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Protein / target

Ras-related C3 botulinum toxin substrate 1

Encoded byRAC1P63000Homo sapiensSwiss-Prot
Small-molecule tractable
Druggability
Structure with Ligand
2
Research papers

Protein at a glance

Biological role

Rho GDP-dissociation inhibitor binding

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene RAC1 · Genetic evidence · score 0.66

Research activity

Emerging research

2 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states.

View complete UniProt function annotation

Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles (PubMed:1643658, PubMed:22843693, PubMed:23512198, PubMed:28886345). Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity (PubMed:9121475). In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (PubMed:1643658). In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity). In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity). Required for DSG3 translocation to cell-cell junctions, DSG3-mediated organization of cortical F-actin bundles and anchoring of actin at cell junctions; via interaction with DSG3 (PubMed:22796473). Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:38355798)

Subcellular location

Cell membraneMelanosomeCytoplasmCell projection, lamellipodiumCell projection, dendriteSynapseNucleusCell projection, ruffle membrane
Domains and Gene Ontology detail (104)

Gene Ontology

  • Ccell cortex
  • Ccell projection
  • Ccytoplasm
  • Ccytoplasmic ribonucleoprotein granule
  • Ccytoplasmic vesicle
  • Ccytoskeleton
  • Ccytosol
  • Cdendrite
  • Cearly endosome membrane
  • Cendoplasmic reticulum membrane
  • Cextracellular exosome
  • Cficolin-1-rich granule membrane

192 aa · 21 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationUniProt · GOInhibitory neurotransmissionUniProtGrowth-factor signallingGOImmune signallingUniProt · GOCell adhesionUniProt · GOKinase signallingUniProt · GO
View supporting evidence

Cell migration

  • ·Plasma membrane-associated small GTPase which cycles between active GTP-bound and inacti…
  • ·cell chemotaxis
  • ·cell migration
  • ·cell motility

Inhibitory neurotransmission

  • ·Plasma membrane-associated small GTPase which cycles between active GTP-bound and inacti…

Growth-factor signalling

  • ·hepatocyte growth factor receptor signaling pathway

Immune signalling

  • ·Plasma membrane-associated small GTPase which cycles between active GTP-bound and inacti…
  • ·inflammatory response
  • ·negative regulation of interleukin-23 production
  • ·positive regulation of substrate adhesion-dependent cell spreading

Cell adhesion

  • ·Plasma membrane-associated small GTPase which cycles between active GTP-bound and inacti…
  • ·cell adhesion
  • ·positive regulation of bicellular tight junction assembly
  • ·regulation of cell adhesion involved in heart morphogenesis

Kinase signalling

  • ·Plasma membrane-associated small GTPase which cycles between active GTP-bound and inacti…
  • ·protein kinase binding

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene RAC1

Gene-level evidence surfaced through the gene RAC1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Genetic Diseases, Inborn
0.66Moderately supported

Genetic evidence dominant · Open Targets 0.40

Cutaneous melanoma
0.58Moderately supported

Somatic mutation evidence dominant · Open Targets 0.49

Melanoma
0.53Moderately supported

Somatic mutation evidence dominant · Open Targets 0.54

Squamous Cell Carcinoma of Head and Neck
0.46Limited support

Somatic mutation evidence dominant · Open Targets 0.45

Neoplasms
0.35Preliminary

Pathway evidence dominant · Open Targets 0.40 · no direct causal or clinical evidence

View evidence synthesis (5)
Genetic Diseases, InbornModerately supported
0.66
agreement 0.540.78
Genetic100%

Open Targets aggregate 0.40 · 1 independent evidence family

Cutaneous melanomaModerately supported
0.58
agreement 0.440.71
Somatic mutation56%Pathway34%Literature10%

Open Targets aggregate 0.49 · 3 independent evidence families

MelanomaModerately supported
0.53
agreement 0.370.69
Somatic mutation76%Literature24%

Open Targets aggregate 0.54 · 2 independent evidence families

Squamous Cell Carcinoma of Head and NeckLimited support
0.46
agreement 0.290.62
Somatic mutation75%Literature26%

Open Targets aggregate 0.45 · 2 independent evidence families

NeoplasmsPreliminary
0.35
agreement 0.180.53
Pathway63%Literature37%

Open Targets aggregate 0.40 · 2 independent evidence families · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Melanoma0.54
Cutaneous melanoma0.49
Leishmaniasis, Cutaneous0.46
Squamous Cell Carcinoma of Head and Neck0.45
Genetic Diseases, Inborn0.40
Neoplasms0.40
Neurodegenerative Diseases0.38

Tractability

Small moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketAB · UniProt loc high confAB · GO CC high confPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Nakayama AY · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000

Recent

Europe PMC papers linked directly to this protein.