PIGF

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred localization of PIGF to the ER membrane, where the GPI-anchor biosynthetic machinery resides. This is consistent with the direct biochemistry and with UniProt's subcellular location assignment. Reason: PIGF is a multi-pass ER membrane protein that acts within the ER-localized GPI EtNP-transferase complexes; the IBA localization is well supported and represents a core aspect of the protein's biology. Supporting Evidence: PMID:32156170 The core GPI is assembled on the endoplasmic reticulum (ER) membrane and is transferred en bloc to the precursor proteins immediately after their ER translocation file:human/PIGF/PIGF-uniprot.txt Endoplasmic reticulum membrane
GO:0006506 GPI anchor biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement of PIGF in GPI-anchor biosynthesis. PIGF is required for the two late EtNP-transfer steps of the pathway by stabilizing the catalytic transferases PIGO and PIGG. Reason: This is the core biological process of PIGF and is directly supported by experimental characterization of the human protein and its complexes; the IBA call is at the correct level of specificity. Supporting Evidence: PMID:32156170 Two EtNPs are sequentially transferred to the 6-positions of Man3 and then Man2 by PIGO PMID:32156170 Both PIGO and PIGG are stabilized by association with PIGF
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of ER membrane localization, transferred from the mouse ortholog (O09101), Ensembl compara, InterPro (IPR009580, the Pig-F family domain) and UniProt-SubCell. Concordant with the IBA/ISS/TAS ER-membrane calls. Reason: Correct localization for a multi-pass ER membrane protein of the GPI-biosynthetic machinery; the electronic mapping agrees with the experimentally supported location. Supporting Evidence: file:human/PIGF/PIGF-uniprot.txt Endoplasmic reticulum membrane
GO:0006506 GPI anchor biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of GPI-anchor biosynthesis involvement, transferred from the mouse ortholog, InterPro (IPR009580) and UniPathway (UPA00196, GPI-anchor biosynthesis). Agrees with the core function established experimentally. Reason: The InterPro/UniPathway mapping to GPI-anchor biosynthesis is biologically correct and matches the experimentally supported role of PIGF. Supporting Evidence: file:human/PIGF/PIGF-uniprot.txt glycosylphosphatidylinositol-anchor biosynthesis
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: High-throughput binary (yeast two-hybrid) interaction from the HuRI human interactome map. The recorded partners here (AQP6, GPR152, LYVE1, MANBAL, TIMMDC1, TMEM130, TMEM14B, TMEM86B) are largely unrelated membrane proteins rather than the functionally relevant PIGO/PIGG partners, and 'protein binding' is an uninformative molecular-function term. Reason: Bare 'protein binding' (GO:0005515) conveys no specific molecular function, and these are systematic Y2H hits (a screen of the whole interactome, not a PIGF-focused study) to unrelated membrane proteins; per curation policy this IPI is retained but flagged as over-annotation rather than removed. The functionally meaningful interactions of PIGF are with PIGO and PIGG (captured in the process annotations and core_functions). Supporting Evidence: PMID:32296183 we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'
GO:0005789 endoplasmic reticulum membrane	NAS PMID:32156170 Biosynthesis and biology of mammalian GPI-anchored proteins.	ACCEPT	Summary: Author-stated ER-membrane localization (ComplexPortal annotation citing the Kinoshita 2020 GPI-biosynthesis review), reflecting that GPI biosynthesis including the PIGF-containing EtNP-transferase complexes occurs on the ER membrane. Reason: Correct and well-supported localization; consistent with all other ER-membrane annotations for this protein. Supporting Evidence: PMID:32156170 The core GPI is assembled on the endoplasmic reticulum (ER) membrane and is transferred en bloc to the precursor proteins immediately after their ER translocation
GO:0006506 GPI anchor biosynthetic process	IMP PMID:33386993 PIGF deficiency causes a phenotype overlapping with DOORS sy...	ACCEPT	Summary: Experimental (mutant phenotype) evidence that PIGF is required for GPI-anchor biosynthesis. A homozygous PIGF missense variant (p.Pro172Arg) in patients with a DOORS-syndrome-overlapping phenotype caused defective GPI biosynthesis demonstrated by flow cytometry. Reason: Direct human loss-of-function evidence firmly places PIGF in GPI-anchor biosynthesis and links its deficiency to an inherited GPI-deficiency disorder; this is a core annotation. Supporting Evidence: PMID:33386993 We demonstrate impaired glycosylphosphatidylinositol (GPI) biosynthesis through flow cytometry analysis. PMID:33386993 We thus describe the causal role of a novel disease gene, PIGF, in DOORS syndrome and highlight the overlap between this condition and GPI deficiency disorders.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162742	ACCEPT	Summary: Reactome traceable-author-statement placing PIGF (as part of the EtNP-transfer reaction converting the H6/H7 intermediate to H8) at the ER membrane. Reason: Consistent with the established ER-membrane localization of the GPI-biosynthetic machinery; correct localization annotation. Supporting Evidence: PMID:32156170 The core GPI is assembled on the endoplasmic reticulum (ER) membrane and is transferred en bloc to the precursor proteins immediately after their ER translocation
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity-based (ISS) transfer of ER-membrane localization from the mouse ortholog (O09101). Concordant with the direct human evidence. Reason: Correct localization; the ortholog-based inference matches the experimentally supported ER-membrane location of PIGF. Supporting Evidence: file:human/PIGF/PIGF-uniprot.txt Endoplasmic reticulum membrane
GO:0006506 GPI anchor biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity-based (ISS) transfer of GPI-anchor biosynthesis involvement from the mouse ortholog (O09101). Matches the experimentally established core function. Reason: The ortholog-based inference is biologically correct; PIGF's core process is GPI-anchor biosynthesis. Supporting Evidence: file:human/PIGF/PIGF-uniprot.txt glycosylphosphatidylinositol-anchor biosynthesis
GO:0006506 GPI anchor biosynthetic process	TAS PMID:8463218 Cloning of a human gene, PIG-F, a component of glycosylphosp...	ACCEPT	Summary: Traceable author statement from the original cloning of human PIG-F, which identified it as a component of GPI-anchor biosynthesis functioning at the step of EtNP transfer to the GPI intermediate bearing three mannoses (i.e. the PIGO-mediated EtNP transfer to the third mannose). Reason: This is the foundational identification of PIGF as a GPI-anchor biosynthesis component; the process annotation is core and correct. Supporting Evidence: PMID:8463218 PIG-F takes a part in the step of transfer of ethanolamine phosphate to the GPI intermediate containing three residues of mannose.