Steroid 5-alpha-reductase type 2 (3-oxo-5-alpha-steroid 4-dehydrogenase 2; EC 1.3.1.22), an endoplasmic-reticulum-membrane, NADPH-dependent oxidoreductase that catalyzes the irreversible, stereospecific reduction of the C4-C5 double bond of 3-oxo-Delta4 steroids to their 5alpha-dihydro products. Its most important reaction is the conversion of testosterone to 5alpha-dihydrotestosterone (DHT), the most potent androgen and the preferred ligand for androgen receptor transactivation; it also reduces progesterone and other 3-oxo-Delta4 steroids. The enzyme is a multi-pass membrane protein highly expressed in androgen-target tissues (prostate, genital skin, hair follicle) and is the principal isozyme responsible for DHT production in genital tissue. Loss-of-function variants cause 5alpha-reductase-2 deficiency (pseudovaginal perineoscrotal hypospadias), a form of 46,XY difference of sex development in which affected individuals have normal testosterone but low DHT and undervirilized external genitalia. SRD5A2 is the molecular target of the therapeutic inhibitors finasteride and dutasteride, used to treat benign prostatic hyperplasia and androgenetic alopecia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003865 3-oxo-5-alpha-steroid 4-dehydrogenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the core enzymatic molecular function of the steroid 5-alpha-reductase family. This is the defining, experimentally established activity of SRD5A2. Reason: This is the core molecular function of SRD5A2, directly supported by biochemical characterization of the human enzyme and consistent with the named enzyme. The IBA assignment is at the correct level of specificity. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the PMID:10898110 catalyses the irreversible conversion of testosterone to |
| GO:0006702 androgen biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic assignment of androgen biosynthesis, the core biological process of SRD5A2 (testosterone to DHT is the terminal androgen-activation step producing the most potent androgen). Reason: SRD5A2 produces DHT, the most potent androgen; androgen biosynthesis is a core biological process for this enzyme, supported experimentally in human. Supporting Evidence: PMID:10898110 dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH |
| GO:0008584 male gonad development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic assignment linking the family to male gonad development. SRD5A2 deficiency causes undervirilization in 46,XY individuals, so a developmental role is supported, but it is downstream of the enzyme's core catalytic function rather than a distinct molecular role. Reason: The human deficiency phenotype supports a role in male sexual development, but this is a developmental/physiological consequence of DHT production rather than the enzyme's core molecular function; retain as non-core. Supporting Evidence: PMID:1944596 the major isozyme in genital |
| GO:0043025 neuronal cell body | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic localization to neuronal cell body, propagated from rodent CNS data on family members. This is not the primary localization of the human enzyme, which is an ER/microsomal membrane protein of androgen-target epithelia. Reason: SRD5A2's established subcellular localization is the endoplasmic reticulum (microsome) membrane; neuronal cell body is a CNS-context localization transferred phylogenetically and does not represent the core localization of the human enzyme. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein. |
| GO:0003865 3-oxo-5-alpha-steroid 4-dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (ARBA/InterPro) assignment of the core enzymatic activity, duplicating the IBA/experimental molecular function. Reason: Correct core molecular function, consistent with the experimental EC 1.3.1.22 activity of the human enzyme. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Subcellular-location mapping from UniProt to the ER membrane. This matches the experimentally/curated microsomal (ER) membrane localization of SRD5A2. Reason: SRD5A2 is a multi-pass ER/microsome membrane protein; ER membrane is the correct core localization. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO assignment of the broad lipid metabolic process parent (steroids are lipids). Correct but very general relative to the specific steroid/androgen metabolic role. Reason: Steroid metabolism is a subtype of lipid metabolism, so this is not wrong, but it is a high-level parent that is less informative than the specific steroid/androgen terms; keep as non-core. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0008202 steroid metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO assignment of steroid metabolic process. SRD5A2 reduces a range of 3-oxo-Delta4 steroids (testosterone, progesterone and others), so steroid metabolism is a correct, well-supported process term. Reason: SRD5A2 metabolizes multiple 3-oxo-Delta4 steroids; steroid metabolic process is an accurate biological process assignment. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt it can also act on other steroids, including progesterone, producing |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO generic membrane localization. Correct but non-specific; the informative localization is the ER membrane. Reason: SRD5A2 is a multi-pass membrane protein, so membrane is correct but far less informative than the ER-membrane term; retain as non-core. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein. |
| GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO assignment of a broad oxidoreductase parent. SRD5A2 reduces a C-C double bond of the steroid A-ring, so this parent is correct but less specific than the 3-oxo-5-alpha-steroid 4-dehydrogenase terms. Reason: Accurate but general oxidoreductase parent of the specific EC 1.3.1.22 activity; keep as non-core alongside the specific MF terms. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0047751 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (RHEA/EC) mapping to the NADP+-specific reaction (EC 1.3.1.22). This is the precise catalytic activity of SRD5A2, matching the UniProt catalytic activity blocks. Reason: Precise, correct molecular function; SRD5A2 uses NADPH to reduce 3-oxo-Delta4 steroids (EC 1.3.1.22), consistent with the experimental annotation from PMID:10898110. Supporting Evidence: PMID:10898110 dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare protein-binding annotation from a high-throughput binary interactome map (HuRI). It records a physical interaction (with CYSRT1/GNMT) but conveys no specific molecular function. Reason: Per curation guidelines, bare protein binding is uninformative and does not describe a functional activity; it derives from a proteome-scale screen rather than a characterized functional complex. Retain the interaction record but do not treat as a core function. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt P31213; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-13130472, EBI-3867333; |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare protein-binding annotation from a proteome-scale affinity-purification interactome map (BioPlex; interaction with CLPTM1). Uninformative as a molecular function. Reason: Per curation guidelines, bare protein binding from a high-throughput screen does not describe a specific molecular function; keep the interaction record but not as a core function. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt P31213; O96005: CLPTM1; NbExp=3; IntAct=EBI-13130472, EBI-2873194; |
| GO:0006694 steroid biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl-orthology transfer of steroid biosynthetic process from the rat ortholog (P31214). Consistent with SRD5A2's role in producing bioactive 5alpha-steroids. Reason: Correct but general biosynthetic parent of the more specific androgen/testosterone biosynthetic terms; retain as non-core. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Converts testosterone into 5-alpha- |
| GO:0006702 androgen biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-orthology transfer of androgen biosynthesis from the rat ortholog, duplicating the IBA androgen-biosynthesis annotation. This is a core process for SRD5A2 (DHT production). Reason: SRD5A2 catalyzes the terminal step of androgen activation (testosterone to DHT); androgen biosynthesis is a core biological process. Supporting Evidence: PMID:10898110 dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH |
| GO:0006706 steroid catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of steroid catabolic process. SRD5A2's reaction is a reductive activation (testosterone to the more potent DHT), which is better described as biosynthesis/metabolism than catabolism. Reason: The signature reaction produces a more active androgen rather than degrading steroids; classifying SRD5A2 under steroid catabolism mischaracterizes its role. The steroid/androgen metabolic and biosynthetic terms are the appropriate process annotations. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt the most active androgen in the prostate, as |
| GO:0008209 androgen metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-orthology transfer of androgen metabolic process, duplicating the human IDA annotation. Core process for SRD5A2. Reason: SRD5A2 is central to androgen metabolism (testosterone to DHT); this is a correct core process annotation. Supporting Evidence: PMID:10898110 dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH |
| GO:0008584 male gonad development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl-orthology transfer of male gonad development, duplicating the human IMP/IBA annotations. Supported developmental role, downstream of the core catalytic function. Reason: Developmental consequence of DHT production supported by the human deficiency phenotype; retain as non-core. Supporting Evidence: PMID:1944596 the major isozyme in genital |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent response-to-xenobiotic annotation. This reflects toxicology/expression-response experiments in rat rather than the core enzymatic function of the human enzyme. Reason: A xenobiotic-response phenotype transferred from the rat ortholog does not capture SRD5A2's molecular function; it is a peripheral, context-specific inference. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0018894 dibenzo-p-dioxin metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent dioxin-metabolism association. SRD5A2 is a steroid 5-alpha-reductase and does not metabolize dibenzo-p-dioxin; this is a response/exposure phenotype misattributed as a metabolic process. Reason: SRD5A2 does not enzymatically metabolize dioxins; the annotation reflects a rodent toxicological-response context and over-annotates the enzyme's function. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0018963 phthalate metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent phthalate-metabolism association. SRD5A2 does not metabolize phthalates; this reflects an endocrine-disruptor exposure context rather than enzymatic function. Reason: SRD5A2's substrates are 3-oxo-Delta4 steroids, not phthalates; the annotation over-annotates a toxicological-response context. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt it can also act on other steroids, including progesterone, producing |
| GO:0021766 hippocampus development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent CNS-development annotation (neurosteroid context). Not part of the core function of the human enzyme, whose principal roles are in androgen-target peripheral tissues. Reason: A CNS neurodevelopment role transferred from the rat ortholog is peripheral and context-specific; it over-annotates the enzyme relative to its established androgen-metabolic function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0021854 hypothalamus development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent CNS-development annotation. As with hippocampus development, this reflects a neurosteroid context and is not core to the human enzyme. Reason: Peripheral, CNS-context developmental inference transferred from the rat ortholog; over-annotation relative to the core androgen-metabolic function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0030539 male genitalia development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl-orthology transfer of male genitalia development. This is strongly supported in human by the deficiency phenotype (undervirilized external genitalia), but is a developmental consequence of DHT production rather than the core molecular function. Reason: Well supported physiologically (DHT drives male external genitalia development; SRD5A2 deficiency causes undervirilization), but developmental/downstream of the catalytic role; retain as non-core. Supporting Evidence: PMID:1944596 have male internal urogenital tracts, but female external genitalia file:human/SRD5A2/SRD5A2-uniprot.txt making this reaction a key step in male sexual differentiation during |
| GO:0030540 female genitalia development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of female genitalia development. Poorly supported for the human enzyme, whose defining physiology is male (DHT-dependent) virilization; this looks like an over-broad transfer. Reason: SRD5A2's established developmental role is in male external genitalia via DHT; a female genitalia development role is not supported and over-annotates the enzyme. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt making this reaction a key step in male sexual differentiation during |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent physiological-response annotation. Not a core molecular or biological function of the human enzyme. Reason: A generic environmental-response phenotype transferred from the rat ortholog; peripheral and not informative about SRD5A2 function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0032354 response to follicle-stimulating hormone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent hormone-response annotation (gonadal regulation of expression). Peripheral to the enzyme's core function. Reason: A hormone-response/expression-regulation phenotype from the rat ortholog does not describe SRD5A2's molecular function; over-annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0033574 response to testosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a response-to-testosterone annotation. Testosterone is SRD5A2's principal substrate rather than a stimulus it merely responds to; this recasts the substrate relationship as a generic response process. Reason: SRD5A2 acts on testosterone as an enzymatic substrate (captured by the MF and androgen-metabolic terms); a separate response-to-testosterone process is a context-specific inference that over-annotates the enzyme. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Supporting Evidence: PMID:10898110 catalyses the irreversible conversion of testosterone to |
| GO:0043434 response to peptide hormone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent peptide-hormone-response annotation. Peripheral to the enzyme's core function. Reason: A generic hormone-response phenotype from the rat ortholog; not informative about SRD5A2's molecular function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0048545 response to steroid hormone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a steroid-hormone-response annotation. SRD5A2 metabolizes steroid hormones enzymatically; recasting this as a generic response process is peripheral and less informative than the metabolic terms. Reason: The enzyme acts on steroid hormones as substrates (captured by steroid/androgen metabolic terms); a separate response-to-steroid-hormone process over-annotates it. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt it can also act on other steroids, including progesterone, producing |
| GO:0060348 bone development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a bone-development annotation (androgens influence bone). A distal physiological effect of androgen signaling rather than a core function of the enzyme itself. Reason: Any bone-development link is a downstream systemic effect of DHT/androgen action, not a direct function of SRD5A2; over-annotation transferred from the rat ortholog. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0070852 cell body fiber | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a CNS neuronal localization. Not the core localization of the human enzyme, which is the ER/microsome membrane. Reason: SRD5A2's established localization is the ER membrane; cell body fiber is a CNS-context localization transferred phylogenetically and does not represent the core localization. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of neuronal cell body localization from the rat ortholog (P31214), duplicating the IBA neuronal-cell-body annotation. Not the core localization of the human enzyme, which is the ER/microsome membrane. Reason: SRD5A2's established localization is the ER (microsome) membrane; neuronal cell body is a CNS-context localization transferred from the rat ortholog and does not represent the core localization of the human enzyme. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein. |
| GO:1904614 response to biphenyl | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl-orthology transfer of a rodent response-to-biphenyl (endocrine disruptor) annotation. A toxicological-exposure context, not a core function. Reason: A xenobiotic-exposure response phenotype from the rat ortholog; peripheral and not informative about SRD5A2's molecular function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Catalyzes the irreversible stereospecific reduction of the |
| GO:0006702 androgen biosynthetic process | TAS Reactome:R-HSA-193048 | ACCEPT | Summary: Reactome traceable-author-statement placing SRD5A2 in androgen biosynthesis. Consistent with its role in producing DHT. Reason: SRD5A2 catalyzes the terminal androgen-activation step; androgen biosynthesis is a core process, corroborated by Reactome's Androgen biosynthesis pathway. Supporting Evidence: PMID:10898110 dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH |
| GO:0003865 3-oxo-5-alpha-steroid 4-dehydrogenase activity | TAS Reactome:R-HSA-9705713 | ACCEPT | Summary: Reactome TAS for the core enzymatic activity, based on the SRD5A2-catalyzed testosterone-to-DHT reaction. Matches the experimental and IBA molecular function. Reason: Correct core molecular function, corroborated by the Reactome reaction "SRD5A2 dehydrogenates TEST to DHTEST". Supporting Evidence: PMID:10898110 catalyses the irreversible conversion of testosterone to |
| GO:0047045 testosterone dehydrogenase (NADP+) activity | IDA PMID:10898110 Biochemical and pharmacogenetic dissection of human steroid ... | ACCEPT | Summary: Direct-assay annotation of the NADP+-dependent testosterone-reducing activity, from biochemical characterization of the human enzyme (Km for testosterone 0.9 uM; Km for NADPH 8 uM). This is a specific facet of the core SRD5A2 activity. Reason: Experimentally supported; PMID:10898110 biochemically dissected the human enzyme reducing testosterone with NADPH as cofactor. This is a valid, specific molecular-function facet of the core catalytic activity. Supporting Evidence: PMID:10898110 dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH |
| GO:0047751 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity | EXP PMID:10898110 Biochemical and pharmacogenetic dissection of human steroid ... | ACCEPT | Summary: Experimental (EXP) annotation of the NADP+-dependent 3-oxo-5-alpha-steroid 4-dehydrogenase activity (EC 1.3.1.22), the precise core catalytic activity of SRD5A2. Reason: Directly experimentally supported core molecular function from biochemical characterization of the human enzyme. Supporting Evidence: PMID:10898110 catalyses the irreversible conversion of testosterone to |
| GO:0061370 testosterone biosynthetic process | IDA PMID:10898110 Biochemical and pharmacogenetic dissection of human steroid ... | KEEP AS NON CORE | Summary: Direct-assay annotation to testosterone biosynthetic process. Note that the physiological SRD5A2 reaction consumes testosterone to make DHT (an androgen biosynthetic step); the reverse (DHT to testosterone) direction underlies this term. Given the curator read the full text, this is retained as a supported but non-core facet, with androgen/testosterone-to-DHT biosynthesis being the primary process. Reason: Experimentally annotated by UniProt from PMID:10898110; retained per policy (do not remove experimental annotations whose full text is unverified). Because the dominant physiological role is testosterone-to-DHT conversion (androgen biosynthesis) rather than net testosterone production, this specific term is kept as non-core. Supporting Evidence: PMID:10898110 catalyses the irreversible conversion of testosterone to |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9705713 | ACCEPT | Summary: Reactome TAS localizing SRD5A2 to the ER membrane, matching the curated microsomal (ER) membrane localization. Reason: Correct core localization; SRD5A2 is a multi-pass ER/microsome membrane protein. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9705794 | ACCEPT | Summary: Reactome TAS (inhibitor-binding reaction) localizing SRD5A2 to the ER membrane. Duplicates the ER-membrane localization. Reason: Correct core localization, corroborated by a second Reactome reaction. Supporting Evidence: file:human/SRD5A2/SRD5A2-uniprot.txt Endoplasmic reticulum membrane |
| GO:0007267 cell-cell signaling | TAS PMID:1944596 Deletion of steroid 5 alpha-reductase 2 gene in male pseudoh... | MARK AS OVER ANNOTATED | Summary: Legacy TAS to cell-cell signaling citing the 1991 SRD5A2 cloning/deficiency paper. That paper concerns the enzyme's role in androgen action and male sexual differentiation, not cell-cell signaling; this is a miscast, over-general process. Reason: The cited paper describes SRD5A2 as an enzyme in androgen action and its deletion in pseudohermaphroditism; it does not establish a cell-cell signaling function. This is an inappropriate, over-general process term for the enzyme. Supporting Evidence: PMID:1944596 The conversion of testosterone into dihydrotestosterone by steroid 5 |
| GO:0008209 androgen metabolic process | IDA PMID:1944596 Deletion of steroid 5 alpha-reductase 2 gene in male pseudoh... | ACCEPT | Summary: Direct-assay annotation to androgen metabolic process from the SRD5A2 cloning/functional characterization. Core biological process for the enzyme. Reason: SRD5A2 is central to androgen metabolism (testosterone to DHT); experimentally supported core process. Supporting Evidence: PMID:1944596 The conversion of testosterone into dihydrotestosterone by steroid 5 |
| GO:0008584 male gonad development | IMP PMID:1944596 Deletion of steroid 5 alpha-reductase 2 gene in male pseudoh... | KEEP AS NON CORE | Summary: Mutant-phenotype (IMP) annotation to male gonad development, based on the pseudohermaphroditism phenotype of SRD5A2 gene deletion in 46,XY individuals. Supported developmental role, downstream of the core catalytic function. Reason: Experimentally supported via the human deficiency phenotype (undervirilization in 46,XY males); retained but as a developmental/physiological consequence rather than the core molecular function. Supporting Evidence: PMID:1944596 have male internal urogenital tracts, but female external genitalia |
| GO:0047751 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity | IDA PMID:1944596 Deletion of steroid 5 alpha-reductase 2 gene in male pseudoh... | ACCEPT | Summary: Direct-assay annotation of the NADP+-dependent 3-oxo-5-alpha-steroid 4-dehydrogenase activity from the original SRD5A2 characterization. Core molecular function. Reason: Experimentally supported core catalytic activity (EC 1.3.1.22) of SRD5A2. Supporting Evidence: PMID:1944596 The conversion of testosterone into dihydrotestosterone by steroid 5 |
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