Sec71 (CG7578) is the single Drosophila member of the BIG1/BIG2 (ARFGEF1/ARFGEF2) subfamily of large Sec7-domain guanine nucleotide exchange factors for ARF GTPases. It is a soluble 1653-residue protein with the conserved DCB, HUS, catalytic Sec7 and HDS domains, and is recruited from the cytosol to trans-Golgi network membranes through a direct GTP-dependent interaction between its N-terminal region and the Arf-like GTPase Arl1. At the trans-Golgi it activates Arf1 (Arf79F), preferentially binding GDP-Arf1, and Sec71 and Arf1 depend on each other for Golgi localization. It is the sole brefeldin A target whose inhibition causes Golgi stacks to aggregate, and it keeps Golgi stacks separated. Through Arf1 activation it supports post-Golgi biosynthetic trafficking of apical and basolateral membrane proteins (photoreceptors), and its loss affects processes that depend on this trafficking, including dendrite pruning of sensory neurons, Rab5-dependent endocytosis of Neuroglian, neural stem cell reactivation and neuroblast polarity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005085 guanyl-nucleotide exchange factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that Sec71, as a BIG/Sec7-family member, has guanyl-nucleotide exchange factor activity. Reason: Sec71 is the fly ortholog of BIG1/BIG2 and is inside the Sec7/BIG clade whose GEF activity the PAINT node asserts; the fly gene appears among the experimental seeds because its own GEF activity toward Arf1 was shown (PMID:28420712). No evidence of loss. GO:0005085 is the most specific available term now that ARF GEF activity (GO:0005086) is obsolete. Supporting Evidence: PMID:28420712 We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. PMID:22291037 Sec71 is the Drosophila ortholog of human BIG1/BIG2, although it has not been extensively characterized. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IDA PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | ACCEPT | Summary: Wang et al. 2017 identified Sec71 as a guanine nucleotide exchange factor for Arf1. Reason: Direct experimental support for the core activity of the protein; the cached record is abstract-only, so the assay details are taken on trust from the FlyBase curator. Consistent with the conserved catalytic Sec7 domain. Supporting Evidence: PMID:28420712 We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. file:DROME/Sec71/Sec71-uniprot.txt FT DOMAIN 575..765 FT /note="SEC7" FT /evidence="ECO:0000259|PROSITE:PS50190" |
| GO:0005085 guanyl-nucleotide exchange factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the Sec7 domain (IPR000904, IPR035999) to guanyl-nucleotide exchange factor activity. Reason: The Sec7 domain is the catalytic ARF-GEF domain, and the inference agrees with the experimental data for this gene. Supporting Evidence: file:DROME/Sec71/Sec71-uniprot.txt FT DOMAIN 575..765 FT /note="SEC7" FT /evidence="ECO:0000259|PROSITE:PS50190" PMID:28420712 We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IPI PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | ACCEPT | Summary: GEF activity supported by interaction with the substrate Arf1 (Arf79F, FBgn0010348), preferentially its GDP-bound form. Reason: Preferential binding of GDP-Arf1 is the substrate interaction expected of an exchange factor and agrees with the IDA row from the same paper. Supporting Evidence: PMID:28420712 We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. |
| GO:0005794 Golgi apparatus | IDA PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | ACCEPT | Summary: Sec71 localizes to the Golgi in Drosophila sensory neurons, interdependently with Arf1. Reason: Direct localization evidence for the root organelle term; under the organelle policy this is kept beside the trans-Golgi network rows. The Golgi is where Sec71 activates Arf1. Supporting Evidence: PMID:28420712 Arf1 and Sec71 are interdependent for their localizations on Golgi. PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic Golgi apparatus assignment from the UniProt subcellular-location mapping. Reason: The organelle claim holds: Golgi localization is shown experimentally in S2 cells and sensory neurons (PMID:22291037, PMID:28420712). The row stops at the organelle because it derives from an automatic keyword rule; the trans-Golgi sub-compartment is captured by the IDA and IBA trans-Golgi network rows. Supporting Evidence: PMID:28420712 Arf1 and Sec71 are interdependent for their localizations on Golgi. PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0005802 trans-Golgi network | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that BIG-family GEFs, including Sec71, act at the trans-Golgi network. Reason: Matches the experimental localization of Sec71 to the trans-Golgi in S2 cells, where it is recruited by Arl1; fly Sec71 is itself a seed for this node. Supporting Evidence: PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization PMID:22291037 This indicates that Arl1 recruits Sec71 to Golgi membranes, but it appears that Arl1’s effects are augmented by additional interactions elsewhere in the protein. |
| GO:0005802 trans-Golgi network | IDA PMID:22291037 The small G protein Arl1 directs the trans-Golgi-specific ta... | ACCEPT | Summary: Sec71-GFP in S2 cells overlaps the trans-Golgi marker dGolgin245 and is distinct from cis-Golgi dGM130. Reason: Direct full-text-verified localization to the trans-Golgi, where Sec71 acts as an Arf1 GEF. Supporting Evidence: PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0016020 membrane | IEA GO_REF:0000044 | MODIFY | Summary: Generic membrane assignment from the UniProt subcellular-location mapping. Reason: Sec71 has no transmembrane segment; it is a peripheral protein recruited from the cytosol onto trans-Golgi membranes by Arl1-GTP. The membrane claim is true but too general; the supported location is trans-Golgi network membrane. Proposed replacements: trans-Golgi network membrane Supporting Evidence: PMID:22291037 This indicates that Arl1 recruits Sec71 to Golgi membranes, but it appears that Arl1’s effects are augmented by additional interactions elsewhere in the protein. PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic inference of vesicle-mediated transport for the Sec7/BIG/Mon2 family. Reason: True but very broad. For Sec71 the experimental evidence supports a role in post-Golgi secretory transport (Golgi to plasma membrane protein transport, already carried by IGI, and apical/basolateral biosynthetic trafficking in photoreceptors), so the specific descendant is proposed. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008950430 · PTN008950430 UNRESOLVED Node spans Sec7/BIG and related family members; the vesicle-mediated transport claim is sound at family level, but for Sec71 a post-Golgi transport descendant is supported. Proposed replacements: Golgi to plasma membrane protein transport Supporting Evidence: PMID:31649044 Taken together, our observations indicate that Sec71 contributes to the secretion of both apical and basolateral proteins in PRCs, suggesting a defect in Golgi processing (Figure 3E). PMID:28420712 we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). |
| GO:0030867 rough endoplasmic reticulum membrane | NAS PMID:15901661 CrebA regulates secretory activity in the Drosophila salivar... | REMOVE | Summary: NAS from ComplexPortal CPX-26617, which lists fly Sec71 as a subunit of the ER Sec62/Sec63 translocon complex; rough endoplasmic reticulum membrane follows from that membership. Reason: This is a symbol collision with yeast Sec71 (=Sec66), the small single-pass membrane subunit of the Sec63 complex. Drosophila Sec71 is an unrelated soluble BIG1/BIG2-type Sec7-domain Arf1 GEF at the trans-Golgi network, with no transmembrane segment and no Sec66 domain. The cited paper (PMID:15901661) concerns CrebA-dependent expression of secretory pathway genes and gives no evidence that fly Sec71 is in a translocon complex. The row is a non-experimental mapping that is demonstrably wrong. Supporting Evidence: file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md SEC71 is a synonym of yeast SEC66, the Sec63-complex subunit. file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md Drosophila Sec71 (Q9VJW1) is 1653 residues, has no predicted transmembrane segment, and carries the BIG/Sec7-family ARF-GEF architecture file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md ComplexPortal CPX-26617 "SEC62-SEC63 complex" (Drosophila melanogaster) lists three participants: Q9VJW1 Sec71, Q9VS57 Sec63 and Q9VL49 Trp1 PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0031204 post-translational protein targeting to membrane, translocation | NAS PMID:15901661 CrebA regulates secretory activity in the Drosophila salivar... | REMOVE | Summary: NAS from ComplexPortal CPX-26617, which lists fly Sec71 as a subunit of the ER Sec62/Sec63 translocon complex; post-translational protein targeting to membrane, translocation follows from that membership. Reason: This is a symbol collision with yeast Sec71 (=Sec66), the small single-pass membrane subunit of the Sec63 complex. Drosophila Sec71 is an unrelated soluble BIG1/BIG2-type Sec7-domain Arf1 GEF at the trans-Golgi network, with no transmembrane segment and no Sec66 domain. The cited paper (PMID:15901661) concerns CrebA-dependent expression of secretory pathway genes and gives no evidence that fly Sec71 is in a translocon complex. The row is a non-experimental mapping that is demonstrably wrong. Supporting Evidence: file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md SEC71 is a synonym of yeast SEC66, the Sec63-complex subunit. file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md Drosophila Sec71 (Q9VJW1) is 1653 residues, has no predicted transmembrane segment, and carries the BIG/Sec7-family ARF-GEF architecture file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md ComplexPortal CPX-26617 "SEC62-SEC63 complex" (Drosophila melanogaster) lists three participants: Q9VJW1 Sec71, Q9VS57 Sec63 and Q9VL49 Trp1 PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0031207 Sec62/Sec63 complex | NAS PMID:15901661 CrebA regulates secretory activity in the Drosophila salivar... | REMOVE | Summary: NAS from ComplexPortal CPX-26617, which lists fly Sec71 as a subunit of the ER Sec62/Sec63 translocon complex; Sec62/Sec63 complex follows from that membership. Reason: This is a symbol collision with yeast Sec71 (=Sec66), the small single-pass membrane subunit of the Sec63 complex. Drosophila Sec71 is an unrelated soluble BIG1/BIG2-type Sec7-domain Arf1 GEF at the trans-Golgi network, with no transmembrane segment and no Sec66 domain. The cited paper (PMID:15901661) concerns CrebA-dependent expression of secretory pathway genes and gives no evidence that fly Sec71 is in a translocon complex. The row is a non-experimental mapping that is demonstrably wrong. Supporting Evidence: file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md SEC71 is a synonym of yeast SEC66, the Sec63-complex subunit. file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md Drosophila Sec71 (Q9VJW1) is 1653 residues, has no predicted transmembrane segment, and carries the BIG/Sec7-family ARF-GEF architecture file:DROME/Sec71/Sec71-bioinformatics/RESULTS.md ComplexPortal CPX-26617 "SEC62-SEC63 complex" (Drosophila melanogaster) lists three participants: Q9VJW1 Sec71, Q9VS57 Sec63 and Q9VL49 Trp1 PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization |
| GO:0031267 small GTPase binding | IPI PMID:22291037 The small G protein Arl1 directs the trans-Golgi-specific ta... | ACCEPT | Summary: Sec71 binds the Arf-like GTPase Arl1 (FBgn0000115) directly, in a GTP-dependent manner, through its N-terminal region. Reason: Full-text-verified direct binding (purified Sec71 N-terminus on Arl1-GTP liposomes); this interaction recruits Sec71 to trans-Golgi membranes and so is part of how the GEF is targeted. Small GTPase binding is the appropriate term. Supporting Evidence: PMID:22291037 Applying this to Drosophila melanogaster cell extracts revealed a direct interaction between Arl1 and Sec71, the Drosophila ortholog of the trans-Golgi GEFs BIG1/2. PMID:22291037 This indicates that Arl1 recruits Sec71 to Golgi membranes, but it appears that Arl1’s effects are augmented by additional interactions elsewhere in the protein. |
| GO:0032011 ARF protein signal transduction | IC PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | ACCEPT | Summary: Curator inference from the GEF activity that Sec71 takes part in Arf protein signal transduction. Reason: As the exchange factor that loads Arf1 with GTP, Sec71 performs the activating step of the Arf1 cycle, so it does some of the work of this process; reasonable inference from the IDA GEF row. Supporting Evidence: PMID:28420712 We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. |
| GO:0032012 regulation of ARF protein signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the Sec7 domain to regulation of ARF protein signal transduction. Reason: The direction is known: Sec7-domain GEFs activate Arf GTPases, and Sec71 activates Arf1. The unsigned regulation term should be the positive child. Proposed replacements: positive regulation of ARF protein signal transduction Supporting Evidence: PMID:28420712 We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. file:DROME/Sec71/Sec71-uniprot.txt FT DOMAIN 575..765 FT /note="SEC7" FT /evidence="ECO:0000259|PROSITE:PS50190" |
| GO:0043001 Golgi to plasma membrane protein transport | IGI PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | ACCEPT | Summary: Genetic interaction with Arf1 indicates that Sec71 is needed for Golgi to plasma membrane protein transport. Reason: Consistent with the BIG-family role in post-Golgi trafficking and with the requirement for Sec71 in biosynthetic delivery of apical and basolateral membrane proteins in photoreceptors (PMID:31649044). The cached record is abstract-only; the curator saw the full text. Supporting Evidence: PMID:28420712 we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). PMID:31649044 Taken together, our observations indicate that Sec71 contributes to the secretion of both apical and basolateral proteins in PRCs, suggesting a defect in Golgi processing (Figure 3E). |
| GO:0045807 positive regulation of endocytosis | IMP PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | KEEP AS NON CORE | Summary: Loss of Sec71 impairs Rab5-dependent endocytosis of Neuroglian in sensory neurons. Reason: Experimental, but the abstract presents Sec71/Arf1-mediated trafficking as a prerequisite for endocytosis, i.e. an indirect effect of its Golgi function rather than direct participation in endocytosis. Kept as non-core; full text not available to check further. Supporting Evidence: PMID:28420712 we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Perinuclear region of cytoplasm from an ARBA-based UniProt subcellular location. Reason: The assignment rests on an ARBA rule transferring the mammalian BIG1/BIG2 perinuclear (Golgi ribbon) appearance. Drosophila Golgi exists as dispersed stacks, and Sec71 was localized to trans-Golgi puncta, not a perinuclear zone; the informative location is already covered by the Golgi and trans-Golgi network rows. Supporting Evidence: PMID:22291037 Examination of S2 cells expressing GFP-tagged Sec71 revealed that it was associated with the Golgi and overlapped with a trans-Golgi marker (dGolgin245) while being clearly distinct from a cis-Golgi marker (dGM130), indicating a trans-Golgi localization PMID:33262309 These results indicate that Sec71 is the sole BFA target for BFA body formation and controls Golgi stack separation. |
| GO:1904801 positive regulation of neuron remodeling | IGI PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | KEEP AS NON CORE | Summary: Sec71 is required for dendrite pruning of ddaC sensory neurons during metamorphosis (genetic interaction with FB:FBgn0028538). Reason: Well-supported developmental phenotype, but it reflects the general need for Sec71/Arf1-dependent Golgi trafficking (needed for endocytic removal of Neuroglian) in pruning neurons; a pleiotropic, non-core process for a housekeeping trans-Golgi Arf GEF. Supporting Evidence: PMID:28420712 Like Arf1, Sec71 is also important for dendrite pruning, but not for apoptosis, of sensory neurons. PMID:28420712 we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). |
| GO:1904801 positive regulation of neuron remodeling | IGI PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | KEEP AS NON CORE | Summary: Sec71 is required for dendrite pruning of ddaC sensory neurons during metamorphosis (genetic interaction with FB:FBgn0264975). Reason: Well-supported developmental phenotype, but it reflects the general need for Sec71/Arf1-dependent Golgi trafficking (needed for endocytic removal of Neuroglian) in pruning neurons; a pleiotropic, non-core process for a housekeeping trans-Golgi Arf GEF. Supporting Evidence: PMID:28420712 Like Arf1, Sec71 is also important for dendrite pruning, but not for apoptosis, of sensory neurons. PMID:28420712 we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). |
| GO:1904801 positive regulation of neuron remodeling | IMP PMID:28420712 Sec71 functions as a GEF for the small GTPase Arf1 to govern... | KEEP AS NON CORE | Summary: Sec71 is required for dendrite pruning of ddaC sensory neurons during metamorphosis. Reason: Well-supported developmental phenotype, but it reflects the general need for Sec71/Arf1-dependent Golgi trafficking (needed for endocytic removal of Neuroglian) in pruning neurons; a pleiotropic, non-core process for a housekeeping trans-Golgi Arf GEF. Supporting Evidence: PMID:28420712 Like Arf1, Sec71 is also important for dendrite pruning, but not for apoptosis, of sensory neurons. PMID:28420712 we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). |
Loading supporting content…
Download this section (compressed HTML)Q: Does Sec71 also activate the class II Arf (Arf102F) and Arl1 itself, or only Arf1 (Arf79F), at the trans-Golgi?
Q: Should ComplexPortal CPX-26617 replace Q9VJW1 with a true fly Sec66 ortholog, and does Drosophila have one?
Q: Does Arf1-GTP recognise Sec71 as an effector, forming a positive-feedback loop that stabilises its trans-Golgi recruitment, as proposed for BIG1?
Experiment: Measure Sec71 Sec7-domain catalysed nucleotide exchange on purified myristoylated Arf79F, Arf102F and Arl1 on liposomes, with and without Arl1-GTP, to define substrate specificity and the effect of membrane recruitment on activity.
Experiment: Use the genome-edited BFA-resistant Sec71 allele in vivo to separate Sec71-dependent from other BFA-sensitive (Gartenzwerg/GBF) functions in neuronal dendrite pruning and photoreceptor trafficking.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)