geneontology / go-ontology

Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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GO:0008396 oxysterol 7-alpha-hydroxylase activity with no cross reference #29041

Closed raymond91125 closed 1 week ago

raymond91125 commented 1 month ago

GO:0008396 oxysterol 7-alpha-hydroxylase activity lacks EC/RHEA cross references. PMID:10882791 the reference cited for the definition does not seem to have anything to do with oxysterol. It must be a typo. A good reference PMID:9295351 Identification and Characterization of a Mouse Oxysterol 7a-Hydroxylase cDNA* PMID:10748047 Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol PMID:27687912 Oxysterols: From cholesterol metabolites to key mediators. Mentions human/mouse CPY7B1 and CYP39A1.

raymond91125 commented 1 month ago

oxysterols are oxidized cholesterols (sterols); Sterols are a subgroup of steroids that contain a hydroxyl group (-OH) at the third carbon position; Steroids are a broad class of lipids characterized by a core structure of four fused carbon rings (three cyclohexane rings and one cyclopentane ring).

Thus, GO:0008396 oxysterol 7-alpha-hydroxylase activity should be a subclass of GO:0008387 steroid 7-alpha-hydroxylase activity. (GO:0008396 EXP annotations include 2 genes, CYP39A1 and CYP7B1.) GO:0008123 cholesterol 7-alpha-monooxygenase activity should also be a subclass of GO:0008387 steroid 7-alpha-hydroxylase activity. (GO:0008123 EXP has only one gene (rat/mouse/human) CYP7A1.)

GO:0008387 steroid 7-alpha-hydroxylase activity has one EXP annotation of CYP39A1 and the definition has no publication reference, but has a narrow synonym cytochrome P450 CYP2A12. UniProt assigns CYP2A12 with EC:1.14.14.1 unspecific monooxygenase

Per UniProt, Expasy, and RHEA: CYP7B1 is of EC:1.14.14.29 25/26-hydroxycholesterol 7alpha-hydroxylase, RHEA:24308 and RHEA:19041, GO:0033783 CYP39A1 is of EC:1.14.14.26 24-hydroxycholesterol 7alpha-hydroxylase, RHEA:46124, GO:0033782 CYP7B1 is also of EC:1.14.14.26

raymond91125 commented 1 month ago

Related by not strictly relevant information: Most cytochrome P450 belong to E.C. 1.14.-.- but there are exceptions https://iubmb.org/wp-content/uploads/sites/10116/2018/12/Classification-of-cytochrome-P-450-enzymes-by-the-Enzyme-Commission.pdf. Useful resource for human P450 https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=242

CYP2A12 (the narrow synonym for GO:0008387 steroid 7-alpha-hydroxylase activity) is a bile acid 7-alpha hydroxylase. Per PMID:31645370 CYP2A12 converts deoxycholic acid (DCA) -> cholic acid and lithocholic acid (LCA) -> cheno-deoxycholic acid (CDCA).

pgaudet commented 1 month ago

PMID:10882791 the reference cited for the definition does not seem to have anything to do with oxysterol. It must be a typo.

This reference was still present; removed.

pgaudet commented 1 month ago

Obsolete steroid 22-alpha hydroxylase activity and replace by steroid 22S-hydroxylase activity; represent the same activity.

pgaudet commented 1 month ago

oxysterol 7-alpha-hydroxylase activity seems to correspond to RHEA:68740 7-oxocholesterol + H+ + NADPH = 7alpha-hydroxycholesterol + NADP+

pgaudet commented 1 month ago
pgaudet commented 1 month ago

GO:0008123 cholesterol 7-alpha-monooxygenase activity Change definition to match RHEA:

And change parent from oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen to GO:0016712 ! oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen

pgaudet commented 1 week ago

Done.