| Tag | Content |
|---|
| EKPD ID | EKS-HOS-00145 |
| Classification | | Group/Family | Score | E-Value | Start | End | Domain Length |
|---|
| AGC/Akt | 503.8 | 5.2E-151 | 90 | 347 | 258 |
|
| Status | Reviewed |
| Ensembl Protein | ENSP00000471369 |
| UniProt Accession | P31751; B2RBD8; Q0VAN1; Q68GC0; |
| Protein Name | RAC-beta serine/threonine-protein kinase |
| Protein Synonyms/Alias | Protein kinase Akt-2; Protein kinase B beta; PKB beta; RAC-PK-beta; |
| Gene Name | AKT2 |
| Gene Synonyms/Alias | AKT2; |
| Ensembl Information | |
| Organism | Homo sapiens |
| Functional Description | AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)- response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as 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. 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). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. One of the few specific substrates of AKT2 identifiedrecently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. AKT2 is also specifically involved in skeletal muscle differentiation. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'. |
| Protein Length | 450 |
Protein Sequence
(FASTA) | | MKTERPRPNT FVIRCLQWTT VIERTFHVDS PDEREEWMRA IQMVANSLKQ RAPGEDPMDY 60 | | KCGSPSDSST TEEMEVAVSK ARAKVTMNDF DYLKLLGKGT FGKVILVREK ATGRYYAMKI 120 | | LRKEVIIAKD EVAHTVTESR VLQNTRHPFL TALKYAFQTH DRLCFVMEYA NGGELFFHLS 180 | | RERVFTEERA RFYGAEIVSA LEYLHSRDVV YRDIKLENLM LDKDGHIKIT DFGLCKEGIS 240 | | DGATMKTFCG TPEYLAPEVL EDNDYGRAVD WWGLGVVMYE MMCGRLPFYN QDHERLFELI 300 | | LMEEIRFPRT LSPEAKSLLA GLLKKDPKQR LGGGPSDAKE VMEHRFFLSI NWQDVVQKKL 360 | | LPPFKPQVTS EVDTRYFDDE FTAQSITITP PDRCECLGPP RWCACPRGGG MGSALNSLLK 420 | | EGPRRPPLHV WEISPSLLSG PFAVGPLWTW 450 |
|
Nucleotide Sequence
(FASTA) | | ATGAAGACCG AGAGGCCGCG ACCCAACACC TTTGTCATAC GCTGCCTGCA GTGGACCACA 60 | | GTCATCGAGA GGACCTTCCA CGTGGATTCT CCAGACGAGA GGGAGGAGTG GATGCGGGCC 120 | | ATCCAGATGG TCGCCAACAG CCTCAAGCAG CGGGCCCCAG GCGAGGACCC CATGGACTAC 180 | | AAGTGTGGCT CCCCCAGTGA CTCCTCCACG ACTGAGGAGA TGGAAGTGGC GGTCAGCAAG 240 | | GCACGGGCTA AAGTGACCAT GAATGACTTC GACTATCTCA AACTCCTTGG CAAGGGAACC 300 | | TTTGGCAAAG TCATCCTGGT GCGGGAGAAG GCCACTGGCC GCTACTACGC CATGAAGATC 360 | | CTGCGGAAGG AAGTCATCAT TGCCAAGGAT GAAGTCGCTC ACACAGTCAC CGAGAGCCGG 420 | | GTCCTCCAGA ACACCAGGCA CCCGTTCCTC ACTGCGCTGA AGTATGCCTT CCAGACCCAC 480 | | GACCGCCTGT GCTTTGTGAT GGAGTATGCC AACGGGGGTG AGCTGTTCTT CCACCTGTCC 540 | | CGGGAGCGTG TCTTCACAGA GGAGCGGGCC CGGTTTTATG GTGCAGAGAT TGTCTCGGCT 600 | | CTTGAGTACT TGCACTCGCG GGACGTGGTA TACCGCGACA TCAAGCTGGA AAACCTCATG 660 | | CTGGACAAAG ATGGCCACAT CAAGATCACT GACTTTGGCC TCTGCAAAGA GGGCATCAGT 720 | | GACGGGGCCA CCATGAAAAC CTTCTGTGGG ACCCCGGAGT ACCTGGCGCC TGAGGTGCTG 780 | | GAGGACAATG ACTATGGCCG GGCCGTGGAC TGGTGGGGGC TGGGTGTGGT CATGTACGAG 840 | | ATGATGTGCG GCCGCCTGCC CTTCTACAAC CAGGACCACG AGCGCCTCTT CGAGCTCATC 900 | | CTCATGGAAG AGATCCGCTT CCCGCGCACG CTCAGCCCCG AGGCCAAGTC CCTGCTTGCT 960 | | GGGCTGCTTA AGAAGGACCC CAAGCAGAGG CTTGGTGGGG GGCCCAGCGA TGCCAAGGAG 1020 | | GTCATGGAGC ACAGGTTCTT CCTCAGCATC AACTGGCAGG ACGTGGTCCA GAAGAAGCTC 1080 | | CTGCCACCCT TCAAACCTCA GGTCACGTCC GAGGTCGACA CAAGGTACTT CGATGATGAA 1140 | | TTTACCGCCC AGTCCATCAC AATCACACCC CCTGACCGCT GTGAGTGCCT GGGGCCCCCG 1200 | | CGCTGGTGTG CCTGCCCCAG GGGTGGAGGG ATGGGATCTG CTCTTAACTC ACTTCTCAAG 1260 | | GAGGGCCCTC GAAGGCCCCC GCTTCATGTC TGGGAGATTT CCCCAAGTCT GCTCTCAGGC 1320 | | CCTTTTGCTG TTGGTCCTCT TTGGACCTGG TGA 1353 |
|
| Domain Profile | S: 1 fdllkllGkGtfGkvilvrekatqklyalkilkkevivakdevahtlterrvlkrtkhpf 60 | fd+lkllGkGtfGkvilvrekat+++ya+kil+kevi+akdevaht+te+rvl++t+hpf | Q: 90 FDYLKLLGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPF 149 | 9*********************************************************** |
| S: 61 lvalkysfqtkeklclvleyvnGGelffhlskervfsedrarfygaeivsaldylhskdv 120 | l+alky+fqt+++lc+v+ey+nGGelffhls+ervf+e+rarfygaeivsal+ylhs+dv | Q: 150 LTALKYAFQTHDRLCFVMEYANGGELFFHLSRERVFTEERARFYGAEIVSALEYLHSRDV 209 | ************************************************************ |
| S: 121 vyrdlklenllldkdGhikitdfGlckeeikdgdktktfcGtpeylapevlededygkav 180 | vyrd+klenl+ldkdGhikitdfGlcke+i+dg+++ktfcGtpeylapevled+dyg+av | Q: 210 VYRDIKLENLMLDKDGHIKITDFGLCKEGISDGATMKTFCGTPEYLAPEVLEDNDYGRAV 269 | ************************************************************ |
| S: 181 dwwglGvvlyemlcGrlpfynkdheklfelilleelkfprklseeaksllsGllkkdpkk 240 | dwwglGvv+yem+cGrlpfyn+dhe+lfelil+ee++fpr+ls+eaksll+Gllkkdpk+ | Q: 270 DWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPRTLSPEAKSLLAGLLKKDPKQ 329 | ************************************************************ |
| S: 241 rlGggkddakeireheff 258 | rlGgg++dake++eh+ff | Q: 330 RLGGGPSDAKEVMEHRFF 347 | *****************9 |
|
Domain Sequence
(FASTA) | | FDYLKLLGKG TFGKVILVRE KATGRYYAMK ILRKEVIIAK DEVAHTVTES RVLQNTRHPF 60 | | LTALKYAFQT HDRLCFVMEY ANGGELFFHL SRERVFTEER ARFYGAEIVS ALEYLHSRDV 120 | | VYRDIKLENL MLDKDGHIKI TDFGLCKEGI SDGATMKTFC GTPEYLAPEV LEDNDYGRAV 180 | | DWWGLGVVMY EMMCGRLPFY NQDHERLFEL ILMEEIRFPR TLSPEAKSLL AGLLKKDPKQ 240 | | RLGGGPSDAK EVMEHRFF 258 |
|
| Keyword | 3D-structure; Apoptosis; ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Diabetes mellitus; Disease mutation; Disulfide bond; Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Sugar transport; Transferase; Translation regulation; Transport; Ubl conjugation. |
| Sequence Source | Ensembl |
| Orthology | |
| Gene Ontology | |
| KEGG | |
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| Prints | |
| Created Date | 20-Feb-2013 |