Reviewed,
UniProtKB/Swiss-Prot Q8INB9 (AKT1_DROME)
Last modified
June 16, 2009.
Version 64.
History...
Clusters with 100%,
90%,
50% identity |
Documents (2) |
Third-party data |
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Names and origin
| Protein names | Recommended name: RAC serine/threonine-protein kinase Short name=DRAC-PK Short name=Dakt1 Short name=DAkt EC=2.7.11.1 Alternative name(s): Akt Protein kinase B Short name=PKB | ||||
| Gene names |
| ||||
| Organism | Drosophila melanogaster (Fruit fly) [Complete proteome] | ||||
| Taxonomic identifier | 7227 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora |
Protein attributes
| Sequence length | 611 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Serine/threonine kinase involved in various developmental processes. During early embryogenesis, acts as a survival protein. During mid-embryogenesis, phosphorylates and activates trh, a transcription factor required for tracheal cell fate determination. Also regulates tracheal cell migration. Later in development, acts downstream of PI3K and Pk61C/PDK1 in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and antagonizing FOXO transcription factor. Controls follicle cell size during oogenesis. May also stimulate cell growth by phosphorylating Gig/Tsc2 and inactivating the Tsc complex. Dephosphorylation of 'Ser-586' by Phlpp triggers apoptosis and suppression of tumor growth. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. Ref.2 |
| Subcellular location | Cytoplasm › cytosol. Cell membrane. Note: Recruited to plasma membrane upon activation. |
| Tissue specificity | Ubiquitously expressed. Present in ovary, where it is concentrated at the basal side of follicle cells. Ref.2 |
| Developmental stage | Expressed both maternally and zygotically. Strongly expressed in embryo and pupa. Weakly expressed in larva. Mildly expressed in adult. Ref.17 Ref.2 |
| Domain | Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI3K) results in its targeting to the plasma membrane Probable. |
| Post-translational modification | Phosphorylated and activated by Pk61C/PDK1. Phosphorylated on Ser-586 by the rictor-Tor complex. Ref.8 Ref.10 Ref.18 Ref.19 Ref.20 |
| Disruption phenotype | Death at the first instar larval stage. Ref.6 |
| Sequence similarities | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 protein kinase domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Q9VPE1 | 1 | EBI-162210,EBI-147129 | ||
| Q9VR24 | 1 | EBI-162210,EBI-98854 | ||
| Nle | Q9VPR4 | 1 | EBI-162210,EBI-176424 | |
| PHDP | O76136 | 2 | EBI-162210,EBI-466449 |
Alternative products
| This entry describes 2 isoforms produced by alternative initiation. [Align] [Select] | ||||||
| Isoform C (identifier: Q8INB9-1) Also known as: PK85; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform A (identifier: Q8INB9-2) Also known as: PK66; The sequence of this isoform differs from the canonical sequence as follows: 1-81: Missing. | ||||||
| Note: Major form. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 611 | 611 | RAC serine/threonine-protein kinase | PRO_0000045784 | |||||
Regions | |||||||||
| Domain | 106 – 211 | 106 | PH | ||||||
| Domain | 266 – 523 | 258 | Protein kinase | ||||||
| Domain | 524 – 597 | 74 | AGC-kinase C-terminal | ||||||
| Nucleotide binding | 272 – 280 | 9 | ATP By similarity | ||||||
Sites | |||||||||
| Active site | 389 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 295 | 1 | ATP Probable | ||||||
Amino acid modifications | |||||||||
| Modified residue | 30 | 1 | Phosphoserine Ref.20 | ||||||
| Modified residue | 586 | 1 | Phosphoserine Ref.8 Ref.18 Ref.19 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 81 | 81 | Missing in isoform A. | VSP_018833 | |||||
Experimental info | |||||||||
| Mutagenesis | 180 | 1 | G → S: Fails to be recruited at the membrane upon activation. Ref.13 | ||||||
| Mutagenesis | 260 | 1 | K → A: Abolishes enzymatic activity. | ||||||
| Mutagenesis | 295 | 1 | K → M: Abolishes enzymatic activity. Ref.7 | ||||||
| Mutagenesis | 408 | 1 | F → I: Abolishes enzymatic activity. Ref.6 Ref.13 | ||||||
| Sequence conflict | 73 | 1 | A → T in CAA58499. Ref.2 | ||||||
| Sequence conflict | 200 – 201 | 2 | QQ → HE in CAA81204. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The SH2-like Akt homology (AH) domain of c-akt is present in multiple copies in the genome of vertebrate and invertebrate eucaryotes. Cloning and characterisation of the Drosophila melanogaster c-akt homolog Dakt1." Franke T.F., Tartof K.D., Tsichlis P.N. Oncogene 9:141-148(1994) [PubMed: 8302573] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). |
| [2] | "Developmental regulation of expression and activity of multiple forms of the Drosophila RAC protein kinase." Andjelkovic M., Jones P.F., Grossniklaus U., Cron P., Schier A.F., Dick M., Bilbe G., Hemmings B.A. J. Biol. Chem. 270:4066-4075(1995) [PubMed: 7876156] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE INITIATION (ISOFORMS A AND C), ENZYME ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [3] | "The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. Venter J.C.Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley. |
| [4] | "Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. Lewis S.E.Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE INITIATION. |
| [5] | "A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Embryo. |
| [6] | "Genetic analysis of protein kinase B (AKT) in Drosophila." Staveley B.E., Ruel L., Jin J., Stambolic V., Mastronardi F.G., Heitzler P., Woodgett J.R., Manoukian A.S. Curr. Biol. 8:599-602(1998) [PubMed: 9601646] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF PHE-408, DISRUPTION PHENOTYPE. |
| [7] | "Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB." Verdu J., Buratovich M.A., Wilder E.L., Birnbaum M.J. Nat. Cell Biol. 1:500-506(1999) [PubMed: 10587646] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-295. |
| [8] | "The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila." Scanga S.E., Ruel L., Binari R.C., Snow B., Stambolic V., Bouchard D., Peters M., Calvieri B., Mak T.W., Woodgett J.R., Manoukian A.S. Oncogene 19:3971-3977(2000) [PubMed: 10962553] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-586. |
| [9] | "Regulation of Drosophila tracheal system development by protein kinase B." Jin J., Anthopoulos N., Wetsch B., Binari R.C., Isaac D.D., Andrew D.J., Woodgett J.R., Manoukian A.S. Dev. Cell 1:817-827(2001) [PubMed: 11740943] [Abstract] Cited for: FUNCTION. |
| [10] | "Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway." Cho K.S., Lee J.H., Kim S., Kim D., Koh H., Lee J., Kim C., Kim J., Chung J. Proc. Natl. Acad. Sci. U.S.A. 98:6144-6149(2001) [PubMed: 11344272] [Abstract] Cited for: PHOSPHORYLATION. |
| [11] | "PDK1 regulates growth through Akt and S6K in Drosophila." Rintelen F., Stocker H., Thomas G., Hafen E. Proc. Natl. Acad. Sci. U.S.A. 98:15020-15025(2001) [PubMed: 11752451] [Abstract] Cited for: FUNCTION. |
| [12] | "Akt regulates growth by directly phosphorylating Tsc2." Potter C.J., Pedraza L.G., Xu T. Nat. Cell Biol. 4:658-665(2002) [PubMed: 12172554] [Abstract] Cited for: FUNCTION. |
| [13] | "Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB." Stocker H., Andjelkovic M., Oldham S., Laffargue M., Wymann M.P., Hemmings B.A., Hafen E. Science 295:2088-2091(2002) [PubMed: 11872800] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-180 AND PHE-408. |
| [14] | "Coordinated functions of Akt/PKB and ETS1 in tubule formation." Lavenburg K.R., Ivey J., Hsu T., Muise-Helmericks R.C. FASEB J. 17:2278-2280(2003) [PubMed: 14525946] [Abstract] Cited for: FUNCTION. |
| [15] | "Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway." Puig O., Marr M.T., Ruhf M.L., Tjian R. Genes Dev. 17:2006-2020(2003) [PubMed: 12893776] [Abstract] Cited for: FUNCTION. |
| [16] | "Tsc2 is not a critical target of Akt during normal Drosophila development." Dong J., Pan D. Genes Dev. 18:2479-2484(2004) [PubMed: 15466161] [Abstract] Cited for: FUNCTION. |
| [17] | "dAkt kinase controls follicle cell size during Drosophila oogenesis." Cavaliere V., Donati A., Hsouna A., Hsu T., Gargiulo G. Dev. Dyn. 232:845-854(2005) [PubMed: 15712201] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE. |
| [18] | "PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth." Gao T., Furnari F., Newton A.C. Mol. Cell 18:13-24(2005) [PubMed: 15808505] [Abstract] Cited for: DEPHOSPHORYLATION AT SER-586. |
| [19] | "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex." Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Science 307:1098-1101(2005) [PubMed: 15718470] [Abstract] Cited for: PHOSPHORYLATION AT SER-586. |
| [20] | "Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, MASS SPECTROMETRY. Tissue: Embryo. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| Z26242 mRNA. Translation: CAA81204.1. X83510 Genomic DNA. Translation: CAA58499.2. X83510 Genomic DNA. Translation: CAA58500.1. AE014297 Genomic DNA. Translation: AAF55275.1. AE014297 Genomic DNA. Translation: AAN13699.3. AY069856 mRNA. Translation: AAL40001.1. | |
| PIR | A55888. |
| RefSeq | NP_732113.3. NP_732114.1. |
| UniGene | Dm.1219 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1A06 based on UniProtKB Q63450. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q8INB9. 42 interactions. |
Proteomic databases | |
| PRIDE | Q8INB9. |
Genome annotation databases | |
| Ensembl | FBgn0010379. Drosophila melanogaster. [Contig view] |
| GeneID | 41957. |
| KEGG | dme:Dmel_CG4006. |
Organism-specific databases | |
| FlyBase | FBgn0010379. Akt1. |
Phylogenomic databases | |
| OMA | Q8INB9. SHERIFT. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 48. |
| Reactome | REACT_6313. Insulin receptor mediated signaling. |
Gene expression databases | |
| ArrayExpress | Q8INB9. |
| GermOnline | CG4006. Drosophila melanogaster. |
Family and domain databases | |
| InterPro | IPR000961. AGC-kinase_C. IPR011993. PH_type. IPR017892. Pkinase_C. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. IPR015744. Serine/threonine_Kinase_Rac. [Graphical view] |
| Gene3D | G3DSA:2.30.29.30. PH_type. 1 hit. |
| PANTHER | PTHR22985:SF69. Akt. 1 hit. |
| Pfam | PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view] |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view] |
| PROSITE | PS51285. AGC_KINASE_CTER. 1 hit. PS50003. PH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 826461. |
Entry information
| Entry name | AKT1_DROME | ||||||||
| Accession | Primary (citable) accession number: Q8INB9 Secondary accession number(s): Q0KI65 Q9VEY7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | Drosophila annotation project | ||||||||
Relevant documents
| Drosophila Drosophila: entries, gene names and cross-references to FlyBase |
| SIMILARITY comments Index of protein domains and families |

Clusters with


