id: Q969N2
gene_symbol: PIGT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PIGT (GPI-anchor transamidase component PIG-T) is one of the five subunits of the
  glycosylphosphatidylinositol-anchor transamidase (GPI-T) complex, an endoplasmic
  reticulum membrane enzyme complex that attaches the pre-assembled GPI anchor to the
  C-terminus of GPI-anchored proteins after cleaving their C-terminal GPI-attachment
  signal peptide. The complex comprises the catalytic subunit PIGK (GPI8) together with
  GPAA1, PIGS, PIGU and PIGT as an equimolar heteropentamer. PIGT is a single-pass type
  I ER membrane glycoprotein that acts as a required structural subunit; it forms an
  interchain disulfide bond with the catalytic PIGK/GPI8 (PIGT Cys182 to PIGK Cys92) and
  stabilises and holds the complex together, and it also contributes to binding of the
  GPI lipid substrate. PIGT itself is not an independent enzyme, the transamidation
  catalysis residing in PIGK. Biallelic loss-of-function variants in PIGT cause the
  inherited GPI deficiency multiple congenital anomalies-hypotonia-seizures syndrome 3
  (MCAHS3), and germline plus somatic PIGT variants can produce a paroxysmal nocturnal
  hemoglobinuria-like phenotype (PNH2).
alternative_products:
- name: '1'
  id: Q969N2-1
- name: '2'
  id: Q969N2-2
  sequence_note: VSP_009537
- name: '3'
  id: Q969N2-3
  sequence_note: VSP_009536, VSP_009539, VSP_009540
- name: '4'
  id: Q969N2-4
  sequence_note: VSP_009538
- name: '5'
  id: Q969N2-5
  sequence_note: VSP_043167
- name: '6'
  id: Q969N2-6
  sequence_note: VSP_009540
existing_annotations:
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) annotation to the core biological process of PIGT and its
      orthologues, the attachment of GPI anchors to proteins. This is the well-established,
      correct core function of the gene.
    action: ACCEPT
    reason: >-
      This IBA annotation correctly captures PIGT's core biological role as a subunit of
      the GPI transamidase, which attaches pre-assembled GPI to proteins in the ER. It is
      supported by experimental knockout data and by the entire structural/biochemical
      literature.
    supported_by:
    - reference_id: PMID:11483512
      supporting_text: PIG-S and PIG-T knockout cells were defective in transfer of GPI
    - reference_id: PMID:34576938
      supporting_text: Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA)
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      Phylogenetic (IBA) annotation placing PIGT as a part of the GPI-anchor transamidase
      complex, the correct and core cellular component for this gene.
    action: ACCEPT
    reason: >-
      PIGT is a bona fide subunit of the heteropentameric GPI-T complex (PIGK, GPAA1,
      PIGS, PIGU, PIGT). This is directly established experimentally and structurally.
    supported_by:
    - reference_id: PMID:11483512
      supporting_text: PIG-S and PIG-T form a protein complex with GAA1 and GPI8
    - reference_id: PMID:35551457
      supporting_text: revealing an equimolar
- 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 UniProt Subcellular Location mapping) to the ER
      membrane, the correct localisation of PIGT and the GPI-T complex.
    action: ACCEPT
    reason: >-
      PIGT is a single-pass type I ER membrane protein; the GPI-T complex is an ER
      membrane complex. This IEA mapping is fully consistent with experimental
      localisation data.
    supported_by:
    - reference_id: PMID:15713669
      supporting_text: PIG-T is a type I
    - reference_id: PMID:35165458
      supporting_text: Attaching GPI to the protein in the endoplasmic reticulum (ER) is catalyzed by
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic (combined IEA methods, via mouse ortholog and InterPro PIG-T domain)
      annotation to GPI anchor attachment, the core BP of PIGT.
    action: ACCEPT
    reason: >-
      This electronic annotation agrees with the IBA and multiple experimental
      annotations for the same process. It is correct at an appropriate level of
      specificity.
    supported_by:
    - reference_id: PMID:34576938
      supporting_text: Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA)
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: >-
      Electronic (combined IEA methods) annotation to the GPI-anchor transamidase
      complex, agreeing with the experimental IDA/IBA complex annotations.
    action: ACCEPT
    reason: >-
      Correct complex membership, redundant with but consistent with the experimental and
      phylogenetic annotations of the same complex.
    supported_by:
    - reference_id: PMID:34576938
      supporting_text: 'GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11483512
  qualifier: enables
  review:
    summary: >-
      IntAct IPI capturing PIGT physical interactions with other GPI-T subunits
      (GPAA1/PIGK/PIGS). Bare 'protein binding' is uninformative about the actual
      molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is real and biologically meaningful, but the generic 'protein
      binding' term conveys no functional information beyond what is already captured more
      informatively by the GPI-anchor transamidase complex (GO:0042765) membership. Per
      curation guidance, bare protein binding is discouraged in favour of a more specific
      term. Retained rather than removed because it reflects a genuine curated interaction.
    supported_by:
    - reference_id: PMID:11483512
      supporting_text: PIG-S and PIG-T form a protein complex with GAA1 and GPI8
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12802054
  qualifier: enables
  review:
    summary: >-
      IntAct IPI recording PIGT interaction with GPI-T subunits identified during
      characterisation of PIG-U as the fifth subunit. Bare 'protein binding' is
      uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Genuine interaction within the GPI-T complex, but 'protein binding' is too generic;
      the informative content is already captured by GO:0042765. Retained as a valid
      curated interaction rather than removed.
    supported_by:
    - reference_id: PMID:12802054
      supporting_text: The mammalian GPI transamidase is a
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      IntAct IPI derived from the BioPlex 2.0 large-scale affinity-purification
      interactome. Bare 'protein binding' with no specific functional information.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome data supporting membership in a protein community, but
      the generic 'protein binding' term is uninformative and redundant with the more
      specific complex annotation (GO:0042765).
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: networks of protein-protein interactions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      IntAct IPI derived from the BioPlex 3.0 proteome-scale interactome. Bare 'protein
      binding' term, uninformative about molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Large-scale interactome evidence; generic and redundant with the GPI-anchor
      transamidase complex annotation. Retained as valid interaction data.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Thousands of interactions assemble proteins into modules
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: >-
      IntAct IPI from a multimodal cell-map/interactome study. Bare 'protein binding' term
      without specific molecular-function content.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Systematic interactome mapping; genuine but generic. The informative function is
      captured by complex membership (GO:0042765).
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: Multimodal cell maps as a foundation for structural and functional genomics
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation (UniPathway mapping, UPA00196 glycosylphosphatidylinositol-anchor
      biosynthesis) to the GPI anchor biosynthetic process. PIGT participates in the final
      transamidation/attachment step of this pathway as part of GPI-T.
    action: ACCEPT
    reason: >-
      PIGT participates in the terminal step of GPI anchor biosynthesis (attachment of the
      anchor to protein). This pathway-level BP is correct and consistent with the UniProt
      PATHWAY annotation.
    supported_by:
    - reference_id: PMID:35551457
      supporting_text: covalent attachment of GPI at the new carboxyl terminus are catalyzed by an
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:12802054
  qualifier: located_in
  review:
    summary: >-
      Author-statement (NAS, ComplexPortal) annotation to the ER membrane, matching the
      established localisation of PIGT within the ER-membrane GPI-T complex.
    action: ACCEPT
    reason: >-
      Correct localisation. The GPI transamidase is an ER-membrane complex and PIGT is an
      integral ER membrane protein.
    supported_by:
    - reference_id: PMID:12802054
      supporting_text: posttranslationally attached to the
    - reference_id: PMID:15713669
      supporting_text: PIG-T is a type I
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: NAS
  original_reference_id: PMID:12802054
  qualifier: involved_in
  review:
    summary: >-
      Author-statement (NAS, ComplexPortal) annotation to GPI anchor attachment, the core
      BP of the GPI-T complex to which PIGT belongs.
    action: ACCEPT
    reason: >-
      Correct core process; redundant with but consistent with the IBA and IDA
      annotations for the same term.
    supported_by:
    - reference_id: PMID:12802054
      supporting_text: 'carboxyl-terminus by GPI transamidase. The mammalian GPI transamidase is a'
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IPI
  original_reference_id: PMID:12802054
  qualifier: part_of
  review:
    summary: >-
      IPI (ComplexPortal, CPX-6503) annotation placing PIGT in the GPI-anchor transamidase
      complex, based on affinity-purification of the complex.
    action: ACCEPT
    reason: >-
      Directly supported complex membership; PIGT co-purifies with the other four GPI-T
      subunits. This is the core cellular component for PIGT.
    supported_by:
    - reference_id: PMID:12802054
      supporting_text: The mammalian GPI transamidase is a
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:35165458
  qualifier: involved_in
  review:
    summary: >-
      IDA (cryo-EM structure of the human GPI-T complex) annotation to GPI anchored
      protein biosynthesis, the overall process to which the PIGT-containing complex
      contributes.
    action: ACCEPT
    reason: >-
      The structure confirms PIGT as a subunit of the complex that catalyses GPI-AP
      biogenesis. This BP is correct; it is the pathway output of GPI anchor attachment,
      so somewhat broader/less specific than GO:0016255 but valid.
    supported_by:
    - reference_id: PMID:35165458
      supporting_text: which is essential for
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:35551457
  qualifier: involved_in
  review:
    summary: >-
      IDA (2.53-Angstrom cryo-EM structure of the human GPI-T heteropentamer) annotation
      to GPI anchored protein biosynthesis.
    action: ACCEPT
    reason: >-
      Structure of the GPI-T complex directly implicates PIGT in GPI-AP biogenesis.
      Correct process-level annotation.
    supported_by:
    - reference_id: PMID:35551457
      supporting_text: covalent attachment of GPI at the new carboxyl terminus are catalyzed by an
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:28327575
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment based on functional characterisation of
      MCAHS3 patient variants that impair GPI-anchored protein surface expression.
    action: ACCEPT
    reason: >-
      Patient-variant and rescue assays demonstrate that PIGT function is required for
      attachment of GPI anchors to proteins. Core BP, correctly annotated.
    supported_by:
    - reference_id: PMID:28327575
      supporting_text: 'Mutations in 18 genes that encode'
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:36970549
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment from FACS analysis of PIGT-knockout cells
      rescued with wild-type versus p.Arg507Trp mutant cDNA, showing the variant reduces
      activity.
    action: ACCEPT
    reason: >-
      Functional assay directly links PIGT to GPI anchor attachment activity; pathogenic
      variants reduce it. Core BP, correctly annotated.
    supported_by:
    - reference_id: PMID:36970549
      supporting_text: leads to mildly reduced
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: TAS
  original_reference_id: PMID:37684232
  qualifier: involved_in
  review:
    summary: >-
      TAS annotation to GPI anchor attachment from the liganded GPI-T structural study
      describing the transamidation reaction catalysed by the complex.
    action: ACCEPT
    reason: >-
      The GPI-T complex, of which PIGT is a subunit, replaces the signal peptide with GPI
      via transamidation. Correct core BP.
    supported_by:
    - reference_id: PMID:37684232
      supporting_text: replaces it with GPI via a transamidation reaction
- term:
    id: GO:0034235
    label: GPI anchor binding
  evidence_type: IDA
  original_reference_id: PMID:11483512
  qualifier: enables
  review:
    summary: >-
      IDA annotation that PIGT binds the GPI anchor. This is an informative molecular
      function for PIGT, which contributes lipid-substrate binding residues within the
      GPI-T complex.
    action: ACCEPT
    reason: >-
      This is the most informative MF annotation present for PIGT and is retained.
      Subsequent cryo-EM structures corroborate that the GPI lipid substrate is bound in a
      composite cavity of the complex, with PIGT contributing binding residues (UniProt
      BINDING sites 461/521/523/527). Per policy, an experimental IDA whose full text is
      unavailable to me is not removed; the function is biologically sound.
    supported_by:
    - reference_id: PMID:35551457
      supporting_text: endogenous GPI in the structure defines a composite cavity for the lipid
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:11483512
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchored protein biosynthesis based on PIG-T knockout cells
      being defective in transfer of GPI to proteins.
    action: ACCEPT
    reason: >-
      Knockout data directly implicate PIGT in GPI-AP biogenesis. Correct process
      annotation (pathway output of GPI anchor attachment).
    supported_by:
    - reference_id: PMID:11483512
      supporting_text: PIG-S and PIG-T knockout cells were defective in transfer of GPI
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:12582175
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchored protein biosynthesis from the study of the
      functionally important PIG-T/GPI8 intermolecular disulfide bond.
    action: ACCEPT
    reason: >-
      PIGT is required for full transamidase activity of the complex that produces
      GPI-anchored proteins. Correct process annotation.
    supported_by:
    - reference_id: PMID:12582175
      supporting_text: required for full transamidase activity
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:28327575
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchored protein biosynthesis from functional analysis of
      MCAHS3 patient variants reducing GPI-AP surface display.
    action: ACCEPT
    reason: >-
      Variant/rescue data show PIGT is needed for GPI-AP biogenesis. Correct process
      annotation.
    supported_by:
    - reference_id: PMID:28327575
      supporting_text: 'Mutations in 18 genes that encode'
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:34576938
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchored protein biosynthesis from functional analysis of
      amino-acid mutations across the five GPI-TA subunits including PIGT.
    action: ACCEPT
    reason: >-
      Mutational screening confirms PIGT function within the GPI-TA complex that
      biosynthesises GPI-anchored proteins. Correct process annotation.
    supported_by:
    - reference_id: PMID:34576938
      supporting_text: the absence of any subunit leads to the loss of activity
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:36970549
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchored protein biosynthesis from knockout-rescue functional
      analysis of the p.Arg507Trp PIGT variant.
    action: ACCEPT
    reason: >-
      Functional assay implicates PIGT in GPI-AP biogenesis. Correct process annotation.
    supported_by:
    - reference_id: PMID:36970549
      supporting_text: leads to mildly reduced
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:37684232
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchored protein biosynthesis from the liganded GPI-T
      structural study.
    action: ACCEPT
    reason: >-
      The GPI-T structure, including PIGT, directly informs the biogenesis of
      GPI-anchored proteins. Correct process annotation.
    supported_by:
    - reference_id: PMID:37684232
      supporting_text: replaces it with GPI via a transamidation reaction
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:12802054
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment from the characterisation of the
      five-subunit GPI transamidase complex.
    action: ACCEPT
    reason: >-
      The reconstituted five-subunit complex (including PIGT) performs GPI anchor
      attachment. Core BP, correctly annotated.
    supported_by:
    - reference_id: PMID:12802054
      supporting_text: 'carboxyl-terminus by GPI transamidase. The mammalian GPI transamidase is a'
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:34576938
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment from mutational analysis of the GPI-TA
      complex subunits.
    action: ACCEPT
    reason: >-
      Confirms PIGT contribution to GPI anchor attachment activity of the complex. Core
      BP, correctly annotated.
    supported_by:
    - reference_id: PMID:34576938
      supporting_text: Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA)
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:37684232
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment from the liganded GPI-T structures
      illuminating substrate recognition and transamidation.
    action: ACCEPT
    reason: >-
      The complex containing PIGT attaches GPI to proprotein C-termini by transamidation.
      Core BP, correctly annotated.
    supported_by:
    - reference_id: PMID:37684232
      supporting_text: replaces it with GPI via a transamidation reaction
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:37684232
  qualifier: part_of
  review:
    summary: >-
      IDA (cryo-EM) annotation placing PIGT in the GPI-anchor transamidase complex,
      resolved as a heteropentamer with bound GPI/substrate.
    action: ACCEPT
    reason: >-
      Structurally confirmed complex membership. Core cellular component for PIGT.
    supported_by:
    - reference_id: PMID:37684232
      supporting_text: replaces it with GPI via a transamidation reaction
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:35165458
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment from the first human GPI-T cryo-EM structure,
      which identified the PIGK catalytic triad and the GPI substrate cleft.
    action: ACCEPT
    reason: >-
      The structure directly demonstrates how the PIGT-containing complex attaches GPI to
      proteins. Core BP, correctly annotated.
    supported_by:
    - reference_id: PMID:35165458
      supporting_text: Attaching GPI to the protein in the endoplasmic reticulum (ER) is catalyzed by
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:35551457
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to GPI anchor attachment from the 2.53-Angstrom human GPI-T structure
      with endogenous GPI bound.
    action: ACCEPT
    reason: >-
      Structure of the heteropentameric complex including PIGT elucidates GPI anchor
      attachment. Core BP, correctly annotated.
    supported_by:
    - reference_id: PMID:35551457
      supporting_text: covalent attachment of GPI at the new carboxyl terminus are catalyzed by an
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:35165458
  qualifier: part_of
  review:
    summary: >-
      IDA (cryo-EM) annotation placing PIGT in the GPI-anchor transamidase complex,
      composed of PIGK, PIGU, PIGT, PIGS and GPAA1.
    action: ACCEPT
    reason: >-
      Structurally confirmed complex membership. Core cellular component.
    supported_by:
    - reference_id: PMID:35165458
      supporting_text: The GPIT complex is known to be
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:35551457
  qualifier: part_of
  review:
    summary: >-
      IDA (cryo-EM) annotation placing PIGT in the GPI-anchor transamidase complex,
      resolved as an equimolar heteropentamer.
    action: ACCEPT
    reason: >-
      Structurally confirmed complex membership. Core cellular component.
    supported_by:
    - reference_id: PMID:35551457
      supporting_text: revealing an equimolar
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:12582175
  qualifier: part_of
  review:
    summary: >-
      IDA annotation placing PIGT in the GPI transamidase complex, based on the
      demonstration that GPI8/PIGK and PIG-T form a functionally important disulfide bond
      within the multimeric complex.
    action: ACCEPT
    reason: >-
      PIGT is a subunit that disulfide-links to catalytic PIGK; the intact complex is
      composed of five subunits. Core cellular component.
    supported_by:
    - reference_id: PMID:12582175
      supporting_text: 'two subunits of mammalian GPI transamidase, GPI8 and PIG-T, form'
    - reference_id: PMID:12582175
      supporting_text: these five components are sufficient to
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:34576938
  qualifier: part_of
  review:
    summary: >-
      IDA annotation placing PIGT in the GPI-anchor transamidase complex, from the
      purification and mutational analysis of the five-subunit GPI-TA.
    action: ACCEPT
    reason: >-
      PIGT is one of the five subunits of the purified GPI-TA. Core cellular component.
    supported_by:
    - reference_id: PMID:34576938
      supporting_text: 'GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and'
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:12802054
  qualifier: part_of
  review:
    summary: >-
      IDA annotation placing PIGT in the GPI-anchor transamidase complex, from affinity
      purification of the epitope-tagged complex containing PIG-U and PIGT.
    action: ACCEPT
    reason: >-
      PIGT co-purifies as a subunit of the GPI transamidase complex. Core cellular
      component.
    supported_by:
    - reference_id: PMID:12802054
      supporting_text: The mammalian GPI transamidase is a
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:11483512
  qualifier: part_of
  review:
    summary: >-
      IDA annotation placing PIGT in the GPI-anchor transamidase complex, from the
      original identification of PIG-S and PIG-T as subunits complexing with GAA1 and
      GPI8.
    action: ACCEPT
    reason: >-
      Foundational experimental demonstration that PIGT is a subunit of the GPI
      transamidase complex and stabilises it. Core cellular component.
    supported_by:
    - reference_id: PMID:11483512
      supporting_text: PIG-S and PIG-T form a protein complex with GAA1 and GPI8
    - reference_id: PMID:11483512
      supporting_text: PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: >-
      High-throughput (HDA) proteomics annotation to the generic 'membrane' term, from a
      membrane-proteome analysis of an NK-like cell line.
    action: KEEP_AS_NON_CORE
    reason: >-
      PIGT is indeed a membrane protein, so the annotation is not wrong, but 'membrane' is
      far less specific than the well-supported ER membrane (GO:0005789) localisation.
      Kept as non-core given the more informative CC terms already present.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: Defining the membrane proteome of NK cells
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162836
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) annotation to the ER membrane, from the uPAR GPI-attachment reaction
      catalysed by the ER-membrane GPI transamidase complex.
    action: ACCEPT
    reason: >-
      Correct localisation consistent with all other CC evidence for PIGT and the GPI-T
      complex.
    supported_by:
    - reference_id: Reactome:R-HSA-162836
      supporting_text: a complex of at least five proteins associated with the lumenal surface of the endoplasmic reticulum membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:12052837
  qualifier: located_in
  review:
    summary: >-
      Author-statement (NAS) annotation to the ER membrane, from the study of Gaa1
      recruitment into the ER-localised GPI transamidase complex.
    action: ACCEPT
    reason: >-
      Correct localisation; the GPI transamidase (including PIGT) is an ER-membrane
      complex.
    supported_by:
    - reference_id: PMID:12052837
      supporting_text: Gaa1 is an endoplasmic
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: TAS
  original_reference_id: PMID:11483512
  qualifier: involved_in
  review:
    summary: >-
      TAS annotation to GPI anchor attachment from the original PIG-S/PIG-T identification
      paper.
    action: ACCEPT
    reason: >-
      PIG-T is essential for attachment of GPI anchors to proteins. Core BP, correctly
      annotated.
    supported_by:
    - reference_id: PMID:11483512
      supporting_text: PIG-S and PIG-T knockout cells were defective in transfer of GPI
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15713669
  qualifier: enables
  review:
    summary: >-
      IPI annotation of a PIGT interaction (with GPAA1/O43292) from the study of ER
      localisation of Gaa1 and PIG-T. Bare 'protein binding' term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Genuine interaction with a partner GPI-T subunit, but 'protein binding' is
      uninformative and redundant with the complex membership annotation (GO:0042765).
      Retained as a valid curated interaction.
    supported_by:
    - reference_id: PMID:15713669
      supporting_text: subunits of the
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: TAS
  original_reference_id: PMID:15713669
  qualifier: part_of
  review:
    summary: >-
      TAS annotation placing PIGT in the GPI transamidase complex, from the study of ER
      localisation of two of its subunits (Gaa1 and PIG-T).
    action: ACCEPT
    reason: >-
      PIGT is described as one of the five subunits of the GPI transamidase complex. Core
      cellular component.
    supported_by:
    - reference_id: PMID:15713669
      supporting_text: subunits of the
core_functions:
- description: >-
    As a required structural subunit of the endoplasmic reticulum membrane GPI-anchor
    transamidase (GPI-T) complex, PIGT binds the GPI lipid substrate and, by forming an
    interchain disulfide bond with the catalytic subunit PIGK/GPI8 and stabilising the
    complex, contributes to attachment of pre-assembled GPI anchors to the C-terminus of
    GPI-anchored proteins during GPI anchor biosynthesis.
  molecular_function:
    id: GO:0034235
    label: GPI anchor binding
  directly_involved_in:
  - id: GO:0016255
    label: attachment of GPI anchor to protein
  - id: GO:0006506
    label: GPI anchor biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  in_complex:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  supported_by:
  - reference_id: PMID:11483512
    supporting_text: PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8
  - reference_id: PMID:12582175
    supporting_text: required for full transamidase activity
  - reference_id: PMID:35551457
    supporting_text: endogenous GPI in the structure defines a composite cavity for the lipid
suggested_questions:
- question: >-
    Does PIGT contribute directly to GPI lipid-substrate recognition/binding beyond a
    purely structural role, and can its binding residues (e.g. positions 461/521/523/527)
    be functionally separated from its complex-stabilising function?
- question: >-
    How do specific MCAHS3 missense variants map onto the complex-stabilising versus
    substrate-binding roles of PIGT, and does this explain the mild-versus-severe epilepsy
    phenotype spectrum?
suggested_experiments:
- description: >-
    Structure-guided mutagenesis of PIGT GPI-lipid-binding residues in a PIGT-knockout
    rescue system, measuring cell-surface GPI-anchored protein display (CD59/CD16b) versus
    complex assembly, to dissect PIGT's substrate-binding contribution from its
    structural/stabilising role.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  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:11483512
  title: PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a
    complex with GAA1 and GPI8.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Foundational paper identifying PIG-S and PIG-T as GPI-T subunits and showing PIG-T
      stabilises the complex; verified against cached abstract.
- id: PMID:12052837
  title: Structural requirements for the recruitment of Gaa1 into a functional glycosylphosphatidylinositol
    transamidase complex.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Establishes the ER-localised GPI transamidase as a Gaa1/Gpi8/PIG-S/PIG-T complex;
      supports ER membrane localisation.
- id: PMID:12582175
  title: Two subunits of glycosylphosphatidylinositol transamidase, GPI8 and PIG-T,
    form a functionally important intermolecular disulfide bridge.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Demonstrates the PIGT-PIGK/GPI8 interchain disulfide bond required for full
      transamidase activity; verified against cached abstract.
- id: PMID:12802054
  title: Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that
    attaches GPI-anchors to proteins.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Defines the five-subunit GPI transamidase and its role in attaching GPI to proteins;
      PIGT is one of the subunits.
- id: PMID:15713669
  title: Endoplasmic reticulum localization of Gaa1 and PIG-T, subunits of the glycosylphosphatidylinositol
    transamidase complex.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Shows PIG-T is a type I ER membrane protein retained in the ER via its transmembrane
      span; supports ER membrane localisation.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput membrane proteome; only supports the generic 'membrane' localisation,
      not specific function.
- id: PMID:28327575
  title: Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects
    are a rare cause of developmental disorders.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Identifies biallelic PIGT variants in developmental-disorder trios and demonstrates
      impaired GPI-AP biogenesis; supports MCAHS3 and the GPI-attachment BP.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 2.0 large-scale interactome; supports generic protein-binding interactions
      only.
- 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 proteome-scale interactome; supports generic protein-binding interactions
      only.
- id: PMID:34576938
  title: Functional Analysis of the GPI Transamidase Complex by Screening for Amino
    Acid Mutations in Each Subunit.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Mutational analysis of all five GPI-TA subunits including PIGT; shows loss of any
      subunit abolishes activity.
- id: PMID:35165458
  title: Structure of human glycosylphosphatidylinositol transamidase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      First cryo-EM structure of human GPI-T; PIGK is catalytic, complex is ER-membrane;
      PIGT is a subunit.
- id: PMID:35551457
  title: Molecular insights into biogenesis of glycosylphosphatidylinositol anchor
    proteins.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      2.53-Angstrom cryo-EM structure of the equimolar heteropentameric GPI-T with bound
      GPI; defines the lipid-substrate cavity.
- id: PMID:36970549
  title: 'Case report: Functional analysis of the p.Arg507Trp variant of the PIGT
    gene supporting the moderate epilepsy phenotype of mutations in the C-terminal
    region.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Knockout-rescue FACS assay of a PIGT MCAHS3 variant; directly ties PIGT to
      GPI-anchor attachment activity.
- id: PMID:37684232
  title: Structures of liganded glycosylphosphatidylinositol transamidase illuminate
    GPI-AP biogenesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Substrate/product-bound GPI-T structures describing the transamidation reaction;
      PIGT is a subunit and binds GPI.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Multimodal interactome/cell-map study; supports generic protein-binding interactions
      only.
- id: Reactome:R-HSA-162836
  title: uPAR precursor + acyl-GPI -> uPAR-acyl-GPI + uPAR propeptide
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction catalysed by the ER-membrane GPI transamidase complex; supports ER
      membrane localisation of the complex containing PIGT.