tgrB1

id: Q54V07
gene_symbol: tgrB1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: TgrB1 (Tiger protein B1; formerly LagB1) is a highly polymorphic,
  single-pass type I transmembrane glycoprotein of the social amoeba Dictyostelium
  discoideum. Its long, glycosylated extracellular region contains three IPT/TIG
  (immunoglobulin-like) domains, followed by a single transmembrane helix and a
  short cytoplasmic tail. TgrB1 is displayed on the cell surface and functions as
  the receptor of a matched receptor-ligand pair with the adjacent-gene product
  TgrC1, which is its ligand. TgrB1 binds TgrC1 in trans across the gap between
  neighbouring cells in an allele-specific manner; this heterophilic binding drives
  homodimerization of TgrB1 and assembly of large TgrB1-TgrC1 adhesion complexes,
  mediates cell-cell adhesion, and transduces a signal via the cytoplasmic tail
  (which becomes phosphorylated upon ligand engagement). Because tgrB1 and tgrC1
  are among the most polymorphic loci in the genome and only matching allele pairs
  bind productively, the TgrB1-TgrC1 system provides a self/kin-recognition
  (allorecognition) mechanism that governs the transition from unicellular growth
  to cooperative multicellular development, and underlies preferential cooperation
  with kin, protection against cheaters, and the greenbeard behaviour of the
  organism.
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: TgrB1 is a single-pass type I transmembrane protein displayed at the
      plasma membrane, where it engages TgrC1 on adjacent cells. This electronic
      subcellular-location assignment is confirmed by direct experimental evidence.
    action: ACCEPT
    reason: Plasma membrane localization is directly established experimentally and
      is a core aspect of TgrB1 function as a cell-surface receptor.
    supported_by:
    - reference_id: PMID:29038229
      supporting_text: The TgrB1 and TgrC1 proteins are located on the plasma membrane
        and they bind each other through interactions between specific protein domains
        in trans
- term:
    id: GO:0099138
    label: altruistic, chimeric sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:38734736
  qualifier: involved_in
  review:
    summary: In chimeras, activation of the TgrB1 receptor drives carrier cells into
      the altruistic prestalk/stalk fate while boosting wild-type spore production,
      whereas tgrB1 inactivation causes allotype-specific cheating. TgrB1 thus
      governs altruistic cell-fate allocation in chimeric development. This is a
      downstream social/developmental outcome rather than the core molecular
      function.
    action: KEEP_AS_NON_CORE
    reason: Well supported by IMP evidence, but this is a pleiotropic
      social-development phenotype downstream of TgrB1 receptor activity rather than
      the core molecular function.
    supported_by:
    - reference_id: PMID:38734736
      supporting_text: activation of the TgrB1 receptor confers altruism
- term:
    id: GO:0140986
    label: G protein-coupled chemorepellent receptor signaling pathway
  evidence_type: HMP
  original_reference_id: PMID:35622529
  qualifier: acts_upstream_of_or_within
  review:
    summary: This annotation derives from a REMI genetic screen for components of
      the AprA-induced chemorepulsion pathway. The connection to tgrB1 is uncertain
      the paper labels its screen hit "TgrB1" as a protein encoded by DDB_G0293176,
      whereas this gene (tgrB1/lagB1) is DDB_G0280689, and TgrB1 is an Ig-domain
      single-pass adhesion receptor, not a G-protein-coupled receptor. The
      relationship cannot be verified from the available text.
    action: UNDECIDED
    reason: Cannot verify the annotation; the cited paper attributes the phenotype
      to a protein encoded by a different DDB_G identifier (DDB_G0293176) than this
      gene (DDB_G0280689), and a GPCR chemorepellent role is inconsistent with the
      well-established biology of TgrB1 as a non-GPCR Ig-domain allorecognition
      receptor.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23477311
  qualifier: enables
  review:
    summary: Direct interaction evidence (IPI) documenting that TgrB1 binds TgrC1
      (UniProtKB:P42523) via mutual IPT/TIG domains. This physical interaction is
      genuine, but the bare "protein binding" term is uninformative; the interaction
      underlies TgrB1's transmembrane signaling receptor activity captured elsewhere.
    action: KEEP_AS_NON_CORE
    reason: The TgrB1-TgrC1 interaction is real and central, but GO:0005515 protein
      binding is too generic to convey function. The informative molecular function
      is transmembrane signaling receptor activity (GO:0004888), annotated
      separately.
    supported_by:
    - reference_id: PMID:23477311
      supporting_text: identify TgrB1 as the heterophilic binding partner
- term:
    id: GO:0007157
    label: heterophilic cell-cell adhesion
  evidence_type: IDA
  original_reference_id: PMID:23477311
  qualifier: involved_in
  review:
    summary: TgrB1 and TgrC1 are the heterophilic partners of a cell-adhesion system;
      TgrB1 binds TgrC1 in trans through their respective TIG domains, mediating
      cell-cell adhesion during aggregation and post-aggregative development.
    action: ACCEPT
    reason: Directly supported; heterophilic adhesion via trans TgrB1-TgrC1 binding
      is a core activity of the protein.
    supported_by:
    - reference_id: PMID:23477311
      supporting_text: mapped the cell-binding regions in these two proteins to
    - reference_id: PMID:29038229
      supporting_text: The TgrB1 and TgrC1 proteins are located on the plasma membrane
        and they bind each other through interactions between specific protein domains
        in trans
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:27307293
  qualifier: involved_in
  review:
    summary: Genetic screens for suppressors of the tgrB1-tgrC1 mismatch identified
      downstream signal-transduction components, consistent with TgrB1 acting as a
      cell-surface receptor whose engagement by TgrC1 triggers an intracellular
      signaling pathway.
    action: ACCEPT
    reason: Supported by genetic-interaction evidence and by the demonstration that
      TgrB1 acts as a signaling receptor; this captures its role as a surface
      receptor initiating a signaling pathway.
    supported_by:
    - reference_id: PMID:27307293
      supporting_text: TgrB1 and TgrC1 are cell-surface adhesion proteins that form
        heterophilic interactions in trans
    - reference_id: PMID:29038229
      supporting_text: the receptor activity of TgrB1 has been constitutively activated
        with respect to cooperative development and differentiation
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: IDA
  original_reference_id: PMID:29038229
  qualifier: enables
  review:
    summary: TgrB1 acts as the receptor of the TgrB1-TgrC1 pair. Binding of
      compatible TgrC1 in trans induces phosphorylation of the TgrB1 cytoplasmic
      tail, and dominant tgrB1 alleles behave as constitutively activated receptors,
      demonstrating transmembrane signaling receptor activity.
    action: ACCEPT
    reason: Directly demonstrated core molecular function; TgrB1 is a transmembrane
      signaling receptor for its ligand TgrC1.
    supported_by:
    - reference_id: PMID:29038229
      supporting_text: Here, we show that TgrB1 acts as a receptor with TgrC1 as its
        ligand in cooperative aggregation and differentiation.
    - reference_id: PMID:29038229
      supporting_text: the cytoplasmic tail of TgrB1 becomes phosphorylated upon binding
        to a matching TgrC1 ligand
- term:
    id: GO:0098635
    label: protein complex involved in cell-cell adhesion
  evidence_type: IDA
  original_reference_id: PMID:24490801
  qualifier: is_active_in
  review:
    summary: Trans-interaction of monomeric TgrB1 with TgrC1 homodimers triggers
      TgrB1 homodimerization and the coalescence of TgrB1-TgrC1 clusters into large
      cell-adhesion complexes, of which TgrB1 is an active component.
    action: ACCEPT
    reason: Directly supported; TgrB1 is an active subunit of the TgrB1-TgrC1
      cell-adhesion complex.
    supported_by:
    - reference_id: PMID:24490801
      supporting_text: the coalescence of TgrB1-TgrC1 clusters results in the formation
        of large
    - reference_id: PMID:24490801
      supporting_text: cis-homodimerization is dependent on trans-interaction with
        TgrC1
- term:
    id: GO:0009897
    label: external side of plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24490801
  qualifier: is_active_in
  review:
    summary: The long glycosylated TgrB1 ectodomain, bearing the TIG domains that
      bind TgrC1, faces the extracellular space and engages ligand on adjacent cells,
      consistent with activity on the external side of the plasma membrane.
    action: ACCEPT
    reason: Consistent with the type I topology (extracellular N-terminal region)
      and with trans-binding of TgrC1 across the intercellular gap.
    supported_by:
    - reference_id: PMID:24490801
      supporting_text: In Dictyostelium discoideum, TgrB1 and TgrC1 are partners of
        a heterophilic
    - reference_id: PMID:29038229
      supporting_text: The TgrB1 and TgrC1 proteins are located on the plasma membrane
        and they bind each other through interactions between specific protein domains
        in trans
- term:
    id: GO:0009988
    label: cell-cell recognition
  evidence_type: IMP
  original_reference_id: PMID:19285397
  qualifier: involved_in
  review:
    summary: Disruption of lagB1 (tgrB1) causes strain segregation in chimeras with
      wild-type cells; tgrB1 and tgrC1 are polymorphic and function together in a
      kin/self-recognition mechanism. This is a core recognition function.
    action: ACCEPT
    reason: Directly supported by the null-mutant phenotype; cell-cell recognition
      is a core biological role of TgrB1.
    supported_by:
    - reference_id: PMID:19285397
      supporting_text: lagB1 and lagC1 participate in a common self- or kin-recognition
        mechanism
- term:
    id: GO:0097656
    label: cell-cell self recognition
  evidence_type: IGI
  original_reference_id: PMID:21700835
  qualifier: involved_in
  review:
    summary: A matching pair of tgrB1 and tgrC1 alleles is necessary and sufficient
      for attractive self-recognition, mediated by allele-specific heterotypic
      binding between the extracellular domains on adjacent cells. This is a core
      function of TgrB1.
    action: ACCEPT
    reason: Strongly supported by allele-swap genetic evidence; self-recognition is
      a defining core role of the TgrB1-TgrC1 pair.
    supported_by:
    - reference_id: PMID:21700835
      supporting_text: mediate self-recognition by heterotypic interactions between
        the extracellular protein domains on adjacent cells
    - reference_id: PMID:21700835
      supporting_text: necessary for self-recognition and for development
- term:
    id: GO:0099120
    label: socially cooperative development
  evidence_type: IMP
  original_reference_id: PMID:23910661
  qualifier: involved_in
  review:
    summary: Kin recognition mediated by tgrB1 and tgrC1 protects cooperators against
      cheaters, enabling stable socially cooperative development. This is a
      downstream social outcome of TgrB1-mediated recognition.
    action: KEEP_AS_NON_CORE
    reason: Supported by IMP evidence, but represents a pleiotropic social/population
      outcome downstream of TgrB1's core recognition/receptor function rather than
      the core function itself.
    supported_by:
    - reference_id: PMID:23910661
      supporting_text: kin-recognition genes, tgrB1 and tgrC1
- term:
    id: GO:0099138
    label: altruistic, chimeric sorocarp development
  evidence_type: IDA
  original_reference_id: PMID:28120827
  qualifier: involved_in
  review:
    summary: The polymorphic Tgr locus behaves as a polychromatic greenbeard in
      which partner-specific TgrB1-TgrC1 binding strength predicts partner-specific
      patterns of cooperation during chimeric development. This is a downstream
      social-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Well supported, but this greenbeard/altruistic chimeric-development role
      is a social outcome downstream of the core allorecognition receptor function.
    supported_by:
    - reference_id: PMID:28120827
      supporting_text: partner-specific protein-protein binding strength and recognition
        specificity
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IEP
  original_reference_id: PMID:25887420
  qualifier: acts_upstream_of_or_within
  review:
    summary: tgrB1 mRNA is developmentally regulated with expression during the
      aggregation-to-mound transition, when amoebae must clear an allorecognition
      checkpoint established by tgrB1 and tgrC1. The annotation reflects expression
      timing and the checkpoint role during aggregative development.
    action: KEEP_AS_NON_CORE
    reason: Expression-based (IEP) evidence places TgrB1 at the aggregation stage,
      but this developmental-process involvement is secondary to its core
      receptor/recognition function.
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: amoebae must clear a checkpoint established by the allorecognition
        genes tgrB1 and tgrC1
- term:
    id: GO:0048870
    label: cell motility
  evidence_type: IGI
  original_reference_id: PMID:18164290
  qualifier: acts_upstream_of_or_within
  review:
    summary: This genetic-interaction annotation derives from a REMI suppressor
      screen for cell-migration genes. The cached abstract concerns the phospholipase
      D gene pldB and does not describe tgrB1, so the specific basis for a tgrB1
      cell-motility role cannot be verified from the available text.
    action: UNDECIDED
    reason: The relevant supporting evidence cannot be verified from the available
      (abstract-only) publication, which is about pldB and cell migration and does
      not mention tgrB1.
core_functions:
- description: TgrB1 is the receptor half of the polymorphic TgrB1-TgrC1
    receptor-ligand pair. Displayed on the cell surface via its glycosylated
    IPT/TIG ectodomain, it binds its ligand TgrC1 on adjacent cells in an
    allele-specific manner in trans, driving TgrB1 homodimerization, assembly of
    TgrB1-TgrC1 cell-adhesion complexes, and phosphorylation-coupled transmembrane
    signaling that mediates self/kin recognition and the transition to cooperative
    multicellular development.
  molecular_function:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  directly_involved_in:
  - id: GO:0097656
    label: cell-cell self recognition
  - id: GO:0007157
    label: heterophilic cell-cell adhesion
  - id: GO:0007166
    label: cell surface receptor signaling pathway
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0009897
    label: external side of plasma membrane
  in_complex:
    id: GO:0098635
    label: protein complex involved in cell-cell adhesion
  supported_by:
  - reference_id: PMID:29038229
    supporting_text: Here, we show that TgrB1 acts as a receptor with TgrC1 as its
      ligand in cooperative aggregation and differentiation.
  - reference_id: PMID:29038229
    supporting_text: the cytoplasmic tail of TgrB1 becomes phosphorylated upon binding
      to a matching TgrC1 ligand
  - reference_id: PMID:21700835
    supporting_text: mediate self-recognition by heterotypic interactions between
      the extracellular protein domains on adjacent cells
references:
- 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: PMID:18164290
  title: Screening of genes involved in cell migration in Dictyostelium.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Abstract-only; the paper concerns the phospholipase D gene pldB
      and cell migration and does not mention tgrB1. Basis for the tgrB1 cell-motility
      IGI annotation cannot be verified from the available text.
- id: PMID:19285397
  title: Polymorphic members of the lag gene family mediate kin discrimination in
    Dictyostelium.
  findings:
  - statement: Disruption of lagB1 (tgrB1) arrests development at the loose aggregate
      stage and causes strain segregation in chimeras with wild-type cells.
    supporting_text: lagC1 and lagB1 are essential for aggregation and for subsequent
      development, suggesting common functions
  - statement: lagB1 (tgrB1) and lagC1 (tgrC1) are polymorphic and function together
      in a common self/kin-recognition mechanism.
    supporting_text: lagB1 and lagC1 participate in a common self- or kin-recognition
      mechanism
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Foundational paper identifying lagB1/tgrB1 as a polymorphic
      kin-discrimination determinant; full text verified.
- id: PMID:21700835
  title: Self-recognition in social amoebae is mediated by allelic pairs of tiger
    genes.
  findings:
  - statement: A matching pair of tgrB1 and tgrC1 alleles is necessary and sufficient
      for attractive self-recognition, mediated by heterotypic binding of their
      extracellular domains on adjacent cells.
    supporting_text: mediate self-recognition by heterotypic interactions between
      the extracellular protein domains on adjacent cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes allele-specific self-recognition by matched tgrB1-tgrC1
      pairs; full text verified.
- id: PMID:23477311
  title: TgrC1 mediates cell-cell adhesion by interacting with TgrB1 via mutual IPT/TIG
    domains during development of Dictyostelium discoideum.
  findings:
  - statement: TgrB1 is the heterophilic binding partner of TgrC1; the two type I
      transmembrane proteins bind via their TIG domains to mediate cell-cell adhesion.
    supporting_text: identify TgrB1 as the heterophilic binding partner
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Biochemical identification and domain mapping of the TgrB1-TgrC1
      interaction; cached record is abstract-only but the abstract directly supports
      the cited claims.
- id: PMID:23910661
  title: Kin recognition protects cooperators against cheaters.
  findings:
  - statement: Kin recognition mediated by tgrB1 and tgrC1 protects cooperators
      against cheaters.
    supporting_text: kin-recognition genes, tgrB1 and tgrC1
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Demonstrates the population-level protective role of tgrB1/tgrC1
      kin recognition; full text verified.
- id: PMID:24490801
  title: Assembly of the TgrB1-TgrC1 cell adhesion complex during Dictyostelium discoideum
    development.
  findings:
  - statement: TgrB1 homodimerization depends on trans-interaction with TgrC1, and
      coalescence of TgrB1-TgrC1 clusters forms large cell-adhesion complexes.
    supporting_text: the coalescence of TgrB1-TgrC1 clusters results in the formation
      of large
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines assembly of the TgrB1-TgrC1 adhesion complex; cached record
      is abstract-only but supports the cited claims.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: To develop beyond aggregation, amoebae must clear an allorecognition
      checkpoint established by tgrB1 and tgrC1.
    supporting_text: amoebae must clear a checkpoint established by the allorecognition
      genes tgrB1 and tgrC1
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Transcriptome study; supports developmental-stage expression and
      the aggregation checkpoint role of tgrB1.
- id: PMID:27307293
  title: Gene discovery by chemical mutagenesis and whole-genome sequencing in Dictyostelium.
  findings:
  - statement: TgrB1 and TgrC1 are cell-surface adhesion proteins that form
      heterophilic interactions in trans; loss impairs cell-cell recognition and
      development.
    supporting_text: TgrB1 and TgrC1 are cell-surface adhesion proteins that form
      heterophilic interactions in trans
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Suppressor screen of the tgrB1-tgrC1 mismatch; supports TgrB1's
      role in a cell-surface receptor signaling pathway.
- id: PMID:28120827
  title: A polychromatic 'greenbeard' locus determines patterns of cooperation in
    a social amoeba.
  findings:
  - statement: The Tgr locus is a polychromatic greenbeard in which partner-specific
      TgrB1-TgrC1 binding strength predicts partner-specific cooperation.
    supporting_text: partner-specific protein-protein binding strength and recognition
      specificity
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Establishes the greenbeard behaviour of the Tgr locus; full text
      verified.
- id: PMID:29038229
  title: The polymorphic proteins TgrB1 and TgrC1 function as a ligand-receptor pair
    in Dictyostelium allorecognition.
  findings:
  - statement: TgrB1 acts as a receptor with TgrC1 as its ligand in cooperative
      aggregation and differentiation.
    supporting_text: Here, we show that TgrB1 acts as a receptor with TgrC1 as its
      ligand in cooperative aggregation and differentiation.
  - statement: The TgrB1 cytoplasmic tail becomes phosphorylated upon binding a
      matching TgrC1 ligand, and dominant tgrB1 alleles act as constitutively
      activated receptors.
    supporting_text: the cytoplasmic tail of TgrB1 becomes phosphorylated upon binding
      to a matching TgrC1 ligand
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive demonstration that TgrB1 is the receptor and TgrC1 the
      ligand; full text verified.
- id: PMID:35622529
  title: Identification of novel proteins in the Dictyostelium discoideum chemorepulsion
    pathway using REMI.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: REMI screen for AprA chemorepulsion components. The paper's "TgrB1"
      screen hit is described as encoded by DDB_G0293176, whereas this gene is
      DDB_G0280689; the GPCR chemorepellent-signaling annotation to tgrB1 cannot be
      verified and is inconsistent with TgrB1's known Ig-domain receptor biology.
- id: PMID:38734736
  title: The greenbeard gene tgrB1 regulates altruism and cheating in Dictyostelium
    discoideum.
  findings:
  - statement: Activation of the TgrB1 receptor confers altruism, whereas tgrB1
      inactivation causes allotype-specific cheating.
    supporting_text: activation of the TgrB1 receptor confers altruism
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Direct evidence linking TgrB1 receptor activity to altruism and
      cheating in chimeras; full text verified.