in HEK293T cells overexpressing HSD11β2 was inhibited by CNX (Figure 4B), suggesting that HSD11β2 converts 7β-OHC to 7k-C. UniProtKB:P50233 Catalyzes the conversion of 7-beta-hydroxycholesterol into 7-ketocholesterol |
| GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ortholog transfer from mouse Hsd11b2 of the 7beta-hydroxysteroid oxidation activity, by which the enzyme converts 7beta-hydroxycholesterol to 7-ketocholesterol; a real secondary activity of the enzyme rather than an SDR family-level guess. Reason: The mouse donor is not a family-level inference - HSD11beta2 overexpression generated 7-ketocholesterol from 7beta-hydroxycholesterol specifically, and inhibiting the enzyme lowered cellular and ciliary 7-ketocholesterol (PMID:30340023). The rat UniProt record carries the same conversion and the corresponding Rhea reaction, so the transfer is justified. It is non-core because the rat enzyme's defining activity is high-affinity NAD(+)-dependent oxidation of 11beta-hydroxyglucocorticoids; the caveat on the term itself is its NADP(+) cofactor clause, which has not been verified experimentally for the rat enzyme. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:104720 · mouse Hsd11b2 SUPPORTS TRANSFER Mouse donor annotation is grounded in direct biochemical evidence for the 7beta-hydroxycholesterol to 7-ketocholesterol oxidation (PMID:30340023), and the rat UniProt record carries the same reaction, so the transfer is sound; it is retained as a secondary activity. Supporting Evidence: PMID:30340023 To test whether HSD11β2 can generate 7k-C, we cultured HEK293T cells overexpressing HSD11β2 with 7β-OHC or the related oxysterol 7a-OHC and used HPLC-MS/MS to assess 7k-C production. UniProtKB:P50233 Catalyzes the conversion of 7-beta-hydroxycholesterol into 7-ketocholesterol |
| GO:0034650 cortisol metabolic process | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: cortisol metabolic process is an over-annotation for the rat enzyme; it is an ortholog (ISO) transfer from human, where cortisol is the primary substrate (ISO, GO_REF:0000121). Reason: Rats are a corticosterone-dominated glucocorticoid species, and rat 11beta-HSD2 acts principally on corticosterone, not cortisol. GO:0034650 is specific to cortisol (11-beta-17,21-trihydroxypregn-4-ene-3,20-dione). This ISO annotation derives from ortholog transfer out of the human context, where cortisol is the primary substrate; in the rat the relevant glucocorticoid metabolic process is the corticosterone-directed activity captured by GO:0008211, so the cortisol-specific term over-annotates the rat gene. UniProt makes the species point explicitly in a CAUTION note on the rat record. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P80365 · human HSD11B2 SUPPORTS SOURCE BUT NOT TARGET Human HSD11B2 donor annotation is correct in its own context (cortisol is the primary human glucocorticoid), but rats are corticosterone-dominated, so the cortisol-specific process does not transfer. Supporting Evidence: UniProtKB:P50233 CATALYTIC ACTIVITY: Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone + NADH + H(+) UniProtKB:P50233 Rats and mice do not produce appreciable cortisol, because they do not express the 17-alpha hydroxylase (Cyp17a1) enzyme in the adrenals. |
| GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity | ISO GO_REF:0000121 | ACCEPT | Summary: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity is retained for Hsd11b2 because it matches the documented core enzymatic role or its direct pathway consequence (ISO, GO_REF:0000121). Reason: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity is directly supported by the curated function of Hsd11b2 and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P50233 CATALYTIC ACTIVITY: Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone + NADH + H(+) |
| GO:0008211 glucocorticoid metabolic process | IDA PMID:11755176 Effect of cellular differentiation on 11beta-hydroxysteroid ... | ACCEPT | Summary: glucocorticoid metabolic process is retained for Hsd11b2 because it matches the documented core enzymatic role or its direct pathway consequence (IDA, PMID:11755176). Reason: glucocorticoid metabolic process is directly supported by the curated function of Hsd11b2 and is not merely a downstream phenotype or expression response. Supporting Evidence: PMID:11755176 Type 2 11betaHSD has only oxidase activity converting corticosterone to 11-dehydrocorticosterone. file:rat/Hsd11b2/Hsd11b2-deep-research-falcon.md 11β‑HSD2 is the inactivating dehydrogenase |
| GO:0007565 female pregnancy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ortholog transfer of the mouse annotation placing Hsd11b2 in pregnancy, where the enzyme forms the placental barrier that limits fetal exposure to maternal glucocorticoids; a physiological context for the same enzymatic activity (ISO from mouse Hsd11b2, GO_REF:0000121). Reason: The rat UniProt record states the same role in maintaining glucocorticoid balance during preimplantation and protecting the fetus from excessive maternal corticosterone, so the transferred pregnancy context is well founded. It is non-core because the gene product's function is glucocorticoid inactivation; pregnancy is the tissue and life-stage setting in which that activity matters, not a separate activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:104720 · mouse Hsd11b2 SUPPORTS TRANSFER Mouse donor annotation reflects the placental glucocorticoid barrier, a role the rat UniProt record states explicitly for the rat enzyme, so the transfer is sound; kept as non-core physiological context. Supporting Evidence: UniProtKB:P50233 Plays an important role in maintaining glucocorticoids balance during preimplantation and protects the fetus from excessive maternal corticosterone exposure |
| GO:0001666 response to hypoxia | IEP PMID:19470702 Chronic intermittent hypoxia induces 11beta-hydroxysteroid d... | MARK AS OVER ANNOTATED | Summary: response to hypoxia reflects an expression, phenotype, or systemic context for Hsd11b2, not a direct core gene-product function (IEP, PMID:19470702). Reason: The cited/source evidence links Hsd11b2 to changes in expression or a downstream physiological state; it does not establish Hsd11b2 as an effector of response to hypoxia. Supporting Evidence: PMID:19470702 We first demonstrated that adaptation to CIH led to a significant increase in 11HSD2 transcript levels and activity in the myocardium. |
| GO:0007565 female pregnancy | IEP PMID:19050325 Reciprocal changes in maternal and fetal metabolism of corti... | KEEP AS NON CORE | Summary: female pregnancy is retained as contextual support for Hsd11b2, but it is not the core function (IEP, PMID:19050325). Reason: female pregnancy records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Hsd11b2. Supporting Evidence: PMID:19050325 The final third of gestation is accompanied by reciprocal changes in placental and fetal metabolism of corticosterone due to changes in 11HSD1 and 11HSD2. file:rat/Hsd11b2/Hsd11b2-deep-research-falcon.md 11β‑HSD2 is highly expressed in **placenta and fetal tissues** where it **minimizes fetal exposure to maternal glucocorticoids** |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:10792625 Effects of spironolactone on systolic blood pressure in expe... | MARK AS OVER ANNOTATED | Summary: response to xenobiotic stimulus reflects an expression, phenotype, or systemic context for Hsd11b2, not a direct core gene-product function (IEP, PMID:10792625). Reason: The cited/source evidence links Hsd11b2 to changes in expression or a downstream physiological state; it does not establish Hsd11b2 as an effector of response to xenobiotic stimulus. Supporting Evidence: PMID:10792625 Four weeks after an injection of STZ, the renal 11beta-HSD2 and mRNA levels were significantly lower in diabetic rats than in control rats, and the mean systolic blood pressure was 14.8% higher in diabetic rats than in controls. |
| GO:0032094 response to food | IEP PMID:18548384 Tissue-specific programming expression of glucocorticoid rec... | MARK AS OVER ANNOTATED | Summary: response to food reflects an expression, phenotype, or systemic context for Hsd11b2, not a direct core gene-product function (IEP, PMID:18548384). Reason: The cited/source evidence links Hsd11b2 to changes in expression or a downstream physiological state; it does not establish Hsd11b2 as an effector of response to food. Supporting Evidence: PMID:18548384 This study demonstrated that maternal food restriction has both long-term and tissue-specific effects on gene expression of factors involved in glucocorticoid sensitivity. |
| GO:0032868 response to insulin | IEP PMID:9495277 Gene expression of 11beta-hydroxysteroid dehydrogenase type ... | MARK AS OVER ANNOTATED | Summary: response to insulin reflects an expression, phenotype, or systemic context for Hsd11b2, not a direct core gene-product function (IEP, PMID:9495277). Reason: The cited/source evidence links Hsd11b2 to changes in expression or a downstream physiological state; it does not establish Hsd11b2 as an effector of response to insulin. Supporting Evidence: PMID:9495277 The renal 11beta-HSD2 activity and level of mRNA expression were significantly decreased in diabetic rats. |
| GO:0048545 response to steroid hormone | IEP PMID:18032797 DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding pr... | MARK AS OVER ANNOTATED | Summary: response to steroid hormone reflects an expression, phenotype, or systemic context for Hsd11b2, not a direct core gene-product function (IEP, PMID:18032797). Reason: The cited/source evidence links Hsd11b2 to changes in expression or a downstream physiological state; it does not establish Hsd11b2 as an effector of response to steroid hormone. Supporting Evidence: PMID:18032797 DHEA treatment markedly increased mRNA expression and activity of 11beta-HSD2 in a rat cortical collecting duct cell line and in kidneys of C57BL/6J mice and Sprague-Dawley rats. |
| GO:0051384 response to glucocorticoid | IEP PMID:19490994 Dexamethasone and betamethasone administration during pregna... | MARK AS OVER ANNOTATED | Summary: response to glucocorticoid reflects an expression, phenotype, or systemic context for Hsd11b2, not a direct core gene-product function (IEP, PMID:19490994). Reason: The cited/source evidence links Hsd11b2 to changes in expression or a downstream physiological state; it does not establish Hsd11b2 as an effector of response to glucocorticoid. Supporting Evidence: PMID:19490994 Placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is the key enzyme which protects the fetus from overexposure to glucocorticoids (GCs) by their oxidation into inactive derivates. |
| GO:0002017 regulation of blood volume by renal aldosterone | IMP PMID:15718388 Interactions between 11beta-hydroxysteroid dehydrogenase and... | KEEP AS NON CORE | Summary: regulation of blood volume by renal aldosterone is retained as contextual support for Hsd11b2, but it is not the core function (IMP, PMID:15718388). Reason: regulation of blood volume by renal aldosterone records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Hsd11b2. Supporting Evidence: PMID:15718388 These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11betaHSD2 deficiency and that 11betaHSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development. file:rat/Hsd11b2/Hsd11b2-deep-research-falcon.md 11β‑HSD2 enables aldosterone-specific MR signaling** in target cells by locally removing active glucocorticoids. |
| GO:0005496 steroid binding | IPI PMID:15761036 11{beta}-Hydroxysteroid dehydrogenase 2 in rat leydig cells:... | KEEP AS NON CORE | Summary: steroid binding is retained as contextual support for Hsd11b2, but it is not the core function (IPI, PMID:15761036). Reason: steroid binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Hsd11b2. Supporting Evidence: PMID:15761036 the high-affinity, low-capacity 11beta HSD2 isoform, present at only one thousandth the level of the low-affinity isoform may significantly affect the level of CORT |
| GO:0051287 NAD binding | IDA PMID:15761036 11{beta}-Hydroxysteroid dehydrogenase 2 in rat leydig cells:... | KEEP AS NON CORE | Summary: NAD binding is retained as contextual support for Hsd11b2, but it is not the core function (IDA, PMID:15761036). Reason: NAD binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Hsd11b2. Supporting Evidence: PMID:15761036 the nicotinamide adenine dinucleotide-dependent 11beta HSD2 high-affinity unidirectional oxidase |
| GO:0008211 glucocorticoid metabolic process | IDA PMID:16763064 Expression and functional state of the corticosteroid recept... | ACCEPT | Summary: glucocorticoid metabolic process is retained for Hsd11b2 because it matches the documented core enzymatic role or its direct pathway consequence (IDA, PMID:16763064). Reason: glucocorticoid metabolic process is directly supported by the curated function of Hsd11b2 and is not merely a downstream phenotype or expression response. Supporting Evidence: PMID:16763064 11 beta-Hydroxysteroid-dehydrogenase type 2 (HSD2), an enzyme that inactivates glucocorticoids, was strongly expressed and active in quiescent SC. |
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