RAB8A is a ubiquitously expressed Rab-family small GTPase (Sec4/Rab8 subfamily) that is C-terminally geranylgeranylated and cycles between an inactive GDP-bound form and an active GTP-bound form. It is activated by GEFs including Rabin8 (RAB3IP), GRAB (RAB3IL1), RPGR and the C9ORF72-SMCR8 complex, inactivated by GAPs such as TBC1D30 and TBC1D17, and phosphorylated in its switch II region by LRRK2. Active RAB8A recruits effectors (myosin V motors, MICAL-L1/EHD1, optineurin, OCRL, MICAL1) to direct post-Golgi and recycling-endosome carriers to the plasma membrane, supporting polarized exocytosis, endocytic recycling and delivery of cargoes such as E-cadherin and neurotransmitter receptors. In ciliogenesis, RAB8A is activated by Rabin8 at the mother centriole downstream of RAB11, after the ciliary vesicle has formed, and drives extension of the ciliary membrane; it is the only Rab enriched in the primary cilium, where it resides in the ciliary membrane. It also functions in Golgi organization, cytokinesis (midbody vesicle delivery) and autophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2562526 | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: GTPase activity / G protein activity (IBA, IDA, IEA). Reason: RAB8A is a Rab-family small GTPase that cycles between GDP- and GTP-bound states under the control of GEFs (Rabin8, GRAB, RPGR, C9ORF72-SMCR8) and GAPs (TBC1D30, TBC1D17); intrinsic GTP hydrolysis was measured experimentally. Molecular switch (G protein) activity with GTP hydrolysis is the core molecular function. Supporting Evidence: PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0003924 GTPase activity | IDA PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | ACCEPT | Summary: GTPase activity / G protein activity (IBA, IDA, IEA). Reason: RAB8A is a Rab-family small GTPase that cycles between GDP- and GTP-bound states under the control of GEFs (Rabin8, GRAB, RPGR, C9ORF72-SMCR8) and GAPs (TBC1D30, TBC1D17); intrinsic GTP hydrolysis was measured experimentally. Molecular switch (G protein) activity with GTP hydrolysis is the core molecular function. Supporting Evidence: PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: GTPase activity / G protein activity (IBA, IDA, IEA). Reason: RAB8A is a Rab-family small GTPase that cycles between GDP- and GTP-bound states under the control of GEFs (Rabin8, GRAB, RPGR, C9ORF72-SMCR8) and GAPs (TBC1D30, TBC1D17); intrinsic GTP hydrolysis was measured experimentally. Molecular switch (G protein) activity with GTP hydrolysis is the core molecular function. Supporting Evidence: PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0003925 G protein activity | IDA PMID:21282656 Rab GTPase-Myo5B complexes control membrane recycling and ep... | ACCEPT | Summary: GTPase activity / G protein activity (IBA, IDA, IEA). Reason: RAB8A is a Rab-family small GTPase that cycles between GDP- and GTP-bound states under the control of GEFs (Rabin8, GRAB, RPGR, C9ORF72-SMCR8) and GAPs (TBC1D30, TBC1D17); intrinsic GTP hydrolysis was measured experimentally. Molecular switch (G protein) activity with GTP hydrolysis is the core molecular function. Supporting Evidence: PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | ACCEPT | Summary: GTPase activity / G protein activity (IBA, IDA, IEA). Reason: RAB8A is a Rab-family small GTPase that cycles between GDP- and GTP-bound states under the control of GEFs (Rabin8, GRAB, RPGR, C9ORF72-SMCR8) and GAPs (TBC1D30, TBC1D17); intrinsic GTP hydrolysis was measured experimentally. Molecular switch (G protein) activity with GTP hydrolysis is the core molecular function. Supporting Evidence: PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0005515 protein binding | IPI PMID:15207266 Abnormal alpha-synuclein interactions with rab3a and rabphil... | REMOVE | Summary: Generic protein binding (IPI, PMID:15207266) with SNCA. Reason: Interaction with SNCA comes from an interaction-mapping, pathology or host-pathogen study without evidence that it is part of RAB8A's normal function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | REMOVE | Summary: Generic protein binding (IPI, PMID:15837803) with OPTN (optineurin). Reason: Optineurin is a RAB8 effector linking RAB8 to myosin VI at the Golgi and acting as an adaptor that brings the RAB8 GAP TBC1D17 to RAB8. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005515 protein binding | IPI PMID:16541104 Nucleotide exchange via local protein unfolding--structure o... | REMOVE | Summary: Generic protein binding (IPI, PMID:16541104) with RABIF (MSS4). Reason: MSS4/RABIF is a nucleotide-free Rab chaperone; the structure of the RAB8-MSS4 complex illustrates exchange via local unfolding. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:16902405 Membrane targeting and activation of the Lowe syndrome prote... | REMOVE | Summary: Generic protein binding (IPI, PMID:16902405) with OCRL. Reason: OCRL is a RAB8A effector; the RAB8A-OCRL Rab-binding domain structure was solved and OCRL relies on Rab binding for membrane targeting and ciliary localization. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | REMOVE | Summary: Generic protein binding (IPI, PMID:17646400) with ODF2 (cenexin). Reason: RAB8A binds the basal-body protein cenexin/ODF2, a link relevant to ciliogenesis. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:17646400 Rab8a specifically interacts with cenexin/ODF2, a basal body and microtubule binding protein required for cilium biogenesis |
| GO:0005515 protein binding | IPI PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | REMOVE | Summary: Generic protein binding (IPI, PMID:17646400) with OPTN (optineurin). Reason: Optineurin is a RAB8 effector linking RAB8 to myosin VI at the Golgi and acting as an adaptor that brings the RAB8 GAP TBC1D17 to RAB8. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005515 protein binding | IPI PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | REMOVE | Summary: Generic protein binding (IPI, PMID:17646400) with TBC1D30. Reason: TBC1D30 is a RAB8-specific GAP identified in the ciliogenesis screen. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:18329369 Final stages of cytokinesis and midbody ring formation are c... | REMOVE | Summary: Generic protein binding (IPI, PMID:18329369) with BIRC6 (BRUCE). Reason: BRUCE/BIRC6 was implicated in midbody ring formation together with Rab8-positive vesicles. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:19864458 MICAL-L1 links EHD1 to tubular recycling endosomes and regul... | REMOVE | Summary: Generic protein binding (IPI, PMID:19864458) with MICALL1. Reason: MICAL-L1 is a RAB8 effector that links RAB8A and EHD1 on tubular recycling endosomes. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures |
| GO:0005515 protein binding | IPI PMID:19864458 MICAL-L1 links EHD1 to tubular recycling endosomes and regul... | REMOVE | Summary: Generic protein binding (IPI, PMID:19864458) with EHD1. Reason: EHD1 associates with RAB8A on recycling tubules through MICAL-L1. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures |
| GO:0005515 protein binding | IPI PMID:20308558 Coordination of Rab8 and Rab11 in primary ciliogenesis. | REMOVE | Summary: Generic protein binding (IPI, PMID:20308558) with RAB3IP (Rabin8) isoform. Reason: Rabin8 is the GEF that activates RAB8A; RAB8A is its substrate, so the binding reflects the GEF's activity rather than a RAB8A molecular function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:20388642 Overexpression of optineurin E50K disrupts Rab8 interaction ... | REMOVE | Summary: Generic protein binding (IPI, PMID:20388642) with OPTN (optineurin). Reason: Optineurin is a RAB8 effector linking RAB8 to myosin VI at the Golgi and acting as an adaptor that brings the RAB8 GAP TBC1D17 to RAB8. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005515 protein binding | IPI PMID:20631154 Interaction of retinitis pigmentosa GTPase regulator (RPGR) ... | REMOVE | Summary: Generic protein binding (IPI, PMID:20631154) with RPGR. Reason: RPGR binds GDP-RAB8A and stimulates nucleotide exchange, i.e. RAB8A is the substrate of a GEF-like activity. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange |
| GO:0005515 protein binding | IPI PMID:20643351 Pitchfork regulates primary cilia disassembly and left-right... | REMOVE | Summary: Generic protein binding (IPI, PMID:20643351) with CIMAP3 (Pitchfork). Reason: Pitchfork associates with ciliary targeting complexes during cilia disassembly. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:20643351 Pitchfork regulates primary cilia disassembly and left-right... | REMOVE | Summary: Generic protein binding (IPI, PMID:20643351) with mouse Cimap3 (Pitchfork). Reason: Pitchfork associates with ciliary targeting complexes during cilia disassembly. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:21273506 Primary cilia membrane assembly is initiated by Rab11 and tr... | REMOVE | Summary: Generic protein binding (IPI, PMID:21273506) with RAB3IP (Rabin8). Reason: Rabin8 is the GEF that activates RAB8A; RAB8A is its substrate, so the binding reflects the GEF's activity rather than a RAB8A molecular function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:21378754 A structural basis for Lowe syndrome caused by mutations in ... | REMOVE | Summary: Generic protein binding (IPI, PMID:21378754) with OCRL. Reason: OCRL is a RAB8A effector; the RAB8A-OCRL Rab-binding domain structure was solved and OCRL relies on Rab binding for membrane targeting and ciliary localization. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:22011575 Protein LidA from Legionella is a Rab GTPase supereffector. | REMOVE | Summary: Generic protein binding (IPI, PMID:22011575) with Legionella LidA. Reason: Interaction with Legionella LidA comes from an interaction-mapping, pathology or host-pathogen study without evidence that it is part of RAB8A's normal function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:22159412 Linking cytoplasmic dynein and transport of Rab8 vesicles to... | REMOVE | Summary: Generic protein binding (IPI, PMID:22159412) with DCDC1 (DCDC5). Reason: DCDC5 links RAB8 vesicles to dynein for transport to the midbody. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:22159412 impairs the entry of Golgi-complex-derived Rab8-positive vesicles to the midbody |
| GO:0005515 protein binding | IPI PMID:22543976 OCRL localizes to the primary cilium: a new role for cilia i... | REMOVE | Summary: Generic protein binding (IPI, PMID:22543976) with OCRL. Reason: OCRL is a RAB8A effector; the RAB8A-OCRL Rab-binding domain structure was solved and OCRL relies on Rab binding for membrane targeting and ciliary localization. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:22854040 Optineurin mediates a negative regulation of Rab8 by the GTP... | REMOVE | Summary: Generic protein binding (IPI, PMID:22854040) with OPTN (optineurin). Reason: Optineurin is a RAB8 effector linking RAB8 to myosin VI at the Golgi and acting as an adaptor that brings the RAB8 GAP TBC1D17 to RAB8. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005515 protein binding | IPI PMID:26258637 Structure of Rab11-FIP3-Rabin8 reveals simultaneous binding ... | REMOVE | Summary: Generic protein binding (IPI, PMID:26258637) with RAB3IP (Rabin8) isoform. Reason: Rabin8 is the GEF that activates RAB8A; RAB8A is its substrate, so the binding reflects the GEF's activity rather than a RAB8A molecular function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | REMOVE | Summary: Generic protein binding (IPI, PMID:26824392) with RABIF (MSS4). Reason: MSS4/RABIF is a nucleotide-free Rab chaperone; the structure of the RAB8-MSS4 complex illustrates exchange via local unfolding. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | REMOVE | Summary: Generic protein binding (IPI, PMID:26824392) with OCRL. Reason: OCRL is a RAB8A effector; the RAB8A-OCRL Rab-binding domain structure was solved and OCRL relies on Rab binding for membrane targeting and ciliary localization. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | MODIFY | Summary: Generic protein binding (IPI, PMID:26824392) with LRRK2. Reason: LRRK2 binds and directly phosphorylates RAB8A on Thr72 in switch II, regulating its interactions with GDI and effectors. The interaction is better captured by 'protein kinase binding' (already annotated electronically from rat), recognising that RAB8A is the kinase substrate. Proposed replacements: protein kinase binding Supporting Evidence: PMID:26824392 LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain |
| GO:0005515 protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | REMOVE | Summary: Generic protein binding (IPI, PMID:26824392) with RAB3IP (Rabin8). Reason: Rabin8 is the GEF that activates RAB8A; RAB8A is its substrate, so the binding reflects the GEF's activity rather than a RAB8A molecular function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | REMOVE | Summary: Generic protein binding (IPI, PMID:27103069) with SQSTM1 (p62). Reason: the interaction with p62/SQSTM1 was reported in the context of C9ORF72-dependent RAB8A activation and autophagy. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Generic protein binding (IPI, PMID:27173435) with RAB3IP (Rabin8). Reason: Rabin8 is the GEF that activates RAB8A; RAB8A is its substrate, so the binding reflects the GEF's activity rather than a RAB8A molecular function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29125462 Systematic proteomic analysis of LRRK2-mediated Rab GTPase p... | REMOVE | Summary: Generic protein binding (IPI, PMID:29125462) with SPAG9 (JIP4). Reason: JIP4 is a phospho-Rab effector that binds LRRK2-phosphorylated RAB8A. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29125462 Systematic proteomic analysis of LRRK2-mediated Rab GTPase p... | REMOVE | Summary: Generic protein binding (IPI, PMID:29125462) with RABIF (MSS4). Reason: MSS4/RABIF is a nucleotide-free Rab chaperone; the structure of the RAB8-MSS4 complex illustrates exchange via local unfolding. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29125462 Systematic proteomic analysis of LRRK2-mediated Rab GTPase p... | REMOVE | Summary: Generic protein binding (IPI, PMID:29125462) with OCRL. Reason: OCRL is a RAB8A effector; the RAB8A-OCRL Rab-binding domain structure was solved and OCRL relies on Rab binding for membrane targeting and ciliary localization. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29125462 Systematic proteomic analysis of LRRK2-mediated Rab GTPase p... | REMOVE | Summary: Generic protein binding (IPI, PMID:29125462) with RILPL1. Reason: RILPL1 is a phospho-Rab effector that binds LRRK2-phosphorylated RAB8A. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29125462 Systematic proteomic analysis of LRRK2-mediated Rab GTPase p... | REMOVE | Summary: Generic protein binding (IPI, PMID:29125462) with RILPL2. Reason: RILPL2 is a phospho-Rab effector that binds LRRK2-phosphorylated RAB8A. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro... | MODIFY | Summary: Generic protein binding (IPI, PMID:31046837) with LRRK2. Reason: LRRK2 binds and directly phosphorylates RAB8A on Thr72 in switch II, regulating its interactions with GDI and effectors. The interaction is better captured by 'protein kinase binding' (already annotated electronically from rat), recognising that RAB8A is the kinase substrate. Proposed replacements: protein kinase binding Supporting Evidence: PMID:26824392 LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain |
| GO:0005515 protein binding | IPI PMID:32017888 Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 P... | REMOVE | Summary: Generic protein binding (IPI, PMID:32017888) with SPAG9 (JIP4). Reason: JIP4 is a phospho-Rab effector that binds LRRK2-phosphorylated RAB8A. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32017888 Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 P... | MODIFY | Summary: Generic protein binding (IPI, PMID:32017888) with LRRK2. Reason: LRRK2 binds and directly phosphorylates RAB8A on Thr72 in switch II, regulating its interactions with GDI and effectors. The interaction is better captured by 'protein kinase binding' (already annotated electronically from rat), recognising that RAB8A is the kinase substrate. Proposed replacements: protein kinase binding Supporting Evidence: PMID:26824392 LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain |
| GO:0005515 protein binding | IPI PMID:32017888 Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 P... | REMOVE | Summary: Generic protein binding (IPI, PMID:32017888) with RILPL2. Reason: RILPL2 is a phospho-Rab effector that binds LRRK2-phosphorylated RAB8A. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32344433 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export... | REMOVE | Summary: Generic protein binding (IPI, PMID:32344433) with MICAL1. Reason: MICAL1 links GRAF1b/2 to RAB8A/B in endosomal export of E-cadherin and other cargoes. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32353859 A SARS-CoV-2 protein interaction map reveals targets for dru... | REMOVE | Summary: Generic protein binding (IPI, PMID:32353859) with a SARS-CoV-2 nonstructural protein. Reason: Interaction with a SARS-CoV-2 nonstructural protein comes from an interaction-mapping, pathology or host-pathogen study without evidence that it is part of RAB8A's normal function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33060197 Comparative host-coronavirus protein interaction networks re... | REMOVE | Summary: Generic protein binding (IPI, PMID:33060197) with a SARS-CoV-2 nonstructural protein. Reason: Interaction with a SARS-CoV-2 nonstructural protein comes from an interaction-mapping, pathology or host-pathogen study without evidence that it is part of RAB8A's normal function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI, PMID:33961781) with RABIF (MSS4). Reason: MSS4/RABIF is a nucleotide-free Rab chaperone; the structure of the RAB8-MSS4 complex illustrates exchange via local unfolding. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:36217030 A comprehensive SARS-CoV-2-human protein-protein interactome... | REMOVE | Summary: Generic protein binding (IPI, PMID:36217030) with a SARS-CoV-2 nonstructural protein. Reason: Interaction with a SARS-CoV-2 nonstructural protein comes from an interaction-mapping, pathology or host-pathogen study without evidence that it is part of RAB8A's normal function. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding (IPI, PMID:40205054) with RABIF (MSS4). Reason: MSS4/RABIF is a nucleotide-free Rab chaperone; the structure of the RAB8-MSS4 complex illustrates exchange via local unfolding. As for most Rab-partner interactions, the bare 'protein binding' term carries no functional information; RAB8A's molecular function is captured by GTPase activity/GTP binding, and its roles by the trafficking process and location annotations. Removal does not mean the interaction is false. |
| GO:0005525 GTP binding | IDA PMID:20937701 Family-wide characterization of the DENN domain Rab GDP-GTP ... | ACCEPT | Summary: GTP/GDP binding (IDA, IEA, ARBA). Reason: Nucleotide binding is intrinsic to the Rab switch mechanism; GEF assays use GDP release from RAB8A. Supporting Evidence: PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP/GDP binding (IDA, IEA, ARBA). Reason: Nucleotide binding is intrinsic to the Rab switch mechanism; GEF assays use GDP release from RAB8A. Supporting Evidence: PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange |
| GO:0005737 cytoplasm | EXP PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005764 lysosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Lysosome (IEA, UniProt subcellular location). Reason: RAB8A can be recruited to stressed lysosomes by LRRK2 and phosphorylated there, but lysosomes are not its main compartment. |
| GO:0005768 endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0005794 Golgi apparatus | EXP PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0005813 centrosome | IDA PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | KEEP AS NON CORE | Summary: Centrosome (IDA) / centriole (IEA). Reason: RAB8A localizes to the centrosome/mother centriole region during ciliogenesis, a localization that depends on CEP290 and Talpid3. This reflects vesicles docked at the mother centriole rather than a centriolar protein; non-core. Supporting Evidence: PMID:18694559 Depletion of CEP290 diminishes the localization of Rab8a to centrosomes and prevents its entry into the cilium PMID:24421332 Talpid3 depletion also led to mislocalization of Rab8a, a small GTPase thought to be essential for ciliary vesicle formation |
| GO:0005813 centrosome | IDA PMID:25849865 Actin remodelling factors control ciliogenesis by regulating... | KEEP AS NON CORE | Summary: Centrosome (IDA) / centriole (IEA). Reason: RAB8A localizes to the centrosome/mother centriole region during ciliogenesis, a localization that depends on CEP290 and Talpid3. This reflects vesicles docked at the mother centriole rather than a centriolar protein; non-core. Supporting Evidence: PMID:18694559 Depletion of CEP290 diminishes the localization of Rab8a to centrosomes and prevents its entry into the cilium PMID:24421332 Talpid3 depletion also led to mislocalization of Rab8a, a small GTPase thought to be essential for ciliary vesicle formation |
| GO:0005814 centriole | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosome (IDA) / centriole (IEA). Reason: RAB8A localizes to the centrosome/mother centriole region during ciliogenesis, a localization that depends on CEP290 and Talpid3. This reflects vesicles docked at the mother centriole rather than a centriolar protein; non-core. Supporting Evidence: PMID:18694559 Depletion of CEP290 diminishes the localization of Rab8a to centrosomes and prevents its entry into the cilium PMID:24421332 Talpid3 depletion also led to mislocalization of Rab8a, a small GTPase thought to be essential for ciliary vesicle formation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623519 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623521 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623524 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623525 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623527 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870466 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870469 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876190 | KEEP AS NON CORE | Summary: Cytoplasm / cytosol (EXP, IEA, Reactome TAS). Reason: Prenylated RAB8A partitions between membranes and a cytosolic GDI-bound pool; Reactome places RAB geranylgeranylation and GEF reactions in the cytosol. Correct but uninformative. |
| GO:0005886 plasma membrane | EXP PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | ACCEPT | Summary: Plasma membrane (EXP, IBA, HPA IDA, IEA). Reason: RAB8-positive carriers fuse with the plasma membrane; RAB8 colocalizes with myosin VI in vesicles at the plasma membrane, and HPA detects plasma membrane staining. Correct location for a GTPase controlling exocytic delivery. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (EXP, IBA, HPA IDA, IEA). Reason: RAB8-positive carriers fuse with the plasma membrane; RAB8 colocalizes with myosin VI in vesicles at the plasma membrane, and HPA detects plasma membrane staining. Correct location for a GTPase controlling exocytic delivery. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane (EXP, IBA, HPA IDA, IEA). Reason: RAB8-positive carriers fuse with the plasma membrane; RAB8 colocalizes with myosin VI in vesicles at the plasma membrane, and HPA detects plasma membrane staining. Correct location for a GTPase controlling exocytic delivery. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane (EXP, IBA, HPA IDA, IEA). Reason: RAB8-positive carriers fuse with the plasma membrane; RAB8 colocalizes with myosin VI in vesicles at the plasma membrane, and HPA detects plasma membrane staining. Correct location for a GTPase controlling exocytic delivery. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0005929 cilium | IDA PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0005929 cilium | IDA PMID:21844891 A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and... | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0005929 cilium | IDA PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0005930 axoneme | IEA GO_REF:0000044 | MODIFY | Summary: Axoneme (IEA, UniProt subcellular location). Reason: RAB8A is a prenylated membrane-associated GTPase found in the ciliary membrane, not on axonemal microtubules. The ciliary localization is better represented by ciliary membrane. Proposed replacements: ciliary membrane Supporting Evidence: PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0006887 exocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Exocytosis (IBA). Reason: RAB8 (Sec4 family) directs post-Golgi and recycling-endosome-derived carriers to the plasma membrane; endosomal export of cargo depends on Rab8/10/11. Core process. Supporting Evidence: PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner PMID:21282656 Myosin Vb (Myo5B) is an effector for Rab8a, Rab10, and Rab11a, all of which are implicated in regulating different pathways for recycling of proteins to the plasma membrane |
| GO:0007030 Golgi organization | IMP PMID:26209634 Small GTPase Rab2B and Its Specific Binding Protein Golgi-as... | KEEP AS NON CORE | Summary: Golgi organization (IMP, Aizawa & Fukuda 2015). Reason: RAB8A knockdown fragments the Golgi in HeLa cells, a genuine but indirect consequence of disrupting Golgi-associated trafficking. Supporting Evidence: PMID:26209634 knockdown of any one of the six Rab isoforms (Rab1A/1B/2A/2B/6B/8A) induced fragmentation of the Golgi in HeLa-S3 cells |
| GO:0007409 axonogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Axonogenesis (IEA/ISS from rat Rab8a). Reason: Rab8 supports polarized membrane delivery for neurite outgrowth in rodent neurons; consistent with its exocytic role but developmental and non-core. Supporting Evidence: PMID:12221131 expression of Rab8 promotes the formation of new cell surface domains through reorganization of actin and microtubules |
| GO:0007409 axonogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axonogenesis (IEA/ISS from rat Rab8a). Reason: Rab8 supports polarized membrane delivery for neurite outgrowth in rodent neurons; consistent with its exocytic role but developmental and non-core. Supporting Evidence: PMID:12221131 expression of Rab8 promotes the formation of new cell surface domains through reorganization of actin and microtubules |
| GO:0010008 endosome membrane | IDA PMID:32344433 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export... | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0010506 regulation of autophagy | IMP PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | KEEP AS NON CORE | Summary: Regulation of autophagy (IMP, Sellier et al. 2016). Reason: C9ORF72-SMCR8-WDR41 acts as a GEF for RAB8A and RAB39B to control autophagic flux; RAB8A's contribution to autophagy is a context-specific trafficking role. Supporting Evidence: PMID:27103069 act as a GDP/GTP exchange factor for RAB8a and RAB39b and to thereby control autophagic flux |
| GO:0019003 GDP binding | IDA PMID:20937701 Family-wide characterization of the DENN domain Rab GDP-GTP ... | ACCEPT | Summary: GTP/GDP binding (IDA, IEA, ARBA). Reason: Nucleotide binding is intrinsic to the Rab switch mechanism; GEF assays use GDP release from RAB8A. Supporting Evidence: PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange |
| GO:0019003 GDP binding | IEA GO_REF:0000117 | ACCEPT | Summary: GTP/GDP binding (IDA, IEA, ARBA). Reason: Nucleotide binding is intrinsic to the Rab switch mechanism; GEF assays use GDP release from RAB8A. Supporting Evidence: PMID:20631154 RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein kinase binding (IEA from rat Rab8a). Reason: RAB8A binds the kinase LRRK2, which phosphorylates it in switch II; correct but this reflects RAB8A being a kinase substrate rather than a core activity. Supporting Evidence: PMID:26824392 LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain |
| GO:0030140 trans-Golgi network transport vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0030140 trans-Golgi network transport vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal locations (dendrite, neuronal cell body, synapse, glutamatergic synapse; IEA from rat Rab8a). Reason: Rodent studies place Rab8 in dendrites and at synapses where it supports AMPA-receptor delivery; consistent with its general exocytic role but not core. |
| GO:0030496 midbody | IDA PMID:22159412 Linking cytoplasmic dynein and transport of Rab8 vesicles to... | KEEP AS NON CORE | Summary: Midbody (IDA, Kaplan & Reiner 2011; IEA). Reason: Golgi-derived RAB8-positive vesicles are transported by dynein to the midbody during late cytokinesis. Genuine but peripheral. Supporting Evidence: PMID:22159412 impairs the entry of Golgi-complex-derived Rab8-positive vesicles to the midbody |
| GO:0030496 midbody | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Midbody (IDA, Kaplan & Reiner 2011; IEA). Reason: Golgi-derived RAB8-positive vesicles are transported by dynein to the midbody during late cytokinesis. Genuine but peripheral. Supporting Evidence: PMID:22159412 impairs the entry of Golgi-complex-derived Rab8-positive vesicles to the midbody |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Phagocytic vesicle / membrane (IDA, Seto et al. 2011; IEA). Reason: RAB8A was among many Rabs transiently recruited to bacterial phagosomes in a macrophage screen. A context-specific, non-core location. |
| GO:0031267 small GTPase binding | ISS GO_REF:0000024 | REMOVE | Summary: Small GTPase binding (ISS, with rat GDI1 as the source). Reason: The source entity for this ISS is rat GDI1, a Rab GDP-dissociation inhibitor, not a RAB8A ortholog. GDI1 legitimately binds small GTPases, but transferring that activity to RAB8A (which is itself a small GTPase and the client of GDI) inverts the relationship. There is no evidence that RAB8A binds other small GTPases as a function. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: Cytoplasmic vesicle (IEA from rat Rab8a). Reason: RAB8A decorates post-Golgi and recycling transport vesicles. Correct. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane |
| GO:0031489 myosin V binding | IPI PMID:24006491 Identification and characterization of multiple novel Rab-my... | ACCEPT | Summary: Myosin V binding (IPI, Lindsay et al. 2013). Reason: RAB8A binds class V myosins (MYO5A and MYO5B) as effectors; the RAB8A-Myo5B interaction is required for apical trafficking and lumen formation. A specific and informative effector-binding function. Supporting Evidence: PMID:24006491 Myosin Va is a widely expressed actin-based motor protein that binds members of the Rab GTPase family (3A, 8A, 10, 11A, 27A) PMID:21282656 Myo5B was required for apical membrane trafficking and de novo lumen formation, dependent on association with both Rab8a and Rab11a |
| GO:0032456 endocytic recycling | IBA GO_REF:0000033 | ACCEPT | Summary: Endocytic recycling (IBA). Reason: RAB8 regulates trafficking of transferrin receptor through the recycling compartment and associates with MICAL-L1/EHD1 recycling tubules. Supporting Evidence: PMID:22854040 Rab8 is involved in controlling several trafficking processes, including the trafficking of transferrin receptor from the early endosome to the recycling endosome PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-8876190 | ACCEPT | Summary: Golgi apparatus / Golgi or TGN membrane / TGN transport vesicle (EXP, IBA, IEA, Reactome TAS). Reason: RAB8 associates with the Golgi/trans-Golgi network and with post-Golgi carriers that it directs to the plasma membrane and to the ciliary base; RAB8 colocalizes with myosin VI/optineurin around the Golgi complex. Supporting Evidence: PMID:15837803 myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0032869 cellular response to insulin stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to insulin stimulus (IEA/ISS from rat Rab8a). Reason: Rodent studies implicate Rab8A in insulin-stimulated GLUT4 translocation in muscle cells, an exocytic role in a specialized context. |
| GO:0032869 cellular response to insulin stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular response to insulin stimulus (IEA/ISS from rat Rab8a). Reason: Rodent studies implicate Rab8A in insulin-stimulated GLUT4 translocation in muscle cells, an exocytic role in a specialized context. |
| GO:0032880 regulation of protein localization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of protein localization / protein transport (IEA from rat Rab8a). Reason: Broad terms consistent with RAB8A-controlled membrane trafficking; less informative than exocytosis, endocytic recycling and cilium assembly. |
| GO:0036064 ciliary basal body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ciliary basal body / ciliary base (IEA/ISS from mouse Rab8a). Reason: RAB8A accumulates at the ciliary base/pericentrosomal region during ciliogenesis before entering the cilium; correct but less precise than ciliary membrane. Supporting Evidence: PMID:18694559 Depletion of CEP290 diminishes the localization of Rab8a to centrosomes and prevents its entry into the cilium |
| GO:0036064 ciliary basal body | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ciliary basal body / ciliary base (IEA/ISS from mouse Rab8a). Reason: RAB8A accumulates at the ciliary base/pericentrosomal region during ciliogenesis before entering the cilium; correct but less precise than ciliary membrane. Supporting Evidence: PMID:18694559 Depletion of CEP290 diminishes the localization of Rab8a to centrosomes and prevents its entry into the cilium |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal locations (dendrite, neuronal cell body, synapse, glutamatergic synapse; IEA from rat Rab8a). Reason: Rodent studies place Rab8 in dendrites and at synapses where it supports AMPA-receptor delivery; consistent with its general exocytic role but not core. |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal locations (dendrite, neuronal cell body, synapse, glutamatergic synapse; IEA from rat Rab8a). Reason: Rodent studies place Rab8 in dendrites and at synapses where it supports AMPA-receptor delivery; consistent with its general exocytic role but not core. |
| GO:0045335 phagocytic vesicle | IDA PMID:21255211 Rab GTPases regulating phagosome maturation are differential... | KEEP AS NON CORE | Summary: Phagocytic vesicle / membrane (IDA, Seto et al. 2011; IEA). Reason: RAB8A was among many Rabs transiently recruited to bacterial phagosomes in a macrophage screen. A context-specific, non-core location. |
| GO:0045335 phagocytic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Phagocytic vesicle / membrane (IDA, Seto et al. 2011; IEA). Reason: RAB8A was among many Rabs transiently recruited to bacterial phagosomes in a macrophage screen. A context-specific, non-core location. |
| GO:0048169 regulation of long-term neuronal synaptic plasticity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of long-term neuronal synaptic plasticity (IEA from rat Rab8a). Reason: Rodent Rab8 supports AMPA receptor delivery to synapses during plasticity; a specialized neuronal application of its exocytic role. |
| GO:0048210 Golgi vesicle fusion to target membrane | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: Golgi vesicle fusion to target membrane (IDA, Nachury et al. 2007). Reason: Ciliary membranes are built by transport and fusion of Golgi-derived vesicles at the ciliary base, and RAB8-GTP promotes extension of the ciliary membrane. RAB8 as the vesicle-identity GTPase directly participates in targeting/fusion of these carriers. Supporting Evidence: PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:23435566 Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome |
| GO:0051223 regulation of protein transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of protein localization / protein transport (IEA from rat Rab8a). Reason: Broad terms consistent with RAB8A-controlled membrane trafficking; less informative than exocytosis, endocytic recycling and cilium assembly. |
| GO:0055037 recycling endosome | IEA GO_REF:0000120 | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0055038 recycling endosome membrane | IDA PMID:19864458 MICAL-L1 links EHD1 to tubular recycling endosomes and regul... | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0055038 recycling endosome membrane | IDA PMID:21951725 MICAL-L1 is a tubular endosomal membrane hub that connects R... | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0055038 recycling endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0055038 recycling endosome membrane | TAS Reactome:R-HSA-8854182 | ACCEPT | Summary: Endosome / endosome membrane / recycling endosome (membrane) (IBA, IDA, IEA, Reactome TAS). Reason: GTP-bound RAB8 localizes to tubules emanating from the endocytic recycling compartment, where MICAL-L1 links it to EHD1, and RAB8 controls export of cargo through endosomes. Core trafficking compartment. Supporting Evidence: PMID:22854040 The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0060170 ciliary membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Ciliary membrane (IEA from mouse Rab8a). Reason: Super-resolution and CLEM show RAB8 largely in the ciliary membrane, which it helps to extend. This is the most precise ciliary location for RAB8A. Supporting Evidence: PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Cilium assembly (IBA, IDA, IEA, IMP). Reason: RAB8A is required for primary ciliogenesis: preventing RAB8-GTP production blocks ciliation, RAB8 assembles the ciliary membrane after serum withdrawal, and it acts in ciliary vesicle extension after EHD1-dependent ciliary vesicle formation. Core ciliary function. Supporting Evidence: PMID:17574030 preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish PMID:21273506 upon serum withdrawal Rab8 is observed to assemble the ciliary membrane in βΌ100 min PMID:25686250 with EHD1 important for CV formation and Rab8 functioning in CV extension PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0060271 cilium assembly | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: Cilium assembly (IBA, IDA, IEA, IMP). Reason: RAB8A is required for primary ciliogenesis: preventing RAB8-GTP production blocks ciliation, RAB8 assembles the ciliary membrane after serum withdrawal, and it acts in ciliary vesicle extension after EHD1-dependent ciliary vesicle formation. Core ciliary function. Supporting Evidence: PMID:17574030 preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish PMID:21273506 upon serum withdrawal Rab8 is observed to assemble the ciliary membrane in βΌ100 min PMID:25686250 with EHD1 important for CV formation and Rab8 functioning in CV extension PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Cilium assembly (IBA, IDA, IEA, IMP). Reason: RAB8A is required for primary ciliogenesis: preventing RAB8-GTP production blocks ciliation, RAB8 assembles the ciliary membrane after serum withdrawal, and it acts in ciliary vesicle extension after EHD1-dependent ciliary vesicle formation. Core ciliary function. Supporting Evidence: PMID:17574030 preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish PMID:21273506 upon serum withdrawal Rab8 is observed to assemble the ciliary membrane in βΌ100 min PMID:25686250 with EHD1 important for CV formation and Rab8 functioning in CV extension PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0060271 cilium assembly | IMP PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | ACCEPT | Summary: Cilium assembly (IBA, IDA, IEA, IMP). Reason: RAB8A is required for primary ciliogenesis: preventing RAB8-GTP production blocks ciliation, RAB8 assembles the ciliary membrane after serum withdrawal, and it acts in ciliary vesicle extension after EHD1-dependent ciliary vesicle formation. Core ciliary function. Supporting Evidence: PMID:17574030 preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish PMID:21273506 upon serum withdrawal Rab8 is observed to assemble the ciliary membrane in βΌ100 min PMID:25686250 with EHD1 important for CV formation and Rab8 functioning in CV extension PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0060271 cilium assembly | IMP PMID:21844891 A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and... | ACCEPT | Summary: Cilium assembly (IBA, IDA, IEA, IMP). Reason: RAB8A is required for primary ciliogenesis: preventing RAB8-GTP production blocks ciliation, RAB8 assembles the ciliary membrane after serum withdrawal, and it acts in ciliary vesicle extension after EHD1-dependent ciliary vesicle formation. Core ciliary function. Supporting Evidence: PMID:17574030 preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish PMID:21273506 upon serum withdrawal Rab8 is observed to assemble the ciliary membrane in βΌ100 min PMID:25686250 with EHD1 important for CV formation and Rab8 functioning in CV extension PMID:17646400 the Rab GTPase membrane trafficking regulators Rab8a, -17, and -23, and their cognate GTPase-activating proteins (GAPs), XM_037557, TBC1D7, and EVI5like, are involved in primary cilia formation |
| GO:0061512 protein localization to cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Protein localization to cilium (IEA/ISS from mouse Rab8a). Reason: RAB8 carriers deliver membrane and membrane proteins to the cilium; RAB8-GTP itself enters the cilium. Consistent with its core ciliary trafficking role. Supporting Evidence: PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane |
| GO:0061512 protein localization to cilium | ISS GO_REF:0000024 | ACCEPT | Summary: Protein localization to cilium (IEA/ISS from mouse Rab8a). Reason: RAB8 carriers deliver membrane and membrane proteins to the cilium; RAB8-GTP itself enters the cilium. Consistent with its core ciliary trafficking role. Supporting Evidence: PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA, urinary and B-cell exosome proteomics). Reason: RAB8A is detected in exosome proteomes, as are many abundant cytoplasmic membrane-associated proteins; no exosome-specific function is known. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA, urinary and B-cell exosome proteomics). Reason: RAB8A is detected in exosome proteomes, as are many abundant cytoplasmic membrane-associated proteins; no exosome-specific function is known. |
| GO:0072659 protein localization to plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Protein localization to plasma membrane (IEA/ISS from rat Rab8a). Reason: RAB8-dependent exocytic routes deliver transmembrane cargoes such as E-cadherin, MMP14 and CFTR to the plasma membrane. Consistent with the core function. Supporting Evidence: PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0072659 protein localization to plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Protein localization to plasma membrane (IEA/ISS from rat Rab8a). Reason: RAB8-dependent exocytic routes deliver transmembrane cargoes such as E-cadherin, MMP14 and CFTR to the plasma membrane. Consistent with the core function. Supporting Evidence: PMID:32344433 Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner |
| GO:0097546 ciliary base | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ciliary basal body / ciliary base (IEA/ISS from mouse Rab8a). Reason: RAB8A accumulates at the ciliary base/pericentrosomal region during ciliogenesis before entering the cilium; correct but less precise than ciliary membrane. Supporting Evidence: PMID:18694559 Depletion of CEP290 diminishes the localization of Rab8a to centrosomes and prevents its entry into the cilium |
| GO:0097730 non-motile cilium | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0097730 non-motile cilium | IDA PMID:24648492 Casein kinase 1Ξ΄ functions at the centrosome and Golgi to pr... | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0097730 non-motile cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Cilium / non-motile cilium (IDA from several studies, including colocalization; IEA). Reason: RAB8A is the sole Rab enriched at primary cilia; GTP-bound RAB8 enters the primary cilium and is largely present in the ciliary membrane. Supporting Evidence: PMID:17646400 is the sole Rab enriched at primary cilia PMID:17574030 Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane PMID:25686250 Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0098887 neurotransmitter receptor transport, endosome to postsynaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurotransmitter receptor transport to (or from endosome to) postsynaptic membrane (IBA; IEA from rat Rab8a). Reason: The PAINT node and rat data reflect Rab8-dependent delivery of AMPA receptors to the postsynaptic membrane. Biologically sound as a specialized neuronal instance of RAB8's recycling/exocytic function but not part of the core ciliary/exocytic summary. |
| GO:0098969 neurotransmitter receptor transport to postsynaptic membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neurotransmitter receptor transport to (or from endosome to) postsynaptic membrane (IBA; IEA from rat Rab8a). Reason: The PAINT node and rat data reflect Rab8-dependent delivery of AMPA receptors to the postsynaptic membrane. Biologically sound as a specialized neuronal instance of RAB8's recycling/exocytic function but not part of the core ciliary/exocytic summary. |
| GO:0098969 neurotransmitter receptor transport to postsynaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurotransmitter receptor transport to (or from endosome to) postsynaptic membrane (IBA; IEA from rat Rab8a). Reason: The PAINT node and rat data reflect Rab8-dependent delivery of AMPA receptors to the postsynaptic membrane. Biologically sound as a specialized neuronal instance of RAB8's recycling/exocytic function but not part of the core ciliary/exocytic summary. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal locations (dendrite, neuronal cell body, synapse, glutamatergic synapse; IEA from rat Rab8a). Reason: Rodent studies place Rab8 in dendrites and at synapses where it supports AMPA-receptor delivery; consistent with its general exocytic role but not core. |
| GO:1990782 protein tyrosine kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein tyrosine kinase binding (IEA from rat Rab8a). Reason: Transferred from rat; the underlying interaction is not characterized in human. Not part of RAB8A's core function. |
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Download this section (compressed HTML)Q: Given that RAB8 is activated only after ciliary vesicle assembly, is RAB8A required for distal appendage vesicle delivery at all, or exclusively for ciliary vesicle extension and ciliary membrane growth?
Q: How much do RAB8A and RAB8B (and RAB10) compensate for each other in ciliogenesis and polarized exocytosis in vivo?
Q: Does LRRK2 phosphorylation of RAB8A (Thr72) suppress ciliogenesis in physiologically relevant cells, and through which phospho-Rab effectors (RILPL1, RILPL2, JIP4)?
Experiment: Acute degron-mediated depletion of RAB8A (with RAB8B knockout) in RPE1 cells at defined times after serum starvation, imaged by CLEM, to pinpoint the ciliogenesis step that requires RAB8 activity.
Type: acute depletion and CLEM
Experiment: Phospho-mimetic/phospho-dead Thr72 RAB8A knock-in cells to test the effect of LRRK2 phosphorylation on ciliary membrane assembly and effector recruitment.
Type: knock-in and imaging
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