Rac1 is a ubiquitously expressed Rho-family small GTPase that acts as a molecular switch, cycling between an inactive GDP-bound form, held in the cytosol by RhoGDIalpha, and an active GTP-bound form anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Guanine nucleotide exchange factors (e.g. betaPIX/ARHGEF7, DOCK1, PREX1) activate it and GTPase-activating proteins such as ARHGAP44 terminate signalling by stimulating its intrinsic GTP hydrolysis. GTP-Rac1 binds effectors including PAK kinases, PKN2 and the WAVE regulatory complex to drive Arp2/3-dependent actin polymerisation in lamellipodia and membrane ruffles, and it is a regulatory subunit of the NADPH oxidase complex, activating superoxide production. Through these activities Rac1 controls cell protrusion, spreading, adhesion turnover, migration, phagocytic engulfment and cell polarity. In rat neurons it is activated locally in dendritic spines by the GIT1/PIX module and acts with PAK to shape spines and excitatory synapses and to stabilise GABAA receptor clusters at inhibitory synapses; in rat osteoclasts it organises the actin ring and ruffled border needed for bone resorption. The rat, mouse and human proteins are identical in sequence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IDA PMID:15147909 Cytosol-derived proteins are sufficient for Arp2/3 recruitme... | KEEP AS NON CORE | Summary: Rac is recruited to Golgi membranes through coatomer in an in vitro reconstitution. Reason: Abstract-only paper; the reconstitution shows coatomer-dependent recruitment of Cdc42 or Rac to Golgi membranes. A minor, peripheral pool of Rac1. Supporting Evidence: PMID:15147909 activated ARF1 can stimulate Arp2/3 recruitment to Golgi membranes through coatomer, Cdc42 or Rac, and N-WASP |
| GO:0000242 pericentriolar material | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pericentriolar localisation transferred from mouse Rac1. Reason: A minor localisation reported for mouse Rac1; peripheral to the plasma membrane-based core function. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0001764 neuron migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is required for neuron migration. Reason: Follows from its cytoskeletal switch function; non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0001764 neuron migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rac1 is required for neuron migration. Reason: Follows from its cytoskeletal switch function; non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0001891 phagocytic cup | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is present at phagocytic cups, consistent with its role in engulfment. Reason: Rac1 acts with DOCK1-ELMO1 in phagocytosis of apoptotic cells. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. |
| GO:0001934 positive regulation of protein phosphorylation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Active Rac1 stimulates phosphorylation by its kinase effectors. Reason: GTP-Rac1 stimulates PKN2 and PAK autophosphorylation and substrate phosphorylation; a broad regulatory consequence of effector activation. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. |
| GO:0002093 auditory receptor cell morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in hair-cell morphogenesis (mouse). Reason: Cell-level cytoskeletal morphogenesis downstream of Rac1. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0002551 mast cell chemotaxis | IMP PMID:12413953 Eotaxin induces migration of RBL-2H3 mast cells via a Rac-ER... | KEEP AS NON CORE | Summary: Dominant-negative Rac1 blocks eotaxin-induced chemotaxis of rat RBL-2H3 mast cells. Reason: Rat experimental evidence (abstract); signalling role upstream of cell migration. Supporting Evidence: PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant |
| GO:0003376 sphingosine-1-phosphate receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts downstream of sphingosine-1-phosphate receptors. Reason: Signalling relay role, non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0003382 epithelial cell morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 contributes to epithelial cell morphogenesis. Reason: Cytoskeletal and polarity role (PAR complex). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. |
| GO:0003924 GTPase activity | EXP PMID:25498153 Dynamic recruitment of the curvature-sensitive protein ArhGA... | MODIFY | Summary: Rac1 hydrolyses GTP, but its biological activity is that of a GTP/GDP molecular switch; G protein activity is the more specific supported term. Reason: GTP hydrolysis by Rac1 is demonstrated in rat neurons (GAP-stimulated hydrolysis by ArhGAP44, the basis of UniProt EC 3.6.5.2). Hydrolysis is the off-step of a regulated switch cycle in which GTP-bound Rac1 binds and activates effectors. GO:0003925 G protein activity is_a GO:0003924 GTPase activity (checked with OAK) and captures the switch; the gene already carries it (IEA, ISO). All GTPase activity rows are refined to it. Proposed replacements: G protein activity Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | MODIFY | Summary: Rac1 hydrolyses GTP, but its biological activity is that of a GTP/GDP molecular switch; G protein activity is the more specific supported term. Reason: GTP hydrolysis by Rac1 is demonstrated in rat neurons (GAP-stimulated hydrolysis by ArhGAP44, the basis of UniProt EC 3.6.5.2). Hydrolysis is the off-step of a regulated switch cycle in which GTP-bound Rac1 binds and activates effectors. GO:0003925 G protein activity is_a GO:0003924 GTPase activity (checked with OAK) and captures the switch; the gene already carries it (IEA, ISO). All GTPase activity rows are refined to it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: G protein activity Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003924 GTPase activity | IDA PMID:12672819 The small GTP-binding protein Rac1 induces cardiac myocyte h... | MODIFY | Summary: Rac1 hydrolyses GTP, but its biological activity is that of a GTP/GDP molecular switch; G protein activity is the more specific supported term. Reason: The cited cardiomyocyte paper (abstract only) uses constitutively active and dominant-negative Rac1; the GTPase/switch function of Rac1 is independently established, so the row is refined rather than questioned. GTP hydrolysis by Rac1 is demonstrated in rat neurons (GAP-stimulated hydrolysis by ArhGAP44, the basis of UniProt EC 3.6.5.2). Hydrolysis is the off-step of a regulated switch cycle in which GTP-bound Rac1 binds and activates effectors. GO:0003925 G protein activity is_a GO:0003924 GTPase activity (checked with OAK) and captures the switch; the gene already carries it (IEA, ISO). All GTPase activity rows are refined to it. Proposed replacements: G protein activity Supporting Evidence: PMID:12672819 These findings suggest that Rac1 induces cardiac myocyte hypertrophy mediated through ASK1 and NF-kappaB. file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | MODIFY | Summary: Rac1 hydrolyses GTP, but its biological activity is that of a GTP/GDP molecular switch; G protein activity is the more specific supported term. Reason: GTP hydrolysis by Rac1 is demonstrated in rat neurons (GAP-stimulated hydrolysis by ArhGAP44, the basis of UniProt EC 3.6.5.2). Hydrolysis is the off-step of a regulated switch cycle in which GTP-bound Rac1 binds and activates effectors. GO:0003925 G protein activity is_a GO:0003924 GTPase activity (checked with OAK) and captures the switch; the gene already carries it (IEA, ISO). All GTPase activity rows are refined to it. Proposed replacements: G protein activity Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003924 GTPase activity | ISO GO_REF:0000121 | MODIFY | Summary: Rac1 hydrolyses GTP, but its biological activity is that of a GTP/GDP molecular switch; G protein activity is the more specific supported term. Reason: GTP hydrolysis by Rac1 is demonstrated in rat neurons (GAP-stimulated hydrolysis by ArhGAP44, the basis of UniProt EC 3.6.5.2). Hydrolysis is the off-step of a regulated switch cycle in which GTP-bound Rac1 binds and activates effectors. GO:0003925 G protein activity is_a GO:0003924 GTPase activity (checked with OAK) and captures the switch; the gene already carries it (IEA, ISO). All GTPase activity rows are refined to it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: G protein activity Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003924 GTPase activity | ISO GO_REF:0000121 | MODIFY | Summary: Rac1 hydrolyses GTP, but its biological activity is that of a GTP/GDP molecular switch; G protein activity is the more specific supported term. Reason: GTP hydrolysis by Rac1 is demonstrated in rat neurons (GAP-stimulated hydrolysis by ArhGAP44, the basis of UniProt EC 3.6.5.2). Hydrolysis is the off-step of a regulated switch cycle in which GTP-bound Rac1 binds and activates effectors. GO:0003925 G protein activity is_a GO:0003924 GTPase activity (checked with OAK) and captures the switch; the gene already carries it (IEA, ISO). All GTPase activity rows are refined to it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: G protein activity Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | ACCEPT | Summary: Rac1 is a Rho-family G protein that cycles between GDP- and GTP-bound states and signals through GTP-dependent effector binding. Reason: Core molecular function, supported by the rat UniProt function statement, the experimentally documented GEF/GAP/GDI regulation, and Rho-family membership. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Interacts with the GEF proteins PREX1, RASGRF2, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0003925 G protein activity | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 is a Rho-family G protein that cycles between GDP- and GTP-bound states and signals through GTP-dependent effector binding. Reason: Core molecular function, supported by the rat UniProt function statement, the experimentally documented GEF/GAP/GDI regulation, and Rho-family membership. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Interacts with the GEF proteins PREX1, RASGRF2, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:25498153 A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis |
| GO:0005515 protein binding | IPI PMID:16055727 Signal regulatory protein alpha ligation induces macrophage ... | REMOVE | Summary: Bare protein binding is uninformative. Reason: Per the protein-binding policy the generic GO:0005515 row is removed; this does not mean the reported interaction is false. Informative partner-binding terms are retained elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:20696765 Semaphorin 5A and plexin-B3 inhibit human glioma cell motili... | MODIFY | Summary: The partner is RhoGDIalpha (Arhgdia); the informative term is Rho GDP-dissociation inhibitor binding. Reason: Sema5A promotes Rac1 recruitment to RhoGDIalpha; GO:0051022 Rho GDP-dissociation inhibitor binding (is_a GO:0005515, checked with OAK) states the function and is carried by the gene. The cited paper's abstract describes human glioma cells; the Rac1 sequence is identical in human and rat. Proposed replacements: Rho GDP-dissociation inhibitor binding Supporting Evidence: PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner PMID:20472934 When Ser-34 was mutated to Asp, there was significantly reduced RhoGDIΞ± binding to RhoA (by around 75%) but not Rac1 or Cdc42. file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0005515 protein binding | IPI PMID:20696765 Semaphorin 5A and plexin-B3 inhibit human glioma cell motili... | REMOVE | Summary: Bare protein binding is uninformative. Reason: Per the protein-binding policy the generic GO:0005515 row is removed; this does not mean the reported interaction is false. Informative partner-binding terms are retained elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:22128169 Sh3rf2/POSHER protein promotes cell survival by ring-mediate... | REMOVE | Summary: Bare protein binding is uninformative. Reason: Per the protein-binding policy the generic GO:0005515 row is removed; this does not mean the reported interaction is false. Informative partner-binding terms are retained elsewhere in this review. |
| GO:0005525 GTP binding | IBA GO_REF:0000033 | ACCEPT | Summary: GTP binding is intrinsic to the Rac1 switch cycle. Reason: Rac1 carries the P-loop/G1-G5 GTP-binding motifs of the Ras superfamily (InterPro Small_GTPase, Small_GTPase_Rho) and is activated by GTP loading in rat cells, e.g. netrin-1 rapidly activates Rac1 in commissural neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0005525 GTP binding | IDA PMID:12672819 The small GTP-binding protein Rac1 induces cardiac myocyte h... | ACCEPT | Summary: GTP binding is intrinsic to the Rac1 switch cycle. Reason: Rac1 carries the P-loop/G1-G5 GTP-binding motifs of the Ras superfamily (InterPro Small_GTPase, Small_GTPase_Rho) and is activated by GTP loading in rat cells, e.g. netrin-1 rapidly activates Rac1 in commissural neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0005525 GTP binding | IDA PMID:15788770 Deleted in colorectal cancer binding netrin-1 mediates cell ... | ACCEPT | Summary: GTP binding is intrinsic to the Rac1 switch cycle. Reason: Rac1 carries the P-loop/G1-G5 GTP-binding motifs of the Ras superfamily (InterPro Small_GTPase, Small_GTPase_Rho) and is activated by GTP loading in rat cells, e.g. netrin-1 rapidly activates Rac1 in commissural neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP binding is intrinsic to the Rac1 switch cycle. Reason: Rac1 carries the P-loop/G1-G5 GTP-binding motifs of the Ras superfamily (InterPro Small_GTPase, Small_GTPase_Rho) and is activated by GTP loading in rat cells, e.g. netrin-1 rapidly activates Rac1 in commissural neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0005525 GTP binding | ISO GO_REF:0000121 | ACCEPT | Summary: GTP binding is intrinsic to the Rac1 switch cycle. Reason: Rac1 carries the P-loop/G1-G5 GTP-binding motifs of the Ras superfamily (InterPro Small_GTPase, Small_GTPase_Rho) and is activated by GTP loading in rat cells, e.g. netrin-1 rapidly activates Rac1 in commissural neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0005525 GTP binding | ISO GO_REF:0000121 | ACCEPT | Summary: GTP binding is intrinsic to the Rac1 switch cycle. Reason: Rac1 carries the P-loop/G1-G5 GTP-binding motifs of the Ras superfamily (InterPro Small_GTPase, Small_GTPase_Rho) and is activated by GTP loading in rat cells, e.g. netrin-1 rapidly activates Rac1 in commissural neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Belongs to the small GTPase superfamily. Rho family. PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A pool of active Rac1 enters the nucleus via its C-terminal polybasic region. Reason: Nuclear localisation is documented by similarity to human RAC1 and Rac1 promotes nuclear shuttling of NR3C2 in rat podocytes; a real but secondary location. The nucleus is not covered by the root-organelle policy. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Activation by GTP-binding promotes nuclear localization file:rat/Rac1/Rac1-uniprot.txt In podocytes, promotes nuclear shuttling of NR3C2 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A pool of active Rac1 enters the nucleus via its C-terminal polybasic region. Reason: Nuclear localisation is documented by similarity to human RAC1 and Rac1 promotes nuclear shuttling of NR3C2 in rat podocytes; a real but secondary location. The nucleus is not covered by the root-organelle policy. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Activation by GTP-binding promotes nuclear localization file:rat/Rac1/Rac1-uniprot.txt In podocytes, promotes nuclear shuttling of NR3C2 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A pool of active Rac1 enters the nucleus via its C-terminal polybasic region. Reason: Nuclear localisation is documented by similarity to human RAC1 and Rac1 promotes nuclear shuttling of NR3C2 in rat podocytes; a real but secondary location. The nucleus is not covered by the root-organelle policy. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Activation by GTP-binding promotes nuclear localization file:rat/Rac1/Rac1-uniprot.txt In podocytes, promotes nuclear shuttling of NR3C2 |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A pool of active Rac1 enters the nucleus via its C-terminal polybasic region. Reason: Nuclear localisation is documented by similarity to human RAC1 and Rac1 promotes nuclear shuttling of NR3C2 in rat podocytes; a real but secondary location. The nucleus is not covered by the root-organelle policy. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Activation by GTP-binding promotes nuclear localization file:rat/Rac1/Rac1-uniprot.txt In podocytes, promotes nuclear shuttling of NR3C2 |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Nucleoplasmic Rac1, transferred from human. Reason: Consistent with GTP-dependent nuclear import. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Activation by GTP-binding promotes nuclear localization |
| GO:0005730 nucleolus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Nucleolar Rac1, transferred from human. Reason: Minor location reported for human RAC1. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Cytoplasm is correct but general; the soluble pool of Rac1 is cytosolic, in complex with RhoGDI. Reason: Inactive Rac1 is held in the cytosol by RhoGDIalpha. GO:0005829 cytosol is part_of GO:0005737 cytoplasm (checked with OAK) and the gene already carries it (IDA, ISO). Proposed replacements: cytosol Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In macrophages, cytoplasmic location increases upon CSF1 stimulation PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | MODIFY | Summary: Cytoplasm is correct but general; the soluble pool of Rac1 is cytosolic, in complex with RhoGDI. Reason: Inactive Rac1 is held in the cytosol by RhoGDIalpha. GO:0005829 cytosol is part_of GO:0005737 cytoplasm (checked with OAK) and the gene already carries it (IDA, ISO). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: cytosol Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In macrophages, cytoplasmic location increases upon CSF1 stimulation PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | MODIFY | Summary: Cytoplasm is correct but general; the soluble pool of Rac1 is cytosolic, in complex with RhoGDI. Reason: Inactive Rac1 is held in the cytosol by RhoGDIalpha. GO:0005829 cytosol is part_of GO:0005737 cytoplasm (checked with OAK) and the gene already carries it (IDA, ISO). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: cytosol Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In macrophages, cytoplasmic location increases upon CSF1 stimulation PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | MODIFY | Summary: Cytoplasm is correct but general; the soluble pool of Rac1 is cytosolic, in complex with RhoGDI. Reason: Inactive Rac1 is held in the cytosol by RhoGDIalpha. GO:0005829 cytosol is part_of GO:0005737 cytoplasm (checked with OAK) and the gene already carries it (IDA, ISO). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: cytosol Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In macrophages, cytoplasmic location increases upon CSF1 stimulation PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | MODIFY | Summary: Cytoplasm is correct but general; the soluble pool of Rac1 is cytosolic, in complex with RhoGDI. Reason: Inactive Rac1 is held in the cytosol by RhoGDIalpha. GO:0005829 cytosol is part_of GO:0005737 cytoplasm (checked with OAK) and the gene already carries it (IDA, ISO). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: cytosol Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In macrophages, cytoplasmic location increases upon CSF1 stimulation PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0005802 trans-Golgi network | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Trans-Golgi network pool transferred from human. Reason: Peripheral location. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0005829 cytosol | IDA PMID:20696765 Semaphorin 5A and plexin-B3 inhibit human glioma cell motili... | ACCEPT | Summary: Inactive Rac1 resides in the cytosol bound to RhoGDIalpha. Reason: Cytosolic Rac1-RhoGDI complexes are the reservoir from which Rac1 is delivered to membranes; RhoGDIalpha sequesters Rac1 away from the membrane. The cited paper (abstract only) studies glioma cells described in its title as human; Rac1 is identical in sequence, and the location is independently established. Supporting Evidence: PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner PMID:20472934 When Ser-34 was mutated to Asp, there was significantly reduced RhoGDIΞ± binding to RhoA (by around 75%) but not Rac1 or Cdc42. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Inactive Rac1 resides in the cytosol bound to RhoGDIalpha. Reason: Cytosolic Rac1-RhoGDI complexes are the reservoir from which Rac1 is delivered to membranes; RhoGDIalpha sequesters Rac1 away from the membrane. Supporting Evidence: PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner PMID:20472934 When Ser-34 was mutated to Asp, there was significantly reduced RhoGDIΞ± binding to RhoA (by around 75%) but not Rac1 or Cdc42. |
| GO:0005856 cytoskeleton | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Rac1 regulates the actin cytoskeleton from the plasma membrane rather than being a cytoskeletal constituent. Reason: Rac1 is a prenylated, membrane-anchored signalling switch whose effectors (WAVE, PAK) remodel cortical actin. The Rho-family PAINT node places the location at the generic cytoskeleton; for Rac1 the supported locations are the plasma membrane, ruffles and lamellipodia. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner |
| GO:0005884 actin filament | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Rac1 acts on actin filaments through effectors; it is not an actin filament component. Reason: Co-fractionation or co-staining of Rac1 with F-actin reflects its action at the cell cortex; the supported locations are the plasma membrane and its protrusions. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine |
| GO:0005886 plasma membrane | EXP PMID:16040606 Possible role of direct Rac1-Rab7 interaction in ruffled bor... | ACCEPT | Summary: Active Rac1 is anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Reason: Core location: the plasma membrane is where GEFs activate Rac1 and where it engages effectors. Supported by rat osteoclast data (ruffled border), the UniProt record and Rho-family membership. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine file:rat/Rac1/Rac1-uniprot.txt Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Active Rac1 is anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Reason: Core location: the plasma membrane is where GEFs activate Rac1 and where it engages effectors. Supported by rat osteoclast data (ruffled border), the UniProt record and Rho-family membership. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine file:rat/Rac1/Rac1-uniprot.txt Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Active Rac1 is anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Reason: Core location: the plasma membrane is where GEFs activate Rac1 and where it engages effectors. Supported by rat osteoclast data (ruffled border), the UniProt record and Rho-family membership. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine file:rat/Rac1/Rac1-uniprot.txt Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Active Rac1 is anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Reason: Core location: the plasma membrane is where GEFs activate Rac1 and where it engages effectors. Supported by rat osteoclast data (ruffled border), the UniProt record and Rho-family membership. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine file:rat/Rac1/Rac1-uniprot.txt Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Active Rac1 is anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Reason: Core location: the plasma membrane is where GEFs activate Rac1 and where it engages effectors. Supported by rat osteoclast data (ruffled border), the UniProt record and Rho-family membership. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine file:rat/Rac1/Rac1-uniprot.txt Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0005886 plasma membrane | TAS Reactome:R-RNO-9619811 | ACCEPT | Summary: Active Rac1 is anchored by its C-terminal prenyl group to the inner leaflet of the plasma membrane. Reason: Core location: the plasma membrane is where GEFs activate Rac1 and where it engages effectors. Supported by rat osteoclast data (ruffled border), the UniProt record and Rho-family membership. Supporting Evidence: Reactome:R-RNO-9619811 Camk1-mediated phosphorylation of Arhgef7 (Beta-Pix) at serine S516 enhances guanine nucleotide exchange factor (GEF) activity of Arhgef7, leading to Rac1 activation file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine |
| GO:0005938 cell cortex | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is at the cell cortex, where it organises cortical actin. Reason: Consistent with its plasma-membrane location. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Required for DSG3 translocation to cell-cell junctions, DSG3-mediated organization of cortical F-actin bundles and anchoring of actin at cell junctions |
| GO:0006897 endocytosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in endocytic uptake (e.g. macropinocytosis). Reason: Non-core consequence of its actin regulation. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0006911 phagocytosis, engulfment | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives the actin remodelling of phagocytic engulfment. Reason: With DOCK1-ELMO1 it is the key switch for engulfment of apoptotic cells. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. |
| GO:0006935 chemotaxis | IMP PMID:11756405 Leukotriene B(4) stimulates Rac-ERK cascade to generate reac... | KEEP AS NON CORE | Summary: Rac1 is required for leukotriene B4-induced ROS generation and chemotaxis in rat cells. Reason: Rat dominant-negative experiments (abstract). Supporting Evidence: PMID:11756405 stable expression of Rac(N17), a dominant negative Rac1 mutant, completely blocks leukotriene B(4)-induced ROS generation PMID:11756405 Rac, ERK, and cytosolic phospholipase A(2) all play pivotal roles in mediating the ROS generation that appears to be a prerequisite for leukotriene B(4)-induced chemotaxis |
| GO:0006972 hyperosmotic response | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Hyperosmotic response is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal hyperosmotic response. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0007010 cytoskeleton organization | ISO GO_REF:0000121 | MODIFY | Summary: Cytoskeleton organization is correct but general; Rac1 organises the actin cytoskeleton. Reason: GO:0030036 actin cytoskeleton organization is_a GO:0007010 (checked with OAK) and the gene carries it (IDA). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: actin cytoskeleton organization Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. |
| GO:0007015 actin filament organization | IBA GO_REF:0000033 | ACCEPT | Summary: Rac1 organises actin filaments into lamellipodial and cortical networks. Reason: Core process. Dominant-negative Rac1 blocks eotaxin-induced actin reorganisation in rat mast cells; anti-Rac antibodies disrupt actin rings in rat osteoclasts. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0007015 actin filament organization | IMP PMID:12413953 Eotaxin induces migration of RBL-2H3 mast cells via a Rac-ER... | ACCEPT | Summary: Rac1 organises actin filaments into lamellipodial and cortical networks. Reason: Core process. Dominant-negative Rac1 blocks eotaxin-induced actin reorganisation in rat mast cells; anti-Rac antibodies disrupt actin rings in rat osteoclasts. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0007015 actin filament organization | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 organises actin filaments into lamellipodial and cortical networks. Reason: Core process. Dominant-negative Rac1 blocks eotaxin-induced actin reorganisation in rat mast cells; anti-Rac antibodies disrupt actin rings in rat osteoclasts. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0007015 actin filament organization | ISS GO_REF:0000024 | ACCEPT | Summary: Rac1 organises actin filaments into lamellipodial and cortical networks. Reason: Core process. Dominant-negative Rac1 blocks eotaxin-induced actin reorganisation in rat mast cells; anti-Rac antibodies disrupt actin rings in rat osteoclasts. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0007155 cell adhesion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 participates in cell adhesion. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0007160 cell-matrix adhesion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates cell-matrix adhesion assembly and turnover. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. |
| GO:0007163 establishment or maintenance of cell polarity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 contributes to establishment of cell polarity. Reason: Rac1 is part of the PAR3-PAR6-aPKC complex. Non-core. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. |
| GO:0007167 enzyme-linked receptor protein signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 relays signals from enzyme-linked receptors. Reason: Broad signalling context, non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0007186 G protein-coupled receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 relays signals downstream of GPCRs. Reason: E.g. LTB4 and eotaxin receptors in rat cells. Non-core. Supporting Evidence: PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant PMID:11756405 stable expression of Rac(N17), a dominant negative Rac1 mutant, completely blocks leukotriene B(4)-induced ROS generation |
| GO:0007264 small GTPase-mediated signal transduction | ISO GO_REF:0000121 | MODIFY | Summary: Small GTPase-mediated signal transduction is correct; the specific term is Rac protein signal transduction. Reason: GO:0016601 Rac protein signal transduction is_a GO:0007264 (checked with OAK) and is carried by the gene (IBA, ISO, TAS). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: Rac protein signal transduction Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0007264 small GTPase-mediated signal transduction | ISO GO_REF:0000121 | MODIFY | Summary: Small GTPase-mediated signal transduction is correct; the specific term is Rac protein signal transduction. Reason: GO:0016601 Rac protein signal transduction is_a GO:0007264 (checked with OAK) and is carried by the gene (IBA, ISO, TAS). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: Rac protein signal transduction Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0007411 axon guidance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in growth-cone responses during axon guidance. Reason: Netrin-1/DCC activates Rac1 and recruits it into a signalling complex in rat commissural neurons. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 PMID:15788770 netrin-1 recruits Cdc42, Rac1, Pak1, and N-WASP into a complex with the intracellular domain of DCC and Nck1 |
| GO:0008045 motor neuron axon guidance | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac GTPases act in motor axon guidance (fly and worm donors). Reason: The inherited growth-cone function is plausible for Rac1; tissue-specific context, non-core. Supporting Evidence: PMID:15788770 the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1 |
| GO:0008360 regulation of cell shape | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 regulates cell shape through actin remodelling. Reason: Non-core consequence of core activity. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0010591 regulation of lamellipodium assembly | ISO GO_REF:0000121 | MODIFY | Summary: Rac1 positively regulates lamellipodium assembly; the sign-specific term is supported. Reason: GO:0010592 positive regulation of lamellipodium assembly is_a GO:0010591 (checked with OAK) and is carried by the gene (IMP). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: positive regulation of lamellipodium assembly Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac PMID:12105187 GAP-resistant, constitutively active V12Rac reversed this inhibition, supporting a critical role for Rac inhibition in the response to stretch |
| GO:0010592 positive regulation of lamellipodium assembly | IMP PMID:12105187 Effects of cell tension on the small GTPase Rac. | ACCEPT | Summary: Active Rac1 drives lamellipodium formation. Reason: In rat VSM cells, stretch suppresses lamellipodia by inactivating Rac and constitutively active V12Rac restores them (full text read). Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac PMID:12105187 GAP-resistant, constitutively active V12Rac reversed this inhibition, supporting a critical role for Rac inhibition in the response to stretch PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0010592 positive regulation of lamellipodium assembly | ISO GO_REF:0000121 | ACCEPT | Summary: Active Rac1 drives lamellipodium formation. Reason: In rat VSM cells, stretch suppresses lamellipodia by inactivating Rac and constitutively active V12Rac restores them (full text read). Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac PMID:12105187 GAP-resistant, constitutively active V12Rac reversed this inhibition, supporting a critical role for Rac inhibition in the response to stretch PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0010592 positive regulation of lamellipodium assembly | ISO GO_REF:0000121 | ACCEPT | Summary: Active Rac1 drives lamellipodium formation. Reason: In rat VSM cells, stretch suppresses lamellipodia by inactivating Rac and constitutively active V12Rac restores them (full text read). Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac PMID:12105187 GAP-resistant, constitutively active V12Rac reversed this inhibition, supporting a critical role for Rac inhibition in the response to stretch PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0010595 positive regulation of endothelial cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes endothelial cell migration. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0010762 regulation of fibroblast migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates fibroblast migration. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. |
| GO:0010764 negative regulation of fibroblast migration | ISO GO_REF:0000121 | UNDECIDED | Summary: Negative regulation of fibroblast migration, transferred from human, runs counter to Rac1's usual pro-migratory role. Reason: Rac1 generally promotes protrusion and migration; a negative sign may reflect a specific context in the human source that could not be inspected here. Neither accepted nor removed. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: UNRESOLVED Failure modes: REGULATORY SIGN INVERSION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. |
| GO:0014041 regulation of neuron maturation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of neuron maturation is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal regulation of neuron maturation. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0016020 membrane | IDA PMID:20696765 Semaphorin 5A and plexin-B3 inhibit human glioma cell motili... | MODIFY | Summary: Membrane is correct but general; Rac1's membrane is the plasma membrane. Reason: The membrane pool of Rac1 is the inner leaflet of the plasma membrane, from which RhoGDIalpha extracts it. GO:0005886 plasma membrane is a descendant of GO:0016020 and the gene carries it. The cited paper (abstract only) studies glioma cells described in its title as human; Rac1 is identical in sequence, and the location is independently established. Proposed replacements: plasma membrane Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0016020 membrane | ISO GO_REF:0000121 | MODIFY | Summary: Membrane is correct but general; Rac1's membrane is the plasma membrane. Reason: The membrane pool of Rac1 is the inner leaflet of the plasma membrane, from which RhoGDIalpha extracts it. GO:0005886 plasma membrane is a descendant of GO:0016020 and the gene carries it. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: plasma membrane Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner |
| GO:0016358 dendrite development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in dendrite development. Reason: CDKL5-Rac1 signalling regulates dendritic arborisation in rat neurons. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 |
| GO:0016477 cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives cell migration through lamellipodial protrusion. Reason: Non-core process outcome of the core activity. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0016477 cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives cell migration through lamellipodial protrusion. Reason: Non-core process outcome of the core activity. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0016601 Rac protein signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Rac1 is the signalling GTPase of Rac protein signal transduction. Reason: Core process: GEF-activated GTP-Rac1 relays signals to effectors (PAK, WAVE, NOX). Rat examples include LTB4-Rac-ERK signalling and betaPIX-mediated Rac1 activation in neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states PMID:11756405 stable expression of Rac(N17), a dominant negative Rac1 mutant, completely blocks leukotriene B(4)-induced ROS generation Reactome:R-RNO-9619811 Camk1-mediated phosphorylation of Arhgef7 (Beta-Pix) at serine S516 enhances guanine nucleotide exchange factor (GEF) activity of Arhgef7, leading to Rac1 activation |
| GO:0016601 Rac protein signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 is the signalling GTPase of Rac protein signal transduction. Reason: Core process: GEF-activated GTP-Rac1 relays signals to effectors (PAK, WAVE, NOX). Rat examples include LTB4-Rac-ERK signalling and betaPIX-mediated Rac1 activation in neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states PMID:11756405 stable expression of Rac(N17), a dominant negative Rac1 mutant, completely blocks leukotriene B(4)-induced ROS generation Reactome:R-RNO-9619811 Camk1-mediated phosphorylation of Arhgef7 (Beta-Pix) at serine S516 enhances guanine nucleotide exchange factor (GEF) activity of Arhgef7, leading to Rac1 activation |
| GO:0016601 Rac protein signal transduction | TAS PMID:11756405 Leukotriene B(4) stimulates Rac-ERK cascade to generate reac... | ACCEPT | Summary: Rac1 is the signalling GTPase of Rac protein signal transduction. Reason: Core process: GEF-activated GTP-Rac1 relays signals to effectors (PAK, WAVE, NOX). Rat examples include LTB4-Rac-ERK signalling and betaPIX-mediated Rac1 activation in neurons. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states PMID:11756405 stable expression of Rac(N17), a dominant negative Rac1 mutant, completely blocks leukotriene B(4)-induced ROS generation Reactome:R-RNO-9619811 Camk1-mediated phosphorylation of Arhgef7 (Beta-Pix) at serine S516 enhances guanine nucleotide exchange factor (GEF) activity of Arhgef7, leading to Rac1 activation |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | MODIFY | Summary: Enzyme binding is true but too general; the best-characterised enzyme partners of Rac1 are its kinase effectors. Reason: Rac1 binds and activates kinases such as PAK1-3 and PKN2 and binds other enzymes (PPP5C, NOX subunits). The specific supported term already carried by the gene is protein kinase binding (GO:0019901 is_a GO:0019899, checked with OAK). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: protein kinase binding Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 |
| GO:0019901 protein kinase binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 binds protein kinases, including its PAK and PKN2 effectors and the upstream kinase CDKL5. Reason: Kinase binding is how active Rac1 relays its signal (PAK, PKN2), and CDKL5 forms a complex with Rac1 in rat neurons. Retained as non-core because the binding term is subsidiary to the core G protein activity. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 |
| GO:0019901 protein kinase binding | IPI PMID:20861382 CDKL5, a protein associated with rett syndrome, regulates ne... | KEEP AS NON CORE | Summary: Rac1 binds protein kinases, including its PAK and PKN2 effectors and the upstream kinase CDKL5. Reason: Kinase binding is how active Rac1 relays its signal (PAK, PKN2), and CDKL5 forms a complex with Rac1 in rat neurons. Retained as non-core because the binding term is subsidiary to the core G protein activity. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 |
| GO:0019901 protein kinase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 binds protein kinases, including its PAK and PKN2 effectors and the upstream kinase CDKL5. Reason: Kinase binding is how active Rac1 relays its signal (PAK, PKN2), and CDKL5 forms a complex with Rac1 in rat neurons. Retained as non-core because the binding term is subsidiary to the core G protein activity. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 |
| GO:0021799 cerebral cortex radially oriented cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in radial migration of cortical neurons (mouse). Reason: Neuronal migration consequence of the cytoskeletal function. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0021831 embryonic olfactory bulb interneuron precursor migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in migration of olfactory bulb interneuron precursors (mouse). Reason: Neuronal migration consequence. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0021894 cerebral cortex GABAergic interneuron development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cerebral cortex GABAergic interneuron development is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal cerebral cortex gabaergic interneuron development. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0022604 regulation of cell morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates cell morphogenesis. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | ACCEPT | Summary: Rac1 localises to lamellipodia, the protrusions it drives. Reason: Core location of the activity. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030027 lamellipodium | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 localises to lamellipodia, the protrusions it drives. Reason: Core location of the activity. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030027 lamellipodium | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 localises to lamellipodia, the protrusions it drives. Reason: Core location of the activity. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030027 lamellipodium | ISS GO_REF:0000024 | ACCEPT | Summary: Rac1 localises to lamellipodia, the protrusions it drives. Reason: Core location of the activity. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030032 lamellipodium assembly | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 drives lamellipodium assembly. Reason: Core actin-protrusion process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner |
| GO:0030032 lamellipodium assembly | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 drives lamellipodium assembly. Reason: Core actin-protrusion process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac file:rat/Rac1/Rac1-uniprot.txt Localizes to the lamellipodium in a SH3RF1-dependent manner |
| GO:0030036 actin cytoskeleton organization | IDA PMID:10350213 Rac-GTPase, osteoclast cytoskeleton and bone resorption. | ACCEPT | Summary: Rac1 organises the actin cytoskeleton. Reason: Rat osteoclast antibody-inhibition data (abstract) and extensive orthologous evidence; core process. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0030036 actin cytoskeleton organization | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 organises the actin cytoskeleton. Reason: Rat osteoclast antibody-inhibition data (abstract) and extensive orthologous evidence; core process. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0030041 actin filament polymerization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts upstream of actin polymerisation via WAVE/Arp2/3 effectors. Reason: Rac1 does not itself polymerise actin. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0030334 regulation of cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 regulates cell migration. Reason: Non-core consequence of protrusion control. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030334 regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates cell migration. Reason: Non-core consequence of protrusion control. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030334 regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates cell migration. Reason: Non-core consequence of protrusion control. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030334 regulation of cell migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rac1 regulates cell migration. Reason: Non-core consequence of protrusion control. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Rac1 is present in dendrites. Reason: Neuronal location from UniProt subcellular-location mapping; consistent with dendritic spine signalling. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, localizes at synapses, where it is activated PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. |
| GO:0030672 synaptic vesicle membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Presynaptic Rac1 on synaptic vesicle membranes, transferred from mouse. Reason: Peripheral neuronal location. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0030742 GTP-dependent protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 binds effectors preferentially in its GTP-bound state. Reason: GTP-dependent effector binding is a corollary of the switch function (e.g. PKN2 binds the GTP-bound form preferentially). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. |
| GO:0030838 positive regulation of actin filament polymerization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes actin polymerisation through its effectors. Reason: Indirect, via WAVE/Arp2/3. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0030865 cortical cytoskeleton organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 organises the cortical actin cytoskeleton. Reason: Supported by DSG3-dependent cortical F-actin organisation. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Required for DSG3 translocation to cell-cell junctions, DSG3-mediated organization of cortical F-actin bundles and anchoring of actin at cell junctions |
| GO:0030900 forebrain development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Forebrain development is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal forebrain development. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0031267 small GTPase binding | IPI PMID:16040606 Possible role of direct Rac1-Rab7 interaction in ruffled bor... | KEEP AS NON CORE | Summary: Rac1 binds the GTP-bound form of Rab7. Reason: Yeast two-hybrid and colocalisation in rat osteoclasts show Rac1 binding to GTP-Rab7 at the ruffled border; a specific but peripheral interaction. Supporting Evidence: PMID:16040606 Here we report a new Rab7-interacting protein, Rac1, another small GTPase protein that binds to the GTP-form of Rab7 as found with a two-hybrid system. PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0031410 cytoplasmic vesicle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 is found on cytoplasmic vesicles (endosomes, macropinosomes). Reason: Endosomal/vesicular pools are documented (Rab7 colocalisation, ACKR2 trafficking). Non-core. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt up-regulation of ACKR2 from endosomal compartment to cell membrane PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0031410 cytoplasmic vesicle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is found on cytoplasmic vesicles (endosomes, macropinosomes). Reason: Endosomal/vesicular pools are documented (Rab7 colocalisation, ACKR2 trafficking). Non-core. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt up-regulation of ACKR2 from endosomal compartment to cell membrane PMID:16040606 Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts |
| GO:0031901 early endosome membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Early endosome membrane pool transferred from mouse. Reason: Peripheral location. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt up-regulation of ACKR2 from endosomal compartment to cell membrane |
| GO:0031996 thioesterase binding | ISO GO_REF:0000121 | UNDECIDED | Summary: Thioesterase binding is transferred from human RAC1 without an evident basis in the rat literature. Reason: The human source annotation could not be inspected here and no rat or UniProt statement describes a Rac1-thioesterase interaction; neither accepted nor rejected. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: UNRESOLVED Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0032496 response to lipopolysaccharide | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Response to lipopolysaccharide is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal response to lipopolysaccharide. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0032587 ruffle membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 localises to membrane ruffles, which it induces. Reason: Ruffle membrane is part of the plasma membrane and is where Rac1 drives protrusion. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0032587 ruffle membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 localises to membrane ruffles, which it induces. Reason: Ruffle membrane is part of the plasma membrane and is where Rac1 drives protrusion. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0032707 negative regulation of interleukin-23 production | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of interleukin-23 production is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal negative regulation of interleukin-23 production. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0032956 regulation of actin cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: Rac1 regulates actin cytoskeleton organization. Reason: Core; inherited across the Rho family. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac |
| GO:0034446 substrate adhesion-dependent cell spreading | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives cell spreading on substrates. Reason: Lamellipodial protrusion consequence. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0034446 substrate adhesion-dependent cell spreading | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives cell spreading on substrates. Reason: Lamellipodial protrusion consequence. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0034446 substrate adhesion-dependent cell spreading | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives cell spreading on substrates. Reason: Lamellipodial protrusion consequence. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0034446 substrate adhesion-dependent cell spreading | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rac1 drives cell spreading on substrates. Reason: Lamellipodial protrusion consequence. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0035567 non-canonical Wnt signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in non-canonical Wnt signalling (mouse). Reason: Signalling context, non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus | IMP PMID:23412604 Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates ... | KEEP AS NON CORE | Summary: Rac1 is required for glucose-stimulated insulin secretion through F-actin remodelling. Reason: Rat INS-1 knockdown and mouse beta-cell knockout data (full text read). Rac1 acts upstream by clearing cortical F-actin; non-core. Supporting Evidence: PMID:23412604 In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels PMID:23412604 F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion |
| GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is required for glucose-stimulated insulin secretion through F-actin remodelling. Reason: Rat INS-1 knockdown and mouse beta-cell knockout data (full text read). Rac1 acts upstream by clearing cortical F-actin; non-core. Supporting Evidence: PMID:23412604 In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels PMID:23412604 F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion |
| GO:0036464 cytoplasmic ribonucleoprotein granule | ISO GO_REF:0000121 | UNDECIDED | Summary: Cytoplasmic ribonucleoprotein granule localisation transferred from human RAC1. Reason: No rat or UniProt statement supports an RNP-granule pool; the human source could not be inspected. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: UNRESOLVED Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0038166 angiotensin-activated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts downstream of angiotensin receptors (mouse). Reason: Signalling context (NOX activation). Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Melanosome localisation transferred from human RAC1 (melanosome proteomics). Reason: Peripheral, proteomics-derived location; not where the core function acts. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0042470 melanosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Melanosome localisation transferred from human RAC1 (melanosome proteomics). Reason: Peripheral, proteomics-derived location; not where the core function acts. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0042470 melanosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Melanosome localisation transferred from human RAC1 (melanosome proteomics). Reason: Peripheral, proteomics-derived location; not where the core function acts. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0042554 superoxide anion generation | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 is the GTPase switch that activates NADPH oxidase to generate superoxide. Reason: Rac1 is an intrinsic NOX component in rat macrophages and is required for agonist-induced ROS in rat cells. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) PMID:16055727 the small GTPase Rac1, an intrinsic component of the NOX complex PMID:11756405 stable expression of Rac(N17), a dominant negative Rac1 mutant, completely blocks leukotriene B(4)-induced ROS generation |
| GO:0042734 presynaptic membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Presynaptic membrane pool, transferred from mouse. Reason: Peripheral neuronal location. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0042826 histone deacetylase binding | IPI PMID:22679019 Histone deacetylase 3 mediates allergic skin inflammation by... | KEEP AS NON CORE | Summary: Rac1 interacts with HDAC3 in antigen-stimulated rat basophilic leukaemia cells. Reason: Co-immunoprecipitation in RBL-2H3 cells (full text read). A context-specific interaction, peripheral to Rac1 core function. Supporting Evidence: PMID:22679019 Antigen stimulation led to an interaction between HDAC3 and Rac1 at the membrane |
| GO:0043020 NADPH oxidase complex | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 is a regulatory subunit of the NADPH oxidase complex. Reason: Rac1 is an intrinsic NOX component in rat macrophages and is part of the phagocyte NADPH oxidase complex. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Component of the phagocyte NADPH oxidase complex composed of an obligatory core heterodimer formed by the membrane proteins CYBA and CYBB PMID:16055727 the small GTPase Rac1, an intrinsic component of the NOX complex |
| GO:0043131 erythrocyte enucleation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Erythrocyte enucleation is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal erythrocyte enucleation. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0043652 engulfment of apoptotic cell | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives engulfment of apoptotic cells. Reason: DOCK1-ELMO1-Rac1 pathway. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. |
| GO:0044877 protein-containing complex binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 binds multiprotein complexes (e.g. DOCK1-ELMO1, PAR polarity complex, NADPH oxidase). Reason: Broad but true; the specific complexes are captured by other terms. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. file:rat/Rac1/Rac1-uniprot.txt Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. |
| GO:0045202 synapse | EXP PMID:15800193 A GIT1/PIX/Rac/PAK signaling module regulates spine morphoge... | ACCEPT | Summary: Rac1 localises to and is activated at synapses in hippocampal neurons. Reason: FRET imaging in rat hippocampal neurons shows local Rac activation in dendritic spines. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, localizes at synapses, where it is activated PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. |
| GO:0045202 synapse | IEA GO_REF:0000044 | ACCEPT | Summary: Rac1 localises to and is activated at synapses in hippocampal neurons. Reason: FRET imaging in rat hippocampal neurons shows local Rac activation in dendritic spines. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, localizes at synapses, where it is activated PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. |
| GO:0045211 postsynaptic membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Postsynaptic membrane pool, transferred from mouse. Reason: Consistent with spine activation of Rac1. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. |
| GO:0045216 cell-cell junction organization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 contributes to cell-cell junction organization. Reason: DSG3-dependent junctional actin. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Required for DSG3 translocation to cell-cell junctions, DSG3-mediated organization of cortical F-actin bundles and anchoring of actin at cell junctions |
| GO:0045428 regulation of nitric oxide biosynthetic process | IGI PMID:16055727 Signal regulatory protein alpha ligation induces macrophage ... | KEEP AS NON CORE | Summary: Rac1 regulates nitric oxide production in rat macrophages via NOX-derived H2O2. Reason: Full text read; SIRPalpha-induced NO production requires PI3-K-dependent Rac1 activation and NOX. Indirect, non-core. Supporting Evidence: PMID:16055727 triggering of SIRPΞ± in macrophages involves the PI3-K-dependent activation of Rac1, which contributes to NOX activation |
| GO:0045453 bone resorption | IDA PMID:10350213 Rac-GTPase, osteoclast cytoskeleton and bone resorption. | KEEP AS NON CORE | Summary: Rac1 is required for bone resorption by rat osteoclasts. Reason: Antibody inhibition reduced resorption (abstract); acts via the actin cytoskeleton. Supporting Evidence: PMID:10350213 Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. |
| GO:0045740 positive regulation of DNA replication | IMP PMID:9487126 The Ras/Rac1/Cdc42/SEK/JNK/c-Jun cascade is a key pathway by... | KEEP AS NON CORE | Summary: Rac1 lies upstream of JNK-driven DNA synthesis in rat hepatocytes. Reason: Dominant-negative Rac1 blunted agonist-stimulated DNA synthesis (full text); an upstream signalling role, non-core. Supporting Evidence: PMID:9487126 multiple agonists stimulate DNA synthesis in primary cultures of hepatocytes via a Ras/Rac1/Cdc42/SEK/JNK/c-Jun pathway |
| GO:0046425 regulation of receptor signaling pathway via JAK-STAT | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 modulates JAK-STAT signalling (mouse). Reason: Indirect signalling context. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0048012 hepatocyte growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in HGF receptor signalling. Reason: Signalling context. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0048168 regulation of neuronal synaptic plasticity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates synaptic plasticity. Reason: Via spine actin. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX |
| GO:0048532 anatomical structure arrangement | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Anatomical structure arrangement is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal anatomical structure arrangement. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0048812 neuron projection morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives neuron projection morphogenesis. Reason: CDKL5-Rac1 signalling in rat neurons. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 |
| GO:0048813 dendrite morphogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in dendrite morphogenesis. Reason: Rat neuron data. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:20861382 CDKL5 colocalized and formed a protein complex with Rac1 file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX |
| GO:0048870 cell motility | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 drives cell motility. Reason: Non-core process outcome. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. |
| GO:0048870 cell motility | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rac1 drives cell motility. Reason: Non-core process outcome. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. |
| GO:0048871 multicellular organismal-level homeostasis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Multicellular organismal-level homeostasis is an uninformative ARBA prediction. Reason: This electronic rule-based term says nothing about Rac1's activity; Rac1 contributes only indirectly to organismal homeostasis. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0048873 homeostasis of number of cells within a tissue | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Homeostasis of number of cells within a tissue is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal homeostasis of number of cells within a tissue. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0051022 Rho GDP-dissociation inhibitor binding | IPI PMID:22564631 Cellular function of RhoGDI-Ξ± mediates the cycling of Rac1 a... | ACCEPT | Summary: Rac1 binds RhoGDIalpha, which extracts it from membranes and holds it inactive in the cytosol. Reason: RhoGDIalpha pull-downs from rat embryo fibroblast lysate retain Rac1 (PMID:20472934, full text), and Rac1-RhoGDIalpha association is regulated in INS-1E beta cells (PMID:22564631). GDI binding is an integral part of the Rac1 activation cycle. Supporting Evidence: PMID:20472934 When Ser-34 was mutated to Asp, there was significantly reduced RhoGDIΞ± binding to RhoA (by around 75%) but not Rac1 or Cdc42. PMID:20472934 compared in GTPase pulldown assays with lysate from rat embryo fibroblasts PMID:22564631 Rac1 binding to RhoGDI-Ξ± decreased after MPA treatment file:rat/Rac1/Rac1-uniprot.txt Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. |
| GO:0051117 ATPase binding | IPI PMID:20671235 Unexpected role of the copper transporter ATP7A in PDGF-indu... | KEEP AS NON CORE | Summary: Rac1 co-immunoprecipitates with the copper ATPase ATP7A in rat vascular smooth muscle cells. Reason: Full text read; ATP7A recruits Rac1 to lipid rafts at the leading edge during PDGF-induced migration. Specific, context-dependent interaction. Supporting Evidence: PMID:20671235 Co-immunoprecipitation analysis showed that ATP7A associated with Rac1 in the basal state, which was further enhanced after PDGF stimulation |
| GO:0051491 positive regulation of filopodium assembly | IMP PMID:15788770 Deleted in colorectal cancer binding netrin-1 mediates cell ... | KEEP AS NON CORE | Summary: Rac1 is required for netrin-1-induced growth-cone expansion including filopodia. Reason: Rat commissural neuron data (abstract). Non-core. Supporting Evidence: PMID:15788770 netrin-1 recruits Cdc42, Rac1, Pak1, and N-WASP into a complex with the intracellular domain of DCC and Nck1 |
| GO:0051492 regulation of stress fiber assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 influences stress fibre assembly. Reason: Rac1 and RhoA cross-regulate; non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0051496 positive regulation of stress fiber assembly | ISO GO_REF:0000121 | UNDECIDED | Summary: Positive regulation of stress fibre assembly, transferred from human, is atypical for Rac1. Reason: Stress fibres are classically RhoA-driven and Rac1 often antagonises them; a positive role may be context-specific in the human source, which could not be inspected. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: UNRESOLVED Failure modes: REGULATORY SIGN INVERSION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0051668 localization within membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Active Rac1 recruits partners such as SYNJ2 and PPP5C to the plasma membrane. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts with SYNJ2; this interaction is GTP-dependent and mediates the translocation of SYNJ2 from the cytoplasm to the plasma membrane |
| GO:0051894 positive regulation of focal adhesion assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes focal adhesion (focal complex) assembly. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts upstream of PI3K/AKT signalling (mouse). Reason: Signalling context. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0051932 synaptic transmission, GABAergic | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is needed for GABAergic synaptic transmission. Reason: Rat neuron data show disrupting Rac1 impairs inhibitory transmission. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0055038 recycling endosome membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Recycling endosome membrane pool transferred from human. Reason: Peripheral location (note: CC term). Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt up-regulation of ACKR2 from endosomal compartment to cell membrane |
| GO:0060071 Wnt signaling pathway, planar cell polarity pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts in planar cell polarity signalling (mouse). Reason: Signalling context. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0060091 kinocilium | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Kinocilium localisation in inner-ear hair cells, transferred from mouse. Reason: Peripheral, cell-type-specific location. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-bioinformatics/RESULTS.md are identical over all 192 residues |
| GO:0060263 regulation of respiratory burst | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates the respiratory burst through NADPH oxidase. Reason: Follows from its NOX subunit role. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) |
| GO:0060326 cell chemotaxis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Rac1 acts in cell chemotaxis. Reason: Rat mast-cell and LTB4 chemotaxis data. Non-core. Supporting Evidence: PMID:12413953 Eotaxin-induced cell migration was completely blocked in RBL-RacN17 cells expressing a dominant negative Rac1 mutant PMID:11756405 Rac, ERK, and cytosolic phospholipase A(2) all play pivotal roles in mediating the ROS generation that appears to be a prerequisite for leukotriene B(4)-induced chemotaxis |
| GO:0060999 positive regulation of dendritic spine development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes dendritic spine development. Reason: GIT1/PIX/Rac/PAK module in rat hippocampal neurons. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX |
| GO:0061344 regulation of cell adhesion involved in heart morphogenesis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of cell adhesion involved in heart morphogenesis is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal regulation of cell adhesion involved in heart morphogenesis. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0070376 regulation of ERK5 cascade | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates the ERK5 cascade (mouse). Reason: Part of a MAP2K3/MAP3K3/CCM2 complex. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:0071260 cellular response to mechanical stimulus | IDA PMID:12105187 Effects of cell tension on the small GTPase Rac. | KEEP AS NON CORE | Summary: Rac activity is regulated by mechanical stretch in rat VSM cells. Reason: Full text read; stretch deactivates Rac to suppress lamellipodia. Non-core. Supporting Evidence: PMID:12105187 equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac |
| GO:0071526 semaphorin-plexin signaling pathway | IMP PMID:20696765 Semaphorin 5A and plexin-B3 inhibit human glioma cell motili... | KEEP AS NON CORE | Summary: Rac1 is the downstream target inactivated in Sema5A/plexin-B3 signalling. Reason: Abstract-only paper; Rac1 inactivation via RhoGDIalpha mediates the motility effect. Non-core. Supporting Evidence: PMID:20696765 Sema5A promotes Rac1 recruitment to RhoGDIΞ± and reduces its membrane localization in a plexin-B3-dependent manner PMID:20696765 This represents a novel signaling of semaphorin and plexin in the control of cell motility by indirect inactivation of Rac1 through RhoGDIΞ±. |
| GO:0071542 dopaminergic neuron differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Dopaminergic neuron differentiation is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal dopaminergic neuron differentiation. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0072659 protein localization to plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Active Rac1 promotes translocation of partners (SYNJ2, ACKR2) to the plasma membrane. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Interacts with SYNJ2; this interaction is GTP-dependent and mediates the translocation of SYNJ2 from the cytoplasm to the plasma membrane file:rat/Rac1/Rac1-uniprot.txt up-regulation of ACKR2 from endosomal compartment to cell membrane |
| GO:0090023 positive regulation of neutrophil chemotaxis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes neutrophil chemotaxis. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0090023 positive regulation of neutrophil chemotaxis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes neutrophil chemotaxis. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0090103 cochlea morphogenesis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cochlea morphogenesis is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal cochlea morphogenesis. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:0097178 ruffle assembly | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 drives membrane ruffle assembly. Reason: Core actin-protrusion process; growth-factor induced ruffling. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0097178 ruffle assembly | ISO GO_REF:0000121 | ACCEPT | Summary: Rac1 drives membrane ruffle assembly. Reason: Core actin-protrusion process; growth-factor induced ruffling. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:0098794 postsynapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 is active in the postsynapse. Reason: Consistent with spine and inhibitory-synapse functions. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. |
| GO:0098974 postsynaptic actin cytoskeleton organization | EXP PMID:25284783 GIT1 and Ξ²PIX are essential for GABA(A) receptor synaptic st... | ACCEPT | Summary: Rac1 organises the postsynaptic actin cytoskeleton at inhibitory synapses. Reason: Rat hippocampal neuron data (full text read): Rac1 and PAK stabilise F-actin and GABAA receptor clusters. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0098974 postsynaptic actin cytoskeleton organization | IDA PMID:25284783 GIT1 and Ξ²PIX are essential for GABA(A) receptor synaptic st... | ACCEPT | Summary: Rac1 organises the postsynaptic actin cytoskeleton at inhibitory synapses. Reason: Rat hippocampal neuron data (full text read): Rac1 and PAK stabilise F-actin and GABAA receptor clusters. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0098974 postsynaptic actin cytoskeleton organization | IMP PMID:25284783 GIT1 and Ξ²PIX are essential for GABA(A) receptor synaptic st... | ACCEPT | Summary: Rac1 organises the postsynaptic actin cytoskeleton at inhibitory synapses. Reason: Rat hippocampal neuron data (full text read): Rac1 and PAK stabilise F-actin and GABAA receptor clusters. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts at glutamatergic synapses (dendritic spines). Reason: Supported by rat spine FRET data. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 acts at glutamatergic synapses (dendritic spines). Reason: Supported by rat spine FRET data. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: PMID:15800193 We also show that Rac is locally activated in dendritic spines using fluorescence resonance energy transfer. |
| GO:0098982 GABA-ergic synapse | EXP PMID:25284783 GIT1 and Ξ²PIX are essential for GABA(A) receptor synaptic st... | ACCEPT | Summary: Rac1 acts at GABA-ergic synapses to stabilise GABAA receptor clusters. Reason: Rat hippocampal neuron data (full text read) show Rac1 activity at inhibitory synapses downstream of GIT1/betaPIX. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0098982 GABA-ergic synapse | IDA PMID:25284783 GIT1 and Ξ²PIX are essential for GABA(A) receptor synaptic st... | ACCEPT | Summary: Rac1 acts at GABA-ergic synapses to stabilise GABAA receptor clusters. Reason: Rat hippocampal neuron data (full text read) show Rac1 activity at inhibitory synapses downstream of GIT1/betaPIX. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0098982 GABA-ergic synapse | IMP PMID:25284783 GIT1 and Ξ²PIX are essential for GABA(A) receptor synaptic st... | ACCEPT | Summary: Rac1 acts at GABA-ergic synapses to stabilise GABAA receptor clusters. Reason: Rat hippocampal neuron data (full text read) show Rac1 activity at inhibitory synapses downstream of GIT1/betaPIX. A mutant phenotype cannot by itself establish a location; the location is supported by the IDA/EXP rows from the same paper, so this row takes the same action and the evidence code is flagged for checking. Supporting Evidence: PMID:25284783 We find that Rac1 activity stabilizes GABAARs at inhibitory synapses while disrupting GIT1, Rac1 or PAK all lead to impaired inhibitory transmission. file:rat/Rac1/Rac1-uniprot.txt In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization |
| GO:0150052 regulation of postsynapse assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates postsynapse assembly. Reason: Via spine actin. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX |
| GO:1900026 positive regulation of substrate adhesion-dependent cell spreading | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes substrate adhesion-dependent cell spreading. Reason: Non-core. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:1900029 positive regulation of ruffle assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes ruffle assembly. Reason: Non-core restatement of ruffle assembly. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles |
| GO:1900242 regulation of synaptic vesicle endocytosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 regulates synaptic vesicle endocytosis (mouse). Reason: Presynaptic actin role. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states |
| GO:1903348 positive regulation of bicellular tight junction assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Rac1 promotes tight junction assembly. Reason: Non-core junctional role. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. |
| GO:1903348 positive regulation of bicellular tight junction assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rac1 promotes tight junction assembly. Reason: Non-core junctional role. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. |
| GO:1904948 midbrain dopaminergic neuron differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Midbrain dopaminergic neuron differentiation is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal midbrain dopaminergic neuron differentiation. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
| GO:2000386 positive regulation of ovarian follicle development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Positive regulation of ovarian follicle development is a downstream phenotype-level process, not a function Rac1 performs. Reason: Rac1 is required in mouse for normal positive regulation of ovarian follicle development. This is a tissue-, organ- or organism-level outcome of Rac1 loss in mouse (or human) studies; Rac1 contributes through its general cytoskeletal switch function and does not perform a step specific to this process. Rat, mouse and human RAC1 are identical in sequence, so the transfer itself carries no divergence risk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Supporting Evidence: file:rat/Rac1/Rac1-uniprot.txt Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states file:rat/Rac1/Rac1-deep-research-manual.md are pleiotropic downstream outcomes of Rac1 loss rather than processes Rac1 performs. |
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Download this section (compressed HTML)Q: PMID:20696765 (Sema5A/plexin-B3) describes human glioma cells in its title and abstract, yet its rows (cytosol, membrane, semaphorin-plexin signalling, protein binding) are on rat Rac1. Were rat cells (e.g. C6) used, or should these rows be on human RAC1 (P63000)?
Q: Which human RAC1 experiments underlie the ISO transfers of negative regulation of fibroblast migration, positive regulation of stress fiber assembly, thioesterase binding and cytoplasmic ribonucleoprotein granule?
Q: How do PAK-mediated (Ser101/Ser174) and PKC-mediated (Ser34) RhoGDIalpha phosphorylation combine to set the relative release of Rac1 and RhoA in rat fibroblast adhesion?
Experiment: Image Rac1 activity with a FRET biosensor at inhibitory versus excitatory synapses of rat hippocampal neurons while acutely inhibiting betaPIX or PAK, and measure GABAA receptor cluster lifetime.
Hypothesis: Local, synapse-type-specific Rac1 activation by GIT1/betaPIX controls GABAA receptor surface stability through PAK-dependent F-actin stabilisation.
Experiment: Knock out Rac1 in rat osteoclast precursors and rescue with wild-type, fast-cycling and effector-binding mutants to separate cytoskeletal (PAK/WAVE) from NADPH oxidase roles in ruffled-border formation and resorption.
Hypothesis: Ruffled-border formation and resorption require Rac1 effector signalling to actin, independent of its NOX role.
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Download this section (compressed HTML)Script: compare_orthologs.py (fetches canonical sequences from the UniProt REST API).
Raw output: output.txt.
The canonical sequences of rat Rac1 (Q6RUV5), human RAC1 (P63000) and mouse Rac1 (P63001)
are identical over all 192 residues (192/192 identical positions for both human and mouse versus rat).
Because the three proteins are identical in sequence, molecular-function and cellular-component
annotations transferred by ISO/ISS from human or mouse RAC1 carry no sequence-divergence risk.
Whether a transferred biological-process term is appropriate depends only on whether the
source annotation describes a function Rac1 itself performs, not on sequence.
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