Linked Life Data

CPATH-114984

Source:http://cbio.mskcc.org/cpath#CPATH-114984

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
http://www.biopax.org/relea...
http://www.biopax.org/relea...
RAC-alpha serine/threonine-protein kinase, RAC-alpha serine/threonine-protein kinase
http://www.biopax.org/relea...
AKT1_MOUSE, AKT1_MOUSE
http://www.biopax.org/relea...
http://www.biopax.org/relea...
2.7.11.1, 2.7.11.1, AKT1 kinase, AKT1 kinase, PKB, PKB, Protein kinase B, Protein kinase B, Proto-oncogene c-Akt, Proto-oncogene c-Akt, RAC-PK-alpha, RAC-PK-alpha, Thymoma viral proto-oncogene, Thymoma viral proto-oncogene
http://www.biopax.org/relea...
FUNCTION: General protein kinase capable of phosphorylating several known proteins. Phosphorylates TBC1D4. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). Plays a role in glucose transport by mediating insulin-induced translocation of the GLUT4 glucose transporter to the cell surface. Mediates the antiapoptotic effects of IGF-I. Mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1465', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (By similarity). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Promotes glycogen synthesis by mediating the insulin-induced activation of glycogen synthase. The activated form can suppress FoxO gene transcription and promote cell cycle progression. Essential for the SPATA13- mediated regulation of cell migration and adhesion assembly and disassembly (By similarity). Involved in the regulation of the placental development. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation. SUBUNIT: Interacts with AGAP2 isoform 2 (PIKE-A) in the presence of guanine nucleotides. The C-terminus interacts with CCDC88A/GRDN and THEM4. Interacts with AKTIP (By similarity). Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression. Interacts with TRAF6 (By similarity). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE/14-3-3-binding. Interacts with TNK2. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane (By similarity). Note=Nucleus after activation by integrin-linked protein kinase 1 (ILK1) (By similarity). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. TISSUE SPECIFICITY: Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis. DEVELOPMENTAL STAGE: Expressed in trophoblast and vessel endothelial cells of the placenta and in the brain at 14.5 dpc (at protein level). DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- kinase alpha (PI(3)K) results in its targeting to the plasma membrane.The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction. DOMAIN: The AGC-kinase C-terminal mediates interaction with THEM4 (By similarity). PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA. This phosphorylated form localizes to the plasma membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation. Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1. PTM: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'- polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome (By similarity). DISRUPTION PHENOTYPE: Show fetal growth impairment and reduced vascularization in the placenta; majority of pups died within 10 days. SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 protein kinase domain. GENE SYNONYMS: Akt Rac. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., FUNCTION: General protein kinase capable of phosphorylating several known proteins. Phosphorylates TBC1D4. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). Plays a role in glucose transport by mediating insulin-induced translocation of the GLUT4 glucose transporter to the cell surface. Mediates the antiapoptotic effects of IGF-I. Mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1465', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (By similarity). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Promotes glycogen synthesis by mediating the insulin-induced activation of glycogen synthase. The activated form can suppress FoxO gene transcription and promote cell cycle progression. Essential for the SPATA13- mediated regulation of cell migration and adhesion assembly and disassembly (By similarity). Involved in the regulation of the placental development. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation. SUBUNIT: Interacts with AGAP2 isoform 2 (PIKE-A) in the presence of guanine nucleotides. The C-terminus interacts with CCDC88A/GRDN and THEM4. Interacts with AKTIP (By similarity). Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression. Interacts with TRAF6 (By similarity). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE/14-3-3-binding. Interacts with TNK2. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane (By similarity). Note=Nucleus after activation by integrin-linked protein kinase 1 (ILK1) (By similarity). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. TISSUE SPECIFICITY: Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis. DEVELOPMENTAL STAGE: Expressed in trophoblast and vessel endothelial cells of the placenta and in the brain at 14.5 dpc (at protein level). DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- kinase alpha (PI(3)K) results in its targeting to the plasma membrane.The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction. DOMAIN: The AGC-kinase C-terminal mediates interaction with THEM4 (By similarity). PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA. This phosphorylated form localizes to the plasma membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation. Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1. PTM: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'- polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome (By similarity). DISRUPTION PHENOTYPE: Show fetal growth impairment and reduced vascularization in the placenta; majority of pups died within 10 days. SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 protein kinase domain. GENE SYNONYMS: Akt Rac. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
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