PIGH (phosphatidylinositol N-acetylglucosaminyltransferase subunit H, PIG-H) is a non-catalytic subunit of the glycosylphosphatidylinositol N-acetylglucosaminyltransferase (GPI-GnT) complex, the endoplasmic reticulum enzyme that carries out the first committed step of GPI-anchor biosynthesis. In this step the complex transfers N-acetylglucosamine from UDP-GlcNAc onto phosphatidylinositol to generate GlcNAc-PI on the cytoplasmic face of the ER. The catalytic subunit is PIGA; PIGH is one of the required accessory subunits, and the assembled complex contains at least PIGA, PIGC, PIGH, PIGP, PIGQ (GPI1), PIGY and DPM2. PIGH is an endoplasmic reticulum membrane protein. Biallelic loss-of-function variants in PIGH cause an inherited glycosylphosphatidylinositol-deficiency disorder (GPI biosynthesis defect 17, GPIBD17), a developmental and epileptic encephalopathy featuring developmental delay, seizures, microcephaly and autistic features.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IBA GO_REF:0000033 | ACCEPT | Summary: PIGH is a subunit of the GPI-GnT complex. This phylogenetically inferred annotation matches the extensive experimental evidence that PIGH is a component of the multi-subunit GPI-GlcNAc transferase. Reason: Core, well-supported cellular component. PIGH is one of the accessory subunits of the GPI-GnT complex, consistent with the IBA inference and with the experimental complex-membership annotations below. Supporting Evidence: PMID:9463366 The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in |
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PIGH participates in GPI anchor biosynthesis as a subunit of the GPI-GnT complex that catalyzes the first step (GlcNAc transfer to phosphatidylinositol). Reason: Core biological process. The phylogenetic inference agrees with the experimental evidence that the PIGH-containing complex performs the first step of GPI-anchor biosynthesis. Supporting Evidence: PMID:8900170 N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate GlcNAc-PI |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO maps the PIG-H InterPro signature (IPR044215) to the GPI-GnT complex. This is consistent with PIGH being a dedicated subunit of that complex. Reason: Correct electronic inference; PIGH's family signature is specific to the GPI-GnT complex subunit, so the CC mapping is appropriate and redundant with the experimental annotations. Supporting Evidence: PMID:9463366 The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from the UniProt subcellular-location vocabulary places PIGH at the ER membrane, matching the curated UniProt location and the experimental EXP/IDA annotations. Reason: Correct localization. PIGH is an ER membrane protein (UniProt models it as a multi-pass ER membrane protein); this IEA is redundant with the experimental ER-membrane annotations. Supporting Evidence: file:human/PIGH/PIGH-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated methods (InterPro/UniPathway UPA00196) assign PIGH to GPI-anchor biosynthesis, matching its curated role as a GPI-GnT complex subunit. Reason: Correct electronic inference, redundant with the experimental and phylogenetic BP annotations. Supporting Evidence: PMID:8900170 N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate GlcNAc-PI |
| GO:0005515 protein binding | IPI PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding annotation (with PIGA, UniProtKB:P37287). The biologically meaningful content is that PIGH is a subunit of the GPI-GnT complex, which is already captured by the GPI-GnT complex CC term. Reason: Bare "protein binding" is uninformative as a molecular function. The underlying interaction reflects PIGH's membership in the GPI-GnT complex, which is better represented by the complex CC annotation (GO:0000506). Retained per policy (not removed) but flagged as over-annotation. Supporting Evidence: PMID:10944123 GPI-GnT is a uniquely complex glycosyltransferase, consisting of at least four |
| GO:0005515 protein binding | IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | MARK AS OVER ANNOTATED | Summary: IntAct-derived binding annotation (with PIGA, UniProtKB:P37287) supporting PIGH's membership in the GPI-GnT complex. Reason: Bare "protein binding" is uninformative; the interaction reflects GPI-GnT complex membership captured by GO:0000506. Retained per policy, flagged as over-annotation. Supporting Evidence: PMID:16162815 consisting of at least six |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: High-throughput AP-MS interactome (BioPlex) annotation, capturing interactions of PIGH with GPI-GnT complex members (UniProtKB:P37287 PIGA and UniProtKB:Q9BRB3 PIGQ). Reason: Bare "protein binding" from a proteome-scale interactome screen is uninformative as a molecular function; the biologically meaningful content (GPI-GnT complex membership) is captured by GO:0000506. Retained per policy. Supporting Evidence: PMID:33961781 complex membership for thousands of proteins |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Multimodal cell-map (AP-MS + imaging) interaction annotation (with PIGQ, UniProtKB:Q9BRB3), consistent with PIGH being part of the GPI-GnT assembly. Reason: Bare "protein binding" from a proteome-scale mapping study is uninformative; the interaction reflects GPI-GnT complex membership captured by GO:0000506. Retained per policy. Supporting Evidence: PMID:40205054 yielding structures for 111 |
| GO:0005515 protein binding | IPI PMID:8900170 PIG-A and PIG-H, which participate in glycosylphosphatidylin... | MARK AS OVER ANNOTATED | Summary: Interaction annotation from the study demonstrating PIGH forms a complex with PIGA (UniProtKB:P37287) in the ER, underpinning GPI-GnT complex membership. Reason: Bare "protein binding" is uninformative. The specific, informative claim (PIGH-PIGA complex / GPI-GnT membership) is captured by GO:0000506. Retained per policy, flagged as over-annotation. Supporting Evidence: PMID:8900170 cytoplasmically oriented, ER-associated protein; and 3) that they form a protein |
| GO:0005515 protein binding | IPI PMID:9463366 The first step of glycosylphosphatidylinositol biosynthesis ... | MARK AS OVER ANNOTATED | Summary: Interaction annotation (with PIGQ, UniProtKB:Q9BRB3) from the study showing the four-component GPI-GnT complex; supports PIGH's complex membership. Reason: Bare "protein binding" is uninformative; the interaction reflects GPI-GnT complex membership captured by GO:0000506. Retained per policy. Supporting Evidence: PMID:9463366 The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:8900170 PIG-A and PIG-H, which participate in glycosylphosphatidylin... | ACCEPT | Summary: Experimental localization of PIGH to the ER membrane, from the study that characterized PIG-H as an ER-associated component of the GPI GlcNAc transferase. Reason: Core localization, experimentally supported. PIGH resides in the ER membrane where the GPI-GnT complex acts. Supporting Evidence: PMID:8900170 cytoplasmically oriented, ER-associated protein; and 3) that they form a protein |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: ComplexPortal-curated membership of PIGH in the GPI-GnT complex, based on the study defining the seven-component complex (PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY, DPM2). Reason: Core, experimentally supported complex membership. Supporting Evidence: PMID:16162815 consisting of at least six |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct localization of PIGH (as part of the GPI-GnT complex) to the ER membrane. Reason: Core localization, experimentally supported and consistent with the other ER-membrane annotations. Supporting Evidence: PMID:16162815 consisting of at least six |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct experimental evidence that PIGH is a component of the GPI-GnT complex (UniProt-curated from the seven-component study). Reason: Core, experimentally supported complex membership; duplicate term/reference with different assigning source, which is acceptable. Supporting Evidence: PMID:16162815 consisting of at least six |
| GO:0006506 GPI anchor biosynthetic process | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct experimental evidence linking PIGH (via the GPI-GnT complex) to the GPI-anchor biosynthetic process, in which the complex catalyzes the first step of GPI synthesis. Reason: Core biological process, experimentally supported. The PIG-Y study functionally characterized the PIGH-containing GPI-GnT complex that initiates GPI biosynthesis. Supporting Evidence: PMID:16162815 binding directly to the catalytic subunit PIG-A. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-162730 | ACCEPT | Summary: Reactome (traceable author statement) places the GPI-GnT reaction, and hence PIGH, at the ER membrane, where the first step of GPI synthesis occurs. Reason: Core localization, consistent with experimental ER-membrane annotations. Supporting Evidence: Reactome:R-HSA-162730 N-acetylglucosamine from cytosolic UDP-N-acetylglucosamine to phosphatidyl inositol (PI) in the endoplasmic |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | ACCEPT | Summary: Direct experimental evidence (MGI-assigned) that PIGH is a subunit of the GPI-GnT complex, from the study identifying PIG-P and DPM2 as additional components. Reason: Core, experimentally supported complex membership. Supporting Evidence: PMID:10944123 GPI-GnT is a uniquely complex glycosyltransferase, consisting of at least four |
| GO:0005783 endoplasmic reticulum | TAS PMID:8900170 PIG-A and PIG-H, which participate in glycosylphosphatidylin... | ACCEPT | Summary: Traceable author statement localizing PIGH to the endoplasmic reticulum. This is a less specific (parent) term relative to the ER membrane annotations. Reason: Correct but less specific than "endoplasmic reticulum membrane". Retained as an accurate broader localization; the ER-membrane annotations provide the precise compartment. Supporting Evidence: PMID:8900170 cytoplasmically oriented, ER-associated protein; and 3) that they form a protein |
| GO:0006506 GPI anchor biosynthetic process | TAS PMID:8900170 PIG-A and PIG-H, which participate in glycosylphosphatidylin... | ACCEPT | Summary: Traceable author statement that PIGH participates in GPI-anchor biosynthesis via the first step, transfer of GlcNAc to phosphatidylinositol. Reason: Core biological process, consistent with all other BP annotations and the literature. Supporting Evidence: PMID:8900170 N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate GlcNAc-PI |
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