ID:RAC1_HUMAN DESCRIPTION: RecName: Full=Ras-related C3 botulinum toxin substrate 1; AltName: Full=Cell migration-inducing gene 5 protein; AltName: Full=Ras-like protein TC25; AltName: Full=p21-Rac1; Flags: Precursor; 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 (By similarity). 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. FUNCTION: 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. ENZYME REGULATION: 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. SUBUNIT: 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 and mediated through PLXNB3 (By similarity). 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, 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). INTERACTION: P53365:ARFIP2; NbExp=9; IntAct=EBI-413628, EBI-638194; Q9UQB8:BAIAP2; NbExp=3; IntAct=EBI-413628, EBI-525456; Q14185:DOCK1; NbExp=8; IntAct=EBI-413628, EBI-446740; P19878:NCF2; NbExp=2; IntAct=EBI-413628, EBI-489611; Q13153:PAK1; NbExp=7; IntAct=EBI-413628, EBI-1307; O75914:PAK3; NbExp=2; IntAct=EBI-413628, EBI-3389553; Q9NPB6:PARD6A; NbExp=2; IntAct=EBI-413628, EBI-81876; Q9BYG5:PARD6B; NbExp=3; IntAct=EBI-413628, EBI-295391; Q9BYG4:PARD6G; NbExp=2; IntAct=EBI-413628, EBI-295417; P41743:PRKCI; NbExp=3; IntAct=EBI-413628, EBI-286199; SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity). Melanosome. Cytoplasm (By similarity). 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). 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. DOMAIN: The effector region mediates interaction with DEF6. PTM: AMPylation at Tyr-32 and Thr-35 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo. PTM: GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome. SIMILARITY: Belongs to the small GTPase superfamily. Rho family. SEQUENCE CAUTION: Sequence=AAZ80485.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rac1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P63000
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
HH837097 - Sequence 24 from Patent EP2231168. HH837098 - Sequence 25 from Patent EP2231168. HH837099 - Sequence 26 from Patent EP2231168. HI214738 - Sequence 24 from Patent EP2076526. HI214739 - Sequence 25 from Patent EP2076526. HI214740 - Sequence 26 from Patent EP2076526. HV601540 - JP 2011500003-A/24: Novel siRNA Structures. HV601541 - JP 2011500003-A/25: Novel siRNA Structures. HV601542 - JP 2011500003-A/26: Novel siRNA Structures. HV708915 - JP 2012506450-A/13: Methods for treating eye disorders. HV856613 - JP 2010507387-A/24: Novel siRNAs and Methods of Use Thereof. HV856614 - JP 2010507387-A/25: Novel siRNAs and Methods of Use Thereof. HV856615 - JP 2010507387-A/26: Novel siRNAs and Methods of Use Thereof. HW061151 - JP 2012529430-A/26: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. HW061152 - JP 2012529430-A/27: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. HW165100 - JP 2013102767-A/24: Novel siRNA's and Use Thereof. HW165101 - JP 2013102767-A/25: Novel siRNA's and Use Thereof. HW165102 - JP 2013102767-A/26: Novel siRNA's and Use Thereof. HW675608 - JP 2014210789-A/24: Novel siRNA Structures. HW675609 - JP 2014210789-A/25: Novel siRNA Structures. HW675610 - JP 2014210789-A/26: Novel siRNA Structures. HW835296 - JP 2015051004-A/24: Novel siRNA's and Use Thereof. HW835297 - JP 2015051004-A/25: Novel siRNA's and Use Thereof. HW835298 - JP 2015051004-A/26: Novel siRNA's and Use Thereof. JA482106 - Sequence 89 from Patent WO2011072091. JA482107 - Sequence 90 from Patent WO2011072091. JA538139 - Sequence 24 from Patent EP2371958. JA538140 - Sequence 25 from Patent EP2371958. JA538141 - Sequence 26 from Patent EP2371958. JB251959 - Sequence 26 from Patent EP2440214. JB251960 - Sequence 27 from Patent EP2440214. JC102699 - Sequence 1 from Patent WO2013179292. JD590310 - Sequence 1 from Patent WO2015015496. JD590323 - Sequence 1 from Patent WO2015015498. JE980398 - Sequence 89 from Patent EP2862929. JE980399 - Sequence 90 from Patent EP2862929. LP764858 - Sequence 26 from Patent EP3276004. LP764859 - Sequence 27 from Patent EP3276004. AK054993 - Homo sapiens cDNA FLJ30431 fis, clone BRACE2008968, highly similar to Ras-related C3 botulinum toxin substrate 1 precursor. BC107748 - Homo sapiens ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), mRNA (cDNA clone MGC:111543 IMAGE:6699945), complete cds. AK291806 - Homo sapiens cDNA FLJ75553 complete cds, highly similar to Homo sapiens ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) (RAC1), transcript variant Rac1, mRNA. AB209410 - Homo sapiens mRNA for ras-related C3 botulinum toxin substrate 1 isoform Rac1b variant protein. BC050687 - Homo sapiens ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), mRNA (cDNA clone MGC:60264 IMAGE:6149377), complete cds. AK291815 - Homo sapiens cDNA FLJ77333 complete cds, highly similar to Homo sapiens ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) (RAC1), transcript variant Rac1b, mRNA. AY279384 - Homo sapiens migration-inducing protein 5 (MIG5) mRNA, complete cds. BC004247 - Homo sapiens ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), mRNA (cDNA clone MGC:10547 IMAGE:3610745), complete cds. CU690768 - Synthetic construct Homo sapiens gateway clone IMAGE:100021271 5' read RAC1 mRNA. M31467 - Human ras-like protein mRNA, complete cds, clone TC25. AB451363 - Homo sapiens RAC1 mRNA for ras-related C3 botulinum toxin substrate 1 isoform Rac1, partial cds, clone: FLJ08036AAAF. AB464133 - Synthetic construct DNA, clone: pF1KB8254, Homo sapiens RAC1 gene for ras-related C3 botulinum toxin substrate 1, without stop codon, in Flexi system. KJ905889 - Synthetic construct Homo sapiens clone ccsbBroadEn_15559 RAC1 gene, encodes complete protein. BT007121 - Homo sapiens ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) mRNA, complete cds. KJ897437 - Synthetic construct Homo sapiens clone ccsbBroadEn_06831 RAC1 gene, encodes complete protein. AB451238 - Homo sapiens RAC1 mRNA for ras-related C3 botulinum toxin substrate 1 isoform Rac1, complete cds, clone: FLJ08036AAAN. AF136373 - Homo sapiens ras-related C3 botulinum toxin substrate isoform mRNA, complete cds. AF498964 - Homo sapiens small GTP binding protein RAC1 (RAC1) mRNA, complete cds. AJ132694 - Homo sapiens mRNA for small GTPase rac1b. M29870 - Human ras-related C3 botulinum toxin substrate (rac) mRNA, complete cds. EU831965 - Synthetic construct Homo sapiens clone HAIB:100066994; DKFZo008F0623 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) protein (RAC1) gene, encodes complete protein. EU832058 - Synthetic construct Homo sapiens clone HAIB:100067087; DKFZo004F0624 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) protein (RAC1) gene, encodes complete protein. EU832640 - Synthetic construct Homo sapiens clone HAIB:100067669; DKFZo008E0131 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) protein (RAC1) gene, encodes complete protein. EU832717 - Synthetic construct Homo sapiens clone HAIB:100067746; DKFZo004E0132 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) protein (RAC1) gene, encodes complete protein. JD024426 - Sequence 5450 from Patent EP1572962. JD025051 - Sequence 6075 from Patent EP1572962. JD029090 - Sequence 10114 from Patent EP1572962. JD024675 - Sequence 5699 from Patent EP1572962. JD414421 - Sequence 395445 from Patent EP1572962. JD200355 - Sequence 181379 from Patent EP1572962. JD106308 - Sequence 87332 from Patent EP1572962. JD033048 - Sequence 14072 from Patent EP1572962. DQ589813 - Homo sapiens piRNA piR-56925, complete sequence. AK122742 - Homo sapiens cDNA FLJ16267 fis, clone KIDNE2002768. JD534711 - Sequence 515735 from Patent EP1572962. AJ012502 - Homo sapiens mRNA activated in tumor suppression, clone TSAP22. LF382484 - JP 2014500723-A/189987: Polycomb-Associated Non-Coding RNAs. D25274 - Homo sapiens mRNA, clone: PO2ST9. MA618061 - JP 2018138019-A/189987: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_actinYPathway - Y branching of actin filaments h_arfPathway - Tumor Suppressor Arf Inhibits Ribosomal Biogenesis h_pyk2Pathway - Links between Pyk2 and Map Kinases h_bcrPathway - BCR Signaling Pathway h_crebPathway - Transcription factor CREB and its extracellular signals h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells h_rac1Pathway - Rac 1 cell motility signaling pathway h_rasPathway - Ras Signaling Pathway h_tcrPathway - T Cell Receptor Signaling Pathway h_ptdinsPathway - Phosphoinositides and their downstream targets. h_cdc42racPathway - Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration h_salmonellaPathway - How does salmonella hijack a cell h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling h_malPathway - Role of MAL in Rho-Mediated Activation of SRF h_nkcellsPathway - Ras-Independent pathway in NK cell-mediated cytotoxicity h_ucalpainPathway - uCalpain and friends in Cell spread h_agrPathway - Agrin in Postsynaptic Differentiation h_edg1Pathway - Phospholipids as signalling intermediaries h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_mapkPathway - MAPKinase Signaling Pathway h_p38mapkPathway - p38 MAPK Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P63000 (Reactome details) participates in the following event(s):