Git

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045202 synapse	IBA GO_REF:0000033	ACCEPT	Summary: Git localizes to presynaptic active zones and is involved in synaptic vesicle recycling. IBA annotation is phylogenetically sound and supported by direct evidence in Drosophila from PMID:24882013. Reason: The IBA annotation reflects conserved synaptic localization across the GIT family. Direct Drosophila evidence shows dGIT at presynaptic active zones (IDA from PMID:24882013) and involvement in synaptic vesicle recycling (IMP from PMID:24882013). The synapse annotation appropriately captures this localization. Supporting Evidence: PMID:24882013 GIT1 and its D. melanogaster ortholog, dGIT, are shown to directly associate with the endocytic adaptor stonin 2/stoned B. In Drosophila dgit mutants, stoned B and synaptotagmin levels are reduced and stoned B is partially mislocalized. file:DROME/Git/Git-deep-research-falcon.md model: Edison Scientific Literature
GO:0007420 brain development	IBA GO_REF:0000033	ACCEPT	Summary: Git is required for brain development in Drosophila, with mutants showing decreased central brain size and abnormal mushroom body morphology. IBA annotation is well-supported by direct experimental evidence in fly. Reason: The IBA annotation is strongly supported by direct Drosophila evidence (IMP from PMID:25792865). dGit mutants show severely decreased central brain size and defects in mushroom body development. Supporting Evidence: PMID:25792865 dGitex21C Drosophila mutants also exhibited severely decreased central brain size
GO:0005096 GTPase activator activity	IBA GO_REF:0000033	ACCEPT	Summary: Git contains a well-characterized ARF-GAP domain and functions as a GTPase activating protein for ARF family members. This is a core molecular function supported by domain architecture and genetic/interaction data. Reason: GTPase activator activity is the primary enzymatic function of Git. The protein contains an ArfGAP domain (aa 32-168) with a C4-type zinc finger, and genetic evidence places Git upstream of Arf79F in Hippo signaling (PMID:38240353). This represents a core function. Supporting Evidence: PMID:18996366 GIT1-like proteins are GTPase-activating proteins (GAPs) for Arfs and interact with a variety of signaling molecules to function as integrators of pathways controlling cytoskeletal organization and cell motility.
GO:0008277 regulation of G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: While Git was originally named for "G protein-coupled receptor kinase interacting protein", evidence for direct GPCR signaling regulation in Drosophila is limited. The IBA annotation likely derives from mammalian orthologs where this connection is better established. Reason: The GIT family was initially identified through interaction with G-protein coupled receptor kinases in mammals, but direct evidence for this role in Drosophila Git is lacking. The primary functions of dGit appear to be in adhesion-cytoskeletal signaling, synaptic function, and Hippo pathway regulation. Keep as non-core pending additional Drosophila-specific evidence. Supporting Evidence: PMID:18996366 GIT1-like proteins are GTPase-activating proteins (GAPs) for Arfs and interact with a variety of signaling molecules to function as integrators of pathways controlling cytoskeletal organization and cell motility.
GO:0031267 small GTPase binding	IBA GO_REF:0000033	ACCEPT	Summary: Git binds to small GTPases including Arf79F (ARF1 ortholog) to regulate their activity. This is consistent with Git's ARF-GAP function. Reason: As an ARF-GAP, Git necessarily binds to ARF family small GTPases as substrates. Proximity ligation assays in PMID:38240353 demonstrate Git-Arf79F interaction in larval tissues. This binding is essential for Git's GAP activity. Supporting Evidence: PMID:38240353 Git, which also bind to the Hippo protein (Hpo) and are involved in the activation of the Hippo pathway. Additionally, we show that the ADP ribosylation factor Arf79F (Arf1), which is a Hpo interactor
GO:0032012 regulation of ARF protein signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: Git regulates ARF protein signaling through its GAP activity on Arf79F. This is a core function supported by genetic and physical interaction data. Reason: Git functions as an ARF-GAP that restrains Arf79F activity. Genetic evidence from PMID:38240353 shows that Arf79F knockdown rescues Hippo pathway defects in lgl mutants, placing Git in a pathway that negatively regulates Arf79F to activate Hippo signaling. Supporting Evidence: PMID:38240353 Lgl acts via Vap33 to activate the Hippo pathway by a dual mechanism: (1) through interaction with RtGEF, Git and Arf79F
GO:0036465 synaptic vesicle recycling	IBA GO_REF:0000033	ACCEPT	Summary: Git is required for proper synaptic vesicle recycling at the neuromuscular junction. IBA annotation is directly supported by experimental evidence in Drosophila. Reason: The IBA annotation is well-supported by IMP evidence from PMID:24882013 showing that dgit mutants have morphological and functional defects in synaptic vesicle recycling. Supporting Evidence: PMID:24882013 Moreover, dgit mutants show morphological and functional defects in SV recycling. These data establish a presynaptic role for GIT in SV recycling and suggest a connection between the AZ cytomatrix and the endocytic machinery.
GO:0000922 spindle pole	IEA GO_REF:0000044	UNDECIDED	Summary: Spindle pole localization is inferred from mammalian ortholog data in UniProt. Direct evidence for spindle pole localization of dGit in Drosophila is not available. Reason: This IEA annotation is based on mammalian ortholog localization data. While GIT family proteins may localize to spindle poles in some contexts, direct Drosophila evidence is lacking. The primary characterized localizations for dGit are cytoplasm, cell leading edge, focal adhesion-like structures, and presynaptic active zones.
GO:0005096 GTPase activator activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation based on InterPro domain (ArfGAP) correctly captures Git's enzymatic function. Duplicates the IBA annotation but with different evidence. Reason: Git contains a well-defined ArfGAP domain (IPR001164) with the characteristic zinc finger. The IEA annotation from domain mapping is correct and complements the IBA annotation. Supporting Evidence: PMID:12618308 I surveyed Drosophila and human sequence databases for genes predicting proteins related to GAPs for Ras superfamily members
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Cytoplasmic localization is supported by direct IDA evidence in Drosophila (PMID:18996366). The IEA annotation is consistent with experimental data. Reason: The IEA annotation is consistent with direct experimental evidence from PMID:18996366 showing cytoplasmic localization of dGit protein in embryonic muscle syncytia. Supporting Evidence: PMID:18996366 The dGIT protein is concentrated at the termini of growing myotubes and localizes to muscle attachment sites in late stage embryos.
GO:0005813 centrosome	IEA GO_REF:0000044	UNDECIDED	Summary: Centrosome localization is inferred from mammalian ortholog data. Direct Drosophila evidence for centrosome localization is not available. Reason: This IEA annotation is based on mammalian ortholog data. Direct evidence for centrosome localization of dGit in Drosophila has not been reported. The characterized Drosophila localizations are cytoplasm, leading edge, focal adhesions, and presynaptic zones.
GO:0005925 focal adhesion	IEA GO_REF:0000044	ACCEPT	Summary: Git localizes to focal adhesion-like structures in Drosophila epithelia via its paxillin-binding domain. IEA annotation is well-supported by Drosophila studies. Reason: Although annotated via IEA, focal adhesion localization is strongly supported by primary Drosophila literature. Git's C-terminal paxillin-binding domain mediates targeting to basal focal adhesion-like structures in follicular epithelium. Supporting Evidence: PMID:18996366 The dGIT protein is concentrated at the termini of growing myotubes and localizes to muscle attachment sites in late stage embryos.
GO:0007420 brain development	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro mapping. Brain development role is well-established by direct experimental evidence in Drosophila. Reason: The IEA annotation correctly captures Git's role in brain development, which is directly demonstrated in Drosophila by IMP evidence (PMID:25792865) showing reduced brain size and mushroom body defects in dGit mutants. Supporting Evidence: PMID:25792865 dGitex21C Drosophila mutants also exhibited severely decreased central brain size
GO:0008270 zinc ion binding	IEA GO_REF:0000043	ACCEPT	Summary: Git contains a C4-type zinc finger (aa 49-72) within its ArfGAP domain that coordinates zinc ions. This is structurally well-supported. Reason: The zinc ion binding annotation correctly reflects the presence of a C4-type zinc finger within the ArfGAP domain. This zinc finger is essential for the structural integrity and function of the GAP domain.
GO:0030027 lamellipodium	IEA GO_REF:0000044	ACCEPT	Summary: Lamellipodium localization is inferred from mammalian ortholog data. In Drosophila, Git localizes to leading edges of cells, which includes lamellipodia-like structures. Reason: While annotated via IEA, the localization is consistent with direct Drosophila evidence showing Git at "the leading edge of growing myotubes" (PMID:18996366). Cell leading edge structures include lamellipodia. Supporting Evidence: PMID:18996366 The dGIT protein is concentrated at the termini of growing myotubes and localizes to muscle attachment sites in late stage embryos
GO:0032012 regulation of ARF protein signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro correctly captures Git's role in ARF signaling regulation. Git regulates Arf79F in the Hippo pathway. Reason: The IEA annotation is correct and consistent with the IBA annotation and experimental data showing Git's function in regulating ARF signaling, particularly Arf79F in the context of Hippo pathway activation. Supporting Evidence: PMID:38240353 Lgl acts via Vap33 to activate the Hippo pathway by a dual mechanism: (1) through interaction with RtGEF, Git and Arf79F
GO:0045202 synapse	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for synapse localization is consistent with direct experimental evidence showing Git at presynaptic active zones in Drosophila. Reason: The IEA annotation is well-supported by IDA evidence from PMID:24882013 showing dGit at the presynaptic active zone. Git functions in synaptic vesicle recycling at the synapse. Supporting Evidence: PMID:24882013 Here, we identify the scaffold G protein coupled receptor kinase 2 interacting (GIT) protein as a component of the AZ-associated cytomatrix
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: Metal ion binding is a parent term of zinc ion binding. Git binds zinc through its C4-type zinc finger. Reason: This is a correct parent annotation to zinc ion binding. Git's ArfGAP domain contains a zinc-coordinating C4-type zinc finger motif.
GO:0005515 protein binding	IPI PMID:14605208 A protein interaction map of Drosophila melanogaster.	MODIFY	Summary: High-throughput two-hybrid screen identified Git interactions with RtGEF (dPix). While protein binding is uninformative, the interaction with RtGEF is functionally significant for Git's scaffold function. Reason: The protein binding (GO:0005515) term is uninformative. Git functions as a molecular adaptor that specifically binds dPix/RtGEF and PAK. The more informative annotation GO:0060090 (molecular adaptor activity) is already captured with IMP evidence from PMID:25484297. Proposed replacements: molecular adaptor activity Supporting Evidence: PMID:14605208 A two-hybrid-based protein-interaction map of the fly proteome...The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components.
GO:0005515 protein binding	IPI PMID:38944040 Next-generation Drosophila protein interactome map and its f...	MODIFY	Summary: Next-generation protein interactome study confirming Git-RtGEF interaction. While the specific interaction is meaningful, protein binding is uninformative. Reason: The protein binding annotation is too general to be informative. Git's key function is as a scaffold/adaptor protein that brings together specific partners (dPix, PAK, Hpo, Arf79F). The interaction with RtGEF supports Git's molecular adaptor function. Proposed replacements: molecular adaptor activity Supporting Evidence: PMID:38944040 Epub 2024 Jun 28. Next-generation Drosophila protein interactome map and its functional implications.
GO:0035332 positive regulation of hippo signaling	IGI PMID:38240353 The Drosophila tumour suppressor Lgl and Vap33 activate the ...	ACCEPT	Summary: Git is part of the Vap33-RtGEF-Git-Arf79F module that activates Hippo signaling. Genetic interaction data shows Git knockdown rescues Hippo pathway defects in V-ATPase mutants. Reason: Well-supported by genetic evidence from PMID:38240353. Vap33 physically interacts with RtGEF and Git, which bind to Hpo. Git knockdown rescues reduced Diap1 expression in Vha68-2 mutant clones, demonstrating Git's role in Hippo pathway activation. Supporting Evidence: PMID:38240353 Git knockdown rescues the reduced Hippo pathway target gene expression in Vha68-2 mutant clones
GO:0007420 brain development	IMP PMID:25792865 A Critical Role of GIT1 in Vertebrate and Invertebrate Brain...	ACCEPT	Summary: dGit mutants show decreased central brain size and abnormal mushroom body development, directly demonstrating Git's role in brain development. Reason: Direct experimental evidence from mutant analysis. dGitex21C mutants show severely decreased central brain size and defects in mushroom body alpha and beta lobe development. Supporting Evidence: PMID:25792865 Consistent with Git1-/- mice, dGitex21C Drosophila mutants also exhibited severely decreased central brain size
GO:0046621 negative regulation of organ growth	IGI PMID:25484297 The GTPase regulatory proteins Pix and Git control tissue gr...	ACCEPT	Summary: Git and Pix control tissue growth via the Hippo pathway. Git promotes Hpo activation, which restricts tissue growth. This is a core function linking Git to growth control. Reason: Strong genetic evidence from PMID:25484297. Git and Pix form an oligomeric scaffold that promotes Hpo dimerization and autophosphorylation, thereby activating Hippo signaling and restricting organ growth. Supporting Evidence: PMID:25484297 We show that Pix and Git regulate Hippo-pathway-dependent tissue growth in D. melanogaster and that they do this in parallel to the known upstream regulator Fat cadherin.
GO:0035332 positive regulation of hippo signaling	IGI PMID:25484297 The GTPase regulatory proteins Pix and Git control tissue gr...	ACCEPT	Summary: Git and Pix promote Hpo kinase activation by facilitating Hpo dimerization and autophosphorylation. This is a core signaling function. Reason: Well-characterized mechanism from PMID:25484297. Pix and Git act as scaffold proteins to promote Hpo dimerization and autophosphorylation of its activation loop, thereby activating the Hippo pathway. Supporting Evidence: PMID:25484297 Pix and Git influence activity of the Hpo kinase by acting as a scaffold complex, rather than enzymes, and promote Hpo dimerization and autophosphorylation of Hpo's activation loop.
GO:0060090 molecular adaptor activity	IMP PMID:25484297 The GTPase regulatory proteins Pix and Git control tissue gr...	ACCEPT	Summary: Git functions as a molecular adaptor/scaffold that brings together dPix, PAK, and Hpo to facilitate signaling. This is a core molecular function. Reason: Well-supported core function. Git acts as a scaffold rather than an enzyme in promoting Hippo pathway activation. Git's adaptor function is also demonstrated in its role bringing together dPix and PAK at adhesion sites. Supporting Evidence: PMID:25484297 Pix and Git influence activity of the Hpo kinase by acting as a scaffold complex, rather than enzymes
GO:1905383 protein localization to presynapse	IMP PMID:24882013 A presynaptic role for the cytomatrix protein GIT in synapti...	ACCEPT	Summary: Git is required for proper localization of synaptic proteins (stoned B, synaptotagmin) to the presynapse. dgit mutants show reduced and mislocalized stoned B. Reason: Direct evidence from PMID:24882013. In dgit mutants, stoned B levels are reduced and the protein is partially mislocalized from the presynaptic compartment. Supporting Evidence: PMID:24882013 In Drosophila dgit mutants, stoned B and synaptotagmin levels are reduced and stoned B is partially mislocalized.
GO:0005515 protein binding	IPI PMID:24882013 A presynaptic role for the cytomatrix protein GIT in synapti...	MODIFY	Summary: Git interacts with stonin 2/stoned B at the presynapse. While the specific interaction is meaningful for synaptic function, protein binding is uninformative. Reason: The protein binding term is too general. The functionally relevant annotation is the specific interaction with stoned B that facilitates synaptic vesicle endocytosis. This interaction supports Git's role as a presynaptic scaffold. Proposed replacements: molecular adaptor activity Supporting Evidence: PMID:24882013 GIT1 and its D. melanogaster ortholog, dGIT, are shown to directly associate with the endocytic adaptor stonin 2/stoned B.
GO:0048786 presynaptic active zone	IDA PMID:24882013 A presynaptic role for the cytomatrix protein GIT in synapti...	ACCEPT	Summary: Direct localization evidence showing Git at the presynaptic active zone cytomatrix. This is a well-supported subcellular localization. Reason: Direct assay evidence from PMID:24882013 demonstrating Git localization to the active zone-associated cytomatrix. Supporting Evidence: PMID:24882013 Here, we identify the scaffold G protein coupled receptor kinase 2 interacting (GIT) protein as a component of the AZ-associated cytomatrix
GO:0048788 cytoskeleton of presynaptic active zone	IDA PMID:24882013 A presynaptic role for the cytomatrix protein GIT in synapti...	ACCEPT	Summary: Git colocalizes with the cytoskeletal components of the presynaptic active zone. The annotation uses "colocalizes_with" qualifier, appropriately reflecting the colocalization rather than integral association. Reason: Direct evidence from PMID:24882013 showing Git association with the presynaptic cytomatrix. Git's scaffold function at the active zone involves the cytoskeletal framework. Supporting Evidence: PMID:24882013 Here, we identify the scaffold G protein coupled receptor kinase 2 interacting (GIT) protein as a component of the AZ-associated cytomatrix
GO:0099504 synaptic vesicle cycle	IMP PMID:24882013 A presynaptic role for the cytomatrix protein GIT in synapti...	ACCEPT	Summary: Git is required for normal synaptic vesicle cycling. dgit mutants show defects in both exo- and endocytic aspects of the vesicle cycle. Reason: Direct evidence from mutant analysis in PMID:24882013 showing morphological and functional defects in synaptic vesicle cycling in dgit mutants. Supporting Evidence: PMID:24882013 dgit mutants show morphological and functional defects in SV recycling. These data establish a presynaptic role for GIT in SV recycling
GO:0036465 synaptic vesicle recycling	IMP PMID:24882013 A presynaptic role for the cytomatrix protein GIT in synapti...	ACCEPT	Summary: Git is specifically required for synaptic vesicle recycling, the endocytic retrieval phase of the vesicle cycle. This is a core synaptic function. Reason: Direct evidence from PMID:24882013. Git associates with the endocytic adaptor stoned B and is required for proper SV recycling. This is a core presynaptic function. Supporting Evidence: PMID:24882013 dgit mutants show morphological and functional defects in SV recycling. These data establish a presynaptic role for GIT in SV recycling and suggest a connection between the AZ cytomatrix and the endocytic machinery.
GO:0016319 mushroom body development	IMP PMID:25792865 A Critical Role of GIT1 in Vertebrate and Invertebrate Brain...	ACCEPT	Summary: dGit mutants show defects in mushroom body development, with abnormal alpha and beta lobe morphology. This is a well-supported developmental function. Reason: Direct mutant analysis in PMID:25792865 shows dGitex21C mutants have abnormal mushroom body development, with the most common defect being early termination of one alpha-lobe (58%). Supporting Evidence: PMID:25792865 was significantly affected by the deletion of dGit. (Fig. 4C). However, the penetrance of this impaired mushroom body development was incomplete
GO:0005096 GTPase activator activity	ISM PMID:12618308 GAPs galore! A survey of putative Ras superfamily GTPase act...	ACCEPT	Summary: ISM annotation based on computational survey of GAP domains. Git is correctly identified as an ARF-GAP based on sequence analysis. Reason: The computational survey in PMID:12618308 correctly identified Git (CG16728) as encoding an ARF-GAP based on domain analysis. This is consistent with the experimentally validated function. Supporting Evidence: PMID:12618308 To facilitate genetic analysis, I surveyed Drosophila and human sequence databases for genes predicting proteins related to GAPs for Ras superfamily members
GO:0005737 cytoplasm	IDA PMID:18996366 The Drosophila homologue of Arf-GAP GIT1, dGIT, is required ...	ACCEPT	Summary: Direct localization evidence showing Git in the cytoplasm of embryonic muscle cells. This is a core localization. Reason: Direct assay evidence from PMID:18996366 showing dGit protein in the cytoplasm of embryonic muscle syncytia. Supporting Evidence: PMID:18996366 The dGIT protein is concentrated at the termini of growing myotubes and localizes to muscle attachment sites in late stage embryos
GO:0007525 somatic muscle development	IMP PMID:18996366 The Drosophila homologue of Arf-GAP GIT1, dGIT, is required ...	ACCEPT	Summary: dGit is required for proper muscle morphogenesis and myotube guidance during embryogenesis. dgit mutants show muscle patterning defects. Reason: Core developmental function supported by mutant analysis in PMID:18996366. dgit mutant embryos show muscle patterning defects including aberrant targeting in subsets of muscles, particularly ventral oblique muscles VO5 and VO6. Supporting Evidence: PMID:18996366 dgit mutant embryos show muscle patterning defects and aberrant targeting in subsets of their muscles
GO:0031252 cell leading edge	IDA PMID:18996366 The Drosophila homologue of Arf-GAP GIT1, dGIT, is required ...	ACCEPT	Summary: Git localizes to the leading edge of growing myotubes during muscle development. This is a core localization related to Git's role in cell motility and morphogenesis. Reason: Direct localization evidence from PMID:18996366 showing Git enrichment at the leading edge of growing myotubes, particularly at the base of membrane protrusions. Supporting Evidence: PMID:18996366 The dGIT protein is concentrated at the termini of growing myotubes
GO:0035591 signaling adaptor activity	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations.
GO:0110020 regulation of actomyosin structure organization	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations.
TEMP:dPix-Git-PAK_complex dPix-Git-PAK complex	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function complex term not present in existing_annotations.

Gene Description

Existing Annotations Review

Core Functions

Git stimulates GTP hydrolysis on Arf79F (ARF1 ortholog), inactivating ARF signaling to promote Hippo pathway activation and regulate membrane trafficking.

Git acts as a signaling adaptor at focal adhesion-like structures, scaffolding the dPix-Git-PAK complex via its paxillin-binding domain to limit myosin II activation and maintain epithelial organization during morphogenesis.

Git scaffolds Hpo dimerization and autophosphorylation as part of the Lgl-Vap33-RtGEF-Git-Arf79F module, activating Hippo signaling to restrict organ growth.

Git localizes to the presynaptic active zone cytomatrix and associates with stoned B to facilitate synaptic vesicle recycling at the neuromuscular junction.

References

Deep Research

Falcon

📚 Additional Documentation

Bioreason Rl Predictions

Bioreason Rl Review

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