PIGH

UniProt ID: Q14442
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

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.

Existing Annotations Review

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

Core Functions

As a non-catalytic accessory subunit of the GPI-GlcNAc transferase (GPI-GnT) complex, PIGH contributes to the first committed step of GPI-anchor biosynthesis, in which the complex transfers N-acetylglucosamine from UDP-GlcNAc onto phosphatidylinositol to form GlcNAc-PI on the cytoplasmic face of the ER membrane. The catalytic subunit is PIGA; PIGH is required for complex activity.

Directly Involved In:
GPI anchor biosynthetic process
Cellular Locations:
endoplasmic reticulum membrane
In Complex:
glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex
Supporting Evidence:
  • PMID:8900170
    PIG-A and PIG-H are subunits of the GPI GlcNAc transferase that transfers GlcNAc
  • PMID:16162815
    binding directly to the catalytic subunit PIG-A.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10944123
Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2.
PMID:16162815
The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:8900170
PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.
PMID:9463366
The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.
Reactome:R-HSA-162730
phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-PI + UDP
file:human/PIGH/PIGH-uniprot.txt
UniProtKB entry Q14442 (PIGH_HUMAN)

📚 Additional Documentation

Notes

(PIGH-notes.md)

PIGH (Q14442) review notes

Human PIGH — Phosphatidylinositol N-acetylglucosaminyltransferase subunit H (PIG-H).
188 aa, ER membrane protein (UniProt: multi-pass; two predicted TM helices 40-60 and
63-83). HGNC:8964. Chromosome 14. Gene MIM 600154; disease MIM 618010 (GPIBD17).

Deep research: falcon provider was OUT OF CREDITS (HTTP 402) at review time, so no
-deep-research-falcon.md was generated. This review is grounded in the UniProt record
(PIGH-uniprot.txt), the seeded GOA (PIGH-goa.tsv), the cached primary publications,
and the Reactome entry.

Core biology (verified)

PIGH is a non-catalytic (accessory) subunit of the GPI-GlcNAc transferase (GPI-GnT)
complex, the multi-subunit ER enzyme that catalyzes the first committed step of
GPI-anchor biosynthesis: transfer of GlcNAc from UDP-GlcNAc onto phosphatidylinositol
(PI) to yield GlcNAc-PI, on the cytoplasmic face of the ER.

  • The catalytic subunit is PIGA (homologous to a bacterial GlcNAc transferase); PIGH
    is one of the required accessory subunits.
  • The complex comprises at least PIGA, PIGC, PIGH, PIGP, PIGQ (GPI1), PIGY and DPM2.
    PMID:16162815
    [UniProt SUBUNIT: "composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2"]

Provenance of key claims

  • First step / GlcNAc transfer / complex:
    PMID:8900170
    PMID:8900170
    PMID:9463366
  • PIG-H is ER-associated, cytoplasmically oriented; forms complex with PIG-A:
    PMID:8900170
    (UniProt models the mature protein as a multi-pass ER membrane protein; GOA carries
    ER membrane EXP/IDA. I defer to GOA/UniProt for the ER-membrane CC.)
  • Interactions: PIGH interacts with PIGA (P37287) and PIGQ (Q9BRB3) within the complex.
    [UniProt INTERACTION: "Q14442; P37287: PIGA" and "Q14442; Q9BRB3: PIGQ"]
  • PIG-P / DPM2 components: PMID:10944123

Molecular function

The GOA carries no catalytic MF term for PIGH — only GO:0005515 protein binding
(IPI, from complex/interactome studies). This is consistent with PIGH being a
non-catalytic subunit; the GlcNAc-transferase catalytic activity belongs to the complex
(and specifically to PIGA). I therefore do NOT assign a catalytic MF in core_functions;
I record PIGH's contribution via directly_involved_in the BP and in_complex the
GPI-GnT complex, plus ER-membrane location.

Disease

Biallelic PIGH variants cause GPI biosynthesis defect 17 (GPIBD17) [MIM:618010], an
autosomal-recessive inherited GPI-deficiency disorder (developmental/epileptic
encephalopathy): developmental delay, epilepsy/seizures, microcephaly, autistic features,
skeletal manifestations. Variants: start-codon disruption (PMID:29573052),
p.Ser103Pro (PMID:29603516, PMID:33156547 — reduced GPI-anchored protein surface
expression), p.Arg163Trp (PMID:33156547, PMID:35445667). Disease refs are not in the
GOA and are used only for the top-level description/context (no supporting_text quotes
needed since they are not cached).

GOA annotation inventory (21 lines -> 20 review entries)

MF: GO:0005515 protein binding (IPI) x6 references (7 GOA lines; two PMID:33961781 lines
with different partners P37287/Q9BRB3 collapse to one review entry).
CC: GO:0000506 GPI-GnT complex (IBA, IEA, IPI, IDA x2) ; GO:0005789 ER membrane
(IEA, EXP, IDA, TAS) ; GO:0005783 ER (TAS).
BP: GO:0006506 GPI anchor biosynthetic process (IBA, IEA, IDA, TAS).

Curation decisions summary

  • CC GPI-GnT complex (all evidence): ACCEPT — core, well-supported.
  • CC ER membrane / ER (all evidence): ACCEPT — core localization.
  • BP GPI anchor biosynthetic process (all evidence): ACCEPT — core.
  • MF protein binding (all IPI): MARK_AS_OVER_ANNOTATED — uninformative bare
    protein binding; the real informative content (subunit of GPI-GnT) is captured by the
    complex CC term. Per policy, do NOT REMOVE bare protein-binding IPIs.

📄 View Raw YAML

 
id: Q14442
gene_symbol: PIGH
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9463366
      supporting_text: The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity
        in
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: PIGH participates in GPI anchor biosynthesis as a subunit of the GPI-GnT
      complex that catalyzes the first step (GlcNAc transfer to phosphatidylinositol).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8900170
      supporting_text: N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate
        GlcNAc-PI
- term:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9463366
      supporting_text: The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity
        in
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PIGH/PIGH-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Combined automated methods (InterPro/UniPathway UPA00196) assign PIGH to
      GPI-anchor biosynthesis, matching its curated role as a GPI-GnT complex subunit.
    action: ACCEPT
    reason: Correct electronic inference, redundant with the experimental and
      phylogenetic BP annotations.
    supported_by:
    - reference_id: PMID:8900170
      supporting_text: N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate
        GlcNAc-PI
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10944123
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: GPI-GnT is a uniquely complex glycosyltransferase, consisting
        of at least four
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16162815
  qualifier: enables
  review:
    summary: IntAct-derived binding annotation (with PIGA, UniProtKB:P37287) supporting
      PIGH's membership in the GPI-GnT complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" is uninformative; the interaction reflects GPI-GnT
      complex membership captured by GO:0000506. Retained per policy, flagged as
      over-annotation.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: consisting of at least six
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: High-throughput AP-MS interactome (BioPlex) annotation, capturing
      interactions of PIGH with GPI-GnT complex members (UniProtKB:P37287 PIGA and
      UniProtKB:Q9BRB3 PIGQ).
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: complex membership for thousands of proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-map (AP-MS + imaging) interaction annotation (with PIGQ,
      UniProtKB:Q9BRB3), consistent with PIGH being part of the GPI-GnT assembly.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: yielding structures for 111
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8900170
  qualifier: enables
  review:
    summary: Interaction annotation from the study demonstrating PIGH forms a complex
      with PIGA (UniProtKB:P37287) in the ER, underpinning GPI-GnT complex membership.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:8900170
      supporting_text: cytoplasmically oriented, ER-associated protein; and 3) that
        they form a protein
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9463366
  qualifier: enables
  review:
    summary: Interaction annotation (with PIGQ, UniProtKB:Q9BRB3) from the study
      showing the four-component GPI-GnT complex; supports PIGH's complex membership.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" is uninformative; the interaction reflects GPI-GnT
      complex membership captured by GO:0000506. Retained per policy.
    supported_by:
    - reference_id: PMID:9463366
      supporting_text: The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity
        in
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:8900170
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Core localization, experimentally supported. PIGH resides in the ER
      membrane where the GPI-GnT complex acts.
    supported_by:
    - reference_id: PMID:8900170
      supporting_text: cytoplasmically oriented, ER-associated protein; and 3) that
        they form a protein
- term:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  evidence_type: IPI
  original_reference_id: PMID:16162815
  qualifier: part_of
  review:
    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).
    action: ACCEPT
    reason: Core, experimentally supported complex membership.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: consisting of at least six
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:16162815
  qualifier: located_in
  review:
    summary: Direct localization of PIGH (as part of the GPI-GnT complex) to the ER
      membrane.
    action: ACCEPT
    reason: Core localization, experimentally supported and consistent with the other
      ER-membrane annotations.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: consisting of at least six
- term:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  evidence_type: IDA
  original_reference_id: PMID:16162815
  qualifier: part_of
  review:
    summary: Direct experimental evidence that PIGH is a component of the GPI-GnT
      complex (UniProt-curated from the seven-component study).
    action: ACCEPT
    reason: Core, experimentally supported complex membership; duplicate term/reference
      with different assigning source, which is acceptable.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: consisting of at least six
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:16162815
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Core biological process, experimentally supported. The PIG-Y study
      functionally characterized the PIGH-containing GPI-GnT complex that initiates
      GPI biosynthesis.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: binding directly to the catalytic subunit PIG-A.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162730
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Core localization, consistent with experimental ER-membrane annotations.
    supported_by:
    - reference_id: Reactome:R-HSA-162730
      supporting_text: N-acetylglucosamine from cytosolic UDP-N-acetylglucosamine to
        phosphatidyl inositol (PI) in the endoplasmic
- term:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  evidence_type: IDA
  original_reference_id: PMID:10944123
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    reason: Core, experimentally supported complex membership.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: GPI-GnT is a uniquely complex glycosyltransferase, consisting
        of at least four
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:8900170
  qualifier: located_in
  review:
    summary: Traceable author statement localizing PIGH to the endoplasmic reticulum.
      This is a less specific (parent) term relative to the ER membrane annotations.
    action: ACCEPT
    reason: Correct but less specific than "endoplasmic reticulum membrane". Retained
      as an accurate broader localization; the ER-membrane annotations provide the
      precise compartment.
    supported_by:
    - reference_id: PMID:8900170
      supporting_text: cytoplasmically oriented, ER-associated protein; and 3) that
        they form a protein
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: TAS
  original_reference_id: PMID:8900170
  qualifier: involved_in
  review:
    summary: Traceable author statement that PIGH participates in GPI-anchor
      biosynthesis via the first step, transfer of GlcNAc to phosphatidylinositol.
    action: ACCEPT
    reason: Core biological process, consistent with all other BP annotations and the
      literature.
    supported_by:
    - reference_id: PMID:8900170
      supporting_text: N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate
        GlcNAc-PI
core_functions:
- description: As a non-catalytic accessory subunit of the GPI-GlcNAc transferase
    (GPI-GnT) complex, PIGH contributes to the first committed step of GPI-anchor
    biosynthesis, in which the complex transfers N-acetylglucosamine from UDP-GlcNAc
    onto phosphatidylinositol to form GlcNAc-PI on the cytoplasmic face of the ER
    membrane. The catalytic subunit is PIGA; PIGH is required for complex activity.
  directly_involved_in:
  - id: GO:0006506
    label: GPI anchor biosynthetic process
  in_complex:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:8900170
    supporting_text: PIG-A and PIG-H are subunits of the GPI GlcNAc transferase that
      transfers GlcNAc
  - reference_id: PMID:16162815
    supporting_text: binding directly to the catalytic subunit PIG-A.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10944123
  title: Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P
    and is regulated by DPM2.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Identifies PIG-P and DPM2 as GPI-GnT components; establishes PIGH as
      part of the multi-subunit GPI-GnT complex.
- id: PMID:16162815
  title: The initial enzyme for glycosylphosphatidylinositol biosynthesis requires
    PIG-Y, a seventh component.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the seven-component GPI-GnT complex (PIGA, PIGC, PIGH, PIGP,
      PIGQ, PIGY, DPM2) and identifies PIGA as the catalytic subunit; supports PIGH
      complex membership and BP.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Proteome-scale AP-MS interactome (BioPlex); source of high-throughput
      protein-binding IPI annotations, not gene-specific functional characterization.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Proteome-scale multimodal cell-mapping study; source of a
      high-throughput protein-binding IPI annotation, not gene-specific
      characterization of PIGH.
- id: PMID:8900170
  title: PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor
    biosynthesis, form a protein complex in the endoplasmic reticulum.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary characterization of PIG-H as an ER-associated subunit of the
      GPI GlcNAc transferase that complexes with PIG-A; supports ER localization,
      complex membership and BP.
- id: PMID:9463366
  title: The first step of glycosylphosphatidylinositol biosynthesis is mediated by
    a complex of PIG-A, PIG-H, PIG-C and GPI1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Demonstrates the PIGA/PIGH/PIGC/GPI1 complex has GPI-GnT activity in
      vitro; supports PIGH complex membership and the first-step BP.
- id: Reactome:R-HSA-162730
  title: phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-PI
    + UDP
  findings: []
- id: file:human/PIGH/PIGH-uniprot.txt
  title: UniProtKB entry Q14442 (PIGH_HUMAN)
  findings: []