HSD11B2

UniProt ID: P80365
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

11-beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2; corticosteroid 11-beta-dehydrogenase isozyme 2; SDR9C3) is an endoplasmic-reticulum-membrane, NAD+-dependent, unidirectional dehydrogenase of the short-chain dehydrogenase/reductase (SDR) family. It inactivates the glucocorticoids cortisol to cortisone and corticosterone to 11-dehydrocorticosterone, oxidizing active 11beta-hydroxyglucocorticoids to inert 11-oxosteroids using NAD+. In aldosterone-target epithelia (distal nephron, colon, salivary gland) it destroys cortisol locally, protecting the intrinsically non-selective mineralocorticoid receptor from illicit activation by cortisol and thereby conferring aldosterone specificity; it is also highly expressed in placenta, where it shields the fetus from maternal glucocorticoid. Loss-of-function variants cause the syndrome of apparent mineralocorticoid excess (AME), an autosomal-recessive juvenile low-renin hypertension with hypokalemia and metabolic alkalosis, in which cortisol illicitly activates the mineralocorticoid receptor.

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

Core Functions

NAD+-dependent 11beta-hydroxysteroid dehydrogenase that oxidizes active 11beta-hydroxyglucocorticoids (cortisol, corticosterone) to inactive 11-oxosteroids (cortisone, 11-dehydrocorticosterone) on the endoplasmic reticulum membrane, thereby inactivating glucocorticoids and, in aldosterone-target epithelia, protecting the mineralocorticoid receptor from illicit activation by cortisol.

Molecular Function:
11-beta-hydroxysteroid dehydrogenase (NAD+) activity
Directly Involved In:
cortisol metabolic process glucocorticoid metabolic process
Cellular Locations:
endoplasmic reticulum membrane
Supporting Evidence:
  • PMID:8538347
    catalyses the interconversion of hormonally active cortisol to inactive cortisone
  • file:human/HSD11B2/HSD11B2-uniprot.txt
    Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);

References

GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000116
Automatic Gene Ontology annotation based on Rhea mapping
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:8538347
Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11 beta-hydroxysteroid dehydrogenase type 2 gene.
Reactome:R-HSA-194023
HSD11B2,HSD11B1 dimer oxidise CORT to COR
Reactome:R-HSA-9759259
HSD11B2 dehydrogenates PREDL to PREDN
file:human/HSD11B2/HSD11B2-uniprot.txt
UniProtKB entry P80365 (DHI2_HUMAN), 11-beta-hydroxysteroid dehydrogenase type 2

📚 Additional Documentation

Notes

(HSD11B2-notes.md)

HSD11B2 (P80365) review notes

Verified core biology (from UniProt P80365 + PMID:8538347 abstract + Reactome)

HSD11B2 = 11-beta-hydroxysteroid dehydrogenase type 2 (corticosteroid 11-beta-dehydrogenase
isozyme 2; SDR9C3). Short-chain dehydrogenase/reductase (SDR) family, Rossmann-fold NAD-binding
domain (UniProt: Pfam PF00106 adh_short; PROSITE ADH_SHORT; act site Tyr232 proton acceptor;
NAD binding 82..111).

Molecular function. NAD(+)-dependent 11beta-hydroxysteroid dehydrogenase. Oxidises active
11beta-hydroxyglucocorticoids to inactive 11-oxosteroids: cortisol -> cortisone (RHEA:50208),
corticosterone -> 11-dehydrocorticosterone (RHEA:42204), and the generic reaction
"11beta-hydroxysteroid + NAD+ = 11-oxosteroid + NADH + H+" (RHEA:53116). PhysiologicalDirection
is left-to-right (unidirectional dehydrogenase in vivo), in contrast to HSD11B1 which acts as an
11-oxosteroid reductase. UniProt FUNCTION: "Catalyzes the conversion of biologically active
11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as cortisol, to inactive
11-ketoglucocorticoids (11-oxosteroid) such as cortisone, in the presence of NAD(+)".
KM for cortisol ~26-84 nM; for corticosterone ~5-6 nM (high-affinity). Uses NAD+ (not NADP+)
as cofactor — Glu115 in cofactor-binding domain dictates NAD+ specificity (mutagenesis
E115K/Q abolishes cofactor specificity, PubMed:11238516).

Physiological role. UniProt: "Functions as a dehydrogenase (oxidase), thereby decreasing
the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid
receptor from occupation by glucocorticoids." In aldosterone-target epithelia (distal nephron,
colon, salivary gland) it pre-receptor destroys cortisol locally, conferring aldosterone
specificity on the (intrinsically non-selective) mineralocorticoid receptor NR3C2. PMID:8538347
abstract: "11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the interconversion of
hormonally active cortisol to inactive cortisone and is vital for dictating specificity for the
mineralocorticoid receptor." Highly expressed in placenta (shields fetus from maternal
glucocorticoid) — HPA tissue enrichment: intestine, kidney, salivary gland. Also interacts with
ligand-free cytoplasmic NR3C2 (PubMed:11350956).

Localization. ER membrane (GO:0005789), microsome. N-terminal anchor sequence determines
orientation in the ER membrane (PubMed:10497248). SubCell keyword -> GO:0005783 ER (IEA).

Disease. Loss-of-function variants cause Apparent Mineralocorticoid Excess (AME, MIM:218030),
an autosomal-recessive low-renin juvenile hypertension with hypokalemia/metabolic alkalosis,
nephrocalcinosis; cortisol illicitly activates the MR. Many characterized AME variants in UniProt
(R208C/H, R213C, A328V, RY337-338->H, R374X truncation etc.), all reducing/abolishing enzyme
activity. Liquorice (glycyrrhetinic acid) inhibits the enzyme -> acquired AME-like hypertension.
PMID:8538347 = R374X (374..405 del) truncation in AME kindred; supports both cortisol metabolic
process (IMP) and 11beta-HSD (NAD+) activity (IMP).

Secondary / minor activities (over-annotation candidates)

  • 11-oxidation of 11beta-hydroxyandrogens to 11-ketoandrogens (11beta-hydroxytestosterone ->
    11-ketotestosterone; 11beta-OH-androstenedione -> 11-ketoandrostenedione), RHEA:69368/69408
    (PubMed:22796344, 23685396, 27927697). Real human activity but part of same 11beta-HSD MF
    (same enzyme, extended substrate set) — captured by the general 11beta-HSD MF term.
  • 7-beta-hydroxysteroid dehydrogenase (NADP+) activity GO:0047022: only By similarity to
    P51661 (mouse) / one in-vitro oxysterol paper (7beta-hydroxycholesterol -> 7-ketocholesterol,
    and 7beta,25-diOH-chol -> 7-oxo,25-OH-chol, PubMed:30902677). NADP+, opposite cofactor to the
    physiological NAD+ dehydrogenase; a minor side activity -> MARK_AS_OVER_ANNOTATED (not the
    core/evolved MF; wrong cofactor for the enzyme's physiological role).
  • positive regulation of smoothened signaling pathway GO:0045880 (IEA GO_REF:0000107 from
    mouse P51661; ISS GO_REF:0000024 from MGI): distal, By-similarity-only, via 7-ketocholesterol ->
    7-keto,27-OH-cholesterol (an SMO activator). Not demonstrated for human HSD11B2 and downstream/
    indirect -> MARK_AS_OVER_ANNOTATED.

Ensembl-projected (GO_REF:0000107, ECO:0000265 from rat P50233) BP terms

These are electronically projected from rat ortholog experimental data. Adjudication:
- GO:0008211 glucocorticoid metabolic process — CORE, well supported (dup of IBA). ACCEPT.
- GO:0002017 regulation of blood volume by renal aldosterone — mechanistically apt (pre-receptor
protection of MR in distal nephron confers aldosterone specificity; AME is low-renin
hypertension). KEEP_AS_NON_CORE (downstream physiology, not the molecular core).
- GO:0007565 female pregnancy — placental 11beta-HSD2 shields fetus from maternal glucocorticoid;
plausible, high placental expression. KEEP_AS_NON_CORE.
- GO:0051384 response to glucocorticoid — substrate/context term; KEEP_AS_NON_CORE.
- GO:0048545 response to steroid hormone — broad parent of the above; KEEP_AS_NON_CORE.
- GO:0001666 response to hypoxia — HSD11B2 is placental/hypoxia-regulated in rat; peripheral.
KEEP_AS_NON_CORE.
- GO:0009410 response to xenobiotic stimulus — inhibited by liquorice/xenobiotics but "response
to" implies a regulated cellular response, weak for this enzyme; MARK_AS_OVER_ANNOTATED.
- GO:0032094 response to food, GO:0032868 response to insulin — physiological-context projections
from rat; peripheral, not the gene's molecular role. MARK_AS_OVER_ANNOTATED.
- GO:0005496 steroid binding (MF, ECO:0000265) — substrate binding implicit in the catalytic MF;
keep as supporting/non-core. KEEP_AS_NON_CORE.

MF / broad-parent electronic terms

  • GO:0016616 oxidoreductase activity, acting on CH-OH group of donors, NAD or NADP as acceptor
    (ARBA IEA) — correct but a broad parent of GO:0070523. ACCEPT (acceptable broader IEA).
  • GO:0051287 NAD binding (MF) — correct (NAD+-dependent enzyme, Rossmann fold). KEEP_AS_NON_CORE
    (supporting MF, not the core catalytic function).

Core function synthesis

  • MF: GO:0070523 11-beta-hydroxysteroid dehydrogenase (NAD+) activity
  • BP: GO:0034650 cortisol metabolic process (and its parent GO:0008211 glucocorticoid metabolic process)
  • CC: GO:0005789 endoplasmic reticulum membrane

📄 View Raw YAML

 
id: P80365
gene_symbol: HSD11B2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 11-beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2; corticosteroid
  11-beta-dehydrogenase isozyme 2; SDR9C3) is an endoplasmic-reticulum-membrane,
  NAD+-dependent, unidirectional dehydrogenase of the short-chain dehydrogenase/reductase
  (SDR) family. It inactivates the glucocorticoids cortisol to cortisone and corticosterone
  to 11-dehydrocorticosterone, oxidizing active 11beta-hydroxyglucocorticoids to inert
  11-oxosteroids using NAD+. In aldosterone-target epithelia (distal nephron, colon,
  salivary gland) it destroys cortisol locally, protecting the intrinsically non-selective
  mineralocorticoid receptor from illicit activation by cortisol and thereby conferring
  aldosterone specificity; it is also highly expressed in placenta, where it shields
  the fetus from maternal glucocorticoid. Loss-of-function variants cause the syndrome
  of apparent mineralocorticoid excess (AME), an autosomal-recessive juvenile low-renin
  hypertension with hypokalemia and metabolic alkalosis, in which cortisol illicitly
  activates the mineralocorticoid receptor.
existing_annotations:
- term:
    id: GO:0070523
    label: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
    - reference_id: PMID:8538347
      supporting_text: 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.
- term:
    id: GO:0008211
    label: glucocorticoid metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: HSD11B2 is a bona fide glucocorticoid-metabolizing enzyme; this process
      term is well supported and represents a core biological process.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Functions as a dehydrogenase (oxidase), thereby decreasing
        the
    - reference_id: PMID:8538347
      supporting_text: catalyses the interconversion of hormonally active cortisol
        to inactive cortisone
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: SubCell-keyword-derived ER localization. Correct but less specific than
      the experimentally supported endoplasmic reticulum membrane localization.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Microsome'
- term:
    id: GO:0016616
    label: oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP
      as acceptor
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: A correct broader parent of GO:0070523. Acceptable as a general electronic
      annotation; the specific term GO:0070523 captures the core function.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
- term:
    id: GO:0070523
    label: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: The Rhea reaction mappings correspond exactly to the enzyme's NAD+-dependent
      11beta-HSD activity. Core molecular function (duplicate term id, correctly annotated).
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone
        + NADH +
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Plausible as electronically projected regulation/response, but peripheral
      to the enzyme's core dehydrogenase function. Retain as non-core context.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: 'TISSUE SPECIFICITY: Expressed in kidney, placenta, pancreas,
        prostate,'
- term:
    id: GO:0002017
    label: regulation of blood volume by renal aldosterone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_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.
    supported_by:
    - reference_id: PMID:8538347
      supporting_text: is vital for dictating specificity for the mineralocorticoid
        receptor
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: thus protecting the
- term:
    id: GO:0005496
    label: steroid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Correct (the enzyme binds steroid substrates) but subsumed by the catalytic
      molecular function; retain as non-core supporting activity.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
- term:
    id: GO:0007565
    label: female pregnancy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Supported by the enzyme's high placental expression and its barrier role
      against maternal glucocorticoids, but represents peripheral physiology. Retain
      as non-core.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: 'TISSUE SPECIFICITY: Expressed in kidney, placenta, pancreas,
        prostate,'
    - reference_id: PMID:8538347
      supporting_text: first characterised in placental tissue
- term:
    id: GO:0008211
    label: glucocorticoid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-projected duplicate of the IBA glucocorticoid metabolic process
      annotation. Correct core biological process.
    action: ACCEPT
    reason: Duplicate of the well-supported core process term; HSD11B2 metabolizes
      glucocorticoids.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Functions as a dehydrogenase (oxidase), thereby decreasing
        the
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: 'ACTIVITY REGULATION: Inhibited by glycyrrhetinic acid (derived
        from'
- term:
    id: GO:0032094
    label: response to food
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-projected from rat ortholog. A physiological-context response
      term with no clear connection to the enzyme's molecular mechanism in humans.
    action: MARK_AS_OVER_ANNOTATED
    reason: Peripheral response-to-stimulus term projected from rodent physiology,
      not reflecting a core function of HSD11B2. Likely over-annotation.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Functions as a dehydrogenase (oxidase), thereby decreasing
        the
- term:
    id: GO:0032868
    label: response to insulin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-projected from rat ortholog. A physiological-context response
      term; not part of the enzyme's core molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Peripheral response-to-stimulus term projected from rodent data; not a
      core function of the enzyme. Likely over-annotation.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Functions as a dehydrogenase (oxidase), thereby decreasing
        the
- term:
    id: GO:0045880
    label: positive regulation of smoothened signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: which activates smoothened (SMO) and the smoothened
- term:
    id: GO:0047022
    label: 7-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=7-oxocholesterol + NADPH + H(+) = 7beta-hydroxycholesterol
        +
- term:
    id: GO:0048545
    label: response to steroid hormone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Broad context term subsumed by the enzyme's steroid-metabolizing function;
      retain as non-core rather than core.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
- term:
    id: GO:0051287
    label: NAD binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
- term:
    id: GO:0051384
    label: response to glucocorticoid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Reflects the substrate context of the enzyme; subsumed by its glucocorticoid-metabolizing
      function. Retain as non-core.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Functions as a dehydrogenase (oxidase), thereby decreasing
        the
- term:
    id: GO:0045880
    label: positive regulation of smoothened signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: which activates smoothened (SMO) and the smoothened
- term:
    id: GO:0047022
    label: 7-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: ISS transfer from mouse ortholog (P51661) of the minor NADP+-dependent
      oxysterol interconversion activity. Not the enzyme's core NAD+-dependent function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: Reaction=7-oxocholesterol + NADPH + H(+) = 7beta-hydroxycholesterol
        +
- term:
    id: GO:0034650
    label: cortisol metabolic process
  evidence_type: IMP
  original_reference_id: PMID:8538347
  qualifier: involved_in
  review:
    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).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8538347
      supporting_text: catalyses the interconversion of hormonally active cortisol
        to inactive cortisone
    - reference_id: PMID:8538347
      supporting_text: NAD-dependent 11 beta-HSD activity was severely attenuated
        in the stillbirth placenta compared with control placental tissue
- term:
    id: GO:0070523
    label: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity
  evidence_type: IMP
  original_reference_id: PMID:8538347
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Directly supported experimental molecular-function annotation; the loss-of-function
      mutation abolishes the NAD-dependent dehydrogenase activity. Core molecular
      function.
    supported_by:
    - reference_id: PMID:8538347
      supporting_text: NAD-dependent 11 beta-HSD activity was severely attenuated
        in the stillbirth placenta compared with control placental tissue
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-194023
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Well supported (Reactome plus experimental UniProt evidence); the enzyme
      is an ER-membrane protein. Core cellular component.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Microsome'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9759259
  qualifier: located_in
  review:
    summary: Reactome TAS localization to the ER membrane (duplicate term id from a
      second Reactome reaction). Consistent with the enzyme's ER-membrane residence.
    action: ACCEPT
    reason: Duplicate of the well-supported ER-membrane localization; correct core
      cellular component.
    supported_by:
    - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Microsome'
core_functions:
- description: NAD+-dependent 11beta-hydroxysteroid dehydrogenase that oxidizes active
    11beta-hydroxyglucocorticoids (cortisol, corticosterone) to inactive 11-oxosteroids
    (cortisone, 11-dehydrocorticosterone) on the endoplasmic reticulum membrane, thereby
    inactivating glucocorticoids and, in aldosterone-target epithelia, protecting
    the mineralocorticoid receptor from illicit activation by cortisol.
  molecular_function:
    id: GO:0070523
    label: 11-beta-hydroxysteroid dehydrogenase (NAD+) activity
  directly_involved_in:
  - id: GO:0034650
    label: cortisol metabolic process
  - id: GO:0008211
    label: glucocorticoid metabolic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:8538347
    supporting_text: catalyses the interconversion of hormonally active cortisol to
      inactive cortisone
  - reference_id: file:human/HSD11B2/HSD11B2-uniprot.txt
    supporting_text: Reaction=cortisol + NAD(+) = cortisone + NADH + H(+);
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:8538347
  title: Hypertension in the syndrome of apparent mineralocorticoid excess due to
    mutation of the 11 beta-hydroxysteroid dehydrogenase type 2 gene.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified case report of an AME kindred with an R374X truncating
      mutation showing severely attenuated NAD-dependent 11beta-HSD activity; directly
      supports the enzyme's NAD+-dependent 11beta-HSD activity and its role in cortisol
      metabolism and mineralocorticoid receptor specificity.
- id: Reactome:R-HSA-194023
  title: HSD11B2,HSD11B1 dimer oxidise CORT to COR
  findings: []
- id: Reactome:R-HSA-9759259
  title: HSD11B2 dehydrogenates PREDL to PREDN
  findings: []
- id: file:human/HSD11B2/HSD11B2-uniprot.txt
  title: UniProtKB entry P80365 (DHI2_HUMAN), 11-beta-hydroxysteroid dehydrogenase
    type 2
  findings: []