---
id: Q95RG8
gene_symbol: Git
aliases: [dGIT, arfgap2, CG16728]
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: ARF GTPase-activating protein that functions as a multidomain scaffold
  protein, forming a conserved dPix-Git-PAK complex at focal adhesion-like sites.
  Git stimulates GTP hydrolysis on ARF family GTPases (particularly Arf79F, the fly
  ARF1 ortholog), acts as a molecular adaptor targeting the complex basally via its
  paxillin-binding domain, and regulates actomyosin dynamics, synaptic vesicle recycling,
  and Hippo pathway signaling.
existing_annotations:
  - term:
      id: GO:0045202
      label: synapse
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: 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.
        - reference_id: file:DROME/git/git-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0007420
      label: brain development
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25792865
          supporting_text: dGitex21C Drosophila mutants also exhibited severely decreased
            central brain size
  - term:
      id: GO:0005096
      label: GTPase activator activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: 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.
  - term:
      id: GO:0008277
      label: regulation of G protein-coupled receptor signaling pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: 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.
  - term:
      id: GO:0031267
      label: small GTPase binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Git binds to small GTPases including Arf79F (ARF1 ortholog) to regulate
        their activity. This is consistent with Git's ARF-GAP function.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:38240353
          supporting_text: 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
  - term:
      id: GO:0032012
      label: regulation of ARF protein signal transduction
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Git regulates ARF protein signaling through its GAP activity on Arf79F.
        This is a core function supported by genetic and physical interaction data.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:38240353
          supporting_text: 'Lgl acts via Vap33 to activate the Hippo pathway by a
            dual mechanism: (1) through interaction with RtGEF, Git and Arf79F'
  - term:
      id: GO:0036465
      label: synaptic vesicle recycling
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Git is required for proper synaptic vesicle recycling at the neuromuscular
        junction. IBA annotation is directly supported by experimental evidence in
        Drosophila.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: 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.
  - term:
      id: GO:0000922
      label: spindle pole
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: UNDECIDED
      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.
  - term:
      id: GO:0005096
      label: GTPase activator activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation based on InterPro domain (ArfGAP) correctly captures
        Git's enzymatic function. Duplicates the IBA annotation but with different
        evidence.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12618308
          supporting_text: I surveyed Drosophila and human sequence databases for
            genes predicting proteins related to GAPs for Ras superfamily members
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Cytoplasmic localization is supported by direct IDA evidence in Drosophila
        (PMID:18996366). The IEA annotation is consistent with experimental data.
      action: ACCEPT
      reason: The IEA annotation is consistent with direct experimental evidence from
        PMID:18996366 showing cytoplasmic localization of dGit protein in embryonic
        muscle syncytia.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: The dGIT protein is concentrated at the termini of growing
            myotubes and localizes to muscle attachment sites in late stage embryos.
  - term:
      id: GO:0005813
      label: centrosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Centrosome localization is inferred from mammalian ortholog data. Direct
        Drosophila evidence for centrosome localization is not available.
      action: UNDECIDED
      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.
  - term:
      id: GO:0005925
      label: focal adhesion
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Git localizes to focal adhesion-like structures in Drosophila epithelia
        via its paxillin-binding domain. IEA annotation is well-supported by Drosophila
        studies.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: The dGIT protein is concentrated at the termini of growing
            myotubes and localizes to muscle attachment sites in late stage embryos.
  - term:
      id: GO:0007420
      label: brain development
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: IEA annotation from InterPro mapping. Brain development role is well-established
        by direct experimental evidence in Drosophila.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25792865
          supporting_text: dGitex21C Drosophila mutants also exhibited severely decreased
            central brain size
  - term:
      id: GO:0008270
      label: zinc ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Git contains a C4-type zinc finger (aa 49-72) within its ArfGAP domain
        that coordinates zinc ions. This is structurally well-supported.
      action: ACCEPT
      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.
  - term:
      id: GO:0030027
      label: lamellipodium
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Lamellipodium localization is inferred from mammalian ortholog data.
        In Drosophila, Git localizes to leading edges of cells, which includes lamellipodia-like
        structures.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: The dGIT protein is concentrated at the termini of growing
            myotubes and localizes to muscle attachment sites in late stage embryos
  - term:
      id: GO:0032012
      label: regulation of ARF protein signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: IEA annotation from InterPro correctly captures Git's role in ARF signaling
        regulation. Git regulates Arf79F in the Hippo pathway.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:38240353
          supporting_text: 'Lgl acts via Vap33 to activate the Hippo pathway by a
            dual mechanism: (1) through interaction with RtGEF, Git and Arf79F'
  - term:
      id: GO:0045202
      label: synapse
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: IEA annotation for synapse localization is consistent with direct experimental
        evidence showing Git at presynaptic active zones in Drosophila.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: Here, we identify the scaffold G protein coupled receptor
            kinase 2 interacting (GIT) protein as a component of the AZ-associated
            cytomatrix
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Metal ion binding is a parent term of zinc ion binding. Git binds zinc
        through its C4-type zinc finger.
      action: ACCEPT
      reason: This is a correct parent annotation to zinc ion binding. Git's ArfGAP
        domain contains a zinc-coordinating C4-type zinc finger motif.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14605208
    review:
      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.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0060090
          label: molecular adaptor activity
      supported_by:
        - reference_id: PMID:14605208
          supporting_text: A two-hybrid-based protein-interaction map of the fly proteome...The
            network recapitulated known pathways, extended pathways, and uncovered
            previously unknown pathway components.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:38944040
    review:
      summary: Next-generation protein interactome study confirming Git-RtGEF interaction.
        While the specific interaction is meaningful, protein binding is uninformative.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0060090
          label: molecular adaptor activity
      supported_by:
        - reference_id: PMID:38944040
          supporting_text: Epub 2024 Jun 28. Next-generation Drosophila protein interactome
            map and its functional implications.
  - term:
      id: GO:0035332
      label: positive regulation of hippo signaling
    evidence_type: IGI
    original_reference_id: PMID:38240353
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:38240353
          supporting_text: Git knockdown rescues the reduced Hippo pathway target
            gene expression in Vha68-2 mutant clones
  - term:
      id: GO:0007420
      label: brain development
    evidence_type: IMP
    original_reference_id: PMID:25792865
    review:
      summary: dGit mutants show decreased central brain size and abnormal mushroom
        body development, directly demonstrating Git's role in brain development.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25792865
          supporting_text: Consistent with Git1-/- mice, dGitex21C Drosophila mutants
            also exhibited severely decreased central brain size
  - term:
      id: GO:0046621
      label: negative regulation of organ growth
    evidence_type: IGI
    original_reference_id: PMID:25484297
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25484297
          supporting_text: 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.
  - term:
      id: GO:0035332
      label: positive regulation of hippo signaling
    evidence_type: IGI
    original_reference_id: PMID:25484297
    review:
      summary: Git and Pix promote Hpo kinase activation by facilitating Hpo dimerization
        and autophosphorylation. This is a core signaling function.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25484297
          supporting_text: 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.
  - term:
      id: GO:0060090
      label: molecular adaptor activity
    evidence_type: IMP
    original_reference_id: PMID:25484297
    review:
      summary: Git functions as a molecular adaptor/scaffold that brings together
        dPix, PAK, and Hpo to facilitate signaling. This is a core molecular function.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:25484297
          supporting_text: Pix and Git influence activity of the Hpo kinase by acting
            as a scaffold complex, rather than enzymes
  - term:
      id: GO:1905383
      label: protein localization to presynapse
    evidence_type: IMP
    original_reference_id: PMID:24882013
    review:
      summary: Git is required for proper localization of synaptic proteins (stoned
        B, synaptotagmin) to the presynapse. dgit mutants show reduced and mislocalized
        stoned B.
      action: ACCEPT
      reason: Direct evidence from PMID:24882013. In dgit mutants, stoned B levels
        are reduced and the protein is partially mislocalized from the presynaptic
        compartment.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: In Drosophila dgit mutants, stoned B and synaptotagmin
            levels are reduced and stoned B is partially mislocalized.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24882013
    review:
      summary: Git interacts with stonin 2/stoned B at the presynapse. While the specific
        interaction is meaningful for synaptic function, protein binding is uninformative.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0060090
          label: molecular adaptor activity
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: GIT1 and its D. melanogaster ortholog, dGIT, are shown
            to directly associate with the endocytic adaptor stonin 2/stoned B.
  - term:
      id: GO:0048786
      label: presynaptic active zone
    evidence_type: IDA
    original_reference_id: PMID:24882013
    review:
      summary: Direct localization evidence showing Git at the presynaptic active
        zone cytomatrix. This is a well-supported subcellular localization.
      action: ACCEPT
      reason: Direct assay evidence from PMID:24882013 demonstrating Git localization
        to the active zone-associated cytomatrix.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: Here, we identify the scaffold G protein coupled receptor
            kinase 2 interacting (GIT) protein as a component of the AZ-associated
            cytomatrix
  - term:
      id: GO:0048788
      label: cytoskeleton of presynaptic active zone
    evidence_type: IDA
    original_reference_id: PMID:24882013
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: Here, we identify the scaffold G protein coupled receptor
            kinase 2 interacting (GIT) protein as a component of the AZ-associated
            cytomatrix
  - term:
      id: GO:0099504
      label: synaptic vesicle cycle
    evidence_type: IMP
    original_reference_id: PMID:24882013
    review:
      summary: Git is required for normal synaptic vesicle cycling. dgit mutants show
        defects in both exo- and endocytic aspects of the vesicle cycle.
      action: ACCEPT
      reason: Direct evidence from mutant analysis in PMID:24882013 showing morphological
        and functional defects in synaptic vesicle cycling in dgit mutants.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: dgit mutants show morphological and functional defects
            in SV recycling. These data establish a presynaptic role for GIT in SV
            recycling
  - term:
      id: GO:0036465
      label: synaptic vesicle recycling
    evidence_type: IMP
    original_reference_id: PMID:24882013
    review:
      summary: Git is specifically required for synaptic vesicle recycling, the endocytic
        retrieval phase of the vesicle cycle. This is a core synaptic function.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:24882013
          supporting_text: 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.
  - term:
      id: GO:0016319
      label: mushroom body development
    evidence_type: IMP
    original_reference_id: PMID:25792865
    review:
      summary: dGit mutants show defects in mushroom body development, with abnormal
        alpha and beta lobe morphology. This is a well-supported developmental function.
      action: ACCEPT
      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%).
      supported_by:
        - reference_id: PMID:25792865
          supporting_text: was significantly affected by the deletion of dGit. (Fig.
            4C). However, the penetrance of this impaired mushroom body development
            was incomplete
  - term:
      id: GO:0005096
      label: GTPase activator activity
    evidence_type: ISM
    original_reference_id: PMID:12618308
    review:
      summary: ISM annotation based on computational survey of GAP domains. Git is
        correctly identified as an ARF-GAP based on sequence analysis.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12618308
          supporting_text: To facilitate genetic analysis, I surveyed Drosophila and
            human sequence databases for genes predicting proteins related to GAPs
            for Ras superfamily members
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:18996366
    review:
      summary: Direct localization evidence showing Git in the cytoplasm of embryonic
        muscle cells. This is a core localization.
      action: ACCEPT
      reason: Direct assay evidence from PMID:18996366 showing dGit protein in the
        cytoplasm of embryonic muscle syncytia.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: The dGIT protein is concentrated at the termini of growing
            myotubes and localizes to muscle attachment sites in late stage embryos
  - term:
      id: GO:0007525
      label: somatic muscle development
    evidence_type: IMP
    original_reference_id: PMID:18996366
    review:
      summary: dGit is required for proper muscle morphogenesis and myotube guidance
        during embryogenesis. dgit mutants show muscle patterning defects.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: dgit mutant embryos show muscle patterning defects and
            aberrant targeting in subsets of their muscles
  - term:
      id: GO:0031252
      label: cell leading edge
    evidence_type: IDA
    original_reference_id: PMID:18996366
    review:
      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.
      action: ACCEPT
      reason: Direct localization evidence from PMID:18996366 showing Git enrichment
        at the leading edge of growing myotubes, particularly at the base of membrane
        protrusions.
      supported_by:
        - reference_id: PMID:18996366
          supporting_text: The dGIT protein is concentrated at the termini of growing
            myotubes
  - term:
      id: GO:0035591
      label: signaling adaptor activity
    evidence_type: NAS
    review:
      summary: Added to align core_functions with existing annotations.
      action: NEW
      reason: Core function term not present in existing_annotations.
  - term:
      id: GO:0110020
      label: regulation of actomyosin structure organization
    evidence_type: NAS
    review:
      summary: Added to align core_functions with existing annotations.
      action: NEW
      reason: Core function term not present in existing_annotations.
  - term:
      id: TEMP:dPix-Git-PAK_complex
      label: dPix-Git-PAK complex
    evidence_type: NAS
    review:
      summary: Added to align core_functions with existing annotations.
      action: NEW
      reason: Core function complex term not present in existing_annotations.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
      vocabulary mapping, accompanied by conservative changes to GO terms applied
      by UniProt
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:12618308
    title: GAPs galore! A survey of putative Ras superfamily GTPase activating proteins
      in man and Drosophila.
    findings:
      - statement: Git (CG16728) is computationally identified as encoding an ARF-GAP
          based on conserved domain analysis in a systematic survey of Drosophila
          and human GAP genes.
        supporting_text: To facilitate genetic analysis, I surveyed Drosophila and
          human sequence databases for genes predicting proteins related to GAPs for
          Ras superfamily members. Remarkably, close to 0.5% of genes in both species
          (173 human and 64 Drosophila genes) predict proteins related to GAPs for
          Arf, Rab, Ran, Rap, Ras, Rho, and Sar family GTPases.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
  - id: PMID:14605208
    title: A protein interaction map of Drosophila melanogaster.
    findings:
      - statement: Git interacts with RtGEF (dPix) in a high-throughput two-hybrid
          screen of the Drosophila proteome, supporting the conserved Pix-Git protein
          complex.
        supporting_text: A two-hybrid-based protein-interaction map of the fly proteome.
          A total of 10,623 predicted transcripts were isolated and screened against
          standard and normalized complementary DNA libraries to produce a draft map
          of 7048 proteins and 20,405 interactions... The network recapitulated known
          pathways, extended pathways, and uncovered previously unknown pathway components.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
  - id: PMID:18996366
    title: The Drosophila homologue of Arf-GAP GIT1, dGIT, is required for proper
      muscle morphogenesis and guidance during embryogenesis.
    findings:
      - statement: dGIT is a GTPase-activating protein for ARF family members that
          integrates signaling pathways controlling cytoskeletal organization and
          cell motility.
        supporting_text: 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.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: dGIT is required for proper muscle morphogenesis and myotube guidance
          during embryogenesis.
        supporting_text: we describe the characterization of a Drosophila homologue
          of GIT1, dGIT, and show that it is required for proper muscle morphogenesis
          and myotube guidance in the fly embryo.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: dGIT protein localizes to the leading edge of growing myotubes
          and to muscle attachment sites.
        supporting_text: The dGIT protein is concentrated at the termini of growing
          myotubes and localizes to muscle attachment sites in late stage embryos.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: dgit mutant embryos show muscle patterning defects and aberrant
          targeting in subsets of muscles.
        supporting_text: dgit mutant embryos show muscle patterning defects and aberrant
          targeting in subsets of their muscles.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: dGIT is required for proper localization of dPak to myotube termini
          and forms a complex with dPak in the presence of dPIX.
        supporting_text: dgit mutant muscles fail to localize the p21-activated kinase,
          dPak, to their termini. dPak and dGIT form a complex in the presence of
          dPIX and dpak mutant embryos show similar muscle morphogenesis and targeting
          phenotypes to that of dgit.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
  - id: PMID:24882013
    title: A presynaptic role for the cytomatrix protein GIT in synaptic vesicle recycling.
    findings:
      - statement: GIT is a component of the active zone (AZ)-associated cytomatrix
          at presynaptic terminals.
        supporting_text: Here, we identify the scaffold G protein coupled receptor
          kinase 2 interacting (GIT) protein as a component of the AZ-associated cytomatrix
          and as a regulator of SV endocytosis.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: GIT directly associates with the endocytic adaptor stonin 2/stoned
          B, linking the active zone cytomatrix to endocytic machinery.
        supporting_text: GIT1 and its D. melanogaster ortholog, dGIT, are shown to
          directly associate with the endocytic adaptor stonin 2/stoned B.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: In dgit mutants, stoned B and synaptotagmin levels are reduced
          and stoned B is partially mislocalized from the presynapse.
        supporting_text: In Drosophila dgit mutants, stoned B and synaptotagmin levels
          are reduced and stoned B is partially mislocalized.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: dgit mutants show morphological and functional defects in synaptic
          vesicle recycling.
        supporting_text: 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.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
  - id: PMID:25484297
    title: The GTPase regulatory proteins Pix and Git control tissue growth via the
      Hippo pathway.
    findings:
      - statement: Pix and Git were identified as prominent Hippo (Hpo) kinase interactors
          through proteomics.
        supporting_text: we used proteomics to identify proteins that bind to the
          Hippo (Hpo) kinase. Prominent among these were PAK-interacting exchange
          factor (known as Pix or RtGEF) and G-protein-coupled receptor kinase-interacting
          protein (Git).
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: Git is the single Drosophila melanogaster homolog of mammalian
          GIT1 and GIT2 proteins.
        supporting_text: Git is the single Drosophila melanogaster homolog of the
          mammalian GIT1 and GIT2 proteins, which were originally identified in the
          search for molecules that interact with G-protein-coupled receptor kinases.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: Pix and Git form an oligomeric scaffold to facilitate sterile 20-like
          kinase activation.
        supporting_text: Pix and Git form an oligomeric scaffold to facilitate sterile
          20-like kinase activation and have also been linked to GTPase regulation.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: Pix and Git regulate Hippo-pathway-dependent tissue growth in parallel
          to the known upstream regulator Fat cadherin.
        supporting_text: 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.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
      - statement: Pix and Git act as a scaffold complex (not enzymes) to promote
          Hpo dimerization and autophosphorylation of Hpo's activation loop.
        supporting_text: 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.
        reference_section_type: ABSTRACT
        full_text_unavailable: true
  - id: PMID:25792865
    title: A Critical Role of GIT1 in Vertebrate and Invertebrate Brain Development.
    findings:
      - statement: dGit shows remarkable conservation with mammalian Git1 both structurally
          and functionally, forming a signaling complex with dPix and dPak.
        supporting_text: dGit, a Drosophila ortholog of Git1, shows remarkable conservation
          with mammalian Git1 both structurally and functionally. dGit forms signaling
          complex with dPix and dPak, and the dGit-dPix-dPak signaling pathway plays
          an essential role for the development in Drosophila.
        reference_section_type: INTRODUCTION
        full_text_unavailable: false
      - statement: Adult dGit mutants exhibit severely decreased central brain size,
          consistent with mammalian Git1 knockout phenotypes.
        supporting_text: Consistent with Git1-/- mice, dGitex21C Drosophila mutants
          also exhibited severely decreased central brain size
        reference_section_type: RESULTS
        full_text_unavailable: false
      - statement: dGit deletion significantly affects mushroom body development,
          with the most common defect being early termination of one alpha-lobe (58%).
        supporting_text: Moreover, the development of alpha- or/and beta-lobe of the
          mushroom body, which is known to be important for learning and memory in
          Drosophila [30], was significantly affected by the deletion of dGit
        reference_section_type: RESULTS
        full_text_unavailable: false
      - statement: dGit regulates the subcellular localization and activation of the
          dPix-Rac-dPak signaling complex, and its dysregulation causes brain size
          reduction and abnormal mushroom body development.
        supporting_text: subcellular localization and activation of the dPix-Rac-dPak
          signaling complex is modulated by dGit, and dysregultion of this signaling
          complex causes severe defects, leading to brain size reduction and abnormal
          mushroom body development.
        reference_section_type: DISCUSSION
        full_text_unavailable: false
      - statement: GIT1 plays a conserved and critical role in brain development across
          invertebrates and vertebrates.
        supporting_text: severe developmental deficits shown in Git1-/- mice as well
          as adult dGit1ex21C Drosophila mutants indicate the conserved and critical
          role of GIT1 in brain development.
        reference_section_type: DISCUSSION
        full_text_unavailable: false
  - id: PMID:38240353
    title: The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway
      through a dual mechanism.
    findings:
      - statement: Vap33 physically and genetically interacts with Git, which binds
          to Hpo and is involved in Hippo pathway activation.
        supporting_text: Vap33 physically and genetically interacts with the actin
          cytoskeletal regulators RtGEF (Pix) and Git, which also bind to the Hippo
          protein (Hpo) and are involved in the activation of the Hippo pathway.
        reference_section_type: ABSTRACT
        full_text_unavailable: false
      - statement: Lgl activates the Hippo pathway via Vap33 through a mechanism involving
          RtGEF, Git, and Arf79F.
        supporting_text: 'Altogether, our data suggest that Lgl acts via Vap33 to
          activate the Hippo pathway by a dual mechanism: (1) through interaction
          with RtGEF, Git and Arf79F, and (2) through interaction and inhibition of
          the V-ATPase, thereby controlling epithelial tissue growth.'
        reference_section_type: ABSTRACT
        full_text_unavailable: false
      - statement: Git knockdown rescues reduced Hippo pathway target gene expression
          in Vha68-2 mutant clones, demonstrating Git's role in Hippo pathway regulation.
        supporting_text: Git knockdown rescues the reduced Hippo pathway target gene
          expression in Vha68-2 mutant clones
        reference_section_type: RESULTS
        full_text_unavailable: false
      - statement: Vap33, Lgl, RtGEF, Git, Arf79F, and Hpo form a protein interaction
          network that regulates the Hippo pathway.
        supporting_text: Vap33 and Lgl form a protein interaction network with RtGEF,
          Git, Arf79F and Hpo
        reference_section_type: RESULTS
        full_text_unavailable: false
  - id: PMID:38944040
    title: Next-generation Drosophila protein interactome map and its functional implications.
    findings:
      - statement: Git interactions were identified in the next-generation Drosophila
          protein interactome map (DPIM2) using affinity purification-mass spectrometry,
          confirming its role in protein complexes.
        supporting_text: We describe a next-generation Drosophila protein interaction
          map-"DPIM2"-established from affinity purification-mass spectrometry of
          5,805 baits, covering the largest fraction of the Drosophila proteome
        reference_section_type: ABSTRACT
        full_text_unavailable: true
  - id: file:DROME/git/git-deep-research-falcon.md
    title: Deep research report on Git
    findings: []
core_functions:
  - description: Git stimulates GTP hydrolysis on Arf79F (ARF1 ortholog), inactivating
      ARF signaling to promote Hippo pathway activation and regulate membrane trafficking.
    molecular_function:
      id: GO:0005096
      label: GTPase activator activity
    directly_involved_in:
      - id: GO:0032012
        label: regulation of ARF protein signal transduction
      - id: GO:0035332
        label: positive regulation of hippo signaling
    locations:
      - id: GO:0005737
        label: cytoplasm
      - id: GO:0005925
        label: focal adhesion
    substrates:
      - id: UniProtKB:P32387
        label: Arf79F (Drosophila ARF1)
  - description: 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.
    supported_by:
      - reference_id: PMID:25484297
        supporting_text: Pix and Git influence activity of the Hpo kinase by acting
          as a scaffold complex, rather than enzymes
      - reference_id: file:DROME/git/git-deep-research-falcon.md
        supporting_text: dPix-Git localizes to basal, focal-adhesion-like structures
          and leading edges; Git's paxillin-binding domain mediates targeting; the
          complex limits myosin II activity and ensures monolayer integrity
    molecular_function:
      id: GO:0035591
      label: signaling adaptor activity
    directly_involved_in:
      - id: GO:0110020
        label: regulation of actomyosin structure organization
      - id: GO:0007525
        label: somatic muscle development
    locations:
      - id: GO:0005925
        label: focal adhesion
      - id: GO:0031252
        label: cell leading edge
  - description: Git scaffolds Hpo dimerization and autophosphorylation as part of
      the Lgl-Vap33-RtGEF-Git-Arf79F module, activating Hippo signaling to restrict
      organ growth.
    molecular_function:
      id: GO:0060090
      label: molecular adaptor activity
    directly_involved_in:
      - id: GO:0035332
        label: positive regulation of hippo signaling
      - id: GO:0046621
        label: negative regulation of organ growth
    locations:
      - id: GO:0005737
        label: cytoplasm
  - description: Git localizes to the presynaptic active zone cytomatrix and associates
      with stoned B to facilitate synaptic vesicle recycling at the neuromuscular
      junction.
    molecular_function:
      id: GO:0060090
      label: molecular adaptor activity
    directly_involved_in:
      - id: GO:0036465
        label: synaptic vesicle recycling
      - id: GO:1905383
        label: protein localization to presynapse
    locations:
      - id: GO:0048786
        label: presynaptic active zone
      - id: GO:0048788
        label: cytoskeleton of presynaptic active zone