csaA

id: P08796
gene_symbol: csaA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: Contact site A protein (csA, also known as gp80) is a developmentally
  regulated, glycolipid-anchored cell-surface glycoprotein of the social amoeba
  Dictyostelium discoideum. Its expression is restricted to the aggregation stage
  of development and is induced by pulsatile cAMP signaling acting through
  cell-surface cAMP receptors. csA mediates EDTA-resistant (Ca2+-independent)
  cell-cell adhesion through homophilic binding, in which csA molecules on one cell
  surface bind directly to csA molecules on adjacent cells. The mature protein
  carries N-linked glycans and is attached to the outer face of the plasma membrane
  by an unusual phosphoceramide-containing (GPI-like) lipid anchor. csA is enriched
  at cell-cell contact regions and on filopodia, where it partitions into
  sterol-rich, detergent-resistant membrane microdomains and colocalizes with the
  underlying cortical actin cytoskeleton. It provides a fast, shear-resistant form
  of intercellular cohesion during the transition from unicellular amoebae to a
  multicellular aggregate; loss of csA abolishes EDTA-stable adhesion, and under
  natural or semi-natural conditions csA-null cells show reduced cell-cell cohesion,
  increased substratum adhesion, slower motility, and a competitive disadvantage,
  whereas strong overexpression perturbs morphogenesis.
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: csA is a plasma membrane-associated glycoprotein, attached to the outer
      face of the membrane by a GPI-like lipid anchor. Plasma membrane localization
      is correct and consistent with direct experimental evidence.
    action: ACCEPT
    reason: csA is a bona fide plasma membrane protein. The UniProt subcellular
      location mapping is corroborated by direct evidence that gp80 is a
      lipid-anchored membrane component enriched at the cell surface.
    supported_by:
    - reference_id: PMID:11278598
      supporting_text: the phospholipid-anchored cell adhesion molecule gp80
- term:
    id: GO:0007156
    label: homophilic cell-cell adhesion
  evidence_type: IDA
  original_reference_id: PMID:3320049
  qualifier: involved_in
  review:
    summary: Direct binding assays (gp80-coated Covaspheres, filter-binding, and
      inhibition of cell reassociation by soluble gp80) demonstrate that csA/gp80
      mediates cell-cell binding via homophilic interaction. This is the core
      function of the gene product.
    action: ACCEPT
    reason: This is the defining, experimentally demonstrated function of csA -
      homophilic cell-cell adhesion at the aggregation stage.
    supported_by:
    - reference_id: PMID:3320049
      supporting_text: gp80 mediates cell-cell binding at the aggregation stage of
        development via homophilic interaction
- term:
    id: GO:0016338
    label: calcium-independent cell-cell adhesion
  evidence_type: IMP
  original_reference_id: PMID:2515990
  qualifier: acts_upstream_of_or_within
  review:
    summary: Gene disruption of csA drastically reduced EDTA-stable
      (Ca2+-independent) adhesion, directly confirming that csA is responsible for
      the calcium-independent form of cell-cell adhesion in aggregating cells.
    action: ACCEPT
    reason: Loss-of-function evidence establishes csA as the mediator of
      EDTA-stable, Ca2+-independent adhesion; this is a core aspect of its function.
    supported_by:
    - reference_id: PMID:2515990
      supporting_text: This protein has been implicated in the EDTA-stable
        (Ca2(+)-independent) type of cell adhesion of aggregating cells
    - reference_id: PMID:2515990
      supporting_text: EDTA-stable adhesion was drastically reduced as compared to
        wild type, confirming that the contact site A glycoprotein acts as a
        cell-adhesion molecule
- term:
    id: GO:0098632
    label: cell-cell adhesion mediator activity
  evidence_type: IDA
  original_reference_id: PMID:3320049
  qualifier: enables
  review:
    summary: Purified gp80 conjugated to beads binds cells in a developmentally
      regulated, antibody-blockable manner, showing that gp80 participates directly
      in cell binding. This is the core molecular function.
    action: ACCEPT
    reason: Direct binding evidence supports cell-cell adhesion mediator activity as
      the core molecular function of csA.
    supported_by:
    - reference_id: PMID:3320049
      supporting_text: gp80 participates directly in cell binding
- term:
    id: GO:0009897
    label: external side of plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:6191197
  qualifier: is_active_in
  review:
    summary: csA/gp80 is displayed on the external face of the plasma membrane via
      its lipid anchor, where it engages in intercellular adhesion. This
      localization is consistent with its function as a surface adhesion molecule.
    action: ACCEPT
    reason: csA is an outer-leaflet, lipid-anchored surface glycoprotein; the
      external side of the plasma membrane is where its adhesive activity operates.
    supported_by:
    - reference_id: PMID:6191197
      supporting_text: gp80, a membrane glycoprotein implicated in intercellular
        adhesion of Dictyostelium discoideum
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: TAS
  original_reference_id: PMID:15366765
  qualifier: located_in
  review:
    summary: csA/gp80 is a developmentally regulated cell-surface glycoprotein. The
      cell-surface localization is well established from multiple primary studies.
    action: ACCEPT
    reason: Cell-surface localization is a correct and well-supported location for
      this GPI-anchored adhesion glycoprotein.
    supported_by:
    - reference_id: PMID:3320049
      supporting_text: developmentally regulated cell surface glycoprotein of Mr
        80,000 (gp80)
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:11278598
  qualifier: is_active_in
  review:
    summary: gp80 colocalizes with F-actin, porin, and comitin at cell-cell contacts
      during development, consistent with its adhesive activity operating at
      cell-cell junction/contact regions.
    action: ACCEPT
    reason: Direct evidence places csA at cell-cell contact regions where it mediates
      adhesion.
    supported_by:
    - reference_id: PMID:11278598
      supporting_text: gp80 colocalized with F-actin, porin, and comitin at
        cell-cell contacts
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:8806827
  qualifier: is_active_in
  review:
    summary: gp80 becomes concentrated in contact regions among cells within
      well-developed streams during aggregation, supporting its localization to
      cell-cell junctions/contact sites.
    action: ACCEPT
    reason: Independent evidence confirms csA enrichment at cell-cell contact regions
      during aggregation.
    supported_by:
    - reference_id: PMID:8806827
      supporting_text: gp80 is concentrated in contact regions among cells within
        well-developed streams
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: TAS
  original_reference_id: PMID:15366765
  qualifier: located_in
  review:
    summary: csA/gp80 partitions into a sterol-enriched, Triton-insoluble floating
      fraction (a lipid raft-like microdomain), consistent with membrane raft
      localization of this lipid-anchored protein.
    action: ACCEPT
    reason: gp80 associates with detergent-resistant, sterol-rich membrane
      microdomains, supporting membrane raft localization.
    supported_by:
    - reference_id: PMID:11278598
      supporting_text: confirmed the association of gp80 and comitin with TIFF
        membranes
    - reference_id: PMID:11278598
      supporting_text: the sterol/phospholipid ratio of TIFF was 10-fold higher than
        that of the bulk plasma membrane
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: IDA
  original_reference_id: PMID:3934167
  qualifier: involved_in
  review:
    summary: Class I anti-gp80 monoclonal antibodies block EDTA-resistant contact
      sites and inhibit cell reassociation at the aggregation stage, consistent with
      a direct role of gp80 in cell-cell binding.
    action: ACCEPT
    reason: Antibody-blocking evidence supports the general cell-cell adhesion role;
      this is a core function (more specifically captured as homophilic,
      Ca2+-independent adhesion).
    supported_by:
    - reference_id: PMID:3934167
      supporting_text: consistent with a direct role of gp80 in cell-cell binding
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:8660574
  qualifier: enables
  review:
    summary: Biosensor experiments show that immobilized csA interacts with csA in
      solution, establishing that csA molecules engage in homophilic (self) binding.
      This identical protein binding is the molecular basis of csA-mediated
      adhesion, and is more informative than bare protein binding.
    action: ACCEPT
    reason: The homophilic self-interaction (identical protein binding) is the
      mechanistic basis of csA adhesion and is directly demonstrated in vitro.
    supported_by:
    - reference_id: PMID:8660574
      supporting_text: Interaction of the immobilized csA protein with csA in
        solution established that the bound molecules are capable of taking part in
        homophilic interactions
- term:
    id: GO:0010225
    label: response to UV-C
  evidence_type: IDA
  original_reference_id: PMID:25858552
  qualifier: acts_upstream_of_or_within
  review:
    summary: This study reports that csA mRNA expression is markedly reduced
      following UV-C irradiation of Dictyostelium cells. csA is used here as a
      developmentally regulated readout of UV-C-induced developmental impairment,
      not as a functional effector of the UV-C response. There is no evidence that
      csA acts within a UV-C damage-response pathway.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence is a change in csA transcript level after UV-C exposure,
      which reflects downstream disruption of the aggregation program rather than a
      role for csA in responding to UV-C. Annotating csA as acting upstream of or
      within the UV-C response over-interprets an expression readout.
    supported_by:
    - reference_id: PMID:25858552
      supporting_text: expression of csA and ctnA was markedly reduced
- term:
    id: GO:0030175
    label: filopodium
  evidence_type: IDA
  original_reference_id: PMID:3553212
  qualifier: located_in
  review:
    summary: Immunoelectron microscopy shows gp80 preferentially localized on
      filopodia (about twofold higher gold density) in addition to contact regions,
      where filopodia participate in initial cell-cell contact formation.
    action: ACCEPT
    reason: Direct localization evidence places csA on filopodia, a genuine (though
      not sole) site of the adhesion protein.
    supported_by:
    - reference_id: PMID:3553212
      supporting_text: gold particles were found preferentially localized on
        filopodia
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:3934167
  qualifier: located_in
  review:
    summary: gp80 is characterized as an 80,000-dalton surface/membrane glycoprotein,
      supporting direct-evidence plasma membrane localization.
    action: ACCEPT
    reason: Plasma membrane localization is directly supported; consistent with the
      IEA subcellular-location annotation.
    supported_by:
    - reference_id: PMID:3934167
      supporting_text: a surface glycoprotein with an apparent Mr of 80,000 (gp80)
- term:
    id: GO:1904643
    label: response to curcumin
  evidence_type: IDA
  original_reference_id: PMID:26449461
  qualifier: involved_in
  review:
    summary: Curcumin treatment suppresses expression of cell adhesion proteins
      including csA, with consequent delays in adhesion and development. csA is a
      developmentally regulated readout affected by curcumin, not a mediator of the
      curcumin response.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence is downregulation of csA expression by curcumin (an effect
      on the aggregation program), not a function of csA in responding to curcumin.
      Annotating csA as involved in the curcumin response over-interprets an
      expression change.
    supported_by:
    - reference_id: PMID:26449461
      supporting_text: expression of the extracellular matrix/cell adhesion proteins
        (DdCAD and csA)
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:1328260
  qualifier: acts_upstream_of_or_within
  review:
    summary: Strong overexpression of csA under its own cAMP-regulated promoter
      delays aggregation and substantially alters morphogenesis, linking csA levels
      to the aggregation phase of sorocarp (fruiting body) development.
    action: ACCEPT
    reason: Perturbation of csA expression alters aggregation and morphogenesis,
      supporting a role in aggregation during sorocarp development.
    supported_by:
    - reference_id: PMID:1328260
      supporting_text: When the csA protein was strongly overexpressed under the
        developmental control of the csA promoter, morphogenesis was substantially
        altered
    - reference_id: PMID:1328260
      supporting_text: Aggregation was delayed
- 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: csaA is expressed as a cell-cell adhesion gene during aggregation, with
      induction kinetics tied to pulsatile cAMP, consistent with its role in the
      aggregation phase. This is expression-pattern (IEP) evidence supporting the
      same process captured by stronger mutant evidence.
    action: ACCEPT
    reason: The expression-pattern evidence corroborates csA involvement in the
      aggregation phase of sorocarp development, consistent with the gain- and
      loss-of-function evidence for the same process.
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: several of its putative target genes involved in aggregation
        (such as the cell-cell adhesion gene csaA)
- term:
    id: GO:0030587
    label: sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:9689085
  qualifier: acts_upstream_of_or_within
  review:
    summary: Under semi-natural (soil) conditions, csA-null cells display reduced
      cell-cell adhesion, increased substratum adhesion, and slower motility, and
      csA is required for efficient development, demonstrating a role in sorocarp
      development beyond the mild laboratory phenotype.
    action: ACCEPT
    reason: Sensitive assays reveal that csA is required for efficient development,
      supporting its role in sorocarp development.
    supported_by:
    - reference_id: PMID:9689085
      supporting_text: evidence is provided that csA is required for development
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: IMP
  original_reference_id: PMID:6191197
  qualifier: acts_upstream_of_or_within
  review:
    summary: gp80 is implicated in the EDTA-resistant intercellular adhesions
      (contact sites A) that appear during development, and it carries the
      determinants associated with adhesion. This supports a role in cell-cell
      adhesion, consistent with the broader body of evidence.
    action: ACCEPT
    reason: csA/gp80 is implicated in intercellular adhesion; cell-cell adhesion is a
      core biological process for this gene.
    supported_by:
    - reference_id: PMID:6191197
      supporting_text: gp80 has been implicated in the formation of the
        EDTA-resistant adhesions
- term:
    id: GO:0030866
    label: cortical actin cytoskeleton organization
  evidence_type: TAS
  original_reference_id: PMID:15366765
  qualifier: acts_upstream_of_or_within
  review:
    summary: csA/gp80 colocalizes with F-actin at cell-cell contacts and recruits
      F-actin and associated proteins into gp80 caps, linking csA-mediated adhesion
      to the underlying cortical actin cytoskeleton. This is a secondary,
      adhesion-associated role rather than the core adhesion function itself.
    action: KEEP_AS_NON_CORE
    reason: There is evidence that csA-based contacts organize/recruit cortical
      actin, but this is a downstream consequence of adhesion rather than the core
      molecular function of csA.
    supported_by:
    - reference_id: PMID:11278598
      supporting_text: These proteins were also recruited to gp80 caps induced by
        antibody cross-linking
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:11278598
  title: Involvement of a triton-insoluble floating fraction in Dictyostelium cell-cell
    adhesion.
  findings:
  - statement: gp80 is a phospholipid-anchored cell adhesion molecule that partitions
      into a sterol-rich, Triton-insoluble floating fraction and colocalizes with
      F-actin at cell-cell contacts.
    supporting_text: gp80 colocalized with F-actin, porin, and comitin at cell-cell
      contacts
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary study directly demonstrating gp80 association with
      raft-like microdomains and cortical actin at contact regions.
- id: PMID:1328260
  title: Overexpression of the csA cell adhesion molecule under its own cAMP-regulated
    promoter impairs morphogenesis in Dictyostelium.
  findings:
  - statement: Strong overexpression of csA delays aggregation and alters
      morphogenesis.
    supporting_text: When the csA protein was strongly overexpressed under the
      developmental control of the csA promoter, morphogenesis was substantially
      altered
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Gain-of-function evidence linking csA levels to aggregation and
      morphogenesis.
- id: PMID:15366765
  title: 'Comparison of molecular mechanisms mediating cell contact phenomena in model
    developmental systems: an exploration of universality.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Broad comparative review; used as TAS source for cell-surface,
      membrane raft, and cortical actin annotations, but does not itself provide
      csA-specific primary data.
- id: PMID:2515990
  title: Selective elimination of the contact site A protein of Dictyostelium discoideum
    by gene disruption.
  findings:
  - statement: Gene disruption of csA drastically reduces EDTA-stable
      (Ca2+-independent) adhesion, confirming csA acts as a cell-adhesion molecule.
    supporting_text: EDTA-stable adhesion was drastically reduced as compared to wild
      type, confirming that the contact site A glycoprotein acts as a cell-adhesion
      molecule
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive loss-of-function evidence for csA in Ca2+-independent
      adhesion.
- id: PMID:25858552
  title: Response of Dictyostelium discoideum to UV-C and involvement of poly (ADP-ribose)
    polymerase.
  findings:
  - statement: csA expression is markedly reduced following UV-C irradiation, as a
      developmental readout rather than an effector of the UV-C response.
    supporting_text: expression of csA and ctnA was markedly reduced
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: csA is an expression readout affected by UV-C; supports an
      over-annotation judgment for response to UV-C.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: csaA is a cAMP-induced cell-cell adhesion gene expressed during
      aggregation.
    supporting_text: several of its putative target genes involved in aggregation
      (such as the cell-cell adhesion gene csaA)
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Transcriptome time-course confirming csaA expression during the
      aggregation stage.
- id: PMID:26449461
  title: 'Curcumin inhibits development and cell adhesion in Dictyostelium discoideum:
    Implications for YakA signaling and GST enzyme function.'
  findings:
  - statement: Curcumin suppresses expression of cell adhesion proteins including
      csA, delaying adhesion and development.
    supporting_text: expression of the extracellular matrix/cell adhesion proteins
      (DdCAD and csA)
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: csA is downregulated by curcumin; supports an over-annotation
      judgment for response to curcumin.
- id: PMID:3320049
  title: The contact site A glycoprotein mediates cell-cell adhesion by homophilic
    binding in Dictyostelium discoideum.
  findings:
  - statement: Purified gp80 mediates cell-cell binding at the aggregation stage via
      homophilic interaction.
    supporting_text: gp80 mediates cell-cell binding at the aggregation stage of
      development via homophilic interaction
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Key primary study establishing homophilic adhesion as the core
      mechanism.
- id: PMID:3553212
  title: Filopodia are enriched in a cell cohesion molecule of Mr 80,000 and participate
    in cell-cell contact formation in Dictyostelium discoideum.
  findings:
  - statement: gp80 is preferentially localized on filopodia and at contact regions.
    supporting_text: gold particles were found preferentially localized on filopodia
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Immuno-EM localization of gp80 to filopodia and contact regions.
- id: PMID:3934167
  title: Inhibition of cell-cell binding at the aggregation stage of Dictyostelium
    discoideum development by monoclonal antibodies directed against an 80,000-dalton
    surface glycoprotein.
  findings:
  - statement: Anti-gp80 monoclonal antibodies block EDTA-resistant contacts and
      inhibit reassociation, indicating a direct role of gp80 in cell-cell binding.
    supporting_text: consistent with a direct role of gp80 in cell-cell binding
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Antibody-blocking evidence for direct adhesion function.
- id: PMID:6191197
  title: Monoclonal antibody recognizing gp80, a membrane glycoprotein implicated
    in intercellular adhesion of Dictyostelium discoideum.
  findings:
  - statement: gp80 is a membrane glycoprotein implicated in EDTA-resistant contact
      site A adhesions.
    supporting_text: gp80 has been implicated in the formation of the EDTA-resistant
      adhesions
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Characterization of a gp80 monoclonal antibody; notes gp80 carries
      adhesion-associated determinants.
- id: PMID:8660574
  title: Oriented binding of a lipid-anchored cell adhesion protein onto a biosensor
    surface using hydrophobic immobilization and photoactive crosslinking.
  findings:
  - statement: Immobilized csA interacts with csA in solution, demonstrating
      homophilic (identical protein) binding.
    supporting_text: Interaction of the immobilized csA protein with csA in solution
      established that the bound molecules are capable of taking part in homophilic
      interactions
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: In vitro biosensor evidence for csA-csA homophilic interaction.
- id: PMID:8806827
  title: Novel redistribution of the Ca(2+)-dependent cell adhesion molecule DdCAD-1
    during development of Dictyostelium discoideum.
  findings:
  - statement: gp80 becomes concentrated in contact regions among cells within
      well-developed streams during aggregation.
    supporting_text: gp80 is concentrated in contact regions among cells within
      well-developed streams
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Although focused on DdCAD-1, the paper directly documents gp80
      enrichment at contact regions during aggregation.
- id: PMID:9689085
  title: 'Detection of subtle phenotypes: the case of the cell adhesion molecule csA
    in Dictyostelium.'
  findings:
  - statement: Under semi-natural conditions csA is required for efficient
      development and confers a selective advantage; csA-null cells show reduced
      adhesion and motility.
    supporting_text: evidence is provided that csA is required for development
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Demonstrates a genuine developmental requirement for csA masked
      under standard laboratory conditions.
core_functions:
- description: csA is a GPI-anchored cell-surface glycoprotein that functions as a
    homophilic cell-cell adhesion molecule. csA molecules displayed on the outer
    face of the plasma membrane of one cell bind directly to csA molecules on
    adjacent cells, generating EDTA-resistant (Ca2+-independent) intercellular
    cohesion during the aggregation stage of development.
  molecular_function:
    id: GO:0098632
    label: cell-cell adhesion mediator activity
  directly_involved_in:
  - id: GO:0007156
    label: homophilic cell-cell adhesion
  - id: GO:0016338
    label: calcium-independent cell-cell adhesion
  locations:
  - id: GO:0009897
    label: external side of plasma membrane
  - id: GO:0005911
    label: cell-cell junction
  - id: GO:0030175
    label: filopodium
  supported_by:
  - reference_id: PMID:3320049
    supporting_text: gp80 mediates cell-cell binding at the aggregation stage of
      development via homophilic interaction
  - reference_id: PMID:8660574
    supporting_text: Interaction of the immobilized csA protein with csA in solution
      established that the bound molecules are capable of taking part in homophilic
      interactions
  - reference_id: PMID:2515990
    supporting_text: EDTA-stable adhesion was drastically reduced as compared to wild
      type, confirming that the contact site A glycoprotein acts as a cell-adhesion
      molecule