P62999 (RAC1_CANFA) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 93. History...
Names and origin
|Protein names||Recommended name:|
Ras-related C3 botulinum toxin substrate 1
|Organism||Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]|
|Taxonomic identifier||9615 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis ›|
|Sequence length||192 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript 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. 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 plasma membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3 By similarity.
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.
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 By similarity.
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.
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_0000042034|
|Propeptide||190 – 192||3||Removed in mature form By similarity||PRO_0000042035|
|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|
|||"Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell line."|
Chavrier P., Vingron M., Sander C., Simons K., Zerial M.
Mol. Cell. Biol. 10:6578-6585(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Cocker spaniel.
|+||Additional computationally mapped references.|
|X56390 mRNA. Translation: CAA39801.1.|
|RefSeq||NP_001003274.1. NM_001003274.2. |
3D structure databases
|SMR||P62999. Positions 1-177. |
Protein-protein interaction databases
|IntAct||P62999. 1 interaction.|
Protocols and materials databases
Genome annotation databases
Family and domain databases
|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. |
|Accession||Primary (citable) accession number: P62999|
Secondary accession number(s): O95501, P15154, Q9BTB4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families