id: Q9P2M4 gene_symbol: TBC1D14 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: 'TBC1D14 is a TBC (Tre-2/Bub2/Cdc16) domain protein of the Rab GTPase-activating protein family. It is a peripheral membrane protein found on Rab11- and transferrin-receptor-positive recycling endosomes and on the Golgi apparatus, and it shifts towards the Golgi on amino-acid starvation. It keeps the TBC catalytic arginine and glutamine, but recombinant TBC1D14 has no detectable GAP activity towards 47 Rabs, including Rab11, which it binds in the GTP-bound form. It acts instead as a Rab11 effector and adaptor: active Rab11 recruits it to recycling endosomes, and an N-terminal TRAPP-binding region (residues ~120-223) binds the TRAPPIII complex through TRAPPC8. This bridge supports TRAPP-dependent RAB1 activation and a constitutive transport step from peripheral recycling endosomes to the early Golgi that maintains the cycling pool of ATG9. Through this route TBC1D14 regulates starvation-induced autophagosome formation; its depletion increases starvation-induced LC3 lipidation, and its overexpression tubulates recycling endosomes and blocks autophagosome formation. It also binds the autophagy kinase ULK1, but its effect on ATG9 traffic is ULK1-independent.' alternative_products: - name: '1' id: Q9P2M4-1 - name: '2' id: Q9P2M4-2 sequence_note: VSP_041460, VSP_041461 existing_annotations: - term: id: GO:0005096 label: GTPase activator activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - FB:FBgn0038855 - FB:FBgn0262740 - MGI:MGI:1913937 - MGI:MGI:2144695 - MGI:MGI:2385326 - PANTHER:PTN000537561 - SGD:S000002393 - SGD:S000003332 - SGD:S000005237 - SGD:S000005472 - SGD:S000005596 - SGD:S000006170 - UniProtKB:O43147 - UniProtKB:O60447 - UniProtKB:Q2NKQ1 - UniProtKB:Q3MII6 - UniProtKB:Q4KMP7 - UniProtKB:Q8IYX1 - UniProtKB:Q8TBP0 - UniProtKB:Q92738 - UniProtKB:Q96CN4 - UniProtKB:Q96HU1 - UniProtKB:Q9BXI6 - UniProtKB:Q9BYX2 - UniProtKB:Q9Y2I9 - WB:WBGene00007167 - WB:WBGene00022880 - dictyBase:DDB_G0276119 - dictyBase:DDB_G0280955 review: summary: IBA GTPase activator activity propagated from the family-root PAINT node PTN000537561 (PTHR47219), which is seeded by catalytically active TBC RabGAPs from yeast to human; TBC1D14 is not among the seeds. action: MARK_AS_OVER_ANNOTATED reason: 'TBC1D14 sits inside PTHR47219 and keeps the TBC arginine finger (R472) and glutamine finger (Q508), so the root-node inference is phylogenetically reasonable. However, there is target-specific negative evidence: recombinant TBC1D14 showed no GAP activity against a panel of 47 Rabs, including its binding partner Rab11, and the Golgi/Shiga-toxin and autophagy effects of overexpression do not depend on the catalytic arginine (the R472A mutant still inhibits LC3 lipidation; the inactive point mutant blocks Shiga toxin transport). The TBC1D14-specific PAINT nodes (PTN000538677, PTN008586039), which are seeded by Q9P2M4 itself, carry location and autophagosome-assembly terms but no GAP term. Current evidence supports TBC1D14 acting as a Rab11 effector/TRAPP adaptor, not as a GAP. The data do not rule out GAP activity on an untested substrate, so this is flagged as over-annotation rather than removed.' supported_by: - &id016 reference_id: PMID:22613832 supporting_text: We then performed a GAP assay screen using a panel of 47 Rabs loaded with [32P]GTP but were unable to detect GAP activity with either recombinant GST-TBC1D14 - reference_id: PMID:22613832 supporting_text: supporting the data that TBC1D14 has no GAP activity - reference_id: Reactome:R-HSA-8854759 supporting_text: TBC1D14 does not have the GAP activity and may function as Rab11 effector. - &id010 reference_id: PMID:17562788 supporting_text: However, these effects were not caused by Rab inactivation because the inactive point mutant gave a similar phenotype propagation_review: root_cause: PROPAGATION_BAD failure_modes: - FUNCTIONAL_DIVERGENCE source_entities: - source_id: PANTHER:PTN000537561 comment: Family-root IBD for GTPase activator activity, seeded by catalytically active TBC RabGAPs from several kingdoms. TBC1D14 descends from it but is not a seed. source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET - source_id: PANTHER:PTN000538677 comment: TBC1D14-clade node seeded by Q9P2M4; PAINT placed only location terms here, no GAP term. source_status: NOT_RELEVANT - source_id: UniProtKB:Q9P2M4 comment: Target. Recombinant protein lacked detectable GAP activity on 47 Rabs; catalytic residues R472/Q508 are retained, so loss is functional rather than a residue substitution. source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22613832 qualifier: enables supporting_entities: - UniProtKB:O75385 review: summary: IPI with ULK1 (Longatti 2012; yeast two-hybrid and co-IP mapped to the TBC domain). action: MODIFY reason: The interaction is real and reproducible, but bare protein binding is uninformative. ULK1 is a protein kinase, and the same paper already supports GO:0019901 protein kinase binding, which the gene carries. supported_by: - &id007 reference_id: PMID:22613832 supporting_text: A yeast two-hybrid assay revealed an interaction between TBC1D14 and ULK1 - &id008 reference_id: PMID:22613832 supporting_text: In HEK293A cells, we could detect an interaction between the TBC domain of TBC1D14 and HA-ULK1 by coimmunoprecipitation proposed_replacement_terms: - id: GO:0019901 label: protein kinase binding - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22613832 qualifier: enables supporting_entities: - UniProtKB:Q15907 review: summary: IPI with RAB11B (Longatti 2012). TBC1D14 binds activated (GTP-bound) Rab11, which recruits it to recycling endosomes. action: MODIFY reason: Bare protein binding is uninformative. The partner is a Rab small GTPase and the binding is to the active form, so GO:0031267 small GTPase binding is the informative MF. Binding is not accompanied by GAP activity. supported_by: - &id001 reference_id: PMID:22613832 supporting_text: One of these, TBC1D14, binds ULK1 and Rab11 and disrupts recycling endosome (RE) traffic. - &id006 reference_id: PMID:22613832 supporting_text: However, the tubules formed by GFP-TBC1D14 were dependent on Rab11 - reference_id: PMID:22613832 supporting_text: TBC1D14 binds activated Rab11 but is not a proposed_replacement_terms: - id: GO:0031267 label: small GTPase binding - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q9UBU9 review: summary: IPI with NXF1 from the HuRI binary yeast two-hybrid reference map (Luck 2020). action: REMOVE reason: Bare protein binding is uninformative, and a single high-throughput Y2H pair with the mRNA export receptor NXF1 has no functional follow-up and no plausible link to TBC1D14 biology. Removal does not assert that the interaction is false. supported_by: [] - term: id: GO:0005768 label: endosome evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in supporting_entities: - ARBA:ARBA00028568 review: summary: ARBA machine-learning prediction of endosome localization. action: MODIFY reason: Correct but general. Experimental data place TBC1D14 specifically on Rab11/transferrin-receptor-positive recycling endosomes; the gene already carries GO:0055037 recycling endosome by IDA. supported_by: - *id001 - &id009 reference_id: PMID:17562788 supporting_text: TBC1D14NDRecyclingendosomesRecyclingendosomes proposed_replacement_terms: - id: GO:0055037 label: recycling endosome - term: id: GO:0005776 label: autophagosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - PANTHER:PTN000538677 - UniProtKB:Q9P2M4 review: summary: IBA from TBC1D14-clade node PTN000538677, seeded only by Q9P2M4's own IDA. action: KEEP_AS_NON_CORE reason: The colocalization with LC3 is partial and minor; the predominant locations are recycling endosomes and, on starvation, the Golgi. TBC1D14 regulates autophagosome formation upstream (ATG9/RE membrane supply) rather than acting as a resident autophagosome component. The location is not wrong, so it is kept, but as peripheral. The IBA row merely re-expresses the same human IDA at the vertebrate node and gets the same action. supported_by: - &id002 reference_id: PMID:22613832 supporting_text: Endogenous TBC1D14 also shows partial colocalization with LC3 - &id003 reference_id: PMID:22613832 supporting_text: Amino acid starvation causes TBC1D14 to relocalize from REs to the - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:22613832 qualifier: located_in review: summary: 'IDA (Longatti 2012): partial colocalization of endogenous TBC1D14 with LC3 and low LC3 on a few overexpression-induced tubules.' action: KEEP_AS_NON_CORE reason: The colocalization with LC3 is partial and minor; the predominant locations are recycling endosomes and, on starvation, the Golgi. TBC1D14 regulates autophagosome formation upstream (ATG9/RE membrane supply) rather than acting as a resident autophagosome component. The location is not wrong, so it is kept, but as peripheral. The IBA row merely re-expresses the same human IDA at the vertebrate node and gets the same action. supported_by: - *id002 - *id003 - term: id: GO:0005794 label: Golgi apparatus evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: HPA immunofluorescence IDA, Golgi apparatus. action: ACCEPT reason: Endogenous TBC1D14 is on the Golgi, and its Golgi pool increases on amino-acid starvation. Sub-Golgi assignments differ between sources (Golgi stack, cis-Golgi network, trans-Golgi network), so Golgi apparatus is the most precise term the combined evidence supports consistently. supported_by: - &id004 reference_id: PMID:26711178 supporting_text: We have previously demonstrated that endogenous TBC1D14 is localised to the Golgi stack - &id005 reference_id: file:human/TBC1D14/TBC1D14-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: Golgi apparatus, cis-Golgi network - reference_id: PMID:26711178 supporting_text: Upon starvation and autophagy activation, TBC1D14 levels increase in the Golgi - term: id: GO:0005794 label: Golgi apparatus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0132 review: summary: UniProt SubCell mapping to Golgi apparatus (UniProt cites cis- and trans-Golgi network from PMID:22613832/26711178). action: ACCEPT reason: Endogenous TBC1D14 is on the Golgi, and its Golgi pool increases on amino-acid starvation. Sub-Golgi assignments differ between sources (Golgi stack, cis-Golgi network, trans-Golgi network), so Golgi apparatus is the most precise term the combined evidence supports consistently. supported_by: - *id004 - *id005 - reference_id: PMID:26711178 supporting_text: Upon starvation and autophagy activation, TBC1D14 levels increase in the Golgi - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000108 qualifier: located_in supporting_entities: - GO:0071955 review: summary: IEA inferred by inter-ontology link from the recycling endosome to Golgi transport annotation. action: KEEP_AS_NON_CORE reason: TBC1D14 is a peripheral membrane protein recruited by Rab11-GTP; when Rab11 is depleted it becomes diffuse, consistent with a soluble cytosolic pool. The term is plausible but carries little information about function. supported_by: - *id006 - term: id: GO:0010507 label: negative regulation of autophagy evidence_type: IMP original_reference_id: PMID:22613832 qualifier: involved_in review: summary: 'IMP (Longatti 2012): siRNA depletion of TBC1D14 increases starvation-induced LC3 lipidation and turnover.' action: ACCEPT reason: Loss-of-function with two siRNAs increases autophagic flux under starvation but not in fed cells, and overexpression inhibits autophagosome formation. This supports a negative regulatory role at the level of autophagy flux. The more mechanistic, sign-neutral autophagosome-assembly term is also carried (GO:2000785). supported_by: - &id013 reference_id: PMID:22613832 supporting_text: In cells in which TBC1D14 levels are substantially reduced, LC3 lipidation and turnover during starvation increase significantly. - reference_id: PMID:22613832 supporting_text: TBC1D14-depleted cells showed little increase in LC3 lipidation in fed conditions - &id012 reference_id: PMID:22613832 supporting_text: TBC1D14WT significantly inhibited formation, but not maturation, of yellow (mRFP-GFP) LC3-positive autophagosomes - term: id: GO:0019901 label: protein kinase binding evidence_type: IPI original_reference_id: PMID:22613832 qualifier: enables supporting_entities: - UniProtKB:O75385 review: summary: IPI with ULK1 (Longatti 2012). action: KEEP_AS_NON_CORE reason: Binding to ULK1 is well supported (Y2H, co-IP, mapped to residues 224-330). Lamb 2016 showed that TBC1D14 and TRAPPIII regulate ATG9 traffic independently of ULK1, so the ULK1 interaction is real but not the core mechanism. supported_by: - *id007 - *id008 - &id011 reference_id: PMID:26711178 supporting_text: These data suggest that TBC1D14 and TRAPP may act upstream of ULK1 in regulating ATG9 traffic, perhaps by maintaining normal traffic into the Golgi. - term: id: GO:0055037 label: recycling endosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - PANTHER:PTN000538677 - UniProtKB:Q9P2M4 review: summary: IBA from TBC1D14-clade node PTN000538677, seeded by Q9P2M4's own experimental annotation. action: ACCEPT reason: 'Recycling endosomes are a core site of TBC1D14 action: Rab11-GTP recruits it to the endocytic recycling compartment, where it in turn recruits TRAPP. Shown in two independent laboratories'' datasets (Fuchs 2007; Longatti 2012; Lamb 2016). The IBA restates this at the vertebrate node.' supported_by: - *id001 - *id009 - *id006 - reference_id: PMID:26711178 supporting_text: TBC1D14 in turn recruits TRAPP - term: id: GO:0055037 label: recycling endosome evidence_type: IDA original_reference_id: PMID:17562788 qualifier: located_in review: summary: 'IDA (Fuchs 2007): TBC1D14 localizes to recycling endosomes.' action: ACCEPT reason: 'Recycling endosomes are a core site of TBC1D14 action: Rab11-GTP recruits it to the endocytic recycling compartment, where it in turn recruits TRAPP. Shown in two independent laboratories'' datasets (Fuchs 2007; Longatti 2012; Lamb 2016). The IBA restates this at the vertebrate node.' supported_by: - *id001 - *id009 - *id006 - reference_id: PMID:26711178 supporting_text: TBC1D14 in turn recruits TRAPP - term: id: GO:0055037 label: recycling endosome evidence_type: TAS original_reference_id: Reactome:R-HSA-8854759 qualifier: located_in review: summary: 'Reactome TAS: TBC1D14 binds RAB11 and ULK1 on recycling endosomes.' action: ACCEPT reason: 'Recycling endosomes are a core site of TBC1D14 action: Rab11-GTP recruits it to the endocytic recycling compartment, where it in turn recruits TRAPP. Shown in two independent laboratories'' datasets (Fuchs 2007; Longatti 2012; Lamb 2016). The IBA restates this at the vertebrate node.' supported_by: - *id001 - *id009 - *id006 - reference_id: PMID:26711178 supporting_text: TBC1D14 in turn recruits TRAPP - term: id: GO:0071955 label: recycling endosome to Golgi transport evidence_type: IMP original_reference_id: PMID:17562788 qualifier: involved_in review: summary: 'IMP (Fuchs 2007): overexpressed TBC1D14 blocks Shiga toxin transport to the Golgi without affecting EGF uptake.' action: ACCEPT reason: 'The original evidence is an overexpression phenotype independent of the catalytic residue, which on its own would be weak. Lamb 2016 independently established the mechanism: TBC1D14 bridges Rab11-positive recycling endosomes to TRAPPIII, its depletion reduces RAB1 activation, and TBC1D14/TRAPPIII regulate a constitutive recycling-endosome-to-early-Golgi step that maintains the cycling pool of ATG9. This is the best-supported process for TBC1D14.' supported_by: - reference_id: PMID:17562788 supporting_text: In the case of TBC1D14, although the Golgi was fragmented, Shiga toxin did not localize to these Golgi fragments, indicating there was a block in transport. - *id010 - &id014 reference_id: PMID:26711178 supporting_text: These data support a model where TBC1D14 acts as a bridge between a TRAPP complex and activated RAB11. - &id015 reference_id: PMID:26711178 supporting_text: However, TBC1D14 depletion resulted in a significant reduction in RAB1B bound to GFP - *id011 - term: id: GO:1902017 label: regulation of cilium assembly evidence_type: IMP original_reference_id: PMID:17646400 qualifier: involved_in negated: true review: summary: 'NOT IMP: in the Yoshimura 2007 overexpression screen of TBC RabGAPs, TBC1D14 did not affect primary cilium formation.' action: ACCEPT reason: TBC1D14 is not named in the cached main text; the per-GAP results are in the screen figure/supplement, which the curator read. The main text states that GAPs other than the hits had no effect on primary cilia, and nothing else links TBC1D14 to cilia. The negative annotation is accepted, deferring to the curator. supported_by: - reference_id: PMID:17646400 supporting_text: Other GAPs either had no effect on primary cilia - term: id: GO:2000785 label: regulation of autophagosome assembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - PANTHER:PTN008586039 - UniProtKB:Q9P2M4 review: summary: IBA from TBC1D14-clade node PTN008586039 (Euteleostomi), seeded by Q9P2M4's own IMP. action: ACCEPT reason: 'TBC1D14 regulates autophagosome formation by controlling membrane and ATG9 supply from recycling endosomes. The sign-neutral regulation term is appropriate: depletion increases starvation-induced autophagy (Longatti 2012), while the Lamb 2016 model places TBC1D14/TRAPPIII in maintaining the ATG9 cycling pool needed for initiation. PAINT placed this term on a TBC1D14-specific node, which supports transfer to TBC1D14 orthologs; the cod tbc1d14 models fall in this clade.' supported_by: - *id012 - *id013 - *id011 - term: id: GO:2000785 label: regulation of autophagosome assembly evidence_type: IMP original_reference_id: PMID:22613832 qualifier: involved_in review: summary: 'IMP (Longatti 2012): TBC1D14 overexpression inhibits formation, not maturation, of autophagosomes; depletion increases starvation-induced LC3 lipidation.' action: ACCEPT reason: 'TBC1D14 regulates autophagosome formation by controlling membrane and ATG9 supply from recycling endosomes. The sign-neutral regulation term is appropriate: depletion increases starvation-induced autophagy (Longatti 2012), while the Lamb 2016 model places TBC1D14/TRAPPIII in maintaining the ATG9 cycling pool needed for initiation. PAINT placed this term on a TBC1D14-specific node, which supports transfer to TBC1D14 orthologs; the cod tbc1d14 models fall in this clade.' supported_by: - *id012 - *id013 - *id011 - term: id: GO:0060090 label: molecular adaptor activity evidence_type: IDA original_reference_id: PMID:26711178 review: summary: 'Proposed: TBC1D14 bridges GTP-bound Rab11 on recycling endosomes to the TRAPPIII complex (via TRAPPC8).' action: NEW reason: Lamb 2016 showed binding of TBC1D14 to TRAPP through its N-terminal TRAPP-binding region and TRAPPC8, recruitment of TRAPP and RAB1 onto Rab11-positive tubules generated by TBC1D14, and reduced RAB1 activation on TBC1D14 depletion. TBC1D14 itself does the bridging work, so this is participation, not mere necessity. No more specific GO term for TRAPP complex binding exists. supported_by: - reference_id: PMID:26711178 supporting_text: These data support a model where TBC1D14 acts as a bridge between a TRAPP complex and activated RAB11. - reference_id: PMID:26711178 supporting_text: TRAPPC8 is required for TBC1D14 to bind the TRAPP complex - reference_id: PMID:26711178 supporting_text: However, TBC1D14 depletion resulted in a significant reduction in RAB1B bound to GFP references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees 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:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000108 title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:17562788 title: Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Overexpression screen; TBC1D14 blocks Shiga toxin transport independently of its catalytic residue and localizes to recycling endosomes. GAP target not determined. - id: PMID:17646400 title: Functional dissection of Rab GTPases involved in primary cilium formation. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Screen of TBC GAPs for cilium formation; TBC1D14 not a hit (basis of the NOT annotation). TBC1D14 is not named in the cached main text. - id: PMID:22613832 title: TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive recycling endosomes. findings: - statement: TBC1D14 has no detectable GAP activity on 47 Rabs; it binds active Rab11, localizes to recycling endosomes, and negatively regulates starvation-induced autophagosome formation. supporting_text: supporting the data that TBC1D14 has no GAP activity reference_review: relevance: HIGH correctness: VERIFIED review_notes: Primary characterization paper; full text cached. Establishes RE localization, ULK1/Rab11 binding, absence of GAP activity, and autophagy phenotypes. - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: HuRI high-throughput binary interactome; source of the NXF1 pair only. - id: Reactome:R-HSA-8854759 title: TBC1D14 binds RAB11 and ULK1 findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Reactome summary of Longatti 2012, notes absence of GAP activity. - id: PMID:26711178 title: TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic. findings: - statement: TBC1D14 bridges Rab11 and TRAPPIII (via TRAPPC8) and is required for RAB1 activation and ATG9 traffic from recycling endosomes to the Golgi. supporting_text: These data support a model where TBC1D14 acts as a bridge between a TRAPP complex and activated RAB11. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text cached. Establishes TRAPPIII/TRAPPC8 binding, RAB1 activation requirement and the RE-to-Golgi ATG9 model. - id: file:human/TBC1D14/TBC1D14-uniprot.txt title: UniProtKB Q9P2M4 entry for TBC1D14 findings: [] core_functions: - description: Rab11 effector and adaptor that links active Rab11 on recycling endosomes to the TRAPPIII complex (via TRAPPC8), supporting TRAPP-dependent RAB1 activation and a constitutive recycling-endosome-to-early-Golgi transport step that maintains the cycling pool of ATG9. Experimentally established in human cells; no GAP activity has been detected. molecular_function: id: GO:0060090 label: molecular adaptor activity directly_involved_in: - id: GO:0071955 label: recycling endosome to Golgi transport locations: - id: GO:0055037 label: recycling endosome - id: GO:0005794 label: Golgi apparatus supported_by: - *id014 - reference_id: PMID:26711178 supporting_text: TBC1D14 in turn recruits TRAPP - reference_id: PMID:26711178 supporting_text: TRAPPC8 is required for TBC1D14 to bind the TRAPP complex - *id015 - *id011 - *id006 - description: Binds GTP-bound Rab11, which recruits TBC1D14 to recycling endosomes; the binding is not accompanied by GAP activity. molecular_function: id: GO:0031267 label: small GTPase binding locations: - id: GO:0055037 label: recycling endosome supported_by: - *id001 - *id006 - *id016 - description: Regulates starvation-induced autophagosome formation by controlling membrane and ATG9 supply from recycling endosomes; depletion increases starvation-induced LC3 lipidation and overexpression inhibits autophagosome formation. molecular_function: id: GO:0060090 label: molecular adaptor activity directly_involved_in: - id: GO:2000785 label: regulation of autophagosome assembly supported_by: - *id013 - *id012 - *id011 suggested_questions: - question: TBC1D14 retains the TBC arginine and glutamine fingers yet shows no GAP activity on 47 Rabs. Is it a GAP for an untested Rab, or has its TBC domain been co-opted as a Rab11-binding effector module? - question: Should the family-root GTPase activator activity IBA (PTN000537561) be blocked at the TBC1D14 clade node, given the human negative biochemical data? - question: Is 'molecular adaptor activity' the best MF for the Rab11-TRAPPIII bridge, or should a GO term for TRAPP complex binding be created? suggested_experiments: - description: Purify TBC1D14 TBC domain and test GAP activity on Rab1, Rab11 and the remaining Rabs with intrinsic hydrolysis controls; compare with an active TBC GAP carrying the same R/Q residues. experiment_type: in vitro biochemistry - description: Reconstitute Rab11-GTP-dependent recruitment of TRAPPIII to liposomes with and without TBC1D14 or its TRAPP-binding region, and measure RAB1 GEF activity. experiment_type: in vitro reconstitution - description: Knock out TBC1D14 in a zebrafish or cell model of a teleost and test ATG9 distribution and starvation-induced autophagy, to check conservation of the human mechanism for transfer to fish orthologs. experiment_type: genetic loss of function