id: M9PFH7 gene_symbol: trn product_type: PROTEIN status: DRAFT taxon: id: NCBITaxon:7227 label: Drosophila melanogaster description: >- Tartan (Trn) is a single-pass type I transmembrane protein of the leucine-rich-repeat (LRR) cell-surface family, closely related to and largely redundant with its paralog Capricious (Caps). Its extracellular region is an LRR horseshoe (roughly ten LRR units capped by an LRR C-terminal cysteine-rich domain) displayed at the plasma membrane, followed by a single transmembrane helix and a short cytoplasmic tail. Trn functions as a cell-surface adhesion/affinity molecule that mediates cell-cell recognition and helps establish differences in affinity between neighbouring cell populations, and it acts largely through its extracellular LRR domain. Through this activity it contributes to the formation of affinity boundaries between cell groups in imaginal discs, to selective recognition of targets during motor and photoreceptor axon guidance, and to epithelial and tracheal morphogenesis, where it provides a permissive substrate for migrating cells. The Trn and Caps LRR domains are interchangeable and are thought to engage a common partner/receptor on apposed cells; the precise molecular binding partners of Trn remain incompletely defined. existing_annotations: - term: id: GO:0038023 label: signaling receptor activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: >- Phylogenetic (IBA) call from GO_Central propagating a signaling-receptor molecular function across an LRR family that also contains bona fide signaling receptors (e.g. human TLR3 and CD180). For tartan there is no evidence of transmembrane signal transduction; the protein acts as a cell-surface LRR adhesion/affinity molecule and exerts its function through its extracellular domain, so a more informative and better supported molecular function is cell-cell adhesion mediator activity. action: MODIFY reason: >- Trn's molecular function is that of a cell-surface LRR adhesion molecule rather than a classical signal-transducing receptor. Its role maps to the extracellular LRR domain, and it is repeatedly described as a candidate homophilic/heterophilic adhesion receptor whose LRR domain is interchangeable with that of Caps and engages a common partner. The IBA 'signaling receptor activity' is over-broad (inherited from a TLR-containing family); cell-cell adhesion mediator activity captures the evidence more precisely. proposed_replacement_terms: - id: GO:0098632 label: cell-cell adhesion mediator activity propagation_review: root_cause: PROPAGATION_BAD failure_modes: - FUNCTIONAL_DIVERGENCE - GRANULARITY_MISMATCH source_entities: - source_id: UniProtKB:O15455 source_label: TLR3 (human) source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: >- Bona fide LRR transmembrane signaling receptor; the signaling-receptor activity does not transfer to the divergent Drosophila adhesion protein trn. - source_id: UniProtKB:Q99467 source_label: CD180/RP105 (human) source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: >- LRR cell-surface receptor of the innate-immune Toll-like family; not evidence for signal-transduction activity in trn. supported_by: - reference_id: PMID:19064711 supporting_text: >- It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors - reference_id: PMID:16764850 supporting_text: >- mesodermal cells and exerts its role in tracheal branch outgrowth through its - reference_id: PMID:18817735 supporting_text: >- The LRR domains of Trn and Caps are interchangeable, suggesting that they can interact with a common receptor - term: id: GO:0007436 label: larval salivary gland morphogenesis evidence_type: IMP original_reference_id: PMID:19064711 qualifier: involved_in review: summary: >- Loss-of-function analysis of caps and tartan mutants in a study of salivary gland tubulogenesis supports a role for trn in salivary gland morphogenesis. This is a specific developmental context for a pleiotropic LRR adhesion protein rather than its core molecular activity. action: KEEP_AS_NON_CORE reason: >- The experimental (IMP) annotation is supported by the cited study, which identified caps/trn as LRR adhesion hits and analysed mutant phenotypes. It is a genuine but context-specific developmental role, so it is retained as non-core rather than as a core function. supported_by: - reference_id: PMID:19064711 supporting_text: >- The analysis of caps and tartan mutant phenotypes suggests a role for these genes in salivary gland morphogenesis. - reference_id: PMID:19064711 supporting_text: >- belong to the family of LRR proteins, suggesting a general role for this class of surface receptors in salivary gland morphogenesis - term: id: GO:0008045 label: motor neuron axon guidance evidence_type: IMP original_reference_id: PMID:18817735 qualifier: involved_in review: summary: >- Well-supported experimental annotation. Trn was recovered in a cell-surface-molecule screen for synaptic target selection, and embryonic loss-of-function analysis shows that Trn and Caps act largely redundantly to guide and target motor axons: trn caps double mutants have stronger motor-axon phenotypes than trn alone, and neuronal Trn expression rescues the phenotype. This is a core neural function of trn. action: ACCEPT reason: >- Direct genetic evidence (loss of function, double-mutant enhancement, and cell-type- specific rescue) supports involvement of trn in motor neuron axon guidance/targeting, acting redundantly with its paralog caps. supported_by: - reference_id: PMID:18817735 supporting_text: >- If so, Trn and Caps might function in a redundant manner to regulate axon guidance and to label muscles as axonal targets. - reference_id: PMID:18817735 supporting_text: >- trn caps double mutant embryos have stronger motor axon phenotypes than trn single mutants - reference_id: PMID:18817735 supporting_text: >- The trn caps phenotype was rescued to ~20% penetrance for both ISNb and SNa phenotypes - term: id: GO:0035147 label: branch fusion, open tracheal system evidence_type: IMP original_reference_id: PMID:16764850 qualifier: involved_in review: summary: >- Supported experimental annotation. Caps and Tartan contribute differently to joining isolated tracheal metameres into a continuous tubular network; Tartan is expressed broadly in the mesoderm and provides a permissive substrate for the outgrowing/fusing tracheal branches. A genuine but context-specific developmental role, retained as non-core. action: KEEP_AS_NON_CORE reason: >- The IMP annotation is supported by the cited study showing that Tartan acts (via its extracellular domain) in the formation of tracheal branch interconnections. It is a specific morphogenetic context rather than trn's core molecular activity. supported_by: - reference_id: PMID:16764850 supporting_text: >- repeat transmembrane proteins Capricious and Tartan contribute differently to - reference_id: PMID:16764850 supporting_text: >- migrating tracheal cells during the network formation. - term: id: GO:0007155 label: cell adhesion evidence_type: NAS original_reference_id: PMID:12717815 qualifier: involved_in review: summary: >- Cell adhesion is a core biological process for tartan: as an LRR cell-surface molecule it mediates cell-cell interactions and cell affinity in imaginal discs, trachea and the nervous system, acting redundantly with Caps. The annotation is biologically correct and well supported by the broader literature, even though the specific NAS reference (a wing-vein-patterning review) is a weak citation for it. action: ACCEPT reason: >- The essence of the annotation - involvement in cell adhesion - is central to trn's function and supported by multiple studies describing Caps/Trn as adhesion molecules mediating cell-cell interactions. Retained as a core biological process. The original NAS reference is retained but flagged as low relevance in the references section. supported_by: - reference_id: PMID:18817735 supporting_text: >- Trn and Caps are involved in cell-cell interactions in tracheae and imaginal discs - reference_id: PMID:19064711 supporting_text: >- It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors - term: id: GO:0016477 label: cell migration evidence_type: TAS original_reference_id: PMID:12508275 qualifier: involved_in review: summary: >- Trn contributes to cell migration indirectly/non-cell-autonomously: in the trachea it is expressed broadly in the mesoderm and provides a permissive substrate for the migrating tracheal branch cells. This is a defensible but peripheral, context-specific role rather than a core function, so it is retained as non-core. action: KEEP_AS_NON_CORE reason: >- The general 'cell migration' term is supported by the concrete role of Tartan as a permissive mesodermal substrate for migrating tracheal cells; it captures a real but indirect and non-core aspect of trn function. The original TAS reference is a short commentary that does not itself discuss trn, so supporting evidence is drawn from the tracheal study. supported_by: - reference_id: PMID:16764850 supporting_text: >- migrating tracheal cells during the network formation. - reference_id: PMID:16764850 supporting_text: >- In contrast, Tartan is expressed broadly in - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: file:DROME/trn/trn-uniprot.txt qualifier: located_in review: summary: >- Trn is a single-pass type I transmembrane protein (N-terminal signal peptide, one predicted transmembrane helix, extracellular LRR ectodomain), consistent with residence in the plasma membrane where it engages neighbouring cell surfaces. UniProt carries an ARBA electronic annotation to the parent term cell periphery (GO:0071944); plasma membrane is the specific compartment for this cell-surface adhesion molecule. Added as a NEW annotation to capture the localization underlying trn's adhesion function. action: NEW reason: >- Localization to the plasma membrane is not present in the GOA set but is strongly implied by the protein architecture and by the existing cell-periphery electronic annotation, and it is required to represent where trn's cell-cell adhesion activity occurs. supported_by: - reference_id: file:DROME/trn/trn-uniprot.txt supporting_text: >- C:cell periphery - reference_id: file:DROME/trn/trn-uniprot.txt supporting_text: >- Transmembrane helix core_functions: - description: >- Tartan acts as a cell-surface leucine-rich-repeat adhesion/affinity molecule at the plasma membrane, mediating cell-cell recognition (largely redundantly with Capricious) to establish affinity differences between cell populations and to select targets during axon guidance. molecular_function: id: GO:0098632 label: cell-cell adhesion mediator activity directly_involved_in: - id: GO:0007155 label: cell adhesion - id: GO:0008045 label: motor neuron axon guidance locations: - id: GO:0005886 label: plasma membrane supported_by: - reference_id: PMID:18817735 supporting_text: >- Trn and Caps are involved in cell-cell interactions in tracheae and imaginal discs - reference_id: PMID:18817735 supporting_text: >- If so, Trn and Caps might function in a redundant manner to regulate axon guidance and to label muscles as axonal targets. - reference_id: PMID:19064711 supporting_text: >- It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors proposed_new_terms: [] suggested_questions: - question: >- What is the direct molecular binding partner of the Tartan LRR ectodomain - does it bind homophilically to Trn/Caps, heterophilically to a shared receptor, or to a distinct ligand? - question: >- Is any part of Tartan's function dependent on its short cytoplasmic tail, or is the extracellular LRR domain fully sufficient across all developmental contexts? suggested_experiments: - description: >- Cell aggregation / bead-binding assays with S2 cells expressing Trn (and Caps) to test directly for homophilic vs heterophilic adhesion and to identify the binding partner. hypothesis: >- Trn mediates cell-cell adhesion by binding a partner (Caps, Trn, or a shared receptor) on apposed cell surfaces. - description: >- Domain-swap and cytoplasmic-tail-truncation rescue experiments across imaginal-disc affinity, axon-targeting, and tracheal contexts to define the minimal functional unit of Trn. hypothesis: >- The extracellular LRR domain is sufficient for Trn function in most or all contexts, with the short cytoplasmic tail largely dispensable. references: - id: file:DROME/trn/trn-uniprot.txt title: UniProt entry M9PFH7 (tartan, Drosophila melanogaster) findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- UniProt/TrEMBL record documenting trn domain architecture (signal peptide, LRR ectodomain, single transmembrane helix, LRRCT) and the electronic cell-periphery localization. - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: PMID:12508275 title: Size isn't everything. findings: [] reference_review: relevance: LOW correctness: MISCITED review_notes: >- Short BioEssays commentary on tissue size/shape and cell affinity; the abstract does not mention trn or cell migration. It is the TAS basis for GO:0016477 but is only background/contextual for trn - the real support for a migration role comes from the tracheal study (PMID:16764850). - id: PMID:12717815 title: 'Pattern formation in the Drosophila wing: The development of the veins.' findings: [] reference_review: relevance: LOW correctness: MISCITED review_notes: >- Wing-vein-patterning review whose abstract does not discuss trn or cell adhesion; a weak/likely-inappropriate NAS citation for GO:0007155 cell adhesion, although the adhesion annotation itself is biologically correct and supported elsewhere. - id: PMID:16764850 title: Distinct functions of the leucine-rich repeat transmembrane proteins capricious and tartan in the Drosophila tracheal morphogenesis. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Directly contrasts Caps and Trn in tracheal branch interconnection; establishes that Tartan is expressed broadly in the mesoderm and acts via its extracellular domain as a permissive substrate for migrating tracheal cells. Verified against cached abstract. - id: PMID:18817735 title: A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Full text available; directly assays trn loss- and gain-of-function in motor-axon targeting, shows trn/caps redundancy and neuronal Trn rescue, and documents the 65% identity and interchangeability of the Trn/Caps LRR domains. - id: PMID:19064711 title: A targeted gain-of-function screen identifies genes affecting salivary gland morphogenesis/tubulogenesis in Drosophila. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: >- Full text; recovers trn/caps as LRR adhesion hits in salivary gland tubulogenesis and states their molecular function is still unclear but likely homophilic/heterophilic adhesion. Supports GO:0007436 and the adhesion framing.