id: P28845
gene_symbol: HSD11B1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an NADP(H)-dependent
  short-chain dehydrogenase/reductase anchored in the endoplasmic reticulum membrane as a
  single-pass type II membrane protein, with its catalytic domain facing the ER lumen. It
  catalyzes the interconversion of the inactive 11-keto glucocorticoid cortisone and the
  active 11-hydroxy glucocorticoid cortisol (and 11-dehydrocorticosterone/corticosterone).
  Although bidirectional in vitro, in vivo it acts predominantly as a reductase (cortisone
  to cortisol); its reductive directionality is set by the supply of NADPH generated in the
  ER lumen by hexose-6-phosphate dehydrogenase (H6PD). By regenerating active glucocorticoids
  locally, 11beta-HSD1 amplifies pre-receptor glucocorticoid action in liver, adipose tissue,
  brain, eye and other tissues, making it a therapeutic target in metabolic syndrome, type 2
  diabetes and obesity. It functions as a homodimer and has broad substrate specificity,
  additionally metabolizing 7-oxo/7-hydroxy oxysterols (e.g. 7-ketocholesterol), 7-oxo bile
  acids, neurosteroids and 11-oxygenated C19 steroids. Loss or reduction of activity causes
  cortisone reductase deficiency.
existing_annotations:
- term:
    id: GO:0006706
    label: steroid catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically-inferred biological process. HSD11B1 does participate in steroid
      metabolism, but its predominant physiological role is reductive activation of
      glucocorticoids (cortisone to cortisol), i.e. metabolism/interconversion rather than
      catabolism. The catabolic framing fits some oxidative or oxysterol reactions but is
      imprecise for the core function.
    action: MODIFY
    reason: Steroid catabolic process mischaracterizes the core in-vivo activity, which is
      reductive regeneration of active cortisol (a glucocorticoid metabolic/interconversion
      process), not steroid breakdown. Generalize/re-target to glucocorticoid metabolic process,
      which correctly covers the bidirectional interconversion of active and inactive
      glucocorticoids.
    proposed_replacement_terms:
    - id: GO:0008211
      label: glucocorticoid metabolic process
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - GRANULARITY_MISMATCH
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: functions as a reductase in vivo, thereby increasing the concentration
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: of active glucocorticoids
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetically-inferred localization to the ER membrane, consistent with direct
      experimental evidence that 11beta-HSD1 is an ER-membrane protein with its catalytic
      domain in the ER lumen. This is the core cellular location where the enzyme acts.
    action: ACCEPT
    reason: Well supported by experimental localization data; the enzyme is active in the ER
      membrane (lumen-facing catalytic domain).
    supported_by:
    - reference_id: PMID:10497248
      supporting_text: localization of both 11beta-HSD1 and
    - reference_id: PMID:10497248
      supporting_text: the catalytic domain containing the C terminus is protruding into the ER
- term:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetically-inferred core molecular function. This is the defining catalytic
      activity of HSD11B1, corroborated by numerous experimental (IDA) annotations and the
      UniProt catalytic-activity record (EC 1.1.1.146; 11beta-hydroxysteroid + NADP(+) =
      11-oxosteroid + NADPH). This is the core molecular function.
    action: ACCEPT
    reason: Definitive, well-supported core enzymatic activity of the gene product.
    supported_by:
    - reference_id: PMID:15513927
      supporting_text: ER-localized membrane protein that catalyzes the interconversion of cortisone
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: Reaction=cortisone + NADPH + H(+) = cortisol + NADP(+);
- term:
    id: GO:0005496
    label: steroid binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetically-inferred steroid binding, reflecting the enzyme's binding of
      steroid substrates (glucocorticoids and other steroid/sterol substrates) in its active
      site. This is a real but generic molecular function that is subsidiary to the catalytic
      activity.
    action: KEEP_AS_NON_CORE
    reason: Substrate binding is genuine but is an aspect of the catalytic mechanism rather than
      an independent core function; the informative core MF is the dehydrogenase activity.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: besides glucocorticoids, it accepts other steroid and sterol substrates
- term:
    id: GO:0004090
    label: carbonyl reductase (NADPH) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: RHEA-based electronic annotation. HSD11B1 does perform NADPH-dependent carbonyl
      (oxo) reductions on several substrates (e.g. 7-oxo bile acids, oxysterols), so the term
      is not wrong, but it is a broad generic parent that is far less informative than the
      specific 11-beta-hydroxysteroid dehydrogenase and cortisol dehydrogenase activities.
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct in essence (NADPH-dependent carbonyl reduction occurs) but overly general;
      the specific dehydrogenase activities better describe the function.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: Reaction=cortisone + NADPH + H(+) = cortisol + NADP(+);
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation from the UniProt Subcellular Location vocabulary mapping,
      consistent with experimental evidence that 11beta-HSD1 is an ER-membrane protein.
    action: ACCEPT
    reason: Correct core localization, agreeing with experimental (IDA) and phylogenetic (IBA)
      evidence.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: type II membrane protein
- term:
    id: GO:0047022
    label: 7-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation (EC 1.1.1.201). HSD11B1 has documented 7-oxosteroid
      reductase / 7beta-hydroxysteroid dehydrogenase activity, interconverting 7-oxo and
      7beta-hydroxy sterols/bile acids/neurosteroids (e.g. 7-ketocholesterol to
      7beta-hydroxycholesterol). This is a real secondary catalytic activity of the enzyme.
    action: ACCEPT
    reason: EC-backed secondary activity supported by the UniProt catalytic-activity record and
      by experimental oxysterol/bile-acid studies; a genuine additional molecular function.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: a 7beta-hydroxysteroid + NADP(+) = a 7-oxosteroid + NADPH +
    - reference_id: PMID:15152005
      supporting_text: potential role in 7-ketocholesterol metabolism.
- term:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation (EC 1.1.1.146) for the core 11beta-HSD activity. Duplicates
      the IBA and IDA annotations of the same term and is fully supported.
    action: ACCEPT
    reason: Correct core molecular function; duplicate of the experimentally and phylogenetically
      supported term.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: Reaction=cortisone + NADPH + H(+) = cortisol + NADP(+);
- term:
    id: GO:0102196
    label: cortisol dehydrogenase (NADP+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: RHEA-based electronic annotation (RHEA:68616, cortisone + NADPH = cortisol +
      NADP(+)) capturing the physiologically dominant reductive reaction of HSD11B1, the
      regeneration of active cortisol from cortisone. This is a specific and accurate
      representation of the core in-vivo function.
    action: ACCEPT
    reason: Specific, biologically accurate term for the enzyme's predominant in-vivo reductase
      reaction (cortisone to cortisol); complements the broader 11beta-HSD activity term.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: Reaction=cortisone + NADPH + H(+) = cortisol + NADP(+);
    - reference_id: PMID:15513927
      supporting_text: ER-localized membrane protein that catalyzes the interconversion of cortisone
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-194023
  qualifier: located_in
  review:
    summary: Reactome-asserted ER-membrane localization for the HSD11B1-containing reaction.
      Consistent with all other localization evidence for this enzyme.
    action: ACCEPT
    reason: Correct core localization, supported by experimental and phylogenetic evidence.
    supported_by:
    - reference_id: PMID:10497248
      supporting_text: localization of both 11beta-HSD1 and
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9757706
  qualifier: located_in
  review:
    summary: Reactome-asserted ER-membrane localization for a hepatic HSD11B1 reaction
      (prednisone to prednisolone reduction). Consistent with all other localization evidence.
    action: ACCEPT
    reason: Correct core localization, supported by experimental and phylogenetic evidence.
    supported_by:
    - reference_id: PMID:10497248
      supporting_text: the catalytic domain containing the C terminus is protruding into the ER
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:10497248
  qualifier: located_in
  review:
    summary: Direct experimental evidence (fluorescence microscopy and protease-protection
      assays) localizing 11beta-HSD1 to the ER membrane, with the catalytic C-terminal domain
      protruding into the ER lumen and the N-terminus cytoplasmic (single-pass type II membrane
      topology). This anchors the core localization.
    action: ACCEPT
    reason: High-quality direct experimental evidence for the core ER-membrane localization.
    supported_by:
    - reference_id: PMID:10497248
      supporting_text: the N terminus of 11beta-HSD1 is cytoplasmic,
    - reference_id: PMID:10497248
      supporting_text: the catalytic domain containing the C terminus is protruding into the ER
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:15513927
  qualifier: enables
  review:
    summary: Crystallographic evidence that human 11beta-HSD1 assembles as a homo-oligomer;
      the structures show the C-termini of subunits converging to form an oligomerization motif.
      UniProt records the enzyme as a homodimer. The homodimerization is genuine but is a
      structural/quaternary property rather than the informative core molecular function.
    action: ACCEPT
    reason: Homodimerization is directly demonstrated by crystal structures and recorded by
      UniProt; a real molecular property, kept but not the core catalytic function.
    supported_by:
    - reference_id: PMID:15513927
      supporting_text: four 11beta-HSD1 C termini converge to form an as yet
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:17919905
  qualifier: enables
  review:
    summary: X-ray co-crystal structure of 11beta-HSD1 (in complex with NADP and an inhibitor)
      supporting the oligomeric assembly of the enzyme. Consistent with the UniProt homodimer
      annotation.
    action: ACCEPT
    reason: Structural evidence supports homodimerization; genuine quaternary structure, retained
      as a non-core property.
    supported_by:
    - reference_id: PMID:17919905
      supporting_text: The binding mode was determined through the X-ray co-crystal
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:18069989
  qualifier: enables
  review:
    summary: X-ray crystallographic characterization of an orally active 11beta-HSD1 inhibitor
      complex, contributing structural support for the homodimeric assembly of the enzyme, as
      recorded by UniProt.
    action: ACCEPT
    reason: Structural evidence supports homodimerization; retained as a real non-core property.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:18485702
  qualifier: enables
  review:
    summary: X-ray crystal structure of 11beta-HSD1 in complex with NADP and an inhibitor,
      contributing structural evidence consistent with the homodimeric assembly recorded by
      UniProt.
    action: ACCEPT
    reason: Structural evidence supports homodimerization; retained as a real non-core property.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:18553955
  qualifier: enables
  review:
    summary: Crystallographic study of benzamide inhibitor complexes of 11beta-HSD1,
      contributing structural support for the enzyme's homodimeric assembly recorded by UniProt.
    action: ACCEPT
    reason: Structural evidence supports homodimerization; retained as a real non-core property.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:19217779
  qualifier: enables
  review:
    summary: Crystallographic study of piperidyl benzamide inhibitor complexes of 11beta-HSD1,
      contributing structural support for the enzyme's homodimeric assembly recorded by UniProt.
    action: ACCEPT
    reason: Structural evidence supports homodimerization; retained as a real non-core property.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0050661
    label: NADP binding
  evidence_type: IDA
  original_reference_id: PMID:15513927
  qualifier: enables
  review:
    summary: NADP(H) is the obligate cofactor of 11beta-HSD1, and crystal structures were solved
      as ternary complexes containing NADP. NADP binding is a genuine molecular function but is
      a cofactor-binding aspect of the catalytic mechanism rather than the informative core MF.
    action: KEEP_AS_NON_CORE
    reason: Cofactor binding is real and structurally demonstrated but subsidiary to the
      dehydrogenase activity, which is the core function.
    supported_by:
    - reference_id: PMID:15513927
      supporting_text: two ternary complexes of 11beta-HSD1
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: cosubstrate NADPH
- term:
    id: GO:0050661
    label: NADP binding
  evidence_type: IDA
  original_reference_id: PMID:17919905
  qualifier: enables
  review:
    summary: X-ray co-crystal structure with NADP demonstrating cofactor binding. Genuine but
      subsidiary to the core dehydrogenase activity.
    action: KEEP_AS_NON_CORE
    reason: Structurally demonstrated cofactor binding, retained as a non-core molecular function.
    supported_by:
    - reference_id: PMID:17919905
      supporting_text: The binding mode was determined through the X-ray co-crystal
- term:
    id: GO:0050661
    label: NADP binding
  evidence_type: IDA
  original_reference_id: PMID:18069989
  qualifier: enables
  review:
    summary: Structural characterization of an 11beta-HSD1 complex demonstrating NADP cofactor
      binding. Genuine but subsidiary to the core dehydrogenase activity.
    action: KEEP_AS_NON_CORE
    reason: Structurally demonstrated cofactor binding, retained as a non-core molecular function.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: cosubstrate NADPH
- term:
    id: GO:0050661
    label: NADP binding
  evidence_type: IDA
  original_reference_id: PMID:18485702
  qualifier: enables
  review:
    summary: Crystal structure of 11beta-HSD1 in complex with NADP demonstrating cofactor
      binding. Genuine but subsidiary to the core dehydrogenase activity.
    action: KEEP_AS_NON_CORE
    reason: Structurally demonstrated cofactor binding, retained as a non-core molecular function.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: cosubstrate NADPH
- term:
    id: GO:0050661
    label: NADP binding
  evidence_type: IDA
  original_reference_id: PMID:18553955
  qualifier: enables
  review:
    summary: Crystallographic evidence of NADP cofactor binding by 11beta-HSD1. Genuine but
      subsidiary to the core dehydrogenase activity.
    action: KEEP_AS_NON_CORE
    reason: Structurally demonstrated cofactor binding, retained as a non-core molecular function.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: cosubstrate NADPH
- term:
    id: GO:0050661
    label: NADP binding
  evidence_type: IDA
  original_reference_id: PMID:19217779
  qualifier: enables
  review:
    summary: Crystallographic evidence of NADP cofactor binding by 11beta-HSD1. Genuine but
      subsidiary to the core dehydrogenase activity.
    action: KEEP_AS_NON_CORE
    reason: Structurally demonstrated cofactor binding, retained as a non-core molecular function.
    supported_by:
    - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
      supporting_text: cosubstrate NADPH
- term:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IDA
  original_reference_id: PMID:10497248
  qualifier: enables
  review:
    summary: Direct experimental measurement of 11beta-HSD1 enzymatic activity (glucocorticoid
      interconversion with defined kinetics for corticosterone and 11-dehydrocorticosterone) in
      the study that also established ER-membrane topology. Supports the core catalytic function.
    action: ACCEPT
    reason: Direct experimental evidence for the core 11beta-HSD (NADP+) activity.
    supported_by:
    - reference_id: PMID:10497248
      supporting_text: regulate the ratio of
    - reference_id: PMID:10497248
      supporting_text: active endogenous glucocorticoids to their inactive keto-metabolites
- term:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IDA
  original_reference_id: PMID:15152005
  qualifier: enables
  review:
    summary: Direct experimental evidence that the ER-lumen-oriented 11beta-HSD1 carries out
      efficient glucocorticoid oxidoreduction (cortisol oxidation shown to depend on luminal
      orientation), establishing the core catalytic activity and its pre-receptor role.
    action: ACCEPT
    reason: Direct experimental evidence for the core 11beta-HSD (NADP+) activity.
    supported_by:
    - reference_id: PMID:15152005
      supporting_text: 11beta-HSD1) exerts an important pre-receptor function
    - reference_id: PMID:15152005
      supporting_text: essential for efficient oxidation of cortisol.
- term:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IDA
  original_reference_id: PMID:17070044
  qualifier: enables
  review:
    summary: Enzyme-inhibition study demonstrating 11beta-HSD1 catalytic activity in liver, fat
      and brain (target of adamantane sulfone/sulfonamide inhibitors), consistent with the core
      dehydrogenase activity of the enzyme.
    action: ACCEPT
    reason: Experimental evidence of the core enzymatic activity via inhibitor-based assays.
    supported_by:
    - reference_id: PMID:17070044
      supporting_text: strongly inhibit liver, fat, and brain HSD1
- term:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  evidence_type: IDA
  original_reference_id: PMID:17919905
  qualifier: enables
  review:
    summary: Enzyme-inhibition and X-ray co-crystal study confirming the 11beta-HSD1 catalytic
      activity used as the assay target, consistent with the core dehydrogenase function.
    action: ACCEPT
    reason: Experimental evidence of the core enzymatic activity in an inhibitor/structure study.
    supported_by:
    - reference_id: PMID:17919905
      supporting_text: 2-anilinothiazolones were prepared as inhibitors of
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput mass-spectrometry membrane-proteome study of an NK-like cell line
      that identified HSD11B1 among ~1843 proteins. "Membrane" is a generic parent of the
      specific and well-supported ER-membrane localization, and the annotation derives from a
      broad proteomics screen rather than targeted localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not wrong (the enzyme is a membrane protein) but uninformatively general relative to
      the specific ER membrane localization; sourced from a high-throughput proteomics dataset.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: identified 1843 proteins with high confidence scores
core_functions:
- description: NADP(H)-dependent 11-beta-hydroxysteroid dehydrogenase / oxoreductase that
    interconverts inactive and active glucocorticoids, acting predominantly in vivo as a
    reductase converting cortisone to cortisol at the ER membrane, thereby amplifying
    pre-receptor glucocorticoid action.
  molecular_function:
    id: GO:0070524
    label: 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
  directly_involved_in:
  - id: GO:0008211
    label: glucocorticoid metabolic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/HSD11B1/HSD11B1-uniprot.txt
    supporting_text: Reaction=cortisone + NADPH + H(+) = cortisol + NADP(+);
  - reference_id: PMID:15513927
    supporting_text: ER-localized membrane protein that catalyzes the interconversion of cortisone
references:
- 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:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/HSD11B1/HSD11B1-uniprot.txt
  title: UniProtKB entry P28845 (DHI1_HUMAN), 11-beta-hydroxysteroid dehydrogenase 1
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProtKB record; source of catalytic-activity, subunit, subcellular
      location and function statements used as file-quote support.
- id: PMID:10497248
  title: The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine
    their orientation in the endoplasmic reticulum membrane.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes ER-membrane localization and single-pass type II topology with
      lumen-facing catalytic domain; also reports enzymatic activity. Abstract-only in cache.
- id: PMID:15152005
  title: Appropriate function of 11beta-hydroxysteroid dehydrogenase type 1 in the
    endoplasmic reticulum lumen is dependent on its N-terminal region sharing similar
    topological determinants with 50-kDa esterase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Supports pre-receptor glucocorticoid function, ER-lumen orientation dependence
      of activity, and 7-ketocholesterol metabolism. Abstract-only in cache.
- id: PMID:15513927
  title: Conformational flexibility in crystal structures of human 11beta-hydroxysteroid
    dehydrogenase type I provide insights into glucocorticoid interconversion and
    enzyme regulation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Crystal structures establishing cortisone/cortisol interconversion,
      oligomerization motif, and adipose-tissue disease relevance. Abstract-only in cache.
- id: PMID:17070044
  title: Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Inhibitor study confirming 11beta-HSD1 activity in liver, fat and brain.
      Abstract-only in cache.
- id: PMID:17919905
  title: The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Inhibitor/X-ray co-crystal study confirming enzymatic activity and structure.
      Abstract-only in cache.
- id: PMID:18069989
  title: Structural characterization and pharmacodynamic effects of an orally active
    11beta-hydroxysteroid dehydrogenase type 1 inhibitor.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Structural inhibitor study; supports homodimeric assembly. Abstract-only in cache.
- id: PMID:18485702
  title: Pyridine amides as potent and selective inhibitors of 11beta-hydroxysteroid
    dehydrogenase type 1.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Structural inhibitor study; supports homodimeric assembly. Abstract-only in cache.
- id: PMID:18553955
  title: Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid
    dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition
    ex vivo model.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Structural inhibitor study; supports homodimeric assembly. Abstract-only in cache.
- id: PMID:19217779
  title: Discovery and optimization of piperidyl benzamide derivatives as a novel
    class of 11beta-HSD1 inhibitors.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Structural inhibitor study; supports homodimeric assembly. Abstract-only in cache.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput membrane-proteome MS screen; source of the generic 'membrane'
      HDA annotation, not targeted localization evidence.
- id: Reactome:R-HSA-194023
  title: HSD11B2,HSD11B1 dimer oxidise CORT to COR
  findings: []
- id: Reactome:R-HSA-9757706
  title: HSD11B1 hydrogenates PREDN to PREDL in hepatic cell
  findings: []