MSMO1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) localization of MSMO1 to the endoplasmic reticulum membrane, consistent with UniProt and Reactome. MSMO1 is a multi-pass ER-membrane sterol oxidase. Reason: The ER membrane is the well-established site of C4-methylsterol oxidation in cholesterol biosynthesis; the IBA call agrees with the UniProt subcellular location and multiple Reactome TAS annotations. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Endoplasmic reticulum membrane file:human/MSMO1/MSMO1-uniprot.txt Multi-pass membrane protein
GO:0036197 zymosterol biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) involvement in zymosterol biosynthesis. MSMO1 performs the C4-demethylation steps between lanosterol and zymosterol, and UniProt places it at the zymosterol-from-lanosterol step of steroid biosynthesis. Reason: Consistent with the pathway placement in UniProt (zymosterol biosynthesis; zymosterol from lanosterol step 3/6). This is a valid, more specific biosynthetic process for MSMO1's role. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
GO:0000254 C-4 methylsterol oxidase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of C-4 methylsterol oxidase activity, the core molecular function of MSMO1/SC4MOL/ERG25 across eukaryotes. Reason: This is the defining molecular function of MSMO1, supported by experimental characterization of the human enzyme and its yeast ERG25 orthologue, and corroborated by EXP, IEA (RHEA/EC 1.14.18.9), and TAS annotations to the same term. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be
GO:0000254 C-4 methylsterol oxidase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (IEA) assignment of C-4 methylsterol oxidase activity via RHEA:55220 / EC 1.14.18.9 mapping, matching the experimentally established function. Reason: The EC/RHEA mapping to EC 1.14.18.9 is correct for MSMO1; UniProt lists this EC number and the corresponding RHEA reaction as the catalytic activity of the enzyme. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt EC=1.14.18.9
GO:0005506 iron ion binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based (IEA) iron ion binding. MSMO1 is a non-heme di-iron oxygenase; its histidine-box motifs coordinate iron required for catalysis, and an Fe cation cofactor is documented. Reason: Iron binding is essential to the C4-methylsterol oxidase mechanism; UniProt records an Fe cation cofactor and notes the histidine boxes are involved in metal ion binding, consistent with the InterPro mapping. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt The histidine box domains may contain the active site and/or be file:human/MSMO1/MSMO1-uniprot.txt Name=Fe cation
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Automated (IEA) ER membrane localization from the UniProt subcellular location keyword mapping, matching the curated ER-membrane location. Reason: Redundant with, and consistent with, the UniProt subcellular location and the IBA/TAS ER-membrane annotations. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Endoplasmic reticulum membrane
GO:0008610 lipid biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based (IEA) lipid biosynthetic process. This is broadly correct (sterols are lipids) but far more general than MSMO1's specific role in cholesterol/sterol biosynthesis. Reason: Not wrong, but a high-level parent term; the more specific cholesterol/sterol biosynthetic process annotations capture the core function. Retained as non-core family-level context. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from high-throughput binary interactome mapping (HuRI) and IntAct, listing partners such as ERG28, CYP4F22, DNAJC30 and several TMEM proteins. Uninformative as a molecular function term. Reason: Bare "protein binding" (GO:0005515) conveys no specific molecular function. The interactions derive from a genome-scale yeast two-hybrid/interactome screen; while an ERG28 interaction is biologically plausible (a scaffold for ER sterol enzymes), the term itself should not be treated as a core function. Retained (not removed) per curation policy for IPI protein-binding annotations. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'
GO:0006695 cholesterol biosynthetic process	TAS Reactome:R-HSA-6807047	ACCEPT	Summary: Reactome TAS placing MSMO1 in cholesterol biosynthesis (Bloch pathway via desmosterol). MSMO1's C4-demethylation is a required step of cholesterol synthesis. Reason: MSMO1 is an established cholesterol-biosynthetic enzyme; the pathway context is correct and central to its biology. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Steroid biosynthesis; cholesterol biosynthesis.
GO:0006695 cholesterol biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: Automated (IEA) cholesterol biosynthetic process from UniPathway mapping, matching the curated pathway role. Reason: Consistent with the UniProt cholesterol-biosynthesis pathway assignment and the Reactome TAS annotations. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Steroid biosynthesis; cholesterol biosynthesis.
GO:0000254 C-4 methylsterol oxidase activity	EXP PMID:21285510 Mutations in the human SC4MOL gene encoding a methyl sterol ...	ACCEPT	Summary: Experimental (EXP) C-4 methylsterol oxidase activity. He et al. identified SC4MOL/MSMO1 mutations causing an inborn error of cholesterol synthesis, with accumulation of C4-methylsterols, establishing the enzyme's demethylase function. Reason: Direct experimental support for the core molecular function; the disease is caused by loss of C4-methylsterol oxidation and consequent methylsterol accumulation. Supporting Evidence: PMID:21285510 catalyzes demethylation of C4-methylsterols in the cholesterol
GO:0000254 C-4 methylsterol oxidase activity	TAS Reactome:R-HSA-194641	ACCEPT	Summary: Reactome TAS for C-4 methylsterol oxidase activity, describing the SC4MOL-catalyzed oxidation of 4,4-dimethylcholesta-8(9),24-dien-3beta-ol in the ER. Reason: Correct core molecular function, redundant with the EXP and IBA annotations to the same term. Supporting Evidence: Reactome:R-HSA-194641 is catalyzed by SC4MOL (C-4 methylsterol oxidase)
GO:0006695 cholesterol biosynthetic process	TAS Reactome:R-HSA-6807062	ACCEPT	Summary: Reactome TAS placing MSMO1 in cholesterol biosynthesis (Kandutsch-Russell / lathosterol pathway), the skin-prominent route to cholesterol. Reason: MSMO1 acts in both the Bloch and Kandutsch-Russell branches of cholesterol biosynthesis; the pathway context is correct. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Steroid biosynthesis; cholesterol biosynthesis.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-194641	ACCEPT	Summary: Reactome TAS for ER-membrane localization, consistent with the curated subcellular location. Reason: Correct compartment; redundant with IBA/IEA ER-membrane annotations. Supporting Evidence: Reactome:R-HSA-194641 This reaction, in the endoplasmic reticulum, is catalyzed by SC4MOL
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-194669	ACCEPT	Summary: Reactome TAS for ER-membrane localization (second demethylation reaction), consistent with the curated subcellular location. Reason: Correct compartment; redundant with the other ER-membrane annotations. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9947203	ACCEPT	Summary: Reactome TAS for ER-membrane localization (MSMO1 oxidation reaction), consistent with the curated subcellular location. Reason: Correct compartment; redundant with the other ER-membrane annotations. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9947207	ACCEPT	Summary: Reactome TAS for ER-membrane localization (MSMO1 oxidation reaction), consistent with the curated subcellular location. Reason: Correct compartment; redundant with the other ER-membrane annotations. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Endoplasmic reticulum membrane
GO:0000254 C-4 methylsterol oxidase activity	TAS PMID:8663358 Characterization of yeast methyl sterol oxidase (ERG25) and ...	ACCEPT	Summary: Older ProtInc TAS for C-4 methylsterol oxidase activity. Li and Kaplan identified the human ERG25 homologue (MSMO1) and characterized methyl sterol oxidase, establishing the function that is now supported experimentally. Reason: Correct core molecular function; the human enzyme was identified as an ERG25 (methyl sterol oxidase) homologue. Supporting Evidence: PMID:8663358 the cloned gene was identical to ERG25, a gene that codes for
GO:0005783 endoplasmic reticulum	TAS PMID:8663358 Characterization of yeast methyl sterol oxidase (ERG25) and ...	ACCEPT	Summary: ProtInc TAS for endoplasmic reticulum localization. Immunofluorescence of the human ERG25 homologue placed it in the ER (and plasma membrane). Reason: The ER assignment is correct and consistent with all later curation; it is a valid (if less specific) parent of ER membrane. Supporting Evidence: PMID:8663358 the proteins are present in the endoplasmic
GO:0005886 plasma membrane	TAS PMID:8663358 Characterization of yeast methyl sterol oxidase (ERG25) and ...	MARK AS OVER ANNOTATED	Summary: ProtInc TAS for plasma-membrane localization, based on 1996 immunofluorescence of the human ERG25 homologue that reported both ER and plasma-membrane signal. Reason: The plasma-membrane call comes from an early immunofluorescence study and is not supported by later, consistent ER-membrane localization in UniProt and Reactome. MSMO1 is a resident ER-membrane cholesterol-biosynthetic enzyme; retained (not removed) but flagged as likely over-annotation. Supporting Evidence: PMID:8663358 the proteins are present in the endoplasmic reticulum and plasma membrane
GO:0006631 fatty acid metabolic process	TAS PMID:8663358 Characterization of yeast methyl sterol oxidase (ERG25) and ...	MARK AS OVER ANNOTATED	Summary: ProtInc TAS for fatty acid metabolic process. The 1996 study reported that iron-limited yeast erg25 mutants accumulated fatty acids, triglycerides, and sterol precursors, an indirect metabolic consequence rather than a direct MSMO1 function. Reason: MSMO1 is a sterol C4-oxidase; the fatty-acid accumulation observed under iron limitation in yeast is a downstream/pleiotropic metabolic effect, not a fatty-acid-metabolic function of the enzyme. Not a core function. Supporting Evidence: PMID:8663358 accumulation of fatty acids,
GO:0008202 steroid metabolic process	TAS PMID:8663358 Characterization of yeast methyl sterol oxidase (ERG25) and ...	KEEP AS NON CORE	Summary: ProtInc TAS for steroid metabolic process. Correct but a high-level parent of the specific sterol/cholesterol biosynthetic process that MSMO1 participates in. Reason: Broadly accurate (sterols are steroids) but general; the specific cholesterol/sterol biosynthetic process annotations better capture the core role. Retained as non-core context. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Steroid biosynthesis; cholesterol biosynthesis.
GO:0016020 membrane	TAS PMID:8663358 Characterization of yeast methyl sterol oxidase (ERG25) and ...	MARK AS OVER ANNOTATED	Summary: ProtInc TAS for the generic "membrane" location. MSMO1 is a multi-pass membrane protein, but the specific ER membrane term is more informative. Reason: "Membrane" is uninformative given the well-supported ER membrane localization; superseded by GO:0005789. Retained but flagged as too general. Supporting Evidence: file:human/MSMO1/MSMO1-uniprot.txt Multi-pass membrane protein

Gene Description

Existing Annotations Review

Core Functions

C-4 methylsterol oxidase; catalyzes the sequential three-step oxidation of the C4-methyl group of 4,4-dimethyl and 4-alpha-methylsterols (the oxidative part of C4-demethylation) in the endoplasmic reticulum membrane as part of cholesterol biosynthesis, using a non-heme di-iron center.

References

📚 Additional Documentation

Notes

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