id: Q92643
gene_symbol: PIGK
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PIGK (also known as GPI8) is the catalytic subunit of the multi-subunit
  glycosylphosphatidylinositol-anchor transamidase (GPI-T) complex, an
  endoplasmic reticulum membrane enzyme that attaches preassembled GPI anchors
  to the C-terminus of GPI-anchored proteins. During maturation of GPI-anchored
  proteins in the ER lumen, GPI-T recognizes a diverse C-terminal GPI-attachment
  signal peptide (lacking a consensus sequence), cleaves it, and forms a new
  amide bond between the exposed C-terminal residue (omega-site) and the amino
  group of the bridging ethanolamine-phosphate of the preassembled GPI, i.e. a
  transamidation reaction. PIGK is a legumain/caspase-like cysteine protease of
  the peptidase C13 family: its catalytic residues (nucleophile Cys206 and
  proton donor His164, completed by Asn58) cleave the signal peptide and form a
  transient acyl(carbonyl)-enzyme thioester intermediate that is then resolved
  by attack of the GPI ethanolamine amine. PIGK is a single-pass type I ER
  membrane protein with its catalytic domain in the ER lumen; it assembles with
  GPAA1, PIGT, PIGS and PIGU into an equimolar heteropentamer, and a disulfide
  bond to PIGT contributes to full activity. Bi-allelic loss-of-function
  variants in PIGK cause an autosomal recessive inherited GPI-deficiency
  disorder (GPIBD), a neurodevelopmental disorder with hypotonia, cerebellar
  atrophy, and (in most patients) seizures.
alternative_products:
- name: '1'
  id: Q92643-1
- name: '2'
  id: Q92643-2
  sequence_note: VSP_056457
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 PIGK -
      attachment of GPI anchor to protein. This is well supported by direct evidence
      for human PIGK and is consistent across the GPI8/PIGK orthologue family.
    action: ACCEPT
    reason: Correct core BP annotation at an appropriate level of specificity. PIGK
      is the catalytic subunit of the GPI transamidase that replaces the C-terminal
      GPI-attachment signal peptide with a preassembled GPI anchor.
    supported_by:
      - reference_id: PMID:34576938
        supporting_text: recognizes and cleaves the C-terminal GPI attachment signal
          of
- 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 PIGK as part of the GPI-anchor
      transamidase complex. This matches direct human evidence that PIGK assembles
      with GPAA1, PIGT, PIGS and PIGU into the GPI-T heteropentamer.
    action: ACCEPT
    reason: Correct core CC annotation; PIGK is a constitutive subunit of the GPI-T
      complex.
    supported_by:
      - reference_id: PMID:34576938
        supporting_text: 'GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS,
          and'
- term:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) annotation to the core molecular function - GPI-anchor
      transamidase activity. PIGK is the catalytic component that provides this activity
      within the GPI-T complex.
    action: ACCEPT
    reason: Correct core MF term. This is the exact term carried by GOA and is the
      informative molecular function of PIGK, confirmed by direct experimental evidence.
    supported_by:
      - reference_id: PMID:35165458
        supporting_text: functions as the catalytic component
- term:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO (IPR028361, GPI_transamidase) electronic mapping to the core
      molecular function GPI-anchor transamidase activity. Fully consistent with the
      curated experimental annotations.
    action: ACCEPT
    reason: Correct and specific IEA mapping to the core MF term; the GPI_transamidase
      InterPro signature is diagnostic for this activity.
    supported_by:
      - reference_id: PMID:35165458
        supporting_text: functions as the catalytic component
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Subcellular-location IEA (UniProtKB-SubCell SL-0097) placing PIGK in the
      endoplasmic reticulum membrane. This is the experimentally established site of
      GPI-T action and is corroborated by an EXP annotation to the same term.
    action: ACCEPT
    reason: Correct core CC term; PIGK is an ER membrane protein whose catalytic domain
      faces the ER lumen where GPI anchoring occurs.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: are catalyzed by an endoplasmic reticulum membrane GPI transamidase
          complex
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO mapping from the Peptidase_C13 domain (IPR001096) to proteolysis.
      PIGK is genuinely a legumain-like cysteine protease that cleaves the C-terminal
      GPI-attachment signal peptide, so this is biologically accurate, but proteolysis
      is only one half of the transamidation reaction and is far less informative than
      GPI-anchor transamidase activity.
    action: KEEP_AS_NON_CORE
    reason: Not incorrect - the C13 peptidase activity underlies signal-peptide cleavage
      - but it captures only the cleavage step and does not describe the integrated
      transamidation function; retained as non-core context.
    supported_by:
      - reference_id: PMID:10793132
        supporting_text: Gpi8p is a catalytic component that cleaves the GPI attachment
          signal peptide
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO mapping from the Peptidase_C13 domain (IPR001096) to the general
      MF peptidase activity. PIGK is a cysteine protease of the C13/legumain family
      (MEROPS C13.005), so the domain-based inference is sound, but peptidase activity
      is a general parent that undersells the specific transamidase activity.
    action: KEEP_AS_NON_CORE
    reason: Accurate at the domain level (C13 cysteine protease) but too general to
      be a core term; the informative MF is GPI-anchor transamidase activity (GO:0003923).
    supported_by:
      - reference_id: file:human/PIGK/PIGK-uniprot.txt
        supporting_text: Belongs to the peptidase C13 family
- 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: Combined-automated-annotation (ARBA/InterPro) electronic annotation to
      the core BP attachment of GPI anchor to protein. Redundant with the IBA and
      IDA annotations to the same term and biologically correct.
    action: ACCEPT
    reason: Correct core BP annotation, consistent with experimental evidence.
    supported_by:
      - reference_id: PMID:34576938
        supporting_text: recognizes and cleaves the C-terminal GPI attachment signal
          of
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Combined-automated-annotation (ARBA/InterPro) electronic annotation placing
      PIGK in the GPI-anchor transamidase complex. Redundant with, and consistent
      with, the curated IDA/IBA complex annotations.
    action: ACCEPT
    reason: Correct core CC annotation; PIGK is a bona fide subunit of the GPI-T 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:10793132
  qualifier: enables
  review:
    summary: IntAct protein-protein interaction (PIGK with GPAA1, UniProtKB:O43292).
      This documents PIGK-GPAA1 association within the GPI-T complex, which is real,
      but the bare term protein binding is uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: 'The interaction (PIGK-GPAA1) is genuine and biologically meaningful, but
      GO:0005515 protein binding is not an informative MF; the interaction is already
      captured by GPI-anchor transamidase complex membership (GO:0042765). Retained
      per curation policy rather than removed.'
    supported_by:
      - reference_id: PMID:10793132
        supporting_text: Gaa1p and Gpi8p are associated with each other
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11483512
  qualifier: enables
  review:
    summary: IntAct protein-protein interaction annotations (PIGK with GPAA1/PIGT/PIGS).
      These document GPI-T subunit associations but the bare protein binding term
      is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Genuine intra-complex interactions, but GO:0005515 is uninformative and
      redundant with the GPI-anchor transamidase complex CC annotation. Retained per
      policy.
    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 protein-protein interaction annotations (PIGK with GPAA1/PIGT).
      Documents intra-complex associations of the GPI-T subunits.
    action: MARK_AS_OVER_ANNOTATED
    reason: Real interaction but uninformative bare protein binding term; complex membership
      is already annotated (GO:0042765). Retained per policy.
    supported_by:
      - reference_id: PMID:12802054
        supporting_text: The GPI transamidase complex affinity-purified from cells
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput interactome (BioPlex-type affinity-purification MS) protein
      binding annotation (PIGK with GPAA1/PIGT). Large-scale interaction screen capturing
      GPI-T subunit associations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare protein binding term from a high-throughput interactome;
      the biologically meaningful content (GPI-T subunit association) is already captured
      by complex membership. Retained per policy.
    additional_reference_ids:
      - PMID:11483512
    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:33961781
  qualifier: enables
  review:
    summary: High-throughput dual-proteome interactome protein binding annotation (PIGK
      with GPAA1/PIGT). Large-scale interaction screen.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare protein binding term from a high-throughput interactome;
      redundant with complex membership. Retained per policy.
    additional_reference_ids:
      - PMID:11483512
    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:40205054
  qualifier: enables
  review:
    summary: High-throughput multimodal cell-map interactome protein binding annotation
      (PIGK with GPAA1/PIGT). Large-scale interaction/proximity screen.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare protein binding term from a high-throughput interactome;
      redundant with complex membership. Retained per policy.
    additional_reference_ids:
      - PMID:11483512
    supported_by:
      - reference_id: PMID:11483512
        supporting_text: PIG-S and PIG-T form a protein complex with GAA1 and GPI8
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162791
  qualifier: involved_in
  review:
    summary: Reactome traceable annotation for the GPI-T reaction attaching a GPI anchor
      to uPAR (a representative GPI-anchored substrate), mapped to attachment of GPI
      anchor to protein. Correctly represents the core BP.
    action: ACCEPT
    reason: Correct core BP annotation via a specific curated Reactome pathway event.
    supported_by:
      - reference_id: PMID:34576938
        supporting_text: recognizes and cleaves the C-terminal GPI attachment signal
          of
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: UniPathway-based electronic annotation (UPA00196) to GPI anchor biosynthetic
      process. GPI-T catalyzes the terminal transamidation step of GPI-anchor biosynthesis,
      so this parent BP is accurate.
    action: ACCEPT
    reason: Correct core BP; the transamidation/attachment step is part of GPI-anchor
      biosynthesis. Consistent with the UniProt PATHWAY (glycosylphosphatidylinositol-anchor
      biosynthesis).
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: are catalyzed by an endoplasmic reticulum membrane GPI transamidase
          complex
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:12802054
  qualifier: located_in
  review:
    summary: ComplexPortal (CPX-6503) non-traceable statement locating the GPI-T complex,
      including PIGK, at the ER membrane. Corroborated by an independent EXP annotation
      to the same term.
    action: ACCEPT
    reason: Correct core CC; PIGK/GPI-T resides in the ER membrane.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: are catalyzed by an endoplasmic reticulum membrane GPI transamidase
          complex
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: NAS
  original_reference_id: PMID:12802054
  qualifier: involved_in
  review:
    summary: ComplexPortal non-traceable statement annotating the GPI-T complex to
      attachment of GPI anchor to protein. Consistent with abundant direct evidence
      for PIGK.
    action: ACCEPT
    reason: Correct core BP annotation.
    supported_by:
      - reference_id: PMID:34576938
        supporting_text: recognizes and cleaves the C-terminal GPI attachment signal
          of
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IPI
  original_reference_id: PMID:12802054
  qualifier: part_of
  review:
    summary: ComplexPortal-curated complex membership of PIGK in the GPI-anchor transamidase
      complex (CPX-6503). PMID:12802054 established PIG-U as the fifth subunit and
      confirmed the affinity-purified GPI8-containing complex.
    action: ACCEPT
    reason: Correct core CC annotation of PIGK as a subunit of the GPI-T complex.
    supported_by:
      - reference_id: PMID:12802054
        supporting_text: The GPI transamidase complex affinity-purified from cells
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:11483512
  qualifier: located_in
  review:
    summary: Experimental evidence localizing PIGK/GPI8 (and the GPI-T complex) to
      the endoplasmic reticulum membrane. This is the definitive experimental support
      for the ER-membrane location.
    action: ACCEPT
    reason: Correct core CC term, directly supported by experiment.
    supported_by:
      - reference_id: PMID:11483512
        supporting_text: The GPI transamidase mediates GPI anchoring
- term:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  evidence_type: IDA
  original_reference_id: PMID:35551457
  qualifier: enables
  review:
    summary: Direct experimental evidence (cryo-EM structure plus structure-based mutagenesis
      of the reconstituted human GPI-T) for GPI-anchor transamidase activity, with
      PIGK as the catalytic subunit. This is the primary core MF annotation.
    action: ACCEPT
    reason: Correct core MF term with strong direct experimental support; matches the
      exact GOA term.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: suggests a legumain-like
- term:
    id: GO:0180046
    label: GPI anchored protein biosynthesis
  evidence_type: IDA
  original_reference_id: PMID:35165458
  qualifier: involved_in
  review:
    summary: Direct experimental evidence (structure and functional analysis of human
      GPI-T) that PIGK participates in GPI anchored protein biosynthesis. GO:0180046
      is the current specific BP for the GPI-AP maturation process.
    action: ACCEPT
    reason: Correct core BP; PIGK is essential for GPI-anchored protein biosynthesis
      (maturation), as shown by the catalytic dyad requirement.
    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: Direct experimental evidence that PIGK/GPI-T is required for GPI anchored
      protein biosynthesis, from the cryo-EM structure and functional mutagenesis of
      the human complex.
    action: ACCEPT
    reason: Correct core BP annotation, redundant with and consistent with the other
      IDA to GO:0180046.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: important step towards the mechanistic understanding of
- term:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  evidence_type: IDA
  original_reference_id: PMID:37684232
  qualifier: enables
  review:
    summary: Direct experimental evidence for GPI-anchor transamidase activity from
      substrate- and product-bound cryo-EM structures of human GPI-T, defining a caspase-like
      catalytic mechanism with PIGK as the catalytic subunit (Cys206 nucleophile /
      His164 proton donor).
    action: ACCEPT
    reason: Correct core MF term with strong structural/mechanistic support.
    supported_by:
      - reference_id: PMID:37684232
        supporting_text: inform a caspase-like catalytic mechanism
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:12802054
  qualifier: involved_in
  review:
    summary: Direct experimental evidence that PIGK/GPI-T is required for attachment
      of GPI anchor to protein. Class-U (PIG-U-deficient) cells lacking a functional
      GPI-T could not cleave the GPI attachment signal peptide.
    action: ACCEPT
    reason: Correct core BP annotation supported by loss-of-function cell evidence.
    supported_by:
      - reference_id: PMID:12802054
        supporting_text: had no ability to cleave the GPI attachment signal peptide
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:34576938
  qualifier: involved_in
  review:
    summary: Direct experimental evidence (subunit mutagenesis affecting GPI-anchor
      attachment to protein) that PIGK is required for attachment of GPI anchor to
      protein.
    action: ACCEPT
    reason: Correct core BP annotation; mutagenesis of PIGK catalytic residues (e.g.
      His164, Cys206) abolishes GPI-anchor attachment.
    supported_by:
      - reference_id: PMID:34576938
        supporting_text: recognizes and cleaves the C-terminal GPI attachment signal
          of
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:37684232
  qualifier: involved_in
  review:
    summary: Direct experimental evidence from substrate/product-bound GPI-T structures
      that PIGK mediates attachment of GPI anchor to protein via the transamidation
      reaction.
    action: ACCEPT
    reason: Correct core BP annotation with mechanistic structural support.
    supported_by:
      - reference_id: PMID:37684232
        supporting_text: replaces it with GPI via a transamida
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:37684232
  qualifier: part_of
  review:
    summary: Direct experimental (cryo-EM) evidence identifying PIGK as a subunit of
      the GPI-anchor transamidase complex, resolved together with GPAA1, PIGS, PIGT
      and PIGU.
    action: ACCEPT
    reason: Correct core CC annotation with direct structural support.
    supported_by:
      - reference_id: PMID:37684232
        supporting_text: 'The transmembrane complex GPI-T'
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:35165458
  qualifier: involved_in
  review:
    summary: Direct experimental evidence (human GPI-T structure and mutagenesis of
      the C206-H164-N58 catalytic triad) that PIGK mediates attachment of GPI anchor
      to protein.
    action: ACCEPT
    reason: Correct core BP annotation with strong structural/functional support.
    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: Direct experimental evidence (2.53-A cryo-EM structure and structure-based
      mutagenesis) that PIGK/GPI-T mediates attachment of GPI anchor to protein.
    action: ACCEPT
    reason: Correct core BP annotation, redundant with and consistent with other IDAs.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: covalent attachment of GPI at the new carboxyl terminus
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:35165458
  qualifier: part_of
  review:
    summary: Direct experimental (cryo-EM) identification of PIGK as the catalytic
      subunit of the GPI-anchor transamidase complex, resolved with the four other
      subunits.
    action: ACCEPT
    reason: Correct core CC annotation with direct structural support.
    supported_by:
      - reference_id: PMID:35165458
        supporting_text: The PIGK subunit
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:35551457
  qualifier: part_of
  review:
    summary: Direct experimental (cryo-EM) evidence resolving PIGK within the equimolar
      heteropentameric GPI-anchor transamidase complex.
    action: ACCEPT
    reason: Correct core CC annotation with direct structural support.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: revealing an equimolar
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:10793132
  qualifier: involved_in
  review:
    summary: Direct experimental evidence that GPI8/PIGK is required for GPI attachment;
      conserved cysteine and histidine residues essential for the carbonyl intermediate
      identify PIGK as the catalytic component that cleaves the GPI signal peptide.
    action: ACCEPT
    reason: Correct core BP annotation, supported by mutagenesis of catalytic residues.
    supported_by:
      - reference_id: PMID:10793132
        supporting_text: Gpi8p is a catalytic component that cleaves the GPI attachment
          signal peptide
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: IDA
  original_reference_id: PMID:9356492
  qualifier: involved_in
  review:
    summary: Direct experimental evidence identifying hGPI8/PIGK as the gene defective
      in the class-K GPI-deficient mutant; reconstitution with hGPI8 restored C-terminal
      processing of GPI-anchored proteins.
    action: ACCEPT
    reason: Foundational functional evidence for the core BP; PIGK loss abolishes,
      and its restoration rescues, GPI anchor attachment.
    supported_by:
      - reference_id: PMID:9356492
        supporting_text: restores the ability
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:12582175
  qualifier: part_of
  review:
    summary: Direct experimental evidence that GPI8/PIGK is a subunit of the multimeric
      mammalian GPI transamidase and forms a functionally important disulfide bond
      with PIG-T within the complex.
    action: ACCEPT
    reason: Correct core CC annotation; PIGK-PIGT disulfide within the GPI-T complex.
    supported_by:
      - reference_id: PMID:12582175
        supporting_text: is a multimeric complex consisting of at least five subunits
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:34576938
  qualifier: part_of
  review:
    summary: Direct experimental evidence (purification and functional analysis of
      the five-subunit human GPI-TA) confirming PIGK as a subunit of the GPI-anchor
      transamidase complex.
    action: ACCEPT
    reason: Correct core CC annotation.
    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: Direct experimental evidence that the GPI8/PIGK-containing GPI transamidase
      complex affinity-purified from cells contains PIG-U and four other components,
      confirming PIGK complex membership.
    action: ACCEPT
    reason: Correct core CC annotation.
    supported_by:
      - reference_id: PMID:12802054
        supporting_text: The GPI transamidase complex affinity-purified from cells
- term:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162836
  qualifier: enables
  review:
    summary: Reactome traceable annotation for the GPI-T-catalyzed reaction (uPAR precursor
      + acyl-GPI -> uPAR-acyl-GPI + propeptide), mapped to GPI-anchor transamidase
      activity - the exact GOA core MF term.
    action: ACCEPT
    reason: Correct core MF annotation via a curated Reactome reaction.
    supported_by:
      - reference_id: PMID:35165458
        supporting_text: functions as the catalytic component
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IDA
  original_reference_id: PMID:11483512
  qualifier: part_of
  review:
    summary: Direct experimental evidence that PIG-S and PIG-T form a complex with
      GAA1 and GPI8/PIGK, establishing PIGK membership in the GPI-anchor transamidase
      complex.
    action: ACCEPT
    reason: Correct core CC annotation.
    supported_by:
      - reference_id: PMID:11483512
        supporting_text: PIG-S and PIG-T form a protein complex with GAA1 and GPI8
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput mass-spectrometry detection of PIGK in an NK-cell membrane
      proteome. Consistent with PIGK being membrane-associated but the generic term
      membrane is far less informative than the established ER membrane location.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not incorrect (PIGK is a membrane protein) but GO:0016020 membrane is uninformatively
      general and is superseded by the specific ER membrane (GO:0005789) annotations.
    supported_by:
      - reference_id: PMID:19946888
        supporting_text: define the composition of the membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162836
  qualifier: located_in
  review:
    summary: Reactome traceable annotation placing the GPI transamidase (including
      PIGK) at the ER membrane, consistent with the experimental EXP annotation.
    action: ACCEPT
    reason: Correct core CC annotation.
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: are catalyzed by an endoplasmic reticulum membrane GPI transamidase
          complex
- term:
    id: GO:0034235
    label: GPI anchor binding
  evidence_type: TAS
  original_reference_id: PMID:10793132
  qualifier: contributes_to
  review:
    summary: Traceable annotation that PIGK contributes_to GPI anchor binding. The
      GPI-T complex binds the preassembled GPI lipid substrate (a composite GPI-binding
      cavity is resolved in structures), and PIGK contributes to this binding as the
      catalytic subunit acting on the GPI ethanolamine.
    action: KEEP_AS_NON_CORE
    reason: 'Biologically reasonable with the contributes_to qualifier: GPI binding
      is a complex-level property to which PIGK contributes, not an independent PIGK
      activity. Retained as non-core supporting MF.'
    supported_by:
      - reference_id: PMID:35551457
        supporting_text: an endogenous GPI in the structure defines a composite cavity
          for the lipid
- term:
    id: GO:0016255
    label: attachment of GPI anchor to protein
  evidence_type: TAS
  original_reference_id: PMID:11483512
  qualifier: involved_in
  review:
    summary: Traceable annotation that PIGK/GPI-T mediates GPI anchor attachment to
      proteins in the ER by replacing the C-terminal GPI-attachment signal peptide.
    action: ACCEPT
    reason: Correct core BP annotation.
    supported_by:
      - reference_id: PMID:11483512
        supporting_text: The GPI transamidase mediates GPI anchoring
- term:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  evidence_type: IMP
  original_reference_id: PMID:10793132
  qualifier: enables
  review:
    summary: Mutational evidence that conserved catalytic cysteine/histidine residues
      of GPI8/PIGK are essential for the carbonyl intermediate, i.e. for GPI-anchor
      transamidase activity. Catalytic-residue mutants abolish activity.
    action: ACCEPT
    reason: Correct core MF term with genetic/mutational support (loss of transamidase
      activity on mutating catalytic residues).
    supported_by:
      - reference_id: PMID:10793132
        supporting_text: essential for generation of a carbonyl intermediate
- term:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  evidence_type: IMP
  original_reference_id: PMID:10793132
  qualifier: part_of
  review:
    summary: Evidence that Gaa1p and Gpi8p/PIGK associate as components of the GPI
      transamidase, placing PIGK in the GPI-anchor transamidase complex.
    action: ACCEPT
    reason: Correct core CC annotation.
    supported_by:
      - reference_id: PMID:10793132
        supporting_text: Gaa1p and Gpi8p are associated with each other
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: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:10793132
  title: Gaa1p and gpi8p are components of a glycosylphosphatidylinositol (GPI) transamidase
    that mediates attachment of GPI to proteins.
  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: []
- id: PMID:12582175
  title: Two subunits of glycosylphosphatidylinositol transamidase, GPI8 and PIG-T,
    form a functionally important intermolecular disulfide bridge.
  findings: []
- id: PMID:12802054
  title: Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that
    attaches GPI-anchors to proteins.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34576938
  title: Functional Analysis of the GPI Transamidase Complex by Screening for Amino
    Acid Mutations in Each Subunit.
  findings: []
- id: PMID:35165458
  title: Structure of human glycosylphosphatidylinositol transamidase.
  findings: []
- id: PMID:35551457
  title: Molecular insights into biogenesis of glycosylphosphatidylinositol anchor
    proteins.
  findings: []
- id: PMID:37684232
  title: Structures of liganded glycosylphosphatidylinositol transamidase illuminate
    GPI-AP biogenesis.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:9356492
  title: The affected gene underlying the class K glycosylphosphatidylinositol (GPI)
    surface protein defect codes for the GPI transamidase.
  findings: []
- id: Reactome:R-HSA-162791
  title: Attachment of GPI anchor to uPAR
  findings: []
- id: Reactome:R-HSA-162836
  title: uPAR precursor + acyl-GPI -> uPAR-acyl-GPI + uPAR propeptide
  findings: []
- id: file:human/PIGK/PIGK-uniprot.txt
  title: UniProtKB entry Q92643 (GPI8_HUMAN)
  findings: []
core_functions:
- description: Catalytic (cysteine-protease-like) subunit of the ER-membrane GPI-anchor
    transamidase (GPI-T) complex that attaches preassembled GPI anchors to proteins.
    PIGK cleaves the C-terminal GPI-attachment signal peptide of nascent proproteins
    (nucleophile Cys206, proton donor His164) forming an acyl(carbonyl)-enzyme thioester
    intermediate, then transfers the GPI anchor onto the newly exposed omega-site via
    a transamidation reaction.
  molecular_function:
    id: GO:0003923
    label: GPI-anchor transamidase activity
  directly_involved_in:
  - id: GO:0006506
    label: GPI anchor biosynthetic process
  - id: GO:0016255
    label: attachment of GPI anchor to protein
  - id: GO:0180046
    label: GPI anchored protein biosynthesis
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  in_complex:
    id: GO:0042765
    label: GPI-anchor transamidase complex
  supported_by:
  - reference_id: PMID:35165458
    supporting_text: The PIGK subunit
  - reference_id: PMID:10793132
    supporting_text: Gpi8p is a catalytic component that cleaves the GPI attachment
      signal peptide
  - reference_id: file:human/PIGK/PIGK-uniprot.txt
    supporting_text: Catalytic subunit of the glycosylphosphatidylinositol-anchor