Protein:AKT1 |
Protein Summary |
 Gene summary |
| Gene name: AKT1 | ASpdb.0 ID: 207 | Gene | Gene symbol | AKT1 | Gene ID | 207 |
| Gene name | AKT serine/threonine kinase 1 |
| Synonyms | AKT|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA |
| Cytomap | 14q32.33 |
| Type of gene | protein-coding |
| Description | RAC-alpha serine/threonine-protein kinaseAKT1mPKB alphaRAC-PK-alphaprotein kinase B alphaproto-oncogene c-Aktrac protein kinase alphaserine-threonine protein kinasev-akt murine thymoma viral oncogene homolog 1v-akt murine thymoma viral oncogene-l |
| Modification date | 20240416 |
| UniProtAcc | P31749 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | AKT1 | GO:0001934 | positive regulation of protein phosphorylation | 19057511 |
| Gene | AKT1 | GO:0004672 | protein kinase activity | 31204173 |
| Gene | AKT1 | GO:0004674 | protein serine/threonine kinase activity | 10102273|10983986|11994271|12172553|14749367|15861136|16139227|16540465|17386266|19667065|23512198|24529379|26440888|30514904|31548394|32322062|33594058 |
| Gene | AKT1 | GO:0004712 | protein serine/threonine/tyrosine kinase activity | 22797923 |
| Gene | AKT1 | GO:0005516 | calmodulin binding | 29104511 |
| Gene | AKT1 | GO:0005524 | ATP binding | 16540465 |
| Gene | AKT1 | GO:0005547 | phosphatidylinositol-3,4,5-trisphosphate binding | 19203586 |
| Gene | AKT1 | GO:0005634 | nucleus | 20333297 |
| Gene | AKT1 | GO:0005654 | nucleoplasm | - |
| Gene | AKT1 | GO:0005737 | cytoplasm | 26440888 |
| Gene | AKT1 | GO:0005737 | cytoplasm | 19203586|25190803 |
| Gene | AKT1 | GO:0005829 | cytosol | 21045808 |
| Gene | AKT1 | GO:0005886 | plasma membrane | 14749367|19203586|20333297 |
| Gene | AKT1 | GO:0006468 | protein phosphorylation | 14749367 |
| Gene | AKT1 | GO:0006468 | protein phosphorylation | 11994271|23431171 |
| Gene | AKT1 | GO:0007173 | epidermal growth factor receptor signaling pathway | 20878056 |
| Gene | AKT1 | GO:0015630 | microtubule cytoskeleton | - |
| Gene | AKT1 | GO:0016020 | membrane | 24529379 |
| Gene | AKT1 | GO:0016301 | kinase activity | 14749367 |
| Gene | AKT1 | GO:0016310 | phosphorylation | 20333297 |
| Gene | AKT1 | GO:0018105 | peptidyl-serine phosphorylation | 16139227|32322062 |
| Gene | AKT1 | GO:0018107 | peptidyl-threonine phosphorylation | 20605787 |
| Gene | AKT1 | GO:0019049 | virus-mediated perturbation of host defense response | 14749367 |
| Gene | AKT1 | GO:0030307 | positive regulation of cell growth | 19203586 |
| Gene | AKT1 | GO:0031982 | vesicle | 16792529 |
| Gene | AKT1 | GO:0032079 | positive regulation of endodeoxyribonuclease activity | 20605787 |
| Gene | AKT1 | GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | 23512198 |
| Gene | AKT1 | GO:0032869 | cellular response to insulin stimulus | 12172553|17386266|24529379 |
| Gene | AKT1 | GO:0032991 | protein-containing complex | 20878056 |
| Gene | AKT1 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 19667065 |
| Gene | AKT1 | GO:0035556 | intracellular signal transduction | 14749367 |
| Gene | AKT1 | GO:0035655 | interleukin-18-mediated signaling pathway | 21321938 |
| Gene | AKT1 | GO:0042803 | protein homodimerization activity | 10983986 |
| Gene | AKT1 | GO:0043066 | negative regulation of apoptotic process | 19203586 |
| Gene | AKT1 | GO:0043325 | phosphatidylinositol-3,4-bisphosphate binding | 19203586 |
| Gene | AKT1 | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 21321938|28147277 |
| Gene | AKT1 | GO:0043536 | positive regulation of blood vessel endothelial cell migration | 20011604 |
| Gene | AKT1 | GO:0046889 | positive regulation of lipid biosynthetic process | 32322062 |
| Gene | AKT1 | GO:0048661 | positive regulation of smooth muscle cell proliferation | 21321938 |
| Gene | AKT1 | GO:0051091 | positive regulation of DNA-binding transcription factor activity | 19057511 |
| Gene | AKT1 | GO:0070141 | response to UV-A | 18483258 |
| Gene | AKT1 | GO:0070848 | response to growth factor | 33505021 |
| Gene | AKT1 | GO:0071364 | cellular response to epidermal growth factor stimulus | 30514904 |
| Gene | AKT1 | GO:0099104 | potassium channel activator activity | 33505021 |
| Gene | AKT1 | GO:0110002 | regulation of tRNA methylation | 15861136 |
| Gene | AKT1 | GO:0150033 | negative regulation of protein localization to lysosome | 24529379 |
| Gene | AKT1 | GO:0160049 | negative regulation of cGAS/STING signaling pathway | 26440888 |
| Gene | AKT1 | GO:1902018 | negative regulation of cilium assembly | 31204173 |
| Gene | AKT1 | GO:1904263 | positive regulation of TORC1 signaling | 12172553|17386266|24529379|30514904|31548394|33594058 |
| Gene | AKT1 | GO:1905552 | positive regulation of protein localization to endoplasmic reticulum | 32322062 |
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 |
| P31749-1 | P31749-1_6hhg_A.pdb | 6HHG | X-ray | 2.3 | A | 3 | 444 |
| 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 |
| P31749 | AKT1 | P31749-1 | P31749-2 | 480 | 418 | 1 | 62 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced AKT1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of AKT1 |
| UniProt-id | ENSG | ENST | ENSP |
| P31749-1 | ENSG00000142208.18 | ENST00000349310.7 | ENSP00000270202.4 |
| P31749-1 | ENSG00000142208.18 | ENST00000402615.6 | ENSP00000385326.2 |
| P31749-1 | ENSG00000142208.18 | ENST00000407796.7 | ENSP00000384293.2 |
| P31749-1 | ENSG00000142208.18 | ENST00000554581.5 | ENSP00000451828.1 |
| P31749-1 | ENSG00000142208.18 | ENST00000554848.5 | ENSP00000451166.1 |
| P31749-1 | ENSG00000142208.18 | ENST00000555528.5 | ENSP00000450688.1 |
| P31749-1 | ENSG00000142208.18 | ENST00000649815.2 | ENSP00000497822.1 |
| P31749-1 | ENSG00000142208.18 | ENST00000683722.1 | ENSP00000507879.1 |
| UniProt-id | NM ID | NP ID |
| P31749-1 | NM_001014431.1 | NP_001014431.1 |
| P31749-1 | NM_001014432.1 | NP_001014432.1 |
| P31749-1 | NM_005163.2 | NP_005154.2 |
| Amino acid sequences of our canonical and alternatively spliced AKT1 |
| accession_id | Protein sequence |
| P31749-1 | MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHV ETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKI LKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNV VYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFEL ILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITIT |
| P31749-2 | MKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEY LKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRE RVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDW WGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLS |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| AKT1 (go to UniProt):P31749 |
| 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 |
| P31749 | Domain | 5 | 108 | Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145 | Type=Deletion;Start=1;End=62 |
Gene Isoform Structures and Expression Levels for AKT1 |
| Gene structures of our canonical and alternative spliced genes of AKT1 * 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 P31749-1 |
| 3D view using mol* of P31749-2 |
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 P31749-1 |
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| pLDDT distribution across the protein length of P31749-2 |
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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 P31749-1 |
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| Ramachandran plot of P31749-2 |
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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 |
| P31749-1 | 1.061 | 167 | 1.063 | 519.988 | 0.498 | 0.789 | 0.997 | 0.568 | 1.076 | 0.528 | 0.843 | 156,157,158,159,160,161,164,177,179,181,186,191,19 4,195,198,211,227,228,229,230,233,234,237,274,276, 278,279,281,291,292,293,294,295,437,438,439,442 |
| P31749-2 | 1.056 | 185 | 1.05 | 593.733 | 0.536 | 0.782 | 1.014 | 0.6 | 1.103 | 0.544 | 1.289 | 18,19,94,95,97,98,99,100,102,115,117,119,124,127,1 28,129,132,133,136,140,149,165,166,167,168,172,174 ,175,212,214,216,217,219,229,230,231,232,233,375,3 76,377,380 |
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 P31749-1_P31749-1_6hhg_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 P31749-1_6hhg_A_P31749-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P31749-1_P31749-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P31749-1_vs_P31749-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P31749-1_vs_P31749-2.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 AKT1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P31749 | AKT1 | DB01169 | Arsenic trioxide | approved, investigational | inducer |
| P31749 | AKT1 | DB01645 | Genistein | investigational | |
| P31749 | AKT1 | DB05971 | Archexin | investigational | |
| P31749 | AKT1 | DB02709 | Resveratrol | investigational | inhibitor |
| P31749 | AKT1 | DB06486 | Enzastaurin | investigational | |
| P31749 | AKT1 | DB01863 | Inositol 1,3,4,5-Tetrakisphosphate | experimental | |
| P31749 | AKT1 | DB06641 | Perifosine | investigational | |
| P31749 | AKT1 | DB07584 | N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine | experimental | |
| P31749 | AKT1 | DB00171 | ATP | investigational, nutraceutical | |
| P31749 | AKT1 | DB07585 | 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine | experimental | |
| P31749 | AKT1 | DB12218 | Capivasertib | approved, investigational | inhibitor |
Related Diseases to AKT1 |
| Previous studies relating to the alternative splicing of AKT1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| AKT1 | 15231831 | BAD is a pro-survival factor prior to activation of its pro-apoptotic function. | The mammalian BAD protein belongs to the BH3-only subgroup of the BCL-2 family. In contrast to its known pro-apoptotic function, we found that endogenous and overexpressed BAD(L) can inhibit cell death in neurons and other cell types. Several mechanisms regulate the conversion of BAD from an anti-death to a pro-death factor, including alternative splicing that produces the N-terminally truncated BAD(S). In addition, caspases convert BAD(L) into a pro-death fragment that resembles the short splice variant. The caspase site that is selectively cleaved during cell death following growth factor (interleukin-3) withdrawal is conserved between human and murine BAD. A second cleavage site that is required for murine BAD to promote death following Sindbis virus infection, gamma-irradiation, and staurosporine treatment is not conserved in human BAD, consistent with the inability of human BAD to promote death with these stimuli. However, loss of the BAD N terminus by any mechanism is not always sufficient to activate its pro-death activity, suggesting that the N terminus is a regulatory domain rather than an anti-death domain. These findings suggest that BAD is more than an inert death factor in healthy cells; it is also a pro-survival factor, prior to its role in promoting cell death. | D018354 | Alphavirus Infections |
| AKT1 | 21045158 | Alternative splicing of caspase 9 is modulated by the phosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a. | Increasing evidence points to the functional importance of alternative splice variations in cancer pathophysiology. Two splice variants are derived from the CASP9 gene via the inclusion (Casp9a) or exclusion (Casp9b) of a four-exon cassette. Here we show that alternative splicing of Casp9 is dysregulated in non-small cell lung cancers (NSCLC) regardless of their pathologic classification. Based on these findings we hypothesized that survival pathways activated by oncogenic mutation regulated this mechanism. In contrast to K-RasV12 expression, epidermal growth factor receptor (EGFR) overexpression or mutation dramatically lowered the Casp9a/9b splice isoform ratio. Moreover, Casp9b downregulation blocked the ability of EGFR mutations to induce anchorage-independent growth. Furthermore, Casp9b expression blocked inhibition of clonogenic colony formation by erlotinib. Interrogation of oncogenic signaling pathways showed that inhibition of phosphoinositide 3-kinase or Akt dramatically increased the Casp9a/9b ratio in NSCLC cells. Finally, Akt was found to mediate exclusion of the exon 3,4,5,6 cassette of Casp9 via the phosphorylation state of the RNA splicing factor SRp30a via serines 199, 201, 227, and 234. Taken together, our findings show that oncogenic factors activating the phosphoinositide 3-kinase/Akt pathway can regulate alternative splicing of Casp9 via a coordinated mechanism involving the phosphorylation of SRp30a. | D002289 | Carcinoma, Non-Small-Cell Lung |
| AKT1 | 21045158 | Alternative splicing of caspase 9 is modulated by the phosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a. | Increasing evidence points to the functional importance of alternative splice variations in cancer pathophysiology. Two splice variants are derived from the CASP9 gene via the inclusion (Casp9a) or exclusion (Casp9b) of a four-exon cassette. Here we show that alternative splicing of Casp9 is dysregulated in non-small cell lung cancers (NSCLC) regardless of their pathologic classification. Based on these findings we hypothesized that survival pathways activated by oncogenic mutation regulated this mechanism. In contrast to K-RasV12 expression, epidermal growth factor receptor (EGFR) overexpression or mutation dramatically lowered the Casp9a/9b splice isoform ratio. Moreover, Casp9b downregulation blocked the ability of EGFR mutations to induce anchorage-independent growth. Furthermore, Casp9b expression blocked inhibition of clonogenic colony formation by erlotinib. Interrogation of oncogenic signaling pathways showed that inhibition of phosphoinositide 3-kinase or Akt dramatically increased the Casp9a/9b ratio in NSCLC cells. Finally, Akt was found to mediate exclusion of the exon 3,4,5,6 cassette of Casp9 via the phosphorylation state of the RNA splicing factor SRp30a via serines 199, 201, 227, and 234. Taken together, our findings show that oncogenic factors activating the phosphoinositide 3-kinase/Akt pathway can regulate alternative splicing of Casp9 via a coordinated mechanism involving the phosphorylation of SRp30a. | D008175 | Lung Neoplasms |
| AKT1 | 26022125 | SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt. | SG2NA in association with striatin and zinedin forms a striatin family of WD-40 repeat proteins. This family of proteins functions as scaffold in different signal transduction pathways. They also act as a regulatory subunit of protein phosphatase 2A. We have shown that SG2NA which evolved first in the metazoan evolution among the striatin family members expresses different isoforms generated out of alternative splicing. We have also shown that SG2NA protects cells from oxidative stress by recruiting DJ-1 and Akt to mitochondria and membrane in the post-mitotic neuronal cells. DJ-1 is both cancer and Parkinson's disease related protein. In the present study we have shown that SG2NA protects DJ-1 from proteasomal degradation in cancer cells. Hence, downregulation of SG2NA reduces DJ-1/Akt colocalization in cancer cells resulting in the reduction of anchorage dependent and independent growth. Thus SG2NA enhances cancer cell survival. Reactive oxygen species enhances SG2NA, DJ-1 and Akt trimerization. Removal of the reactive oxygen species by N-acetyl-cysteine thus reduces cancer cell growth. | D009369 | Neoplasms |
Clinically important variants in AKT1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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