GET3 encodes an ATPase that is the central targeting factor in the GET (Guided Entry of Tail-anchored proteins) pathway. As a homodimer, Get3p recognizes and binds the transmembrane domain of newly synthesized tail-anchored (TA) membrane proteins in the cytosol, shielding the hydrophobic segment from aqueous solvent. ATP binding drives a closed dimer conformation that facilitates TA substrate capture, and the Get3p-substrate complex is then delivered to the ER membrane via the Get1p/Get2p receptor, where ATP hydrolysis triggers substrate release and membrane insertion. Get3p also cooperates with the HDEL receptor Erd2p in ATP-dependent retrograde retrieval of ER-resident proteins from the Golgi, and functions as a guanine nucleotide exchange factor for Gpa1p in pheromone signaling. Under oxidative stress with ATP depletion, Get3p undergoes a conformational switch to act as a holdase chaperone. Orthologous to human GET3/TRC40.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043529 GET complex | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: GET complex is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Functionally, ATP hydrolysis is required for productive insertion because a hydrolysis-deficient Get3 mutant remains substrate-bound and is inactive in insertion assays |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: tail-anchored membrane protein insertion into ER membrane is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Biochemical reconstitution demonstrates Get1/Get2 are the minimal ER membrane machinery for insertion, with **Get2 tethering** membrane-proximal Get3βTA complexes and **Get1 driving ATPase-dependent substrate release** for insertion |
| GO:0006457 protein folding | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Manual review: protein folding may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: Manual review: nucleotide binding is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Manual review: ATP binding is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Manual review: cytoplasm is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: Manual review: endoplasmic reticulum is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Manual review: Golgi apparatus may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: vesicle-mediated transport may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: hydrolase activity may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Functionally, ATP hydrolysis is required for productive insertion because a hydrolysis-deficient Get3 mutant remains substrate-bound and is inactive in insertion assays |
| GO:0043529 GET complex | IEA GO_REF:0000104 | ACCEPT | Summary: Manual review: GET complex is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0045048 protein insertion into ER membrane | IEA GO_REF:0000104 | ACCEPT | Summary: Manual review: protein insertion into ER membrane is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Biochemical reconstitution demonstrates Get1/Get2 are the minimal ER membrane machinery for insertion, with **Get2 tethering** membrane-proximal Get3βTA complexes and **Get1 driving ATPase-dependent substrate release** for insertion |
| GO:0046685 response to arsenic-containing substance | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: response to arsenic-containing substance may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: metal ion binding may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:16260785 The yeast Arr4p ATPase binds the chloride transporter Gef1p ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:16269340 Exploration of the function and organization of the yeast ea... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:16816426 The conserved ATPase Get3/Arr4 modulates the activity of mem... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:18724936 The GET complex mediates insertion of tail-anchored proteins... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:19675567 The structural basis of tail-anchored membrane protein recog... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:20106980 Crystal structure of Get4-Get5 complex and its interactions ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:20850366 A chaperone cascade sorts proteins for posttranslational mem... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:21866104 The mechanism of membrane-associated steps in tail-anchored ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:24727835 Crystal structure of ATP-bound Get3-Get4-Get5 complex reveal... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:25745174 Protein targeting. Structure of the Get3 targeting factor in... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for GET3. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0042802 identical protein binding | IPI PMID:16260785 The yeast Arr4p ATPase binds the chloride transporter Gef1p ... | ACCEPT | Summary: Manual review: identical protein binding captures the obligate Get3 homodimer that forms the tail-anchored protein binding groove. Reason: Retained because Get3 functions as a homodimer; dimer closure generates the hydrophobic groove that binds and shields tail-anchored protein transmembrane domains. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Get3 is described as a **Zn2+-stabilized homodimer** whose dimer interface forms a **composite hydrophobic groove** that binds an Ξ±-helical TA TMD; mutations that increase groove hydrophilicity reduce TA binding, and conformational closure is nucleotide dependent |
| GO:0042802 identical protein binding | IPI PMID:19675567 The structural basis of tail-anchored membrane protein recog... | ACCEPT | Summary: Manual review: identical protein binding captures the obligate Get3 homodimer that forms the tail-anchored protein binding groove. Reason: Retained because Get3 functions as a homodimer; dimer closure generates the hydrophobic groove that binds and shields tail-anchored protein transmembrane domains. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Get3 is described as a **Zn2+-stabilized homodimer** whose dimer interface forms a **composite hydrophobic groove** that binds an Ξ±-helical TA TMD; mutations that increase groove hydrophilicity reduce TA binding, and conformational closure is nucleotide dependent |
| GO:0042802 identical protein binding | IPI PMID:19706470 Model for eukaryotic tail-anchored protein binding based on ... | ACCEPT | Summary: Manual review: identical protein binding captures the obligate Get3 homodimer that forms the tail-anchored protein binding groove. Reason: Retained because Get3 functions as a homodimer; dimer closure generates the hydrophobic groove that binds and shields tail-anchored protein transmembrane domains. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Get3 is described as a **Zn2+-stabilized homodimer** whose dimer interface forms a **composite hydrophobic groove** that binds an Ξ±-helical TA TMD; mutations that increase groove hydrophilicity reduce TA binding, and conformational closure is nucleotide dependent |
| GO:0042802 identical protein binding | IPI PMID:22124326 Tail-anchor targeting by a Get3 tetramer: the structure of a... | ACCEPT | Summary: Manual review: identical protein binding captures the obligate Get3 homodimer that forms the tail-anchored protein binding groove. Reason: Retained because Get3 functions as a homodimer; dimer closure generates the hydrophobic groove that binds and shields tail-anchored protein transmembrane domains. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Get3 is described as a **Zn2+-stabilized homodimer** whose dimer interface forms a **composite hydrophobic groove** that binds an Ξ±-helical TA TMD; mutations that increase groove hydrophilicity reduce TA binding, and conformational closure is nucleotide dependent |
| GO:0042802 identical protein binding | IPI PMID:24727835 Crystal structure of ATP-bound Get3-Get4-Get5 complex reveal... | ACCEPT | Summary: Manual review: identical protein binding captures the obligate Get3 homodimer that forms the tail-anchored protein binding groove. Reason: Retained because Get3 functions as a homodimer; dimer closure generates the hydrophobic groove that binds and shields tail-anchored protein transmembrane domains. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Get3 is described as a **Zn2+-stabilized homodimer** whose dimer interface forms a **composite hydrophobic groove** that binds an Ξ±-helical TA TMD; mutations that increase groove hydrophilicity reduce TA binding, and conformational closure is nucleotide dependent |
| GO:0042802 identical protein binding | IPI PMID:25745174 Protein targeting. Structure of the Get3 targeting factor in... | ACCEPT | Summary: Manual review: identical protein binding captures the obligate Get3 homodimer that forms the tail-anchored protein binding groove. Reason: Retained because Get3 functions as a homodimer; dimer closure generates the hydrophobic groove that binds and shields tail-anchored protein transmembrane domains. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Get3 is described as a **Zn2+-stabilized homodimer** whose dimer interface forms a **composite hydrophobic groove** that binds an Ξ±-helical TA TMD; mutations that increase groove hydrophilicity reduce TA binding, and conformational closure is nucleotide dependent |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:32910895 Structural Basis of Tail-Anchored Membrane Protein Biogenesi... | ACCEPT | Summary: Manual review: endoplasmic reticulum membrane is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0045048 protein insertion into ER membrane | IDA PMID:21866104 The mechanism of membrane-associated steps in tail-anchored ... | ACCEPT | Summary: Manual review: protein insertion into ER membrane is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Biochemical reconstitution demonstrates Get1/Get2 are the minimal ER membrane machinery for insertion, with **Get2 tethering** membrane-proximal Get3βTA complexes and **Get1 driving ATPase-dependent substrate release** for insertion |
| GO:0016887 ATP hydrolysis activity | TAS Reactome:R-SCE-9628646 | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Functionally, ATP hydrolysis is required for productive insertion because a hydrolysis-deficient Get3 mutant remains substrate-bound and is inactive in insertion assays |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IMP PMID:18724936 The GET complex mediates insertion of tail-anchored proteins... | ACCEPT | Summary: Manual review: tail-anchored membrane protein insertion into ER membrane is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Biochemical reconstitution demonstrates Get1/Get2 are the minimal ER membrane machinery for insertion, with **Get2 tethering** membrane-proximal Get3βTA complexes and **Get1 driving ATPase-dependent substrate release** for insertion |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | KEEP AS NON CORE | Summary: Manual review: zinc ion binding may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044183 protein folding chaperone | IDA PMID:25242142 The protein targeting factor Get3 functions as ATP-independe... | KEEP AS NON CORE | Summary: Manual review: protein folding chaperone activity is supported under oxidative or ATP-depleting stress but is not the core GET-pathway function. Reason: Keep as non-core because Get3 has a regulated ATP-independent holdase role during oxidative stress, while the primary function remains ATP-dependent tail-anchored protein targeting to the ER. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md under oxidative stress or ATP depletion, Get3 is converted from ATPase targeting factor into an **ATP-independent holdase chaperone**. |
| GO:0043529 GET complex | IDA PMID:32910895 Structural Basis of Tail-Anchored Membrane Protein Biogenesi... | ACCEPT | Summary: Manual review: GET complex is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005829 cytosol | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005783 endoplasmic reticulum | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Manual review: endoplasmic reticulum is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005829 cytosol | TAS Reactome:R-SCE-9628640 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005829 cytosol | TAS Reactome:R-SCE-9628646 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0005829 cytosol | TAS Reactome:R-SCE-9629050 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
| GO:0034599 cellular response to oxidative stress | IDA PMID:25242142 The protein targeting factor Get3 functions as ATP-independe... | KEEP AS NON CORE | Summary: Manual review: cellular response to oxidative stress may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0051082 unfolded protein binding | IDA PMID:25242142 The protein targeting factor Get3 functions as ATP-independe... | KEEP AS NON CORE | Summary: Manual review: unfolded protein binding is supported for the oxidative-stress holdase state of Get3 but is condition-specific. Reason: Keep as non-core rather than replacing it; Falcon and the source literature support unfolded-protein binding during stress-induced Get3 holdase activity, distinct from the core GET targeting ATPase cycle. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md under oxidative stress or ATP depletion, Get3 is converted from ATPase targeting factor into an **ATP-independent holdase chaperone**. |
| GO:0000750 pheromone-dependent signal transduction involved in conjugation with cellular fusion | IMP PMID:18261907 Coactivation of G protein signaling by cell-surface receptor... | MODIFY | Summary: Manual review: pheromone-dependent signal transduction involved in conjugation with cellular fusion may be context-dependent or peripheral for GET3. Reason: GO obsoleted GO:0000750 as a precomposed term to be represented as a GO-CAM, replaced_by GO:0071507 pheromone response MAPK cascade. That replacement suits the kinases, not Arr4/Get3, which acts upstream of the cascade as a non-receptor GEF for the Galpha Gpa1 and promotes MAPK phosphorylation, new-gene transcription and mating (PMID:18261907). The GO-CAM idiom for a GEF on the pheromone Galpha, as in the S. pombe pheromone model gomodel:693b3c0900000536 (receptor GEF activity positively regulating the cascade), is guanyl-nucleotide exchange factor activity (already on GET3) positively regulating the cascade, so the BP replacement is positive regulation of pheromone response MAPK cascade. That term is itself positioned in conjugation, so no context is lost. Non-core relative to tail-anchored protein targeting. Proposed replacements: positive regulation of pheromone response MAPK cascade Supporting Evidence: PMID:18261907 Arr4 promotes G protein-dependent cellular responses, including mitogen-activated protein kinase (MAPK) phosphorylation,new-gene transcription, and mating |
| GO:0005085 guanyl-nucleotide exchange factor activity | IDA PMID:18261907 Coactivation of G protein signaling by cell-surface receptor... | KEEP AS NON CORE | Summary: Manual review: guanyl-nucleotide exchange factor activity for Gpa1 is directly reported but remains context-specific relative to the canonical GET pathway. Reason: Keep as non-core because one quantitative source supports Arr4/Get3 GEF activity in pheromone signaling, but this role is less integrated with later GET-pathway mechanistic literature than TA-protein targeting. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md A 2008 study reported that Arr4 is a **non-receptor GEF for Gpa1** and indicates that **Arr4 is an alias of Get3** |
| GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane | IDA PMID:20850366 A chaperone cascade sorts proteins for posttranslational mem... | ACCEPT | Summary: Manual review: post-translational protein targeting to endoplasmic reticulum membrane is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Biochemical reconstitution demonstrates Get1/Get2 are the minimal ER membrane machinery for insertion, with **Get2 tethering** membrane-proximal Get3βTA complexes and **Get1 driving ATPase-dependent substrate release** for insertion |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IDA PMID:16269340 Exploration of the function and organization of the yeast ea... | KEEP AS NON CORE | Summary: Manual review: Golgi-to-ER retrograde transport evidence appears indirect for GET3 and should not be treated as core function. Reason: Keep as non-core because the reviewed GET-pathway literature does not provide direct Erd2/HDEL-mediated retrograde-transport evidence for Get3; trafficking effects may be secondary to TA-client targeting or proteostasis defects. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md No direct evidence for Erd2/HDEL-mediated retrograde transport involvement was found in the retrieved primary mechanistic GET literature. |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IMP PMID:16269340 Exploration of the function and organization of the yeast ea... | KEEP AS NON CORE | Summary: Manual review: Golgi-to-ER retrograde transport evidence appears indirect for GET3 and should not be treated as core function. Reason: Keep as non-core because the reviewed GET-pathway literature does not provide direct Erd2/HDEL-mediated retrograde-transport evidence for Get3; trafficking effects may be secondary to TA-client targeting or proteostasis defects. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md No direct evidence for Erd2/HDEL-mediated retrograde transport involvement was found in the retrieved primary mechanistic GET literature. |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IGI PMID:16269340 Exploration of the function and organization of the yeast ea... | KEEP AS NON CORE | Summary: Manual review: Golgi-to-ER retrograde transport evidence appears indirect for GET3 and should not be treated as core function. Reason: Keep as non-core because the reviewed GET-pathway literature does not provide direct Erd2/HDEL-mediated retrograde-transport evidence for Get3; trafficking effects may be secondary to TA-client targeting or proteostasis defects. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md No direct evidence for Erd2/HDEL-mediated retrograde transport involvement was found in the retrieved primary mechanistic GET literature. |
| GO:0009408 response to heat | IMP PMID:12680698 The Saccharomyces cerevisiae Arr4p is involved in metal and ... | KEEP AS NON CORE | Summary: Manual review: response to heat may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0010038 response to metal ion | IMP PMID:12680698 The Saccharomyces cerevisiae Arr4p is involved in metal and ... | KEEP AS NON CORE | Summary: Manual review: response to metal ion may be context-dependent or peripheral for GET3. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:12680698 The Saccharomyces cerevisiae Arr4p is involved in metal and ... | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Functionally, ATP hydrolysis is required for productive insertion because a hydrolysis-deficient Get3 mutant remains substrate-bound and is inactive in insertion assays |
| GO:0043529 GET complex | IPI PMID:16269340 Exploration of the function and organization of the yeast ea... | ACCEPT | Summary: Manual review: GET complex is consistent with known biology of GET3. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/GET3/GET3-deep-research-falcon.md Core pathway evidence places Get3 as a **cytosolic shuttle** that also becomes **ER membrane-associated** via Get1/Get2 during docking/release; membrane association is ATP-sensitive and reversible |
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Download this section (compressed HTML)Guanine nucleotide exchange factor for Gpa1p; amplifies G-protein signaling; subunit of the GET complex involved in ATP-dependent Golgi-to-ER trafficking; binds as a dimer to the transmembrane domain of tail-anchored proteins in the cytosol, shielding them from aqueous solvent until the Get1p/Get2p heterodimer releases the substrate and inserts it into the ER membrane; acts as a chaperone under ATP-depleted oxidative stress conditions; protein abundance increases under DNA replication stress
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