InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RAC1

Summary

InnateDB Protein

IDBP-8117.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RAC1

Protein Name

ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)

Synonyms

p21-Rac1; Rac-1; TC-25;

Species

Homo sapiens

Ensembl Protein

ENSP00000348461

InnateDB Gene

IDBG-8115 (RAC1)

Protein Structure

UniProt Annotation

Function

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 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 glioma cells, promotes cell migration and invasion. 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.

Subcellular Localization

Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Melanosome {ECO:0000269PubMed:17081065, ECO:0000269PubMed:19948726, ECO:0000269PubMed:21693584}. Cytoplasm {ECO:0000250}. Note=Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine (By similarity). Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Isoform B is predominantly identified in skin and epithelial tissues from the intestinal tract. Its expression is elevated in colorectal tumors at various stages of neoplastic progression, as compared to their respective adjacent tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 242 experimentally validated interaction(s) in this database.
They are also associated with 30 interaction(s) predicted by orthology.

Experimentally validated
Total	242 [view]
Protein-Protein	239 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	30 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003924	GTPase activity
GO:0005515	protein binding
GO:0005525	GTP binding
GO:0017137	Rab GTPase binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0030742	GTP-dependent protein binding
GO:0031996	thioesterase binding
GO:0051022	Rho GDP-dissociation inhibitor binding

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0002093	auditory receptor cell morphogenesis
GO:0002551	mast cell chemotaxis
GO:0003382	epithelial cell morphogenesis
GO:0006184	GTP catabolic process
GO:0006897	endocytosis
GO:0006911	phagocytosis, engulfment
GO:0006928	cellular component movement
GO:0006935	chemotaxis
GO:0006954	inflammatory response
GO:0006972	hyperosmotic response
GO:0007010	cytoskeleton organization
GO:0007015	actin filament organization
GO:0007155	cell adhesion
GO:0007160	cell-matrix adhesion
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007264	small GTPase mediated signal transduction
GO:0007411	axon guidance
GO:0007596	blood coagulation
GO:0008283	cell proliferation
GO:0009611	response to wounding
GO:0009653	anatomical structure morphogenesis
GO:0010310	regulation of hydrogen peroxide metabolic process
GO:0010592	positive regulation of lamellipodium assembly
GO:0015031	protein transport
GO:0016032	viral process
GO:0016358	dendrite development
GO:0016477	cell migration
GO:0021799	cerebral cortex radially oriented cell migration
GO:0021831	embryonic olfactory bulb interneuron precursor migration
GO:0030032	lamellipodium assembly
GO:0030036	actin cytoskeleton organization
GO:0030041	actin filament polymerization
GO:0030168	platelet activation
GO:0030334	regulation of cell migration
GO:0030838	positive regulation of actin filament polymerization
GO:0031295	T cell costimulation
GO:0031529	ruffle organization
GO:0032707	negative regulation of interleukin-23 production
GO:0034446	substrate adhesion-dependent cell spreading
GO:0035025	positive regulation of Rho protein signal transduction
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0043065	positive regulation of apoptotic process
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0043652	engulfment of apoptotic cell
GO:0045087	innate immune response (InnateDB)
GO:0045216	cell-cell junction organization
GO:0045453	bone resorption
GO:0045740	positive regulation of DNA replication
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048261	negative regulation of receptor-mediated endocytosis
GO:0048532	anatomical structure arrangement
GO:0048813	dendrite morphogenesis
GO:0048870	cell motility
GO:0050690	regulation of defense response to virus by virus
GO:0051668	localization within membrane
GO:0060071	Wnt signaling pathway, planar cell polarity pathway
GO:0060263	regulation of respiratory burst
GO:0071526	semaphorin-plexin signaling pathway
GO:0071542	dopaminergic neuron differentiation
GO:0072659	protein localization to plasma membrane
GO:0090103	cochlea morphogenesis
GO:0097178	ruffle assembly
GO:0097190	apoptotic signaling pathway

Cellular Component

GO:0000139	Golgi membrane
GO:0001891	phagocytic cup
GO:0005622	intracellular
GO:0005737	cytoplasm
GO:0005802	trans-Golgi network
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0019897	extrinsic component of plasma membrane
GO:0030027	lamellipodium
GO:0031410	cytoplasmic vesicle
GO:0032587	ruffle membrane
GO:0036464	cytoplasmic ribonucleoprotein granule
GO:0042470	melanosome
GO:0042995	cell projection
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR001806 Small GTPase superfamily
IPR003578 Small GTPase superfamily, Rho type
IPR003579 Small GTPase superfamily, Rab type
IPR005225 Small GTP-binding protein domain
IPR013684 Mitochondrial Rho-like
IPR020849 Small GTPase superfamily, Ras type
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00071
PF08477

PRINTS

PR00449

PIRSF

SMART

SM00174
SM00175
SM00173

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt