HSD11B2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred core molecular function. HSD11B2 is an NAD+-dependent 11beta-hydroxysteroid dehydrogenase that oxidizes cortisol to cortisone; this is the correct, specific molecular-function term and the evolved core activity. Reason: Matches the experimentally established NAD+-dependent dehydrogenase activity of the enzyme and is at the appropriate level of specificity. This is a core molecular function. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=cortisol + NAD(+) = cortisone + NADH + H(+); PMID:8538347 the NAD-dependent type 2 isoform (11 beta-HSD2), first characterised in placental tissue, that is expressed in the mineralocorticoid target tissues, kidney and colon.
GO:0008211 glucocorticoid metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred biological process. HSD11B2 metabolizes glucocorticoids (cortisol/corticosterone), so this is a correct core process term, if somewhat broad relative to the more specific cortisol metabolic process. Reason: HSD11B2 is a bona fide glucocorticoid-metabolizing enzyme; this process term is well supported and represents a core biological process. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Functions as a dehydrogenase (oxidase), thereby decreasing the PMID:8538347 catalyses the interconversion of hormonally active cortisol to inactive cortisone
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000044	ACCEPT	Summary: SubCell-keyword-derived ER localization. Correct but less specific than the experimentally supported endoplasmic reticulum membrane localization. Reason: HSD11B2 is an ER-resident enzyme; the ER term is a correct (if broader) compartment. The more specific and core term is ER membrane (GO:0005789). Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt SUBCELLULAR LOCATION: Microsome
GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA GO_REF:0000117	ACCEPT	Summary: ARBA-derived broad oxidoreductase parent term. Correct as a general parent of the specific 11beta-HSD (NAD+) activity, but not informative on its own. Reason: A correct broader parent of GO:0070523. Acceptable as a general electronic annotation; the specific term GO:0070523 captures the core function. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea/RHEA-mapping-derived MF, matching the curated catalytic-activity reactions (RHEA:50208 cortisol->cortisone; RHEA:42204 corticosterone->11-dehydrocorticosterone; RHEA:53116 generic). Correct core molecular function. Reason: The Rhea reaction mappings correspond exactly to the enzyme's NAD+-dependent 11beta-HSD activity. Core molecular function (duplicate term id, correctly annotated). Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone + NADH +
GO:0001666 response to hypoxia	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog (P50233). HSD11B2 expression is modulated by hypoxia in placenta, but this is a physiological-context response term rather than a core molecular role of the enzyme. Reason: Plausible as electronically projected regulation/response, but peripheral to the enzyme's core dehydrogenase function. Retain as non-core context. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt TISSUE SPECIFICITY: Expressed in kidney, placenta, pancreas, prostate,
GO:0002017 regulation of blood volume by renal aldosterone	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog. Mechanistically apt downstream physiology - by destroying cortisol in the distal nephron, HSD11B2 confers aldosterone specificity on the mineralocorticoid receptor, and its loss causes low-renin hypertension (AME). This is a downstream physiological process, not the molecular core. Reason: Well aligned with the enzyme's role in aldosterone-target tissues (pre-receptor protection of the MR), but represents downstream physiology rather than the core molecular function. Retain as non-core. Supporting Evidence: PMID:8538347 is vital for dictating specificity for the mineralocorticoid receptor file:human/HSD11B2/HSD11B2-uniprot.txt thus protecting the
GO:0005496 steroid binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog. The enzyme binds steroid substrates (cortisol, corticosterone) as part of catalysis; substrate binding is implicit in the catalytic MF and is supporting rather than a distinct core function. Reason: Correct (the enzyme binds steroid substrates) but subsumed by the catalytic molecular function; retain as non-core supporting activity. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
GO:0007565 female pregnancy	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog. Placental 11beta-HSD2 shields the fetus from maternal glucocorticoid and is highly expressed in placenta; this is a genuine physiological context but not the molecular core function. Reason: Supported by the enzyme's high placental expression and its barrier role against maternal glucocorticoids, but represents peripheral physiology. Retain as non-core. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt TISSUE SPECIFICITY: Expressed in kidney, placenta, pancreas, prostate, PMID:8538347 first characterised in placental tissue
GO:0008211 glucocorticoid metabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-projected duplicate of the IBA glucocorticoid metabolic process annotation. Correct core biological process. Reason: Duplicate of the well-supported core process term; HSD11B2 metabolizes glucocorticoids. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Functions as a dehydrogenase (oxidase), thereby decreasing the
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-projected from rat ortholog. HSD11B2 is inhibited by xenobiotics such as glycyrrhetinic acid (liquorice) and organotins, but "response to xenobiotic stimulus" implies a regulated cellular response, which is weak for this enzyme; being a drug target is not the same as mounting a xenobiotic response. Reason: The enzyme is inhibited by xenobiotics (it is a pharmacological target), but this does not equate to the gene participating in a cellular response-to-xenobiotic process. Likely an over-annotation from electronic projection. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt ACTIVITY REGULATION: Inhibited by glycyrrhetinic acid (derived from
GO:0032094 response to food	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-projected from rat ortholog. A physiological-context response term with no clear connection to the enzyme's molecular mechanism in humans. Reason: Peripheral response-to-stimulus term projected from rodent physiology, not reflecting a core function of HSD11B2. Likely over-annotation. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Functions as a dehydrogenase (oxidase), thereby decreasing the
GO:0032868 response to insulin	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-projected from rat ortholog. A physiological-context response term; not part of the enzyme's core molecular function. Reason: Peripheral response-to-stimulus term projected from rodent data; not a core function of the enzyme. Likely over-annotation. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Functions as a dehydrogenase (oxidase), thereby decreasing the
GO:0045880 positive regulation of smoothened signaling pathway	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-projected from mouse ortholog (P51661). Proposed to act via oxidation of 7beta-hydroxycholesterol to 7-ketocholesterol, a precursor of an oxysterol that activates smoothened (SMO); this is a By-similarity, distal/indirect link not demonstrated for human HSD11B2 and using the non-physiological NADP+-dependent oxysterol activity. Reason: Indirect, By-similarity-only pathway link via a minor oxysterol side activity; not demonstrated for the human enzyme and downstream of its molecular role. Likely over-annotation. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt which activates smoothened (SMO) and the smoothened
GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Multi-method-IEA (and mouse-ortholog-derived) minor side activity. In vitro HSD11B2 can interconvert oxysterols (7-oxocholesterol/7beta-hydroxycholesterol; 7beta,25-diOH-cholesterol) using NADP+, but this uses the opposite cofactor to its physiological NAD+-dependent dehydrogenase role and is a minor, largely By-similarity activity. Reason: A real but minor in-vitro oxysterol activity with the non-physiological NADP+ cofactor; not the enzyme's core evolved function (NAD+-dependent 11beta-HSD). Likely over-annotation. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=7-oxocholesterol + NADPH + H(+) = 7beta-hydroxycholesterol +
GO:0048545 response to steroid hormone	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog. Broad response-to-steroid-hormone term; HSD11B2 acts on steroid substrates but "response to steroid hormone" is a context term rather than the enzyme's molecular role. Reason: Broad context term subsumed by the enzyme's steroid-metabolizing function; retain as non-core rather than core. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
GO:0051287 NAD binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog. HSD11B2 is an NAD+-dependent enzyme with a Rossmann-fold NAD-binding region (residues 82-111); NAD binding is a correct supporting molecular function. Reason: Correct (NAD+ is the physiological cofactor and the Rossmann fold binds NAD), but a supporting MF subsumed by the catalytic activity; retain as non-core. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
GO:0051384 response to glucocorticoid	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected from rat ortholog. Glucocorticoids are the enzyme's substrates; "response to glucocorticoid" is a context/substrate term rather than the core molecular function. Reason: Reflects the substrate context of the enzyme; subsumed by its glucocorticoid-metabolizing function. Retain as non-core. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Functions as a dehydrogenase (oxidase), thereby decreasing the
GO:0045880 positive regulation of smoothened signaling pathway	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS transfer from mouse ortholog (MGI:104720). Same indirect, By-similarity oxysterol-to-SMO link as the Ensembl-projected annotation; not demonstrated for human HSD11B2. Reason: Indirect, similarity-based pathway link via a minor oxysterol activity; not a core function of the human enzyme (consistent with the duplicate IEA annotation). Likely over-annotation. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt which activates smoothened (SMO) and the smoothened
GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS transfer from mouse ortholog (P51661) of the minor NADP+-dependent oxysterol interconversion activity. Not the enzyme's core NAD+-dependent function. Reason: Minor in-vitro oxysterol activity with the non-physiological NADP+ cofactor; consistent with the duplicate IEA annotation. Likely over-annotation relative to the core NAD+-dependent 11beta-HSD function. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt Reaction=7-oxocholesterol + NADPH + H(+) = 7beta-hydroxycholesterol +
GO:0034650 cortisol metabolic process	IMP PMID:8538347 Hypertension in the syndrome of apparent mineralocorticoid e...	ACCEPT	Summary: Experimental (IMP) annotation from the AME kindred with the R374X truncating mutation, in which NAD-dependent 11beta-HSD activity is severely attenuated and cortisol is not converted to cortisone. This is the specific, core biological process (a child of glucocorticoid metabolic process). Reason: Directly supported experimental annotation - loss of HSD11B2 impairs cortisol->cortisone conversion, defining the enzyme's role in cortisol metabolism. Core biological process at the appropriate level of specificity. Supporting Evidence: PMID:8538347 catalyses the interconversion of hormonally active cortisol to inactive cortisone PMID:8538347 NAD-dependent 11 beta-HSD activity was severely attenuated in the stillbirth placenta compared with control placental tissue
GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity	IMP PMID:8538347 Hypertension in the syndrome of apparent mineralocorticoid e...	ACCEPT	Summary: Experimental (IMP) annotation - the AME-causing R374X truncating mutation severely attenuates NAD-dependent 11beta-HSD activity, confirming the enzyme's core NAD+-dependent 11beta-hydroxysteroid dehydrogenase function. Reason: Directly supported experimental molecular-function annotation; the loss-of-function mutation abolishes the NAD-dependent dehydrogenase activity. Core molecular function. Supporting Evidence: PMID:8538347 NAD-dependent 11 beta-HSD activity was severely attenuated in the stillbirth placenta compared with control placental tissue
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-194023	ACCEPT	Summary: Reactome TAS localization to the ER membrane, consistent with experimental evidence that HSD11B2 is an ER-membrane-anchored enzyme (its N-terminal anchor determines orientation in the ER membrane). Core cellular localization. Reason: Well supported (Reactome plus experimental UniProt evidence); the enzyme is an ER-membrane protein. Core cellular component. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt SUBCELLULAR LOCATION: Microsome
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9759259	ACCEPT	Summary: Reactome TAS localization to the ER membrane (duplicate term id from a second Reactome reaction). Consistent with the enzyme's ER-membrane residence. Reason: Duplicate of the well-supported ER-membrane localization; correct core cellular component. Supporting Evidence: file:human/HSD11B2/HSD11B2-uniprot.txt SUBCELLULAR LOCATION: Microsome

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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