P63001 (RAC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 121. History...
Names and origin
|Protein names||Recommended name:|
Ras-related C3 botulinum toxin substrate 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||192 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. 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 podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. Ref.11
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30 By similarity. Ref.12
Interacts with the GEF proteins PREX1, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. 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 BAIAP2, BAIAP2L1, PLXNB1, CYFIP1/SRA-1 and DEF6. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM; the interaction requires PAK1. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ITGB4. Interacts with the GTP-bound form of RAB7A. Interacts with ARHGEF2. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with NOXA1. Interacts with S100A8 and calprotectin (S100A8/9). Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts with PACSIN2. Interacts with ITGB1BP1 By similarity. Interacts with the GEF protein RASGRF2, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a complex with MAP2K3, MAP3K3 and CCM2. Interacts with NISCH. Interacts with PIP5K1A. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with SRGAP2. Interacts with PLXNB3. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14
Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Melanosome By similarity. Cytoplasm By similarity. Note: Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine. Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts By similarity.
Widely expressed. Ref.1
The effector region mediates interaction with DEF6 By similarity.
GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome By similarity.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 189||189||Ras-related C3 botulinum toxin substrate 1||PRO_0000042038|
|Propeptide||190 – 192||3||Removed in mature form By similarity||PRO_0000042039|
|Nucleotide binding||10 – 17||8||GTP By similarity|
|Nucleotide binding||57 – 61||5||GTP By similarity|
|Nucleotide binding||115 – 118||4||GTP By similarity|
|Motif||32 – 40||9||Effector region Potential|
Amino acid modifications
|Modified residue||189||1||Cysteine methyl ester By similarity|
|Lipidation||189||1||S-geranylgeranyl cysteine By similarity|
|Cross-link||147||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Mutagenesis||12||1||G → V: Constitutively active. Interacts with PARD6 proteins. Ref.5|
|||"The murine rac1 gene: cDNA cloning, tissue distribution and regulated expression of rac1 mRNA by disassembly of actin microfilaments."|
Moll J., Sansig G., Fattori E., van der Putten H.
Oncogene 6:863-866(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Head, Liver, Thymus and Tongue.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II and FVB/N.
Tissue: Mammary tumor.
|||"The exchange factor Ras-GRF2 activates Ras-dependent and Rac-dependent mitogen-activated protein kinase pathways."|
Fan W.-T., Koch C.A., de Hoog C.L., Fam N.P., Moran M.F.
Curr. Biol. 8:935-938(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RASGRF2.
|||"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42."|
Joberty G., Petersen C., Gao L., Macara I.G.
Nat. Cell Biol. 2:531-539(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD6A, MUTAGENESIS OF GLY-12.
|||"A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity."|
Lin D., Edwards A.S., Fawcett J.P., Mbamalu G., Scott J.D., Pawson T.
Nat. Cell Biol. 2:540-547(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD6B.
|||"Type Ialpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly."|
Tolias K.F., Hartwig J.H., Ishihara H., Shibasaki Y., Cantley L.C., Carpenter C.L.
Curr. Biol. 10:153-156(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIP5K1A.
|||"Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock."|
Uhlik M.T., Abell A.N., Johnson N.L., Sun W., Cuevas B.D., Lobel-Rice K.E., Horne E.A., Dell'Acqua M.L., Johnson G.L.
Nat. Cell Biol. 5:1104-1110(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K3; MAP2K3 AND CCM2.
|||"Regulation of p21-activated kinase-independent Rac1 signal transduction by Nischarin."|
Reddig P.J., Xu D., Juliano R.L.
J. Biol. Chem. 280:30994-31002(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NISCH.
|||"Hyaluronan-CD44 interaction stimulates Rac1 signaling and PKN gamma kinase activation leading to cytoskeleton function and cell migration in astrocytes."|
Bourguignon L.Y., Gilad E., Peyrollier K., Brightman A., Swanson R.A.
J. Neurochem. 101:1002-1017(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PKN2.
|||"Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease."|
Shibata S., Nagase M., Yoshida S., Kawarazaki W., Kurihara H., Tanaka H., Miyoshi J., Takai Y., Fujita T.
Nat. Med. 14:1370-1376(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis."|
Guerrier S., Coutinho-Budd J., Sassa T., Gresset A., Jordan N.V., Chen K., Jin W.L., Frost A., Polleux F.
Cell 138:990-1004(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRGAP2, ENZYME REGULATION.
|||"Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase."|
Li X., Lee A.Y.
J. Biol. Chem. 285:32436-32445(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLXNB3.
|||"The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells."|
Wallace S.W., Magalhaes A., Hall A.
Mol. Cell. Biol. 31:81-91(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PKN2.
|+||Additional computationally mapped references.|
|X57277 mRNA. Translation: CAA40545.1.|
AK009017 mRNA. Translation: BAB26027.1.
AK011072 mRNA. Translation: BAB69451.1.
AK034601 mRNA. Translation: BAC28767.1.
AK047969 mRNA. Translation: BAC33203.1.
AK088825 mRNA. Translation: BAC40596.1.
BC003828 mRNA. Translation: AAH03828.1.
BC051053 mRNA. Translation: AAH51053.1.
|RefSeq||NP_033033.1. NM_009007.2. |
3D structure databases
|SMR||P63001. Positions 1-177. |
Protein-protein interaction databases
|BioGrid||202556. 20 interactions.|
|IntAct||P63001. 28 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000080537; ENSMUSP00000079380; ENSMUSG00000001847. |
|UCSC||uc009akk.1. mouse. |
|MGI||MGI:97845. Rac1. |
Enzyme and pathway databases
|Reactome||REACT_188576. Developmental Biology. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.1240. 1 hit. |
|InterPro||IPR027417. P-loop_NTPase. |
|Pfam||PF00071. Ras. 1 hit. |
|PRINTS||PR00449. RASTRNSFRMNG. |
|SMART||SM00174. RHO. 1 hit. |
|SUPFAM||SSF52540. SSF52540. 1 hit. |
|TIGRFAMs||TIGR00231. small_GTP. 1 hit. |
|PROSITE||PS51420. RHO. 1 hit. |
|ChiTaRS||RAC1. mouse. |
|Accession||Primary (citable) accession number: P63001|
Secondary accession number(s): O95501, P15154, Q9BTB4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|