Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RAC1 (P63000) - Overview - Molecular Target Synopsis

Protein


RAC1, Ras-related C3 botulinum toxin substrate 1
UniProt P63000

Also Known as RAC1_HUMAN, RAC1, TC25

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. 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. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. 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 synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3., Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction. Interacts with NISCH. Interacts with PIP5K1A. Interacts with the GTP-bound form of RAB7A. Interacts with SRGAP2. Interacts with CYFIP1/SRA-1. Interacts with PLXNB3. Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with the GEF proteins PREX1, RASGRF2, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with PLXNB1. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM; the interaction requires PAK1. Part of a complex with MAP2K3, MAP3K3, CCM2 and DEF6. Interacts with BAIAP2, BAIAP2L1 and DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2. Interacts with NOXA1. Interacts with ARHGEF2. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with ITGB4. Interacts with S100A8 and calprotectin (S100A8/9). Interacts with PACSIN2. Interacts with ITGB1BP1. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RAPH1 (via Ras associating and PH domains) (PubMed:18499456). Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation (PubMed:20875796). Interacts with PAK2 (PubMed:20696164). Interacts (GTP-bound form) with SH3RF1 and SH3RF3 (PubMed:20696164). Found in a complex with SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2.

6AGP
STRUCTURE OF RAC1 IN THE LOW-AFFINITY STATE FOR MG2+
RCSB/PDB
Inspect Structure
See all 3D Structures for RAC1

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
211ENSG00000136238ENST00000356142ENSP00000348461P63000-2
192ENSG00000136238ENST00000348035ENSP00000258737P62999-1, P63000-1, Q6RUV5-1, P63001-1, P62998-1

Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project RAC1 has gain in 5 cell-lines, loss in 1 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_5, U251, A498

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: BICR 31, NCI-H596, HCC4006

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, SK-N-SH

(see details)

3D Structures


For RAC1 there are:
38 structures (62 chains) solved
30 are solved in complex with at least one small molecule ligand
4 are solved with an approved drug

RAC1 is solved in complex with the approved drug(s):

FMN/RIBOFLAVIN 5'-PHOSPHATE (2WKP_A, 2WKQ_A, 2WKR_A, 5HZH_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RAC1 has been screened with 94 compounds (141 bioactivities). (see details)