CDC42

Summary: CDC42 occurs on Golgi-associated membranes.

Reason: Retain the source ISS inference to Golgi membrane with its rat Q8CFN2 donor. Selected full Results/Figure 4C-D of PMID:16380373 independently examine endogenous CDC42 and brefeldin-A redistribution in HeLa cells; this is human Golgi-compartment corroboration, not a new direct assay of the rat donor or proof of membrane topology. The source-linked author full text and a short excerpt are documented in CDC42-notes.md.

Summary: The donor experiment resolves an insulin secretory granule fraction.

Reason: The mouse donor annotation is traced to PMID:21828338, whose full Figure1C/Methods detect Cdc42 in the VAMP2-marked MIN6 insulin storage/secretory granule fraction. Secretory granule is more informative than storage vacuole. Fractionation does not distinguish lumen from membrane, and the human annotation remains orthology-based.

Proposed replacements: secretory granule

Summary: Acrosomal association is a specialized localization.

Reason: Retain the UniProt cellular-location mapping as a non-core reproductive-cell context. Independent PMID:30189608 describes mouse spermatid acrosome-associated localization; this is not a direct human acrosomal activity experiment.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for heart process as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for cardiac neural crest cell migration involved in outflow tract morphogenesis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 has intrinsic GTP-hydrolysing activity.

Reason: GTP hydrolysis is integral to the CDC42 molecular switch and is directly supported by independent Cdc42 biochemical experiments in PMID:9748241. Retain the source assertion without claiming that every cited cellular GTP-loading or effector-pull-down assay measured purified hydrolysis. PAINT/InterPro/Rhea support is consistent with this established activity; the target appearing in PAINT WITH/FROM is legitimate descendant evidence.

Summary: CDC42 is a small monomeric G protein.

Reason: GO:0003925 includes GTP-controlled molecular function regulators, including small GTPases. CDC42 cycles between GDP- and GTP-bound states and its active state engages effectors; this is the central function, not a heterotrimeric-G-alpha-only term.

Summary: CDC42 association with FLNA is supported.

Reason: The primary abstract directly reports filamin binding by Cdc42; only RalA binding is described as GTP-specific. Retain the observed CDC42–filamin association without importing RalA nucleotide selectivity or filamin actin-crosslinking activity. Retain as non-core under the project’s supported-binding instruction.

Summary: The exact BCAR1 association is not resolved from the accessible abstract.

Reason: The paper describes p130CAS recruitment/phosphorylation and CDC42 signaling, but the exact coassociation experiment and the distinct source accession UniProtKB:P56945 were not independently established. Preserve both original assertions; do not infer direct binding from shared pathway participation.

Summary: The exact BCAR1 association is not resolved from the accessible abstract.

Reason: The paper describes p130CAS recruitment/phosphorylation and CDC42 signaling, but the exact coassociation experiment and the distinct source accession UniProtKB:Q6P5Z4 were not independently established. Preserve both original assertions; do not infer direct binding from shared pathway participation.

Summary: CDC42 association with CDC42SE2/SPEC2 is supported.

Reason: The primary abstract reports the two human SPEC proteins binding Cdc42 in yeast two-hybrid assays and identifies their CRIB motifs. Current UniProt maps Q9NRR3 to SPEC2; retain generic association without assigning SPEC1-specific functional experiments to SPEC2. Retain as non-core under the project’s supported-binding instruction.

Summary: The source supports CDC42 association with Q9JK83.

Reason: Exact source-linked IntAct records EBI-81873, EBI-81899, EBI-81959 match CDC42 and Q9JK83 using coimmunoprecipitation, two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The exact partner is a mouse protein; the cross-species assay is not renamed as a human–human experiment. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q9NPB6.

Reason: Exact source-linked IntAct records EBI-81888, EBI-81907 match CDC42 and Q9NPB6 using two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 association with CDC42EP2/CEP2 is supported.

Reason: The primary abstract explicitly reports CEP2 binding Cdc42; UniProt maps O14613 to CEP2. Cell-shape experiments include NIH3T3 fibroblasts, which are not relabelled as human cells. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 association with CDC42EP5/CEP5 is supported.

Reason: The primary abstract explicitly reports CEP5 binding Cdc42; UniProt maps Q6NZY7 to CEP5. Retain the source pair, without treating all CEP paralogs as experimentally interchangeable. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 associates with the protein kinase PRKCI.

Reason: Exact source-linked IntAct records EBI-295488, EBI-295530, EBI-295543 match CDC42 and P41743 using coimmunoprecipitation, pull down, two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: The source supports CDC42 association with Q9BYG4.

Reason: Exact source-linked IntAct records EBI-295480, EBI-295504 match CDC42 and Q9BYG4 using pull down, two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q9BYG5.

Reason: Exact source-linked IntAct records EBI-295472, EBI-295499, EBI-295543 match CDC42 and Q9BYG5 using coimmunoprecipitation, pull down, two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q9NPB6.

Reason: Exact source-linked IntAct records EBI-295464, EBI-295494 match CDC42 and Q9NPB6 using pull down, two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 association with ITGB1BP1/ICAP1 is supported.

Reason: Selected primary Results and biochemical assays establish ICAP1 binding to Cdc42 and inhibition of GDP dissociation. NIH3T3 spreading and COS activation assays are distinct contexts; CDC42 is the regulated GTPase, not the GDI enzyme. Retain as non-core under the project’s supported-binding instruction.

Summary: The source supports CDC42 association with O52623.

Reason: Exact source-linked IntAct records EBI-602253, EBI-602317 match CDC42 and O52623 using gdp/gtp exchange assay, x-ray crystallography. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Partner variant comparisons are present; loss-of-binding variants do not erase the supported reference interaction. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 associates with the protein kinase PAK1.

Reason: Exact source-linked IntAct records EBI-602824 match CDC42 and Q13153 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The records include CDC42 activation-state or interface mutants; mutant and fragment comparisons are retained as assay context, not proof that all variants have equal activity. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: The source supports CDC42 association with Q9JK83.

Reason: Exact source-linked IntAct records EBI-602788, EBI-602806, EBI-602851 match CDC42 and Q9JK83 using anti tag coimmunoprecipitation, fluorescent resonance energy transfer, x-ray crystallography. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The records include CDC42 activation-state or interface mutants; mutant and fragment comparisons are retained as assay context, not proof that all variants have equal activity. The exact partner is a mouse protein; the cross-species assay is not renamed as a human–human experiment. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with P46940.

Reason: Exact source-linked IntAct records EBI-457807, EBI-457815 match CDC42 and P46940 using pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 associates with the protein kinase PAK1.

Reason: Exact source-linked IntAct records EBI-446664 match CDC42 and Q13153 using pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The records include CDC42 activation-state or interface mutants; mutant and fragment comparisons are retained as assay context, not proof that all variants have equal activity. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 associates with the protein kinase PRKCI.

Reason: Exact source-linked IntAct records EBI-360114, EBI-360119 match CDC42 and P41743 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 associates with the protein kinase MARK4.

Reason: Exact source-linked IntAct records EBI-354787, EBI-349707 match CDC42 and Q96L34 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: The source supports CDC42 association with Q9BYG4.

Reason: Exact source-linked IntAct records EBI-2433997, EBI-2434215, EBI-2434223 match CDC42 and Q9BYG4 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q9BYG5.

Reason: Exact source-linked IntAct records EBI-2434047, EBI-360129, EBI-360134 match CDC42 and Q9BYG5 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q9NPB6.

Reason: Exact source-linked IntAct records EBI-2434095, EBI-307047, EBI-360124 match CDC42 and Q9NPB6 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 associates with the protein kinase CDC42BPA.

Reason: Exact source-linked IntAct records EBI-689161 match CDC42 and Q5VT25 using far western blotting. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 binds the WASP-family GTPase-binding domain.

Reason: Selected full primary Results and Figure 1 in the author-hosted PMID:15361624 PDF describe a WASP residues 201-321 CRIB/GBD reporter and nucleotide-dependent CDC42 binding, with binding-defective H246D/H249D controls. These directly support GO:0032427. Human-neutrophil activity assays and MEF/3T3 imaging are distinct experimental contexts; the reporter binding does not assign actin nucleation to CDC42. The exact primary URL and short source anchor are recorded in CDC42-notes.md.

Proposed replacements: GBD domain binding

Summary: The exact human CDC42–Dictyostelium WASP assay remains unverified.

Reason: The accessible primary abstract studies Dictyostelium actin regulation; it does not resolve whether human CDC42 was used in the supporting biochemical comparison. Retain the exact Q9GSG9 partner and source fields. Neither a wrong-gene removal nor a human construct assumption is justified without the relevant full assay.

Summary: The source supports CDC42 association with Q00587.

Reason: Exact source-linked IntAct records EBI-754756 match CDC42 and Q00587 using two hybrid pooling approach. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 binds the WASP-family GTPase-binding domain.

Reason: The primary abstract explicitly describes the N-WASP GTPase-binding domain and reversal by CDC42 of its autoinhibition-dependent resistance to phosphorylation/dephosphorylation. Together with the exact source-linked O00401 binding record, this supports GBD-domain recognition. GO:0032427 states that molecular specificity without assigning the partner kinase or Arp2/3 activity to CDC42. No additional full-text assay details are claimed from the abstract-only normal cache.

Proposed replacements: GBD domain binding

Summary: CDC42 association with ABCA1 is supported.

Reason: The primary abstract describes apoA-I-dependent Cdc42 coimmunoprecipitation with wild-type ABCA1 in HEK293, unlike ATPase-defective/truncated controls. This supports receptor association, not CDC42 binding directly to apoA-I. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 associates with the protein kinase PAK1.

Reason: Exact source-linked IntAct records EBI-26873917 match CDC42 and Q13153 using pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: The exact human CDC42–Dictyostelium WASP assay remains unverified.

Reason: The accessible primary abstract studies Dictyostelium actin regulation; it does not resolve whether human CDC42 was used in the supporting biochemical comparison. Retain the exact Q9GSG9 partner and source fields. Neither a wrong-gene removal nor a human construct assumption is justified without the relevant full assay.

Summary: CDC42–APC association has independent direct support.

Reason: The original PMID:17145773 record is an APC/Asef exchange-assay context and does not alone establish a purified binary interface. Independent PMID:21311754 directly measures CDC42–APC binding and supports the broad pair. Retain the original source fields, distinguish the independent support, and do not assign APC or Asef catalytic activities to CDC42.

Summary: CDC42 association with IQGAP1 is supported.

Reason: The primary abstract explicitly reports reduced IQGAP1–Cdc42 association during EPEC infection. This is evidence for the measured association, not for direct CDC42 antibacterial activity. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42–IRSp53 binding is established, but the precise source isoform needs verification.

Reason: The accessible primary evidence supports active CDC42 interaction with IRSp53; the exact Q9UQB8-4 construct in this annotation has not been reconciled with the source sequence/Methods. Preserve the isoform-qualified partner rather than generalizing it to canonical IRSp53.

Summary: The source-specific PAK1 binding assay remains unverified.

Reason: The accessible abstract establishes CDC42 activation/phenotype but does not resolve the exact Q13153 pull-down or binding experiment. The source WITH field identifies PAK1; it does not describe the assay. The bounded CDC42/PMID IntAct query returned no matching record for this paper, unlike the positively joined kinase refinements. This absence is not negative biological evidence. Other PAK1 studies establish the general interaction but do not settle this source-specific assertion; retain UNDECIDED pending its primary assay.

Summary: CDC42 association with FNBP1L/TOCA1 is supported.

Reason: Selected full Results/Figure7E show TOCA1 binding purified GTP-loaded Cdc42. The paper separately studies nematode TOCA genetics; those organismal results are not assigned to human CDC42. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 association with MAP3K11/MLK3 is supported.

Reason: Selected primary Results report merlin-dependent inhibition of the Cdc42–MLK3 interaction. Independent exact PMID:25241761 target records corroborate association, with proximity-assay resolution stated separately. Refine to protein kinase binding at the demonstrated association resolution.

Proposed replacements: protein kinase binding

Summary: CDC42–WASL association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–CDC42EP2 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–PAK4 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The checked pair identifies PAK4 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–WAS association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–ARHGDIA association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–CDC42EP1 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–PAK1 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The checked pair identifies PAK1 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–PAK2 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The checked pair identifies PAK2 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–CDC42BPA association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The checked pair identifies CDC42BPA as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–PARD6B association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–PAK6 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The checked pair identifies PAK6 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–CDC42SE1 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–PAK5 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The checked pair identifies PAK5 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–BAIAP2 association is supported by source-linked two-hybrid pooling (PMID:20936779).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42 associates with the protein kinase PAK1.

Reason: Exact source-linked IntAct records EBI-2943980 match CDC42 and Q13153 using pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 associates with the protein kinase LRRK2.

Reason: Exact source-linked IntAct records EBI-6511024, EBI-6511044 match CDC42 and Q5S007 using anti tag coimmunoprecipitation, confocal microscopy. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 association with ARHGEF16 is supported.

Reason: The primary abstract explicitly reports ARHGEF16 coimmunoprecipitation of Cdc42 in the HPV E6 context and recombinant exchange assays. CDC42 is the GEF target, not a guanine nucleotide exchange catalyst. Retain as non-core under the project’s supported-binding instruction.

Summary: The source-specific PAK1 binding assay remains unverified.

Reason: The accessible abstract establishes CDC42 activation/phenotype but does not resolve the exact Q13153 pull-down or binding experiment. The source WITH field identifies PAK1; it does not describe the assay. The bounded CDC42/PMID IntAct query returned no matching record for this paper, unlike the positively joined kinase refinements. This absence is not negative biological evidence. Other PAK1 studies establish the general interaction but do not settle this source-specific assertion; retain UNDECIDED pending its primary assay.

Summary: The source supports CDC42 association with P25054.

Reason: Exact source-linked IntAct records EBI-16881459, EBI-16881497, EBI-16881601 match CDC42 and P25054 using confocal microscopy, fluorescent resonance energy transfer, pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The records include CDC42 activation-state or interface mutants; mutant and fragment comparisons are retained as assay context, not proof that all variants have equal activity. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q9UQB8.

Reason: Exact source-linked IntAct records EBI-16881474 match CDC42 and Q9UQB8 using pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The records include CDC42 activation-state or interface mutants; mutant and fragment comparisons are retained as assay context, not proof that all variants have equal activity. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 association with SopB is supported.

Reason: The primary abstract and independently read full Results explicitly show human Cdc42 binding Salmonella SopB in yeast, including active and non-activatable Cdc42 constructs. UniProt confirms O30916 is SopB; preserve this foreign-effector interaction without assigning SopB catalysis to CDC42. Retain as non-core under the project’s supported-binding instruction.

Summary: The exact bacterial-effector comparison remains unverified.

Reason: The paper directly establishes SopB interaction, but the exact UniProtKB:P74873 control/construct assay has not been inspected. Preserve the original partner; do not transfer SopB evidence to another bacterial effector.

Summary: The exact bacterial-effector comparison remains unverified.

Reason: The paper directly establishes SopB interaction, but the exact UniProtKB:Q7CQD4 control/construct assay has not been inspected. Preserve the original partner; do not transfer SopB evidence to another bacterial effector.

Summary: CDC42 associates with the protein kinase LRRK2.

Reason: Exact source-linked IntAct records EBI-6309671 match CDC42 and Q5S007 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: The source directly detects CDC42 in SopB-associated preparations.

Reason: Selected full PMID:21566117 Results and the Table3 discussion report CDC42 with five/eight unique peptides in two SopB SILAC affinity-capture strategies using HEK293T lysates. Current UniProt maps A0A0H3NA16 to SopB/SigD from the assayed Salmonella SL1344 strain. Retain the exact foreign-effector association at proteomic resolution; no direct purified binary interface or partner catalysis is assigned to CDC42.

Summary: The source supports CDC42 association with P46940.

Reason: Exact source-linked IntAct records EBI-20974621, EBI-20974652, EBI-20974614 match CDC42 and P46940 using anti bait coimmunoprecipitation, cross-linking study. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The exact source target record remains inaccessible or unresolved.

Reason: The primary abstract establishes the study context but not this exact partner assertion, and the bounded target-level record query did not return a match. Database absence is not a negative experiment. Preserve the original source/partner pending the relevant target table or assay.

Summary: The source supports CDC42 association with O14613.

Reason: Exact source-linked IntAct records EBI-3927732 match CDC42 and O14613 using two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with Q00587.

Reason: Exact source-linked IntAct records EBI-3927816 match CDC42 and Q00587 using two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with P42768.

Reason: Exact source-linked IntAct records EBI-22086568 match CDC42 and P42768 using two hybrid. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Partner variant comparisons are present; loss-of-binding variants do not erase the supported reference interaction. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 association with PAK4 is supported.

Reason: The primary abstract directly reports Cdc42 binding to human PAK4 with conformational release of autoinhibition. The retained source assertion is binding; a general statement that every group-II PAK is activated by CDC42 is not inferred. Refine to protein kinase binding at the demonstrated association resolution.

Proposed replacements: protein kinase binding

Summary: CDC42 association with mouse Pak3 is supported.

Reason: Selected full Methods use the Pak3 binding-domain fragment70–106 in pull-down and immobilized-effector assays with nucleotide-loaded Cdc42 before/after histaminylation. This supports domain-level kinase binding; it does not assign histamine transfer to CDC42. The Methods mix a human Cdc42 accession with mouse-tissue cloning wording, so exact target construct species is not silently resolved. Refine to protein kinase binding at the demonstrated association resolution.

Proposed replacements: protein kinase binding

Summary: CDC42 associates with the protein kinase PAK1.

Reason: Exact source-linked IntAct records EBI-11165786, EBI-11165907, EBI-11165949 match CDC42 and Q13153 using pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 associates with the protein kinase PAK1.

Reason: Exact source-linked IntAct records EBI-6256371 match CDC42 and Q13153 using tandem affinity purification. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42–IRSp53 binding is established, but the precise source isoform needs verification.

Reason: The accessible primary evidence supports active CDC42 interaction with IRSp53; the exact Q9UQB8-4 construct in this annotation has not been reconciled with the source sequence/Methods. Preserve the isoform-qualified partner rather than generalizing it to canonical IRSp53.

Summary: CDC42 association with RCC2 is supported.

Reason: Selected full Results/Figure3 identify Cdc42 among proteins coprecipitating with GFP–RCC2 in SILAC proteomics. Direct interface mapping and GEF competition in that paper concern Rac1; retain the CDC42 association at proteomic resolution only. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 associates with the protein kinase MAP3K11.

Reason: Exact source-linked IntAct records EBI-6590677 match CDC42 and Q16584 using proximity ligation assay. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42–CDC42EP2 association is supported by source-linked array, pooling and validated two-hybrid records (PMID:25416956).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–CDC42EP1 association is supported by source-linked array, pooling and validated two-hybrid records (PMID:25416956).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–PAK2 association is supported by source-linked array, pooling and validated two-hybrid records (PMID:25416956).

Reason: The checked pair identifies PAK2 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–PARD6B association is supported by source-linked array, pooling and validated two-hybrid records (PMID:25416956).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: The source supports CDC42 association with P42768.

Reason: Exact source-linked IntAct records EBI-22087355 match CDC42 and P42768 using two hybrid array. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Partner variant comparisons are present; loss-of-binding variants do not erase the supported reference interaction. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The exact source target record remains inaccessible or unresolved.

Reason: The primary abstract establishes the study context but not this exact partner assertion, and the bounded target-level record query did not return a match. Database absence is not a negative experiment. Preserve the original source/partner pending the relevant target table or assay.

Summary: The source supports CDC42 association with P46940.

Reason: Exact source-linked IntAct records EBI-11002356, EBI-11132927 match CDC42 and P46940 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42 association with DOCK8 is supported.

Reason: Selected full Figure6C–H Results describe DOCK8/DHR2 binding to CDC42, including guanine-nucleotide-free G15A trapping, HA-Cdc42 coprecipitation, and purified-domain competition. These are binding/regulatory assays, not CDC42 GEF activity. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42–CDC42SE1 association is supported by HEK293T BioPlex affinity-purification mass spectrometry (PMID:28514442).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration. The BioPlex 2/3 representation of this edge is not independent replication.

Summary: CDC42 associates with the protein kinase PAK4.

Reason: Exact source-linked IntAct records EBI-25816194 match CDC42 and O96013 using anti tag coimmunoprecipitation. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: The source supports CDC42 association with Q92963.

Reason: Exact source-linked IntAct records EBI-25816354, EBI-25421193, EBI-25816237 match CDC42 and Q92963 using anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, confocal microscopy, pull down. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The records include CDC42 activation-state or interface mutants; mutant and fragment comparisons are retained as assay context, not proof that all variants have equal activity. Partner variant comparisons are present; loss-of-binding variants do not erase the supported reference interaction. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: The source supports CDC42 association with P42768.

Reason: Exact source-linked IntAct records EBI-22132656 match CDC42 and P42768 using two hybrid array. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Partner variant comparisons are present; loss-of-binding variants do not erase the supported reference interaction. Retain supported generic binding as non-core under the explicit project instruction; this does not transfer the partner’s activity to CDC42.

Summary: CDC42–IQGAP1 association is supported by FLAG-CDC42 affinity-purification mass spectrometry in HCT116 and HKE3 cells (PMID:31980649).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration.

Summary: CDC42–ARHGDIA association is supported by FLAG-CDC42 affinity-purification mass spectrometry in HCT116 and HKE3 cells (PMID:31980649).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration.

Summary: CDC42–CDC42EP1 association is supported by FLAG-CDC42 affinity-purification mass spectrometry in HCT116 and HKE3 cells (PMID:31980649).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration.

Summary: CDC42–PAK6 association is supported by FLAG-CDC42 affinity-purification mass spectrometry in HCT116 and HKE3 cells (PMID:31980649).

Reason: The checked pair identifies PAK6 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation. The result is an AP-MS association, not a purified direct-binding demonstration.

Proposed replacements: protein kinase binding

Summary: CDC42–CDC42EP2 association is supported by source-linked HuRI two-hybrid records (PMID:32296183).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–CDC42EP1 isoform 2 association is supported by source-linked HuRI two-hybrid records (PMID:32296183).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The tested partner is CDC42EP1 isoform 2; preserve Q00587-2.

Summary: CDC42–PAK2 association is supported by source-linked HuRI two-hybrid records (PMID:32296183).

Reason: The checked pair identifies PAK2 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–HDAC7 isoform 6 association is supported by source-linked HuRI two-hybrid records (PMID:32296183).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The tested partner is HDAC7 isoform 6, fragment 699–974; do not extend this construct result to a full-length isoform-specific mechanism.

Summary: CDC42–PARD6B association is supported by source-linked HuRI two-hybrid records (PMID:32296183).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function.

Summary: CDC42–PAK5 association is supported by source-linked HuRI two-hybrid records (PMID:32296183).

Reason: The checked pair identifies PAK5 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation.

Proposed replacements: protein kinase binding

Summary: CDC42–PAK4 association is supported by tagged-kinase pulldown/mass spectrometry in HEK293 Flp-In T-REx cells (PMID:32707033).

Reason: The checked pair identifies PAK4 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation. The result is an AP-MS association, not a purified direct-binding demonstration.

Proposed replacements: protein kinase binding

Summary: CDC42–PAK2 association is supported by tagged-kinase pulldown/mass spectrometry in HEK293 Flp-In T-REx cells (PMID:32707033).

Reason: The checked pair identifies PAK2 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation. The result is an AP-MS association, not a purified direct-binding demonstration.

Proposed replacements: protein kinase binding

Summary: CDC42–PAK6 association is supported by tagged-kinase pulldown/mass spectrometry in HEK293 Flp-In T-REx cells (PMID:32707033).

Reason: The checked pair identifies PAK6 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation. The result is an AP-MS association, not a purified direct-binding demonstration.

Proposed replacements: protein kinase binding

Summary: CDC42–PAK5 association is supported by tagged-kinase pulldown/mass spectrometry in HEK293 Flp-In T-REx cells (PMID:32707033).

Reason: The checked pair identifies PAK5 as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation. The result is an AP-MS association, not a purified direct-binding demonstration.

Proposed replacements: protein kinase binding

Summary: CDC42–CDC42SE1 association is supported by HEK293T BioPlex affinity-purification mass spectrometry (PMID:33961781).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration. The BioPlex 2/3 representation of this edge is not independent replication.

Summary: CDC42–IQGAP1 association is supported by endogenously tagged CDC42 OpenCell immunoprecipitation/mass spectrometry (PMID:35271311).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration.

Summary: CDC42–CDC42EP1 association is supported by endogenously tagged CDC42 OpenCell immunoprecipitation/mass spectrometry (PMID:35271311).

Reason: The exact source-linked pair supports this association. Retain the generic annotation as non-core under the explicit ClinGen project instruction; this assay does not establish a more specific CDC42 molecular function. The result is an AP-MS association, not a purified direct-binding demonstration.

Summary: CDC42–CDC42BPA association is supported by endogenously tagged CDC42 OpenCell immunoprecipitation/mass spectrometry (PMID:35271311).

Reason: The checked pair identifies CDC42BPA as a protein kinase; refine this source-specific association to GO:0019901 protein kinase binding. The binding result does not by itself establish kinase activation. The result is an AP-MS association, not a purified direct-binding demonstration.

Proposed replacements: protein kinase binding

Summary: CDC42 associates with the protein kinase mouse Pak3.

Reason: Exact source-linked IntAct records EBI-457343 match CDC42 and Q61036 using filter binding. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. The exact partner is a mouse protein; the cross-species assay is not renamed as a human–human experiment. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 association with ARHGDIB/GDI.D4 is supported.

Reason: The primary abstract directly describes human GDI.D4 binding to CDC42Hs and inhibiting GDP dissociation, with weaker affinity than the other RhoGDI. Retain the association without assigning GDI activity to CDC42. Retain as non-core under the project’s supported-binding instruction.

Summary: A conflict between the curated accession and the named experimental partner needs resolution.

Reason: IntAct IM-20287-1/-3 match P60953 and Q9VEX9, but their copied assay descriptions name Bni1p. Current UniProt identifies Q9VEX9 as Drosophila Bin1/SAP18, whereas the primary abstract explicitly concerns Saccharomyces BNI1 formin. Full original construct Methods were not recovered, so retain UNDECIDED rather than treating the accession match as verified biology or declaring a definitive misattribution from the abstract.

Summary: CDC42 associates with the protein kinase CDC42BPA.

Reason: Exact source-linked IntAct records EBI-692659, EBI-692745, EBI-697149 match CDC42 and Q5VT25 using far western blotting, fluorescence microscopy, lambda phage display. This verifies the curated assay/source linkage, not independent replication or an obligatory physiological complex. Partner variant comparisons are present; loss-of-binding variants do not erase the supported reference interaction. The checked kinase identity supports protein kinase binding; this does not assign kinase catalysis or activation to CDC42.

Proposed replacements: protein kinase binding

Summary: CDC42 association with mouse Wasl/N-WASP is supported.

Reason: The primary abstract directly establishes Cdc42–N-WASP interaction and activation; the exact O08816 partner is mouse Wasl in current UniProt. Preserve that cross-species partner and defer exact construct attribution to the original curator; no human–human assay is claimed. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 association with WAS/WASP is supported.

Reason: The primary abstract explicitly distinguishes Cdc42 binding to WASP from the stronger filopodium phenotype of N-WASP. Lack of that phenotype does not negate the measured binding. Retain as non-core under the project’s supported-binding instruction.

Summary: CDC42 binds the WASP-family GTPase-binding domain.

Reason: The primary abstract directly reports GTP-dependent, submicromolar binding of WASP fragments containing the GBD/CRIB region and states that flanking sequence strengthens binding. This supports GO:0032427 without implying that the isolated short CRIB motif is sufficient or transferring actin nucleation to CDC42. The abstract contains the decisive biochemical evidence; a full-text read is not required for this refinement.

Proposed replacements: GBD domain binding

Summary: GTP binding is an intrinsic property of the CDC42 switch.

Reason: Biochemical nucleotide-loading and GTP-dependent effector-binding experiments establish this molecular property. Preserve the original evidence codes; a cell-based activation reporter is not described as a purified nucleotide-affinity measurement.

Summary: GTP binding is an intrinsic property of the CDC42 switch.

Reason: Biochemical nucleotide-loading and GTP-dependent effector-binding experiments establish this molecular property. Preserve the original evidence codes; a cell-based activation reporter is not described as a purified nucleotide-affinity measurement.

Summary: GTP binding is an intrinsic property of the CDC42 switch.

Reason: Biochemical nucleotide-loading and GTP-dependent effector-binding experiments establish this molecular property. Preserve the original evidence codes; a cell-based activation reporter is not described as a purified nucleotide-affinity measurement.

Summary: GTP binding is an intrinsic property of the CDC42 switch.

Reason: Biochemical nucleotide-loading and GTP-dependent effector-binding experiments establish this molecular property. Preserve the original evidence codes; a cell-based activation reporter is not described as a purified nucleotide-affinity measurement.

Summary: GTP binding is an intrinsic property of the CDC42 switch.

Reason: Biochemical nucleotide-loading and GTP-dependent effector-binding experiments establish this molecular property. Preserve the original evidence codes; a cell-based activation reporter is not described as a purified nucleotide-affinity measurement.

Summary: CDC42 has a cytoplasmic pool as well as membrane-associated pools.

Reason: Retain the broad cytoplasmic localization. Membrane recruitment and effector engagement are more informative for core signaling; no activity is assigned merely from cytoplasmic presence.

Summary: CDC42 has a cytoplasmic pool as well as membrane-associated pools.

Reason: Retain the broad cytoplasmic localization. Membrane recruitment and effector engagement are more informative for core signaling; no activity is assigned merely from cytoplasmic presence.

Summary: CDC42 can associate with the endoplasmic reticulum membrane.

Reason: Retain this curated Reactome compartment context, corroborated by the explicit CDC42 translocation and ER-effector records R-HSA-9692800/R-HSA-9692809. The expression event R-HSA-8950637 does not independently constitute a localization assay; none of these rows makes CDC42 an integral membrane transporter.

Summary: CDC42 can associate with the endoplasmic reticulum membrane.

Reason: Retain this curated Reactome compartment context, corroborated by the explicit CDC42 translocation and ER-effector records R-HSA-9692800/R-HSA-9692809. The expression event R-HSA-8950637 does not independently constitute a localization assay; none of these rows makes CDC42 an integral membrane transporter.

Summary: CDC42 can associate with the endoplasmic reticulum membrane.

Reason: Retain this curated Reactome compartment context, corroborated by the explicit CDC42 translocation and ER-effector records R-HSA-9692800/R-HSA-9692809. The expression event R-HSA-8950637 does not independently constitute a localization assay; none of these rows makes CDC42 an integral membrane transporter.

Summary: CDC42 can associate with the endoplasmic reticulum membrane.

Reason: Retain this curated Reactome compartment context, corroborated by the explicit CDC42 translocation and ER-effector records R-HSA-9692800/R-HSA-9692809. The expression event R-HSA-8950637 does not independently constitute a localization assay; none of these rows makes CDC42 an integral membrane transporter.

Summary: CDC42 can associate with the endoplasmic reticulum membrane.

Reason: Retain this curated Reactome compartment context, corroborated by the explicit CDC42 translocation and ER-effector records R-HSA-9692800/R-HSA-9692809. The expression event R-HSA-8950637 does not independently constitute a localization assay; none of these rows makes CDC42 an integral membrane transporter.

Summary: The source-specific centrosome assignment remains unresolved despite verified NEK6 association.

Reason: Official Supplementary FigureS1C shows endogenous CDC42/NEK6 colocalization in HEK293 cells; TableS1 confirms the exact Y2H pair. The inspected CDC42 panel does not include a centrosomal marker, and the relevant main-text marker experiment was not recovered. Preserve this IDA location assertion pending that evidence rather than infer centrosome identity from punctate NEK6 overlap alone.

Summary: Centrosome is a secondary mapped localization.

Reason: Retain the UniProt cellular-location inference at its stated resolution. This does not independently validate the distinct PMID:20873783 experimental row or establish a centrosomal catalytic function.

Summary: CDC42 can localize to the mitotic spindle.

Reason: The electronic location mapping is independently corroborated by endogenous CDC42 immunofluorescence and antibody controls in human HeLaS3 cells. This is a mitotic localization, not the main membrane-associated core.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: CDC42 has a cytosolic pool during regulated membrane cycling.

Reason: Retain this location at its original inference/Reactome resolution. GDI/GEF interactions and compartment cycling do not mean CDC42 is permanently cytosolic or acquires its partners’ catalytic functions.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: The plasma membrane is a principal site of CDC42 signaling.

Reason: Retain this source-specific localization in the context of independently supported human membrane recruitment, effector interactions and spatial GTPase signaling. The named Reactome event is pathway-model provenance, not an independently inspected imaging experiment. PAINT is_active_in is retained as the curator’s inherited activity inference, corroborated by spatial signaling rather than justified by location alone.

Summary: CDC42 is associated with cell junctions.

Reason: Retain the orthology-based location, corroborated by spatial CDC42 activity measurements during human epithelial junction formation. This does not make CDC42 a structural adhesion receptor.

Summary: The exact focal-adhesion proteomics target entry remains unverified.

Reason: The study’s focal-adhesion proteomics methods and abstract are accessible, but the precise CDC42 target entry and its enrichment were not inspected. Do not equate the central role in actin signaling with demonstrated membership of this isolated fraction.

Summary: CDC42 participates in context-dependent endocytic regulation.

Reason: Retain the PAINT curator’s inherited process judgment. CDC42 effector signaling connects membrane dynamics to actin, but endocytosis encompasses multiple mechanisms; no full phylogenetic node reconstruction or universal requirement is claimed.

Summary: Controlled CDC42 cycling regulates actin during particle engulfment.

Reason: Selected primary Figure1/Methods examine macrophage Cdc42G12V: persistent activity retains actin at abortive cups and impairs completion. Activation and subsequent inactivation have different roles. Retain the existing process assertion at the mouse-cell/construct scope rather than calling CDC42 constitutive activity uniformly pro-phagocytic.

Summary: CDC42 regulates actin organization and the establishment of cell polarity.

Reason: Effector binding supplies the regulatory mechanism; human epithelial CDC42 depletion and spatial-activity experiments independently establish polarity/junction defects. Retain the original PAINT, TAS or experimental provenance; this is active regulatory participation, not simply a developmental knockout phenotype.

Summary: Controlled CDC42 cycling regulates actin during particle engulfment.

Reason: Selected primary Figure1/Methods examine macrophage Cdc42G12V: persistent activity retains actin at abortive cups and impairs completion. Activation and subsequent inactivation have different roles. Retain the existing process assertion at the mouse-cell/construct scope rather than calling CDC42 constitutive activity uniformly pro-phagocytic.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing ISS inference for Golgi organization as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: CDC42 regulates actin organization and the establishment of cell polarity.

Reason: Effector binding supplies the regulatory mechanism; human epithelial CDC42 depletion and spatial-activity experiments independently establish polarity/junction defects. Retain the original PAINT, TAS or experimental provenance; this is active regulatory participation, not simply a developmental knockout phenotype.

Summary: Signal transduction is correct but broad.

Reason: The PAINT inference agrees with the established GTP-controlled molecular switch. More informative core synthesis specifies effector regulation, actin organization and polarity; a target entry in WITH/FROM is valid ancestral descendant evidence.

Summary: CDC42 acts downstream of extracellular-matrix/NRP1 signaling in endothelial cells.

Reason: Selected human dermal microvascular endothelial-cell experiments show fibronectin-dependent CDC42 activation and ML141-sensitive protrusions/stress fibers. Retain these pathway and cytoskeletal contexts as non-core; NRP1/ABL1 signaling and mouse/zebrafish angiogenesis results are not all transferred to CDC42 as direct human assays.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for anatomical structure morphogenesis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: Activated CDC42 affects cell morphology.

Reason: Figure7 compares activated human CDC42HsV12 with Rac/Rho in porcine endothelial cells; WASP inhibits the CDC42 morphology. Endogenous human-cell effects were not tested.

Summary: Activated CDC42 affects cell morphology.

Reason: Figure7 compares activated human CDC42HsV12 with Rac/Rho in porcine endothelial cells; WASP inhibits the CDC42 morphology. Endogenous human-cell effects were not tested.

Summary: Microtubule-associated localization is supported in a mitotic context.

Reason: Retain the original GO_REF imaging assertion without inventing its antibody experiment. Independent human HeLaS3 spindle immunofluorescence supports microtubule-cytoskeleton association; this is not direct tubulin binding or a microtubule polymerase activity.

Summary: CDC42 associates with cellular membranes.

Reason: The broad location is consistent with independently established membrane association and recruitment. Preserve the individual source codes; the proteomic or upstream-regulator source is not presented as proof of one particular membrane compartment.

Summary: CDC42 associates with cellular membranes.

Reason: The broad location is consistent with independently established membrane association and recruitment. Preserve the individual source codes; the proteomic or upstream-regulator source is not presented as proof of one particular membrane compartment.

Summary: CDC42 associates with cellular membranes.

Reason: The broad location is consistent with independently established membrane association and recruitment. Preserve the individual source codes; the proteomic or upstream-regulator source is not presented as proof of one particular membrane compartment.

Summary: The actual source supports Golgi localization, not COG-complex membership.

Reason: Selected full Results/Figure 4C-D of PMID:16380373 examine endogenous CDC42 perinuclear localization and brefeldin-A redistribution in HeLa cells. Figure 4E-G further distinguishes CDC42 from endosomal p50RhoGAP. These data support a Golgi compartment, not membership of the eight-subunit COG tethering complex. Propose located_in GO:0005794 Golgi apparatus; the immutable original IMP/part_of fields record the source assertion and are not the proposed replacement relation. The schema has no replacement-qualifier slot, so located_in is specified here. PMID:15361624 independently corroborates Golgi-associated CDC42 activity; its trans-Golgi imaging is in MEF/3T3 cells, not a direct human localization assay.

Proposed replacements: Golgi apparatus

Summary: Binding to protein kinases is a supported CDC42 effector interaction.

Reason: Direct and curated source-linked PAK/LRRK2 interactions support this specific molecular association. Preserve PAINT/electronic versus experimental provenance. Binding to a kinase does not assign kinase catalysis to CDC42 or establish activation of every kinase partner.

Summary: CDC42 binds the PAK3 GTPase-binding domain in the source assay; VopS subsequently disrupts this interaction.

Reason: Selected primary PMID:19039103 Results/Figure1A assay human HeLa-cell CDC42 capture by the GST-tagged PAK3 binding domain during Vibrio infection. Positive capture is observed early, whereas VopS-dependent loss occurs later. This supports the existing protein-kinase-binding annotation in its assay context; it does not assign VopS AMP-transferase activity to CDC42 or establish kinase activation.

Summary: Binding to protein kinases is a supported CDC42 effector interaction.

Reason: Direct and curated source-linked PAK/LRRK2 interactions support this specific molecular association. Preserve PAINT/electronic versus experimental provenance. Binding to a kinase does not assign kinase catalysis to CDC42 or establish activation of every kinase partner.

Summary: The source supplement identifies CDC42 as an hNEK6 interaction partner.

Reason: Official publisher Supplementary TableS1 lists CDC42 AAH03682.1, residues1–191/191, in the human NEK6 yeast-two-hybrid screen. FigureS1C additionally shows endogenous CDC42/NEK6 colocalization in HEK293 cells. Retain protein kinase binding at that source resolution; colocalization alone is not proof of direct binding, kinase activation or CDC42 catalysis.

Summary: Binding to protein kinases is a supported CDC42 effector interaction.

Reason: Direct and curated source-linked PAK/LRRK2 interactions support this specific molecular association. Preserve PAINT/electronic versus experimental provenance. Binding to a kinase does not assign kinase catalysis to CDC42 or establish activation of every kinase partner.

Summary: Binding to protein kinases is a supported CDC42 effector interaction.

Reason: Direct and curated source-linked PAK/LRRK2 interactions support this specific molecular association. Preserve PAINT/electronic versus experimental provenance. Binding to a kinase does not assign kinase catalysis to CDC42 or establish activation of every kinase partner.

Summary: Proteomic abundance in substantia nigra does not by itself establish development.

Reason: The accessible primary abstract compares disease-associated substantia-nigra proteomes; it does not identify a developmental experiment for CDC42. Preserve the HEP source assertion pending the target-level evidence rather than accepting tissue detection as developmental participation or claiming a definitive curation error from an abstract.

Summary: CDC42 regulates actin organization and the establishment of cell polarity.

Reason: Effector binding supplies the regulatory mechanism; human epithelial CDC42 depletion and spatial-activity experiments independently establish polarity/junction defects. Retain the original PAINT, TAS or experimental provenance; this is active regulatory participation, not simply a developmental knockout phenotype.

Summary: CDC42–CEP signaling affects actin organization and protrusions.

Reason: The primary abstract describes CEP binding, dominant-negative CDC42 and CRIB-mutant comparisons in NIH3T3/keratinocyte systems. Retain the specific cellular output with those assay limits; no direct CDC42 actin-assembly catalysis is inferred.

Summary: The source-specific filopodial localization of CDC42 remains unverified.

Reason: Selected full PMID:11035016 Results and Figure 4 legend now confirm Myc-tagged CDC42 immunostaining in NIH-3T3 fibroblasts and an associated filopodial phenotype. The exact CDC42 signal within the filopodial compartment and construct-to-human mapping have not been independently resolved from the figure/Methods, so the source-specific IDA remains UNDECIDED. This is not rejection of CDC42-dependent filopodium assembly. The separate PMID:15361624 biosensor measures active-state distribution rather than total protein, so its lack of filopodial activity in MEF/3T3 cells does not exclude CDC42 localization.

Summary: The cited PAR6 paper does not resolve the macrophage-differentiation assertion in accessible text.

Reason: The abstract establishes human PAR6–CDC42 complexes and polarity signaling but not the macrophage-differentiation evidence. Preserve the TAS row; do not infer a wrong citation merely because macrophages are absent from the abstract.

Summary: The source’s growth phenotype is not yet resolved as host-cell growth.

Reason: Selected full Results support Salmonella intracellular replication and yeast-growth effects of SopB/CDC42 constructs. These must not be equated with positive regulation of human cell growth. Preserve the original IMP assertion pending an exact host-cell-growth experiment.

Summary: CDC42 supports migration/invasion in the tested breast-cancer-cell context.

Reason: Full selected Results/Figure6 show CDC42 RNAi reducing matrix invasion in human MDA-MB231 cells, with modest accompanying CXCR4 changes. Retain the process as non-core and context-specific; the result does not establish a unique normal-tissue metastasis function.

Summary: Neuronal processes and cell bodies can contain CDC42.

Reason: Endogenous CDC42 localization in differentiated human SH-SY5Y soma and neurites is reported in full Figure2/Results of PMID:21048939. Retain these locations as context-specific; the observation is not evidence of a new neurodevelopmental molecular function.

Summary: CDC42 localizes to mitotic spindle and intercellular-bridge structures.

Reason: Full selected PMID:15642749 Results/Figure7 and Methods identify endogenous CDC42 on HeLaS3 spindle microtubules and central spindle/intercellular bridge, with antibody controls. Retain the original compartment granularity; this localization alone does not establish that CDC42 positively controls cytokinesis.

Summary: CDC42 localizes to mitotic spindle and intercellular-bridge structures.

Reason: Full selected PMID:15642749 Results/Figure7 and Methods identify endogenous CDC42 on HeLaS3 spindle microtubules and central spindle/intercellular bridge, with antibody controls. Retain the original compartment granularity; this localization alone does not establish that CDC42 positively controls cytokinesis.

Summary: CDC42 engages proteins in a GTP-dependent manner.

Reason: The term explicitly includes the GTP-loaded binding partner as well as its effector. Direct WASP, PAR6 and kinase-domain binding supports this central state-dependent property without claiming every CDC42 interaction is GTP-specific.

Summary: CDC42 signaling is spatially organized near the cell cortex and leading edge.

Reason: Retain the source orthology-based location or activity inference, consistent with spatial effector biosensing and human epithelial CDC42 activity. The is_active_in row asserts activity at the site, not simply occupancy; the full ancestral/donor experiment was not reconstructed here.

Summary: CDC42 signaling is spatially organized near the cell cortex and leading edge.

Reason: Retain the source orthology-based location or activity inference, consistent with spatial effector biosensing and human epithelial CDC42 activity. The is_active_in row asserts activity at the site, not simply occupancy; the full ancestral/donor experiment was not reconstructed here.

Summary: CDC42–CEP signaling affects actin organization and protrusions.

Reason: The primary abstract describes CEP binding, dominant-negative CDC42 and CRIB-mutant comparisons in NIH3T3/keratinocyte systems. Retain the specific cellular output with those assay limits; no direct CDC42 actin-assembly catalysis is inferred.

Summary: CDC42 inhibits a Borg–septin association.

Reason: The primary abstract directly describes CDC42 inhibition of Borg3 binding to septins. This supports the existing negative-regulation-of-complex-assembly assertion, without making CDC42 a septin or a general complex-disassembly enzyme.

Summary: CDC42 associates with TRE17, but thioesterase-class binding remains unresolved for the tested isoform.

Reason: PMID:12612085 demonstrates preferential association of activated human CDC42 with TRE17 in transfected cells; the authors interpret it as an indirect effector complex. PMID:15509780 identifies the earlier tested form as TRE17(onco), a truncated, catalytically inactive ubiquitin-specific protease isoform. Historical ubiquitin-thioesterase nomenclature for USP6 is legitimate, but it does not establish the enzyme-class identity of the experimentally associated form. The positive association is retained as evidence while this exact thioesterase-binding assertion remains UNDECIDED; no absence of binding, curator error, or automatic transfer from an active USP6 isoform is claimed.

Summary: CDC42 recognizes the WASP GTPase-binding domain.

Reason: Primary biochemical/structural evidence shows binding to the GBD/CRIB region and release of WASP autoinhibition. The domain interaction is a central effector mechanism, not CDC42 actin-polymerase activity.

Summary: CDC42 recognizes the WASP GTPase-binding domain.

Reason: Primary biochemical/structural evidence shows binding to the GBD/CRIB region and release of WASP autoinhibition. The domain interaction is a central effector mechanism, not CDC42 actin-polymerase activity.

Summary: A positive CDC42 role in cytokinesis is not resolved by the selected experiments.

Reason: Full selected PMID:15642749 Results show CDC42-depletion defects in chromosome congression and kinetochore attachment. The explicit high-frequency cytokinesis-failure result concerns Ect2 depletion. CDC42 bridge localization alone does not establish this positive-regulation process, and Ect2 phenotypes are not transferred to CDC42.

Summary: CDC42 regulates actin organization and the establishment of cell polarity.

Reason: Effector binding supplies the regulatory mechanism; human epithelial CDC42 depletion and spatial-activity experiments independently establish polarity/junction defects. Retain the original PAINT, TAS or experimental provenance; this is active regulatory participation, not simply a developmental knockout phenotype.

Summary: The exact source support for membership of a protein complex remains unresolved.

Reason: Official Supplementary TableS1 supports CDC42/NEK6 Y2H association and FigureS1C supports colocalization. The relevant main-text complex/coimmunoprecipitation assay was not inspected. A positive pair and shared punctum do not alone resolve this part_of assertion, so preserve it pending the original complex experiment.

Summary: CDC42 associates with the apolipoprotein A-I receptor ABCA1.

Reason: The source explicitly describes apoA-I-dependent ABCA1–CDC42 coimmunoprecipitation and mutant controls. The term refers to receptor binding, not apoA-I ligand binding; retain this specialized association without making CDC42 an apolipoprotein receptor itself.

Summary: CDC42 signaling helps epithelial junction assembly.

Reason: The source directly depletes CDC42 in human Caco-2 cells and perturbs junctional and apical/basal markers. This is a cellular context of the core polarity switch; CDC42 is not a structural junction component merely because loss disrupts junctions.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for embryonic heart tube development as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: CDC42 is reported in human Staufen-containing cytoplasmic granule assemblies.

Reason: The primary abstract explicitly identifies Cdc42 in purified Staufen complexes and describes granule colocalization in differentiated human neuroblasts. Retain this secondary compartment context without inferring RNA binding or translation catalysis by CDC42.

Summary: CDC42 acts downstream of extracellular-matrix/NRP1 signaling in endothelial cells.

Reason: Selected human dermal microvascular endothelial-cell experiments show fibronectin-dependent CDC42 activation and ML141-sensitive protrusions/stress fibers. Retain these pathway and cytoskeletal contexts as non-core; NRP1/ABL1 signaling and mouse/zebrafish angiogenesis results are not all transferred to CDC42 as direct human assays.

Summary: Cdc42 homodimerization has biochemical support.

Reason: The primary abstract describes reversible Cdc42 homodimers and effects on intrinsic hydrolysis in vitro. Retain the measured self-association as non-core; it does not establish an obligatory native dimer at every signaling site.

Summary: Neuronal processes and cell bodies can contain CDC42.

Reason: Endogenous CDC42 localization in differentiated human SH-SY5Y soma and neurites is reported in full Figure2/Results of PMID:21048939. Retain these locations as context-specific; the observation is not evidence of a new neurodevelopmental molecular function.

Summary: Neuronal processes and cell bodies can contain CDC42.

Reason: Endogenous CDC42 localization in differentiated human SH-SY5Y soma and neurites is reported in full Figure2/Results of PMID:21048939. Retain these locations as context-specific; the observation is not evidence of a new neurodevelopmental molecular function.

Summary: CDC42 perturbation affects a host-dependent viral process.

Reason: The primary abstract includes CDC42 among membrane-trafficking factors required in an HCV replication screen. Keep the existing host perturbation result as non-core; detailed PI4K follow-up in the same paper does not become a CDC42-specific mechanism.

Summary: CDC42 signaling is spatially organized near the cell cortex and leading edge.

Reason: Retain the source orthology-based location or activity inference, consistent with spatial effector biosensing and human epithelial CDC42 activity. The is_active_in row asserts activity at the site, not simply occupancy; the full ancestral/donor experiment was not reconstructed here.

Summary: CDC42 regulates actin organization and the establishment of cell polarity.

Reason: Effector binding supplies the regulatory mechanism; human epithelial CDC42 depletion and spatial-activity experiments independently establish polarity/junction defects. Retain the original PAINT, TAS or experimental provenance; this is active regulatory participation, not simply a developmental knockout phenotype.

Summary: Phagocytic compartments can recruit CDC42.

Reason: Retain the mouse-to-human location inference. Primary macrophage experiments independently visualize activity at forming cups, while distinguishing completion-associated GTPase inactivation from sustained activity.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for positive regulation of pinocytosis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing ISS inference for positive regulation of pinocytosis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for positive regulation of cellular component organization as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: CDC42 localizes to mitotic spindle and intercellular-bridge structures.

Reason: Full selected PMID:15642749 Results/Figure7 and Methods identify endogenous CDC42 on HeLaS3 spindle microtubules and central spindle/intercellular bridge, with antibody controls. Retain the original compartment granularity; this localization alone does not establish that CDC42 positively controls cytokinesis.

Summary: CDC42 is a central regulator of filopodial protrusion.

Reason: Direct effector regulation and human endothelial CDC42 inhibition support filopodium control. Preserve the distinction between PAINT, orthology/ISS and experimental assertions; do not attribute actin nucleation itself to CDC42.

Summary: The cited palmitoylated-protein study supports a CDC42-dependent filopodial response.

Reason: The primary abstract reports inhibition by dominant-negative Cdc42 of protrusions driven by membrane-targeted motifs. This is a bounded perturbation context, not direct evidence that the human CDC42 brain splice form was lipidated in that experiment.

Summary: CDC42 is a central regulator of filopodial protrusion.

Reason: Direct effector regulation and human endothelial CDC42 inhibition support filopodium control. Preserve the distinction between PAINT, orthology/ISS and experimental assertions; do not attribute actin nucleation itself to CDC42.

Summary: CDC42 is a central regulator of filopodial protrusion.

Reason: Direct effector regulation and human endothelial CDC42 inhibition support filopodium control. Preserve the distinction between PAINT, orthology/ISS and experimental assertions; do not attribute actin nucleation itself to CDC42.

Summary: CDC42 is a central regulator of filopodial protrusion.

Reason: Direct effector regulation and human endothelial CDC42 inhibition support filopodium control. Preserve the distinction between PAINT, orthology/ISS and experimental assertions; do not attribute actin nucleation itself to CDC42.

Summary: Activated CDC42 affects cell morphology.

Reason: Figure7 compares activated human CDC42HsV12 with Rac/Rho in porcine endothelial cells; WASP inhibits the CDC42 morphology. Endogenous human-cell effects were not tested.

Summary: CDC42 acts downstream of extracellular-matrix/NRP1 signaling in endothelial cells.

Reason: Selected human dermal microvascular endothelial-cell experiments show fibronectin-dependent CDC42 activation and ML141-sensitive protrusions/stress fibers. Retain these pathway and cytoskeletal contexts as non-core; NRP1/ABL1 signaling and mouse/zebrafish angiogenesis results are not all transferred to CDC42 as direct human assays.

Summary: Activated CDC42 affects cell morphology.

Reason: Figure7 compares activated human CDC42HsV12 with Rac/Rho in porcine endothelial cells; WASP inhibits the CDC42 morphology. Endogenous human-cell effects were not tested.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing ISS inference for establishment of Golgi localization as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: CDC42 regulates kinetochore–microtubule attachment during mitosis.

Reason: Full selected human HeLaS3 RNAi/Results establish chromosome-congression delay, spindle-attachment defects and altered mDia3 recruitment. Retain this mitotic regulatory context separately from the primary membrane/actin polarity core.

Summary: The specific Wnt planar-polarity source claim remains unresolved.

Reason: The accessible review abstract concerns Wnt-dependent dopaminergic development but does not expose the exact CDC42 mechanism supporting this NAS assertion. A general polarity role does not establish participation in this particular Wnt pathway.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for positive regulation of epithelial cell proliferation involved in lung morphogenesis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing IEA inference for dendritic spine morphogenesis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: This inferred process is retained as non-core.

Reason: Retain the existing ISS inference for dendritic spine morphogenesis as a specialized or broad context of CDC42 regulation. The exact source donor/ARBA identifier is preserved; this is not newly presented as a direct human assay, and no target-specific loss of the inferred role was established. It is excluded from the concise molecular core.

Summary: The cited experiments do not establish CDC42 ubiquitin-transfer catalysis.

Reason: Full selected Results/Figures2 and8 of PMID:21435037 show Cdc42-dependent enhancement of SopB ubiquitination in yeast, while a Cdc42-binding-deficient SopB mutant remains ubiquitinated in HeLa infection. They do not demonstrate CDC42 catalysing ubiquitin transfer from a thioester donor to substrate as required by GO:0061630. This is a source-specific catalytic misassignment established from the actual experiments, not from the paper title or the fact that CDC42 is a GTPase.

Summary: The exact extracellular-vesicle proteomics target entry needs verification.

Reason: The accessible source describes an exosome-enriched proteomic preparation, but the exact CDC42 target peptide/protein record was not inspected. Preserve the HDA assertion; do not infer a secreted CDC42 signaling activity or reject the compartment solely because CDC42 normally acts intracellularly.

Summary: The exact extracellular-vesicle proteomics target entry needs verification.

Reason: The accessible source describes an exosome-enriched proteomic preparation, but the exact CDC42 target peptide/protein record was not inspected. Preserve the HDA assertion; do not infer a secreted CDC42 signaling activity or reject the compartment solely because CDC42 normally acts intracellularly.