PIGV

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) localization of PIGV activity to the ER membrane. PIGV is a multi-pass ER membrane enzyme whose GPI-MT-II activity acts on the lumenal face of the ER, so ER membrane is the correct site of action. Consistent with direct experimental localization (PMID:15623507) and UniProt subcellular location. Reason: Correct and specific cellular component for this ER-resident GPI biosynthetic enzyme; supported by direct experimental evidence in addition to the IBA inference. Supporting Evidence: PMID:15623507 Human PIG-V encodes a 493-amino acid, endoplasmic reticulum (ER) resident protein with eight putative transmembrane regions.
GO:0120563 dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the specific GPI-MT-II catalytic activity, the transfer of the second mannose via an alpha-1,6 bond from Dol-P-Man onto the Man1-GlcN-(acyl)PI GPI intermediate. This is the exact enzymatic activity of PIGV and the most informative molecular function term available; it is corroborated by direct human experimental work (PMID:15623507) and yeast/human complementation (PMID:15720390). Reason: This is the core molecular function of PIGV, at the correct level of specificity. Supporting Evidence: PMID:15623507 Here we report the cloning of PIG-V involved in transferring the second mannose in the GPI anchor. PMID:15623507 four Dol-P-Man-dependent mannosyltransferases, GPI-MT-I, -MT-II, -MT-III, and -MT-IV for the first, second, third, and fourth mannoses
GO:0031501 mannosyltransferase complex	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) assignment of PIGV to a mannosyltransferase complex. Mammalian GPI-MT-II activity is attributed to PIG-V acting as the catalyst or as a component of the catalytic complex, so complex membership is plausible. However, the composition of a distinct PIGV mannosyltransferase complex in human is not experimentally well established here, so this is retained as a supporting (non-core) annotation rather than a defining function. Reason: Reasonable at the phylogenetic level and consistent with GPI-MT-II being a component of a catalytic assembly, but it is a supporting structural annotation, not the core catalytic/process function of the gene. Supporting Evidence: Reactome:R-HSA-162873 PIG-V was identified as the catylyst, or a component of the catalyst, of this reaction
GO:0006506 GPI anchor biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment to GPI anchor biosynthesis. PIGV catalyzes the seventh step of the GPI-anchor biosynthetic pathway (second-mannose addition), so this is the correct core biological process. Reason: Core biological process of PIGV; strongly supported by experimental (PMID:15623507, PMID:15720390) and pathway evidence. Supporting Evidence: PMID:15623507 The biosynthetic pathway of GPI is mediated by sequential additions of sugars and other components to phosphatidylinositol. PMID:15720390 A bioinformatics-based strategy identified the essential Saccharomyces cerevisiae Ybr004c protein as a candidate for the second GPI alpha-mannosyltransferase (GPI-MT-II).
GO:0000009 alpha-1,6-mannosyltransferase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO (IEA) mapping from the PIG-V/Gpi18 domain (IPR007315) to alpha-1,6-mannosyltransferase activity. This is a correct but less specific parent of the exact PIGV activity (GO:0120563); PIGV forms the alpha-1,6 mannosyl linkage. Reason: Accurate parent molecular-function term; consistent with the specific GPI-MT-II activity but broader. Kept as a correct (non-core) generalization. Supporting Evidence: PMID:15623507 PIG-V involved in transferring the second mannose in glycosylphosphatidylinositol.
GO:0004376 GPI mannosyltransferase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO (IEA) mapping from the PIG-V/Gpi18 domain (IPR007315) to GPI mannosyltransferase activity. This is a correct parent term of the specific PIGV activity (GO:0120563 is a subclass of GO:0004376) and accurately describes PIGV as a GPI mannosyltransferase. Reason: Accurate parent molecular-function term for this GPI mannosyltransferase; broader than the specific GPI-MT-II term but correct. Supporting Evidence: PMID:15623507 four Dol-P-Man-dependent mannosyltransferases, GPI-MT-I, -MT-II, -MT-III, and -MT-IV for the first, second, third, and fourth mannoses
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location keyword mapping (IEA) to ER membrane, matching the experimentally determined localization of PIGV as a multi-pass ER membrane protein. Reason: Correct localization, consistent with experimental IDA evidence and UniProt. Supporting Evidence: file:human/PIGV/PIGV-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006506 GPI anchor biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Automated (IEA) assignment to GPI anchor biosynthesis via InterPro and UniPathway (UPA00196). This is the correct core biological process for PIGV. Reason: Correct core biological process; independently supported by experimental annotations. Supporting Evidence: PMID:15720390 A bioinformatics-based strategy identified the essential Saccharomyces cerevisiae Ybr004c protein as a candidate for the second GPI alpha-mannosyltransferase (GPI-MT-II).
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Bare 'protein binding' from a large-scale yeast two-hybrid neurodegenerative-disease interactome screen (interactions reported with TGFBR2, CBX5, and SERPINH1). The term is uninformative about molecular function and the proposed partners are not expected physiological interactors of an ER-lumenal GPI biosynthetic enzyme. Reason: Bare protein binding provides no functional insight and derives from a high-throughput Y2H screen; per curation policy this is marked as over-annotated rather than removed. Supporting Evidence: PMID:32814053 systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions
GO:0006506 GPI anchor biosynthetic process	TAS Reactome:R-HSA-162710	ACCEPT	Summary: Reactome (TAS) placement of PIGV in the human GPI synthesis pathway (Synthesis of glycosylphosphatidylinositol). Correct core biological process. Reason: Correct core biological process, curated from Reactome pathway knowledge. Supporting Evidence: Reactome:R-HSA-162710 GPI is synthesized in the endoplasmic reticulum.
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA, IDA) localizing PIGV to the endoplasmic reticulum. Correct but less specific than the ER membrane annotation; PIGV is an integral ER membrane protein. Reason: Experimentally supported ER localization; correct parent of the more specific ER membrane term. Retained as accurate. Supporting Evidence: PMID:15623507 Human PIG-V encodes a 493-amino acid, endoplasmic reticulum (ER) resident protein with eight putative transmembrane regions.
GO:0004376 GPI mannosyltransferase activity	TAS Reactome:R-HSA-162873	ACCEPT	Summary: Reactome (TAS) assignment of GPI mannosyltransferase activity to PIGV for the second-mannose-addition reaction. Correct parent of the specific GPI-MT-II activity (GO:0120563). Reason: Accurate GPI mannosyltransferase molecular function, curated from Reactome; a correct generalization of the specific PIGV activity. Supporting Evidence: Reactome:R-HSA-162873 a second mannose residue is added to the glycolipid on the lumenal face of the endoplasmic reticulum membrane
GO:0120563 dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activity	IMP PMID:15623507 PIG-V involved in transferring the second mannose in glycosy...	ACCEPT	Summary: Direct experimental evidence (IMP) that human PIG-V is the second GPI mannosyltransferase (GPI-MT-II), transferring the second mannose via an alpha-1,6 linkage. Kang et al. cloned PIG-V, defined its catalytic activity and ER topology, and identified functionally important lumenal residues by mutagenesis. This is the exact catalytic activity of PIGV. Reason: Core molecular function with direct experimental support at the correct specificity. Supporting Evidence: PMID:15623507 Here we report the cloning of PIG-V involved in transferring the second mannose in the GPI anchor. PMID:15623507 PIG-V has two functionally important conserved regions facing the ER lumen.
GO:0120563 dol-P-Man:Man(1)GlcN-acyl-PI alpha-1,6-mannosyltransferase activity	IGI PMID:15623507 PIG-V involved in transferring the second mannose in glycosy...	ACCEPT	Summary: Genetic interaction evidence (IGI) supporting the GPI-MT-II activity of PIGV, based on functional complementation with the yeast ortholog GPI18/YBR004C (UniProtKB:P38211). Human PIG-V cDNA rescued the yeast gpi18 deletion mutant, demonstrating conserved second-mannose-transfer function. Reason: Cross-species genetic complementation directly supports the specific catalytic activity; core molecular function. Supporting Evidence: PMID:15623507 Viability of the yeast gpi18 deletion mutant was restored by human PIG-V cDNA.
GO:0000009 alpha-1,6-mannosyltransferase activity	IGI PMID:15720390 Saccharomyces cerevisiae Ybr004c and its human homologue are...	ACCEPT	Summary: Genetic interaction evidence (IGI) with the yeast ortholog Ybr004c/GPI18 (UniProtKB:P38211). Fabre et al. showed the human Ybr004cp homologue (PIGV) substitutes for the yeast protein in vivo, supporting alpha-1,6-mannosyltransferase activity in second-mannose addition. This is a correct parent of the specific GPI-MT-II activity. Reason: Cross-species complementation supports the alpha-1,6-mannosyltransferase function; accurate parent term. Supporting Evidence: PMID:15720390 The human Ybr004cp homologue can substitute for its S. cerevisiae counterpart in vivo.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162873	ACCEPT	Summary: Reactome (TAS) localization of the second-mannose-addition reaction (and PIGV) to the ER membrane, consistent with PIGV being a multi-pass ER membrane enzyme acting on the lumenal face. Reason: Correct localization, curated from Reactome; consistent with experimental evidence. Supporting Evidence: Reactome:R-HSA-162873 a second mannose residue is added to the glycolipid on the lumenal face of the endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	IDA PMID:15623507 PIG-V involved in transferring the second mannose in glycosy...	ACCEPT	Summary: Direct experimental evidence (IDA) that PIGV is an ER-membrane protein. Kang et al. characterized PIG-V as an ER-resident protein with multiple transmembrane regions and mapped its membrane topology, establishing ER membrane localization. Reason: Experimentally determined localization; core cellular component. The multi-pass ER membrane topology is documented in UniProt. Supporting Evidence: PMID:15623507 Human PIG-V encodes a 493-amino acid, endoplasmic reticulum (ER) resident protein with eight putative transmembrane regions. file:human/PIGV/PIGV-uniprot.txt Multi-pass membrane protein
GO:0006506 GPI anchor biosynthetic process	IMP PMID:15623507 PIG-V involved in transferring the second mannose in glycosy...	ACCEPT	Summary: Direct experimental evidence (IMP) placing PIGV in GPI anchor biosynthesis, via characterization of PIG-V as the enzyme transferring the second mannose in GPI assembly. Core biological process. Reason: Core biological process with direct experimental support. Supporting Evidence: PMID:15623507 we suggest that PIG-V is the second mannosyltransferase in GPI anchor biosynthesis
GO:0006506 GPI anchor biosynthetic process	IGI PMID:15623507 PIG-V involved in transferring the second mannose in glycosy...	ACCEPT	Summary: Genetic interaction evidence (IGI) with yeast GPI18/YBR004C (UniProtKB:P38211) supporting the role of PIGV in GPI anchor biosynthesis, via cross-species complementation of the second-mannose-addition step. Reason: Genetic complementation supports involvement in GPI anchor biosynthesis; core biological process. Supporting Evidence: PMID:15623507 Viability of the yeast gpi18 deletion mutant was restored by human PIG-V cDNA.
GO:0006506 GPI anchor biosynthetic process	IGI PMID:15720390 Saccharomyces cerevisiae Ybr004c and its human homologue are...	ACCEPT	Summary: Genetic interaction evidence (IGI) with yeast Ybr004c/GPI18 (UniProtKB:P38211). Fabre et al. showed Ybr004cp-depleted yeast accumulate a single-mannose GPI intermediate and cannot incorporate inositol into proteins, and that the human homologue (PIGV) complements the defect, supporting PIGV's role in GPI anchor biosynthesis. Reason: Cross-species genetic evidence supports involvement in GPI anchor biosynthesis; core biological process. Supporting Evidence: PMID:15720390 accumulate a GPI intermediate having a single mannose that is likely modified with ethanolamine phosphate

Gene Description

Existing Annotations Review

Core Functions

Alpha-1,6-mannosyltransferase (GPI-MT-II) that transfers the second mannose from dolichyl-phosphate-mannose (Dol-P-Man) onto the Man1-GlcN-(acyl)PI GPI intermediate, forming the alpha-1,6 mannosyl linkage, during GPI-anchor biosynthesis on the lumenal face of the ER membrane.

References

📚 Additional Documentation

Notes

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