Notes for DANRE crppa
- Core function is CDP-ribitol production for dystroglycan-linked O-mannosyl glycosylation [file:DANRE/crppa/crppa-uniprot.txt "Catalyzes the formation of CDP-ribitol"].
- The old isoprenoid-biosynthetic-process annotation is removed because the MEP pathway context is absent in vertebrates PMID:22522421.
- Brain and muscle development annotations are retained as non-core phenotypic consequences of defective alpha-dystroglycan glycosylation.
Re-review 2026-09-28
Full re-review of all 20 GOA rows against the cached primary literature; the earlier
templated summaries ("consistent with the synthesized gene function") were replaced with
row-specific arguments.
- Added two primary references that define the enzyme: Gerin et al. 2016 (PMID:27194101,
full text) showing recombinant mammalian ISPD is a CDP-ribitol pyrophosphorylase with no
activity on the MEP substrate PMID:27194101 and that FKTN/FKRP use the
product PMID:27194101; and
Riemersma et al. 2015 (PMID:26687144, abstract only) for cytosolic localization and the
cytidyltransferase domain of human ISPD PMID:26687144. A first attempt to cache the Riemersma paper hit a wrong PMID (26055709 is a
PDE12 paper); the correct id was found by PubMed search and only 26687144 is cited.
- Three PENDING rows resolved: GO:0009101 glycoprotein biosynthetic process (IEA, ARBA)
-> MODIFY to GO:0035269, the specific descendant already carried by IBA/IMP; the second
GO:0010559 IGI row (ispd MO1 x fkrp MO) -> MODIFY to GO:0035269, matching the fktn IGI
and IMP rows; the second GO:0055001 IMP row (ispd MO2) -> KEEP_AS_NON_CORE, matching
the MO1 row PMID:22522421.
- The three GO:0010559 "regulation of glycoprotein biosynthetic process" rows stay MODIFY
-> GO:0035269: the definition of GO:0010559 is a process that modulates the rate of
glycoprotein biosynthesis, whereas crppa is a pathway enzyme that performs a step
(donor synthesis), so the evidence supports participation, not regulation
PMID:22522421.
- GO:0008299 isoprenoid biosynthetic process (IEA, InterPro) stays REMOVE, now with the
direct enzymatic exclusion from Gerin 2016 in addition to the absence of the MEP pathway
in vertebrates PMID:22522421.
- Brain morphogenesis and muscle cell development IMP rows stay KEEP_AS_NON_CORE: the
phenotypes are penetrant and specific but downstream of alpha-dystroglycan
hypoglycosylation PMID:22522421.
- Cytosol rows (IBA/IEA/ISS) are now supported by the human localization experiment rather
than the FUNCTION line. Protein homodimerization (ISS) remains KEEP_AS_NON_CORE with only
the by-similarity SUBUNIT line as support.
- Description rewritten as standalone biology; reference_review added to every PMID;
core_functions re-supported with primary quotes; two suggested questions and
experiments added (direct assay of zebrafish Crppa; ribitol rescue in a mutant line).
- Validation: zero errors.