RAB3IP (Rabin8) is a coiled-coil Sec2-family guanine nucleotide exchange factor that specifically activates RAB8A and RAB8B. It is a cytosolic protein recruited to RAB11-positive, phosphatidylserine-containing vesicles through binding to RAB11-GTP (an effector interaction that also stimulates its exchange activity) and to the TRAPPII complex via TRAPPC14. At the onset of ciliogenesis these vesicles carry Rabin8 to the mother centriole, where NDR2-dependent phosphorylation switches Rabin8 from phosphatidylserine to the exocyst subunit SEC15 and RAB8A is activated to drive ciliary membrane growth; Rabin8 also contacts the BBSome at the basal body. Outside cilia, Rabin8-mediated RAB8 activation supports polarized membrane traffic to the cell cortex and actin-rich protrusions. The catalytic activity of Rabin8 is sufficient to determine where RAB8A is targeted on membranes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005085 guanyl-nucleotide exchange factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Guanyl-nucleotide exchange factor activity (IBA, IDA, IEA, Reactome TAS). Reason: Rabin8/RAB3IP is the Sec2-family GEF for RAB8A/RAB8B: purified Rabin8 stimulates nucleotide exchange on Rab8 but not Rab3A, Rab5 or Rab10, its activity is stimulated by Rab11-GTP, and a Rabin8-RAB8A co-crystal structure exists. GO:0005085 is now the term for Rab GEF activity (GO:0017112 was merged into it). This is the core molecular function. Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:20937701 Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity toward Rab10 PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 |
| GO:0005085 guanyl-nucleotide exchange factor activity | IDA PMID:20937701 Family-wide characterization of the DENN domain Rab GDP-GTP ... | ACCEPT | Summary: Guanyl-nucleotide exchange factor activity (IBA, IDA, IEA, Reactome TAS). Reason: Rabin8/RAB3IP is the Sec2-family GEF for RAB8A/RAB8B: purified Rabin8 stimulates nucleotide exchange on Rab8 but not Rab3A, Rab5 or Rab10, its activity is stimulated by Rab11-GTP, and a Rabin8-RAB8A co-crystal structure exists. GO:0005085 is now the term for Rab GEF activity (GO:0017112 was merged into it). This is the core molecular function. Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:20937701 Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity toward Rab10 PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 |
| GO:0005085 guanyl-nucleotide exchange factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Guanyl-nucleotide exchange factor activity (IBA, IDA, IEA, Reactome TAS). Reason: Rabin8/RAB3IP is the Sec2-family GEF for RAB8A/RAB8B: purified Rabin8 stimulates nucleotide exchange on Rab8 but not Rab3A, Rab5 or Rab10, its activity is stimulated by Rab11-GTP, and a Rabin8-RAB8A co-crystal structure exists. GO:0005085 is now the term for Rab GEF activity (GO:0017112 was merged into it). This is the core molecular function. Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:20937701 Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity toward Rab10 PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-5617816 | ACCEPT | Summary: Guanyl-nucleotide exchange factor activity (IBA, IDA, IEA, Reactome TAS). Reason: Rabin8/RAB3IP is the Sec2-family GEF for RAB8A/RAB8B: purified Rabin8 stimulates nucleotide exchange on Rab8 but not Rab3A, Rab5 or Rab10, its activity is stimulated by Rab11-GTP, and a Rabin8-RAB8A co-crystal structure exists. GO:0005085 is now the term for Rab GEF activity (GO:0017112 was merged into it). This is the core molecular function. Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:20937701 Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity toward Rab10 PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-5623521 | ACCEPT | Summary: Guanyl-nucleotide exchange factor activity (IBA, IDA, IEA, Reactome TAS). Reason: Rabin8/RAB3IP is the Sec2-family GEF for RAB8A/RAB8B: purified Rabin8 stimulates nucleotide exchange on Rab8 but not Rab3A, Rab5 or Rab10, its activity is stimulated by Rab11-GTP, and a Rabin8-RAB8A co-crystal structure exists. GO:0005085 is now the term for Rab GEF activity (GO:0017112 was merged into it). This is the core molecular function. Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:20937701 Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity toward Rab10 PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 |
| GO:0005085 guanyl-nucleotide exchange factor activity | TAS Reactome:R-HSA-8876190 | ACCEPT | Summary: Guanyl-nucleotide exchange factor activity (IBA, IDA, IEA, Reactome TAS). Reason: Rabin8/RAB3IP is the Sec2-family GEF for RAB8A/RAB8B: purified Rabin8 stimulates nucleotide exchange on Rab8 but not Rab3A, Rab5 or Rab10, its activity is stimulated by Rab11-GTP, and a Rabin8-RAB8A co-crystal structure exists. GO:0005085 is now the term for Rab GEF activity (GO:0017112 was merged into it). This is the core molecular function. Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:20937701 Sec2 domain proteins Rabin3/Rabin8 and Rabin3-like/GRAB are specific GEFs for Rab8A and Rab8B and have no activity toward Rab10 PMID:20308558 Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8 |
| GO:0005515 protein binding | IPI PMID:12007189 The cancer-related protein SSX2 interacts with the human hom... | REMOVE | Summary: Generic protein binding (IPI, PMID:12007189) with SSX2. Reason: RAB3IP was identified as an SSX2 interactor by yeast two-hybrid and GST pull-down; the interaction relocates RAB3IP to the nucleus only upon co-expression, and no physiological role has been established. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. Supporting Evidence: PMID:12007189 coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Generic protein binding (IPI, PMID:16189514) with RAB3IL1 (GRAB). Reason: RAB3IL1 (GRAB) is the paralogous Sec2-domain Rab8 GEF; the recurrent binary interaction likely reflects coiled-coil hetero-dimerization of Sec2-family GEFs. Bare 'protein binding' carries no functional information. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | REMOVE | Summary: Generic protein binding (IPI, PMID:19060904) with RAB3IL1 (GRAB). Reason: RAB3IL1 (GRAB) is the paralogous Sec2-domain Rab8 GEF; the recurrent binary interaction likely reflects coiled-coil hetero-dimerization of Sec2-family GEFs. Bare 'protein binding' carries no functional information. 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 TRAPPC6A. Reason: TRAPPC6A is a subunit of the TRAPPII complex, which binds the Rabin8 N-terminal domain (via TRAPPC14) and is required for Rabin8 preciliary targeting to the centrosome. This interaction is functionally important, but 'protein binding' carries no functional information and no specific MF term describes it; the biology is captured by the cilium assembly and vesicle annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:21273506 the transport protein particle (TRAPP) II complex associates with the Rabin8 NH(2)-terminal domain |
| 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 TRAPPC10. Reason: TRAPPC10 is a subunit of the TRAPPII complex, which binds the Rabin8 N-terminal domain (via TRAPPC14) and is required for Rabin8 preciliary targeting to the centrosome. This interaction is functionally important, but 'protein binding' carries no functional information and no specific MF term describes it; the biology is captured by the cilium assembly and vesicle annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:21273506 the transport protein particle (TRAPP) II complex associates with the Rabin8 NH(2)-terminal domain |
| GO:0005515 protein binding | IPI PMID:21273506 Primary cilia membrane assembly is initiated by Rab11 and tr... | MODIFY | Summary: Generic protein binding (IPI, PMID:21273506) with RAB8A. Reason: RAB8A is the substrate of the Rabin8 GEF; the interaction (structurally characterized, and used in kinetic GEF assays) is the physical basis of RAB3IP's core activity. 'Protein binding' is uninformative; the interaction is better expressed as small GTPase binding, with the catalytic consequence captured by the accepted guanyl-nucleotide exchange factor activity annotation. Proposed replacements: small GTPase binding Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:26824392 Kinetic measurements of the dissociation of mant-GDP from non-phosphorylated and T72 phosphorylated Rab8a by Rabin8 |
| 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 interacts with dynein, RAB8A and Rabin8 and supports dynein-dependent transport of Rab8 vesicles to the midbody during cytokinesis. The bare 'protein binding' term is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with PPL. Reason: Interaction with PPL comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with PLOD3. Reason: Interaction with PLOD3 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with TRAPPC6A. Reason: TRAPPC6A is a subunit of the TRAPPII complex, which binds the Rabin8 N-terminal domain (via TRAPPC14) and is required for Rabin8 preciliary targeting to the centrosome. This interaction is functionally important, but 'protein binding' carries no functional information and no specific MF term describes it; the biology is captured by the cilium assembly and vesicle annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:21273506 the transport protein particle (TRAPP) II complex associates with the Rabin8 NH(2)-terminal domain |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Generic protein binding (IPI, PMID:25416956) with RAB3A. Reason: Rabin3/RAB3IP was originally isolated as a RAB3A-interacting protein, but it has no exchange activity on RAB3A (Hattula et al. 2002). The binary interaction is best represented by small GTPase binding rather than bare protein binding. Proposed replacements: small GTPase binding Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with SFN (14-3-3 sigma). Reason: Interaction with SFN (14-3-3 sigma) comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with NAA10. Reason: Interaction with NAA10 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with SSX2. Reason: RAB3IP was identified as an SSX2 interactor by yeast two-hybrid and GST pull-down; the interaction relocates RAB3IP to the nucleus only upon co-expression, and no physiological role has been established. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. Supporting Evidence: PMID:12007189 coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with KRT40. Reason: Interaction with KRT40 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with FAM124A. Reason: Interaction with FAM124A comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with ZNF410. Reason: Interaction with ZNF410 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with BANP. Reason: Interaction with BANP comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with RAB3IL1 (GRAB). Reason: RAB3IL1 (GRAB) is the paralogous Sec2-domain Rab8 GEF; the recurrent binary interaction likely reflects coiled-coil hetero-dimerization of Sec2-family GEFs. Bare 'protein binding' carries no functional information. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with RUFY1. Reason: Interaction with RUFY1 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding (IPI, PMID:25416956) with CHCHD3. Reason: Interaction with CHCHD3 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. 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 RAB8A. Reason: RAB8A is the substrate of the Rabin8 GEF; the interaction (structurally characterized, and used in kinetic GEF assays) is the physical basis of RAB3IP's core activity. 'Protein binding' is uninformative; the interaction is better expressed as small GTPase binding, with the catalytic consequence captured by the accepted guanyl-nucleotide exchange factor activity annotation. Proposed replacements: small GTPase binding Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:26824392 Kinetic measurements of the dissociation of mant-GDP from non-phosphorylated and T72 phosphorylated Rab8a by Rabin8 |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Generic protein binding (IPI, PMID:27173435) with TRAPPC10. Reason: TRAPPC10 is a subunit of the TRAPPII complex, which binds the Rabin8 N-terminal domain (via TRAPPC14) and is required for Rabin8 preciliary targeting to the centrosome. This interaction is functionally important, but 'protein binding' carries no functional information and no specific MF term describes it; the biology is captured by the cilium assembly and vesicle annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:21273506 the transport protein particle (TRAPP) II complex associates with the Rabin8 NH(2)-terminal domain |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MODIFY | Summary: Generic protein binding (IPI, PMID:27173435) with RAB8A. Reason: RAB8A is the substrate of the Rabin8 GEF; the interaction (structurally characterized, and used in kinetic GEF assays) is the physical basis of RAB3IP's core activity. 'Protein binding' is uninformative; the interaction is better expressed as small GTPase binding, with the catalytic consequence captured by the accepted guanyl-nucleotide exchange factor activity annotation. Proposed replacements: small GTPase binding Supporting Evidence: PMID:12221131 stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 PMID:26824392 Kinetic measurements of the dissociation of mant-GDP from non-phosphorylated and T72 phosphorylated Rab8a by Rabin8 |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Generic protein binding (IPI, PMID:27173435) with RAB3IL1 (GRAB). Reason: RAB3IL1 (GRAB) is the paralogous Sec2-domain Rab8 GEF; the recurrent binary interaction likely reflects coiled-coil hetero-dimerization of Sec2-family GEFs. Bare 'protein binding' carries no functional information. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding (IPI, PMID:29892012) with PLOD3. Reason: Interaction with PLOD3 comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:31467083 The C7orf43/TRAPPC14 component links the TRAPPII complex to ... | REMOVE | Summary: Generic protein binding (IPI, PMID:31467083) with TRAPPC14. Reason: TRAPPC14 is a subunit of the TRAPPII complex, which binds the Rabin8 N-terminal domain (via TRAPPC14) and is required for Rabin8 preciliary targeting to the centrosome. This interaction is functionally important, but 'protein binding' carries no functional information and no specific MF term describes it; the biology is captured by the cilium assembly and vesicle annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:31467083 We find that C7orf43 directly binds to Rabin8 and that C7orf43 knockdown diminishes Rabin8 preciliary centrosome accumulation |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI, PMID:33961781) with RAB3IL1 (GRAB). Reason: RAB3IL1 (GRAB) is the paralogous Sec2-domain Rab8 GEF; the recurrent binary interaction likely reflects coiled-coil hetero-dimerization of Sec2-family GEFs. Bare 'protein binding' carries no functional information. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:36217029 A proteome-scale map of the SARS-CoV-2-human contactome. | REMOVE | Summary: Generic protein binding (IPI, PMID:36217029) with a SARS-CoV-2 nonstructural protein. Reason: Interaction with a SARS-CoV-2 nonstructural protein comes from a proteome-scale binary or host-pathogen interaction screen, with no evidence for a role in RAB3IP function. Bare 'protein binding' is uninformative. Removal does not mean the interaction is false. |
| GO:0005634 nucleus | IDA PMID:12007189 The cancer-related protein SSX2 interacts with the human hom... | KEEP AS NON CORE | Summary: Nucleus/nucleoplasm (IDA from de Bruijn et al. 2002 co-expression with SSX2; IEA; IDA from HPA immunofluorescence). Reason: RAB3IP is cytoplasmic in transfected cells and enters the nucleus only when co-expressed with SSX2. HPA nonetheless reports nucleoplasm as a main location for its antibody. No nuclear function is known; Rabin8 acts on cytoplasmic vesicles and at the centrosome. Retained as non-core. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:12007189 coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nucleus/nucleoplasm (IDA from de Bruijn et al. 2002 co-expression with SSX2; IEA; IDA from HPA immunofluorescence). Reason: RAB3IP is cytoplasmic in transfected cells and enters the nucleus only when co-expressed with SSX2. HPA nonetheless reports nucleoplasm as a main location for its antibody. No nuclear function is known; Rabin8 acts on cytoplasmic vesicles and at the centrosome. Retained as non-core. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:12007189 coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleus/nucleoplasm (IDA from de Bruijn et al. 2002 co-expression with SSX2; IEA; IDA from HPA immunofluorescence). Reason: RAB3IP is cytoplasmic in transfected cells and enters the nucleus only when co-expressed with SSX2. HPA nonetheless reports nucleoplasm as a main location for its antibody. No nuclear function is known; Rabin8 acts on cytoplasmic vesicles and at the centrosome. Retained as non-core. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:12007189 coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus |
| GO:0005737 cytoplasm | EXP PMID:12007189 The cancer-related protein SSX2 interacts with the human hom... | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005737 cytoplasm | EXP PMID:31467083 The C7orf43/TRAPPC14 component links the TRAPPII complex to ... | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005813 centrosome | IDA GO_REF:0000052 | ACCEPT | Summary: Centrosome (IDA from HPA; IEA). Reason: Rabin8 accumulates at the centrosome/mother centriole on Rab11 vesicles at the onset of ciliogenesis (Westlake et al. 2011), and HPA reports centrosome (Supported). This is the site where it activates RAB8A for ciliary membrane assembly. Supporting Evidence: PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome PMID:31467083 We find that C7orf43 directly binds to Rabin8 and that C7orf43 knockdown diminishes Rabin8 preciliary centrosome accumulation |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Centrosome (IDA from HPA; IEA). Reason: Rabin8 accumulates at the centrosome/mother centriole on Rab11 vesicles at the onset of ciliogenesis (Westlake et al. 2011), and HPA reports centrosome (Supported). This is the site where it activates RAB8A for ciliary membrane assembly. Supporting Evidence: PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome PMID:31467083 We find that C7orf43 directly binds to Rabin8 and that C7orf43 knockdown diminishes Rabin8 preciliary centrosome accumulation |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | IDA PMID:12007189 The cancer-related protein SSX2 interacts with the human hom... | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623519 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623521 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623524 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623525 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5623527 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638014 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876190 | ACCEPT | Summary: Cytoplasm/cytosol (EXP, IDA, IBA, IEA, Reactome TAS). Reason: Rabin8 is a soluble cytoplasmic protein that cycles between the cytosol and Rab11-positive vesicles, from which it is delivered to the centrosome. Cytoplasm/cytosol is the correct resting compartment of the GEF. Supporting Evidence: PMID:12007189 the RAB3IP protein is normally localized in the cytoplasm PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoskeleton (IEA, UniProt subcellular location). Reason: Rabin8 localizes to cortical actin in non-ciliated cells (Hattula et al. 2002). Correct but generic and non-core. Supporting Evidence: PMID:12221131 Rabin8 localized to the cortical actin |
| GO:0006612 protein targeting to membrane | IDA PMID:23382462 RabGEFs are a major determinant for specific Rab membrane ta... | ACCEPT | Summary: Protein targeting to membrane (IDA, Blumer et al. 2013). Reason: Mistargeting Rabin8 to mitochondria catalytically recruits RAB8A there, showing that the GEF activity itself determines where RAB8A is targeted. RAB3IP thus directly performs the targeting step for its substrate Rab. Supporting Evidence: PMID:23382462 Specific mistargeting of Rabex-5/DrrA/Rabin8 to mitochondria led to catalytic recruitment of Rab5A/Rab1A/Rab8A in a time-dependent manner that required the catalytic activity of the GEF |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Lamellipodium (IEA, UniProt subcellular location). Reason: Rabin8 translocates with Rab8 vesicles to the outer edge of lamellipodial structures after PKC activation. A context-dependent, non-core location. Supporting Evidence: PMID:12221131 Activation of PKC by phorbol esters enhanced translocation of both Rabin8 and Rab8-specific vesicles to the outer edge of lamellipodial structures |
| GO:0031982 vesicle | EXP PMID:31467083 The C7orf43/TRAPPC14 component links the TRAPPII complex to ... | ACCEPT | Summary: Vesicle (EXP, Cuenca et al. 2019; IEA). Reason: Rabin8 binds Rab11-GTP and phosphatidylserine on pericentrosomal vesicles that carry it to the mother centriole; vesicle association is central to its ciliogenic role. Supporting Evidence: PMID:23435566 Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0031982 vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: Vesicle (EXP, Cuenca et al. 2019; IEA). Reason: Rabin8 binds Rab11-GTP and phosphatidylserine on pericentrosomal vesicles that carry it to the mother centriole; vesicle association is central to its ciliogenic role. Supporting Evidence: PMID:23435566 Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (IEA from rat Rab3ip). Reason: Consistent with pericentrosomal accumulation of Rabin8-containing vesicles, but less informative than centrosome. Non-core. Supporting Evidence: PMID:23435566 Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles |
| GO:0051020 GTPase binding | IEA GO_REF:0000107 | ACCEPT | Summary: GTPase binding (IEA from rat Rab3ip). Reason: Rabin8 binds its substrate RAB8 and, through its C-terminal domain, RAB11-GTP as an effector. Correct; small GTPase binding would be a more precise child term. 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:26258637 the C-terminal domain of Rabin8 adopts a previously undescribed fold that interacts with Rab11 at an unusual effector-binding site |
| GO:0051490 negative regulation of filopodium assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of filopodium assembly (IEA from rat Rab3ip). Reason: Rabin8 expression remodels actin and induces polarized cell-surface domains via RAB8 activation; an effect on filopodia in neurons is plausible downstream of RAB8 activity but is peripheral to the core role of RAB3IP. Supporting Evidence: PMID:12221131 We propose that Rabin8 is a Rab8-specific activator that is connected to processes that mediate polarized membrane traffic to dynamic cell surface structures |
| GO:0060271 cilium assembly | TAS Reactome:R-HSA-5620916 | ACCEPT | Summary: Cilium assembly (Reactome TAS). Reason: Rabin8 is delivered on Rab11 vesicles to the centrosome, where it activates RAB8 to drive ciliary membrane assembly; blocking its phosphorylation-dependent switch, its TRAPPII-dependent targeting, or Rab8-GTP production blocks ciliogenesis. RAB3IP performs the activating step of the Rab11-Rab8 cascade within cilium assembly. Supporting Evidence: PMID:21273506 Rab8-dependent ciliary assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome PMID:23435566 NDR2 phosphorylates Rabin8 at Ser-272 and defects in this phosphorylation impair preciliary membrane assembly and ciliogenesis PMID:17574030 This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome PMID:25686250 Rabin8, the guanine nucleotide exchange factor for Rab8, binds to Rab11 and is delivered to the centrosome on vesicles to activate Rab8 to promote ciliary membrane assembly |
| GO:1905349 ciliary transition zone assembly | TAS Reactome:R-HSA-5620912 | MARK AS OVER ANNOTATED | Summary: Ciliary transition zone assembly (Reactome TAS, R-HSA-5620912 'Anchoring of the basal body to the plasma membrane'; automatic replacement of the obsoleted GO:0097711). Reason: This row is the mechanical replacement for the obsoleted 'ciliary basal body-plasma membrane docking' term, and Reactome has since revised the underlying RAB3IP entry. RAB3IP acts upstream, activating RAB8A on preciliary vesicles to supply and extend the ciliary membrane; the transition-zone structure is assembled by TZ components (CEP290, MKS and NPHP modules). EHD1-dependent ciliary vesicle formation, not Rab8 activation, is the step linked to TZ protein recruitment, and Rab8 activation occurs only after ciliary vesicle assembly. RAB3IP is therefore better described by cilium assembly than by transition zone assembly. Supporting Evidence: PMID:25686250 only after ciliary vesicle assembly is Rab8 activated for ciliary growth PMID:25686250 Rabin8, the guanine nucleotide exchange factor for Rab8, binds to Rab11 and is delivered to the centrosome on vesicles to activate Rab8 to promote ciliary membrane assembly |
| GO:1990635 proximal dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Proximal dendrite (IEA from rat Rab3ip). Reason: Neuronal localization transferred from rat; consistent with RAB8-dependent polarized trafficking in neurons but not part of the core ciliary function. |
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Download this section (compressed HTML)Q: Does RAB3IP act only after EHD1/EHD3-dependent ciliary vesicle assembly (as Rab8 activation timing suggests), or is a pool of Rabin8 already required for distal appendage vesicle delivery?
Q: What is the physiological significance of the nucleoplasmic RAB3IP signal reported by HPA, given that RAB3IP enters the nucleus in transfected cells only upon SSX2 co-expression?
Q: How redundant are RAB3IP and its paralog RAB3IL1 (GRAB) as RAB8 GEFs in ciliogenesis in vivo?
Experiment: RAB3IP knockout RPE1 cells imaged by correlative light/electron microscopy during serum starvation to determine whether distal appendage vesicles and the ciliary vesicle form normally and which step of ciliary membrane growth fails; rescue with GEF-dead (catalytic interface) and RAB11-binding-deficient mutants.
Type: knockout, CLEM and rescue
Experiment: RAB3IP/RAB3IL1 double knockout to test GEF redundancy for RAB8A activation (RAB8-GTP pulldown) and ciliogenesis.
Type: genetic interaction
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