id: P57054
gene_symbol: PIGP
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PIGP (phosphatidylinositol N-acetylglucosaminyltransferase subunit P; PIG-P)
  is a small (158 aa) multi-pass endoplasmic reticulum membrane protein that is
  a required, non-catalytic accessory subunit of the GPI-N-acetylglucosaminyltransferase
  (GPI-GnT) complex. GPI-GnT catalyzes the first, committed step of
  glycosylphosphatidylinositol (GPI) anchor biosynthesis: the transfer of
  N-acetylglucosamine from UDP-N-acetylglucosamine onto phosphatidylinositol to
  give GlcNAc-phosphatidylinositol. The catalytic subunit of the complex is PIGA;
  PIGP is one of several accessory components (with PIGC, PIGH, PIGQ/GPI1, PIGY and
  the regulatory protein DPM2) that are together required for enzyme activity, and
  it interacts directly with PIGA and PIGQ. PIGP is broadly (ubiquitously) expressed.
  Biallelic loss-of-function variants in PIGP cause an autosomal-recessive inherited
  GPI-deficiency disorder, developmental and epileptic encephalopathy 55 (DEE55),
  characterized by early-onset refractory seizures, hypotonia and profound
  developmental delay, reflecting reduced surface expression of GPI-anchored proteins.
alternative_products:
- name: B
  id: P57054-1
- name: A
  id: P57054-2
  sequence_note: VSP_004202
- name: C (DCRC-S)
  id: P57054-3
  sequence_note: VSP_004203, VSP_004204
existing_annotations:
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) inference that PIGP is active in the endoplasmic reticulum.
      This is correct: the GPI-GnT complex is an ER-membrane enzyme and PIGP is one
      of its subunits. The more specific ER membrane term (GO:0005789) is also present
      with direct evidence and is the preferred location.
    action: ACCEPT
    reason: >-
      Consistent with the established ER localization of the GPI-GnT complex. PIGP
      is a subunit of this ER-membrane complex (UniProt SUBUNIT; ComplexPortal IDA).
    supported_by:
    - reference_id: file:human/PIGP/PIGP-uniprot.txt
      supporting_text: "acetylglucosaminyltransferase (GPI-GnT) complex composed at least by"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) inference that PIGP is involved in GPI anchor biosynthetic
      process. This is the core biological process of PIGP: as a GPI-GnT subunit it
      participates in the first committed step of GPI-anchor biosynthesis.
    action: ACCEPT
    reason: >-
      Well supported by experimental evidence in human and by the conserved role of
      PIGP orthologs (yeast GPI19, etc.); represents the core function of the gene.
    supported_by:
    - reference_id: PMID:28334793
      supporting_text: "PIGP encodes a subunit of the enzyme that catalyzes"
    - reference_id: PMID:10944123
      supporting_text: "PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic (IEA, multi-method / InterPro + UniPathway) inference of involvement
      in GPI anchor biosynthetic process. Redundant with the IBA/IDA/IMP annotations
      to the same term but biologically correct.
    action: ACCEPT
    reason: >-
      Correct core biological process, consistent with all experimental evidence and
      the UniProt PATHWAY assignment (GPI-anchor biosynthesis).
    supported_by:
    - reference_id: file:human/PIGP/PIGP-uniprot.txt
      supporting_text: "Interacts directly with PIGA and PIGQ (PubMed:10944123)."
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (IEA) annotation to the generic term "membrane", derived from the
      UniProt Subcellular Location keyword (Membrane; Multi-pass membrane protein).
      Correct but uninformative: the specific location is the ER membrane (GO:0005789),
      which is annotated with direct evidence.
    action: KEEP_AS_NON_CORE
    reason: >-
      Not wrong (PIGP is a multi-pass membrane protein) but far too general and
      subsumed by the more precise ER membrane annotation. Retain as a non-core,
      generic location rather than as a core statement.
    supported_by:
    - reference_id: file:human/PIGP/PIGP-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Membrane"
- term:
    id: GO:0017176
    label: phosphatidylinositol N-acetylglucosaminyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Electronic (InterPro2GO, ECO:0000256) inference that PIGP "enables"
      phosphatidylinositol N-acetylglucosaminyltransferase activity. This is the
      complex-level catalytic activity of GPI-GnT, whose catalytic subunit is PIGA.
      PIGP is a required but non-catalytic accessory subunit and does not independently
      have this transferase activity; assigning it via the "enables" qualifier
      over-attributes the whole-complex activity to a single non-catalytic subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The catalytic activity resides in the complex (catalytic subunit PIGA); PIGP
      contributes to but does not independently enable it. The InterPro family
      (IPR016542, PIG-P_GPI19) propagates the pathway-level MF to all members. The
      correct representation of PIGP's relationship to this activity is the parallel
      IDA annotation with the "contributes_to" qualifier, which is accepted. Per policy,
      an IEA that mis-attributes a complex activity to a non-catalytic subunit is
      marked as over-annotated rather than removed.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: "associates with PIG-A and GPI1."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10944123
  qualifier: enables
  review:
    summary: >-
      IPI annotation (IntAct) recording physical interaction of PIGP with PIGA
      (UniProtKB:P37287). This is the functionally meaningful interaction that
      assembles PIGP into the GPI-GnT complex, but the bare "protein binding" term
      is uninformative on its own.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is real and experimentally supported (PIG-P associates directly
      with the catalytic subunit PIG-A), but "protein binding" (GO:0005515) conveys no
      specific molecular function. The biology is captured by the GPI-GnT complex
      membership (GO:0000506, part_of) and the contributes_to GO:0017176 annotation.
      Not removed (experimental IPI); flagged as a non-informative over-annotation.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: "associates with PIG-A and GPI1."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16162815
  qualifier: enables
  review:
    summary: >-
      IPI annotation (IntAct) recording physical interaction of PIGP with PIGA
      (UniProtKB:P37287) in the study defining the seven-component GPI-GnT complex.
      As above, the interaction is meaningful but the bare "protein binding" term is
      uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Real complex-assembly interaction, but "protein binding" is not an informative
      molecular function. The relationship is properly represented by GPI-GnT complex
      membership (GO:0000506) and contributes_to GO:0017176. Not removed (experimental IPI).
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: "complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" IPIs from a proteome-scale binary (yeast two-hybrid)
      interactome map (HuRI). The many recorded partners (e.g. ITGAM, KLF11, PLP1,
      PLP2, PTPN1, FIS1, and other membrane proteins) are high-throughput hits with
      no established functional relationship to PIGP's role in GPI-GnT.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput binary-interactome hits captured as generic "protein binding".
      They add no informative molecular function and largely reflect promiscuous or
      screen-specific membrane-protein interactions. Retained (experimental IPI) but
      flagged as over-annotation.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: "A reference map of the human binary protein interactome"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" IPIs from a neurodegenerative-disease interactome map
      (partners include DNALI1, KLF11, ARL6IP-like membrane proteins). Generic,
      uninformative interaction annotation from a large-scale screen.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput screen interactions recorded as "protein binding"; no specific
      molecular function is conveyed and no functional link to PIGP's GPI-GnT role is
      established. Retained (experimental IPI) but flagged as over-annotation.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: "Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" IPI from a proteome-scale AP-MS interactome (BioPlex 3.0),
      recording interaction with PIGA (UniProtKB:P37287). Consistent with GPI-GnT
      complex membership but conveyed only as generic "protein binding".
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The PIGA interaction is consistent with the known complex, but "protein binding"
      is uninformative. The functional content is captured by GO:0000506 (part_of) and
      contributes_to GO:0017176. Retained (experimental IPI) but flagged as over-annotation.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: "Dual proteome-scale networks reveal cell-specific remodeling of the human"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162730
  qualifier: located_in
  review:
    summary: >-
      Traceable-author (Reactome) statement placing PIGP at the endoplasmic reticulum
      membrane, in the reaction "phosphatidylinositol + UDP-N-acetyl-D-glucosamine ->
      N-acetylglucosaminyl-PI + UDP". This is the correct, specific location of the
      GPI-GnT complex.
    action: ACCEPT
    reason: >-
      Correct and specific subcellular location; the first step of GPI biosynthesis
      occurs on the cytoplasmic face of the ER membrane. Concordant with the IDA
      annotation to the same term.
    supported_by:
    - reference_id: file:human/PIGP/PIGP-uniprot.txt
      supporting_text: "Multi-pass membrane"
- term:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT)
      complex
  evidence_type: IPI
  original_reference_id: PMID:16162815
  qualifier: part_of
  review:
    summary: >-
      PIGP is part of the GPI-GnT complex (GO:0000506). Curated by ComplexPortal from
      the study establishing the seven-component complex (PIGA, PIGC, PIGH, PIGP, PIGQ,
      PIGY, DPM2). This is a core structural/functional annotation.
    action: ACCEPT
    reason: >-
      Directly supported experimental complex-membership annotation and central to
      PIGP's function as a required accessory subunit of GPI-GnT.
    supported_by:
    - reference_id: file:human/PIGP/PIGP-uniprot.txt
      supporting_text: "acetylglucosaminyltransferase (GPI-GnT) complex composed at least by"
    - reference_id: PMID:16162815
      supporting_text: "GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:16162815
  qualifier: located_in
  review:
    summary: >-
      Direct-assay (ComplexPortal IDA) localization of PIGP to the ER membrane. This
      is the correct, specific location of the GPI-GnT complex and PIGP within it.
    action: ACCEPT
    reason: >-
      Specific, experimentally supported location; preferred over the generic
      "membrane" IEA. Consistent with the Reactome TAS and IBA(ER) annotations.
    supported_by:
    - reference_id: file:human/PIGP/PIGP-uniprot.txt
      supporting_text: "Multi-pass membrane"
- 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-assay complex-membership annotation (UniProt) that PIGP is part of the
      GPI-GnT complex. Core annotation, duplicate of the ComplexPortal IPI to the same
      term.
    action: ACCEPT
    reason: >-
      Experimentally supported and central to PIGP function; PIGP is one of the
      required components of the GPI-GnT complex.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: "GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:16162815
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay annotation that PIGP is involved in GPI anchor biosynthetic process,
      from the study characterizing the GPI-GnT complex. Core biological process.
    action: ACCEPT
    reason: >-
      Experimentally supported involvement in the first step of GPI-anchor biosynthesis;
      the core function of the gene.
    supported_by:
    - reference_id: PMID:16162815
      supporting_text: "complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six"
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:28334793
  qualifier: involved_in
  review:
    summary: >-
      Mutant-phenotype (IMP) evidence that PIGP is involved in GPI anchor biosynthetic
      process: biallelic PIGP variants in patients reduce PIGP mRNA and GPI-anchored
      cell-surface proteins, rescued by wild-type PIGP. Core biological process.
    action: ACCEPT
    reason: >-
      Strong loss-of-function genetic evidence in human that PIGP is required for GPI
      anchor biosynthesis; directly links the gene to its core process and to DEE55.
    supported_by:
    - reference_id: PMID:28334793
      supporting_text: "cells showed reduced PIGP mRNA levels, and an associated reduction of"
    - reference_id: PMID:28334793
      supporting_text: "PIGP encodes a subunit of the enzyme that catalyzes"
- 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-assay (MGI) complex-membership annotation that PIGP is part of the GPI-GnT
      complex, from the study that identified PIG-P as an essential component and showed
      it associates with PIG-A and GPI1/PIGQ. Core annotation.
    action: ACCEPT
    reason: >-
      Experimentally supported complex membership; PIG-P associates with the catalytic
      subunit PIG-A and GPI1 and is essential for the complex's activity.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: "associates with PIG-A and GPI1."
- term:
    id: GO:0017176
    label: phosphatidylinositol N-acetylglucosaminyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:10944123
  qualifier: contributes_to
  review:
    summary: >-
      Direct-assay annotation (MGI) with the "contributes_to" qualifier: PIGP
      contributes to the phosphatidylinositol N-acetylglucosaminyltransferase activity
      of the GPI-GnT complex. This is the correct way to record a required, non-catalytic
      subunit's participation in the complex's catalytic activity.
    action: ACCEPT
    reason: >-
      The "contributes_to" qualifier appropriately captures that PIGP is essential for
      the complex-level transferase activity without itself being the catalytic subunit
      (PIGA is catalytic). PIG-P-null cells are GPI-anchor negative, demonstrating its
      necessity for the activity. Preferred over the IEA "enables" annotation to the same term.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: "PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor"
core_functions:
- description: >-
    PIGP is a required, non-catalytic accessory subunit of the GPI-GnT complex, an
    ER-membrane glycosyltransferase that catalyzes the first committed step of GPI-anchor
    biosynthesis (GlcNAc transfer from UDP-GlcNAc to phosphatidylinositol). PIGP does not
    independently possess transferase activity (the catalytic subunit is PIGA) but is
    essential for complex activity: PIG-P-null cells are GPI-anchor negative.
  supported_by:
  - reference_id: PMID:10944123
    supporting_text: "PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor"
  - reference_id: PMID:28334793
    supporting_text: "PIGP encodes a subunit of the enzyme that catalyzes"
  directly_involved_in:
  - id: GO:0006506
    label: GPI anchor biosynthetic process
  contributes_to_molecular_function:
    id: GO:0017176
    label: phosphatidylinositol N-acetylglucosaminyltransferase activity
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  in_complex:
    id: GO:0000506
    label: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex
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: >-
      Abstract-only in cache. Establishes PIG-P as an essential component of GPI-GnT
      that associates with PIG-A and GPI1; PIG-P-null cells are GPI-anchor negative.
      Directly supports the complex-membership, GPI-biosynthesis, and contributes_to
      transferase-activity annotations.
- 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: >-
      Abstract-only in cache. Defines the multi-component GPI-GnT complex (PIGP among
      the components); supports complex membership, ER-membrane localization, and
      GPI-anchor biosynthesis.
- id: PMID:28334793
  title: Compound heterozygous mutations in the gene PIGP are associated with early
    infantile epileptic encephalopathy.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache. Loss-of-function human genetic evidence (DEE55) that
      PIGP is required for GPI-anchor biosynthesis; states PIGP encodes a subunit of
      the enzyme catalyzing the first step of GPI-anchor biosynthesis.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Proteome-scale binary (Y2H) interactome. Source of several generic "protein
      binding" IPIs for PIGP; partners are high-throughput hits with no established
      functional link to GPI-GnT.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale neurodegenerative-disease interactome. Source of generic "protein
      binding" IPIs for PIGP; no specific functional relationship established.
- 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: >-
      BioPlex 3.0 AP-MS interactome. Records a PIGA interaction consistent with GPI-GnT
      but as generic "protein binding".
- id: Reactome:R-HSA-162730
  title: phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-PI
    + UDP
  findings: []
- id: file:human/PIGP/PIGP-uniprot.txt
  title: UniProtKB entry P57054 (PIGP_HUMAN)
  findings: []