Protein:RAC1 |
Protein Summary |
 Gene summary |
| Gene name: RAC1 | ASpdb.0 ID: 5879 | Gene | Gene symbol | RAC1 | Gene ID | 5879 |
| Gene name | Rac family small GTPase 1 |
| Synonyms | MIG5|MRD48|Rac-1|TC-25|p21-Rac1 |
| Cytomap | 7p22.1 |
| Type of gene | protein-coding |
| Description | ras-related C3 botulinum toxin substrate 1cell migration-inducing gene 5 proteinras-like protein TC25ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) |
| Modification date | 20240416 |
| UniProtAcc | P63000 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | RAC1 | GO:0003924 | GTPase activity | 19787194|27917469 |
| Gene | RAC1 | GO:0005525 | GTP binding | 12551911|15467718|15601624|22036506|23620790 |
| Gene | RAC1 | GO:0005634 | nucleus | 12551911 |
| Gene | RAC1 | GO:0005737 | cytoplasm | 19625648 |
| Gene | RAC1 | GO:0005802 | trans-Golgi network | 12915445 |
| Gene | RAC1 | GO:0005884 | actin filament | 19625648 |
| Gene | RAC1 | GO:0005886 | plasma membrane | 10036235 |
| Gene | RAC1 | GO:0005938 | cell cortex | 19126672 |
| Gene | RAC1 | GO:0010592 | positive regulation of lamellipodium assembly | 15467718 |
| Gene | RAC1 | GO:0010764 | negative regulation of fibroblast migration | 19126672 |
| Gene | RAC1 | GO:0016477 | cell migration | 23512198 |
| Gene | RAC1 | GO:0030027 | lamellipodium | 19126672|19625648 |
| Gene | RAC1 | GO:0031529 | ruffle organization | 15467718 |
| Gene | RAC1 | GO:0032587 | ruffle membrane | 20875796 |
| Gene | RAC1 | GO:0032707 | negative regulation of interleukin-23 production | 16982892 |
| Gene | RAC1 | GO:0036464 | cytoplasmic ribonucleoprotein granule | 15121898 |
| Gene | RAC1 | GO:0043197 | dendritic spine | 24352656 |
| Gene | RAC1 | GO:0044877 | protein-containing complex binding | 21107423 |
| Gene | RAC1 | GO:0048870 | cell motility | 19403692 |
| Gene | RAC1 | GO:0051179 | localization | 12874273 |
| Gene | RAC1 | GO:0051496 | positive regulation of stress fiber assembly | 23129259 |
| Gene | RAC1 | GO:0051894 | positive regulation of focal adhesion assembly | 23129259 |
| Gene | RAC1 | GO:0055038 | recycling endosome membrane | 10036235 |
| Gene | RAC1 | GO:0060263 | regulation of respiratory burst | 16636067 |
| Gene | RAC1 | GO:0098794 | postsynapse | 15800193|24352656 |
| Gene | RAC1 | GO:0098978 | glutamatergic synapse | 15800193|24352656 |
| Gene | RAC1 | GO:1900026 | positive regulation of substrate adhesion-dependent cell spreading | 23129259 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P63000-1 | P63000-1_1hh4_A.pdb | 1HH4 | X-ray | 2.7 | A | 2 | 189 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P63000 | RAC1 | P63000-1 | P63000-2 | 192 | 211 | 75 | 75 | Substitution | T | TVGETYGKDITSRGKDKPIA | 75 | 94 |
| Multiple sequence alignment of our canonical and alternatively spliced RAC1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of RAC1 |
| UniProt-id | ENSG | ENST | ENSP |
| P63000-1 | ENSG00000136238.20 | ENST00000348035.9 | ENSP00000258737.7 |
| P63000-2 | ENSG00000136238.20 | ENST00000356142.4 | ENSP00000348461.4 |
| UniProt-id | NM ID | NP ID |
| P63000-1 | NM_006908.4 | NP_008839.2 |
| P63000-2 | NM_018890.3 | NP_061485.1 |
| Amino acid sequences of our canonical and alternatively spliced RAC1 |
| accession_id | Protein sequence |
| P63000-1 | MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTDVFLICFSLVSPASF ENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPP |
| P63000-2 | MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTVGETYGKDITSRGKD KPIADVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALT |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| RAC1 (go to UniProt):P63000 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Gene Isoform Structures and Expression Levels for RAC1 |
| Gene structures of our canonical and alternative spliced genes of RAC1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P63000-1 |
| 3D view using mol* of P63000-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P63000-1 |
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| pLDDT distribution across the protein length of P63000-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P63000-1 |
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| Ramachandran plot of P63000-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P63000-1 | 0.844 | 36 | 0.327 | 57.624 | 0.446 | 0.903 | 1.418 | 0.139 | 2.39 | 0.058 | 0.296 | 12,13,14,15,16,17,18,32,34,35,57,58,59,60,61,116
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| P63000-2 | 0.952 | 146 | 0.977 | 435.953 | 0.629 | 0.625 | 0.845 | 0.516 | 1.036 | 0.498 | 0.954 | 3,5,52,54,56,69,70,73,74,75,76,77,78,79,80,81,82,8 4,85,87,88,89,90,91,92,93,95,123 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P63000-1_P63000-1_1hh4_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P63000-1_1hh4_A_P63000-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P63000-1_P63000-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P63000-1_vs_P63000-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P63000-1_vs_P63000-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to RAC1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P63000 | RAC1 | DB04315 | Guanosine-5'-Diphosphate | experimental | |
| P63000 | RAC1 | DB00993 | Azathioprine | approved | modulator |
Related Diseases to RAC1 |
| Previous studies relating to the alternative splicing of RAC1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| RAC1 | 19602482 | Antagonistic SR proteins regulate alternative splicing of tumor-related Rac1b downstream of the PI3-kinase and Wnt pathways. | The small GTPase Rac1 regulates signaling pathways controlling actin-dependent cell motility as well as gene transcription. An alternative splicing variant Rac1b is overexpressed in a subset of colorectal tumors and is required to sustain tumor cell viability. Thus, it is of therapeutic interest to understand the molecular mechanism behind the overexpression of Rac1b through alternative splicing. Here we describe that ASF/SF2 and SRp20 are two antagonistic splicing factors regulating Rac1b expression in colorectal tumor cells. Using an Rac1 minigene, we identified that SRp20 increased skipping of alternative exon 3b in HT29 colorectal cells, whereas ASF/SF2 increased its inclusion. The depletion of the endogenous expression of these splicing factors by specific small interfering RNA confirmed that ASF/SF2 acts as an enhancer of endogenous Rac1b splicing, whereas SRp20 acts as a silencer. Point mutations in exon 3b defined two adjacent regulatory regions required for skipping or inclusion of exon 3b, which are recognized in vitro by SRp20 and ASF/SF2, respectively. Both splicing factors were found to be regulated by upstream signaling pathways: the inhibition of the phosphatidylinositol 3-kinase pathway increased protein levels of ASF/SF2 and promoted Rac1b, whereas activation of beta-catenin/TCF4 increased expression of SRp20 and inhibited that of Rac1b. Together, these data reveal that signaling pathways act in concert to target independent splicing factors and achieve the correct combinatorial code to regulate alternative splicing of the small GTPase Rac1. | D015179 | Colorectal Neoplasms |
Clinically important variants in RAC1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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