| Tag | Content |
|---|
| EKPD ID | EKS-MUM-00144 |
| Classification | | Group/Family | Score | E-Value | Start | End | Domain Length |
|---|
| AGC/Akt | 503.2 | 3.9E-151 | 152 | 409 | 258 |
|
| Status | Reviewed |
| Ensembl Protein | ENSMUSP00000052103 |
| UniProt Accession | Q60823; |
| 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 | Mus musculus |
| Functional Description | AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinases, 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 identified sofar 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. Phosphorylates CLK2 on 'Thr-343'. |
| Protein Length | 481 |
Protein Sequence
(FASTA) | | MNEVSVIKEG WLHKRGEYIK TWRPRYFLLK SDGSFIGYKE RPEAPDQTLP PLNNFSVAEC 60 | | QLMKTERPRP NTFVIRCLQW TTVIERTFHV DSPDEREEWM RAIQMVANSL KQRGPGEDAM 120 | | DYKCGSPSDS STSEMMEVAV NKARAKVTMN DFDYLKLLGK GTFGKVILVR EKATGRYYAM 180 | | KILRKEVIIA KDEVAHTVTE SRVLQNTRHP FLTALKYAFQ THDRLCFVME YANGGELFFH 240 | | LSRERVFTED RARFYGAEIV SALEYLHSRD VVYRDIKLEN LMLDKDGHIK ITDFGLCKEG 300 | | ISDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF YNQDHERLFE 360 | | LILMEEIRFP RTLGPEAKSL LAGLLKKDPK QRLGGGPSDA KEVMEHRFFL SINWQDVVQK 420 | | KLLPPFKPQV TSEVDTRYFD DEFTAQSITI TPPDRYDSLD PLELDQRTHF PQFSYSASIR 480 | | E 481 |
|
Nucleotide Sequence
(FASTA) | | ATGAATGAGG TATCTGTCAT CAAAGAAGGC TGGCTCCACA AACGTGGTGA ATACATCAAG 60 | | ACCTGGAGGC CACGGTACTT CCTTCTGAAG AGTGATGGAT CTTTCATTGG GTATAAGGAG 120 | | AGGCCCGAGG CCCCTGACCA GACCTTACCC CCCCTGAACA ATTTCTCTGT AGCAGAATGC 180 | | CAGCTGATGA AGACTGAGAG GCCACGACCC AACACCTTTG TCATACGCTG CCTGCAGTGG 240 | | ACCACAGTCA TCGAGAGGAC CTTCCATGTA GACTCTCCAG ATGAGAGGGA AGAGTGGATG 300 | | CGGGCTATCC AGATGGTCGC CAACAGTCTG AAGCAGCGGG GCCCAGGTGA GGACGCCATG 360 | | GATTACAAGT GTGGCTCCCC CAGTGACTCT TCCACATCTG AGATGATGGA GGTAGCTGTC 420 | | AACAAGGCAC GGGCCAAAGT GACCATGAAT GACTTCGATT ATCTCAAACT CCTCGGCAAG 480 | | GGCACCTTCG GCAAGGTCAT TCTGGTTCGA GAGAAGGCCA CTGGCCGCTA TTATGCCATG 540 | | AAGATCCTGC GCAAGGAGGT CATCATTGCA AAGGATGAAG TCGCCCACAC AGTCACAGAG 600 | | AGCCGGGTTC TGCAGAATAC CAGGCACCCC TTCCTTACAG CCCTCAAGTA TGCCTTCCAG 660 | | ACCCATGACC GCCTATGCTT TGTGATGGAG TATGCCAACG GGGGTGAGCT GTTTTTCCAC 720 | | CTCTCTCGGG AGCGAGTCTT CACGGAGGAT CGGGCGCGCT TTTATGGAGC AGAGATTGTG 780 | | TCAGCTCTGG AGTATTTGCA CTCGAGAGAT GTGGTGTACC GTGACATCAA GCTGGAAAAC 840 | | CTTATGTTGG ACAAAGATGG CCACATCAAG ATCACTGACT TTGGCTTGTG CAAAGAGGGC 900 | | ATCAGTGATG GAGCCACCAT GAAAACCTTC TGTGGTACCC CGGAGTACTT GGCGCCTGAG 960 | | GTGCTAGAGG ACAATGACTA TGGGCGAGCA GTGGACTGGT GGGGGCTGGG TGTGGTCATG 1020 | | TATGAGATGA TGTGTGGCCG CCTGCCATTC TACAACCAGG ACCACGAGCG CCTCTTTGAG 1080 | | CTCATTCTTA TGGAGGAGAT CCGCTTCCCG CGCACACTCG GGCCAGAGGC CAAGTCCCTG 1140 | | CTGGCTGGAC TGCTGAAGAA GGACCCAAAG CAGAGGCTCG GCGGAGGTCC CAGTGATGCG 1200 | | AAGGAGGTCA TGGAGCATAG ATTCTTCCTC AGCATCAACT GGCAGGACGT GGTACAGAAA 1260 | | AAGCTCCTGC CACCCTTCAA ACCTCAGGTC ACTTCAGAAG TGGACACAAG GTACTTTGAT 1320 | | GACGAGTTCA CCGCCCAGTC CATCACAATC ACACCCCCAG ACCGATATGA CAGCCTGGAC 1380 | | CCGCTGGAAC TGGACCAGCG GACGCACTTC CCCCAGTTCT CCTACTCAGC CAGCATCCGA 1440 | | GAGTGA 1446 |
|
| Domain Profile | S: 1 fdllkllGkGtfGkvilvrekatqklyalkilkkevivakdevahtlterrvlkrtkhpf 60 | fd+lkllGkGtfGkvilvrekat+++ya+kil+kevi+akdevaht+te+rvl++t+hpf | Q: 152 FDYLKLLGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPF 211 | 9*********************************************************** |
| S: 61 lvalkysfqtkeklclvleyvnGGelffhlskervfsedrarfygaeivsaldylhskdv 120 | l+alky+fqt+++lc+v+ey+nGGelffhls+ervf+edrarfygaeivsal+ylhs+dv | Q: 212 LTALKYAFQTHDRLCFVMEYANGGELFFHLSRERVFTEDRARFYGAEIVSALEYLHSRDV 271 | ************************************************************ |
| S: 121 vyrdlklenllldkdGhikitdfGlckeeikdgdktktfcGtpeylapevlededygkav 180 | vyrd+klenl+ldkdGhikitdfGlcke+i+dg+++ktfcGtpeylapevled+dyg+av | Q: 272 VYRDIKLENLMLDKDGHIKITDFGLCKEGISDGATMKTFCGTPEYLAPEVLEDNDYGRAV 331 | ************************************************************ |
| S: 181 dwwglGvvlyemlcGrlpfynkdheklfelilleelkfprklseeaksllsGllkkdpkk 240 | dwwglGvv+yem+cGrlpfyn+dhe+lfelil+ee++fpr+l++eaksll+Gllkkdpk+ | Q: 332 DWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPRTLGPEAKSLLAGLLKKDPKQ 391 | ************************************************************ |
| S: 241 rlGggkddakeireheff 258 | rlGgg++dake++eh+ff | Q: 392 RLGGGPSDAKEVMEHRFF 409 | *****************9 |
|
Domain Sequence
(FASTA) | | FDYLKLLGKG TFGKVILVRE KATGRYYAMK ILRKEVIIAK DEVAHTVTES RVLQNTRHPF 60 | | LTALKYAFQT HDRLCFVMEY ANGGELFFHL SRERVFTEDR ARFYGAEIVS ALEYLHSRDV 120 | | VYRDIKLENL MLDKDGHIKI TDFGLCKEGI SDGATMKTFC GTPEYLAPEV LEDNDYGRAV 180 | | DWWGLGVVMY EMMCGRLPFY NQDHERLFEL ILMEEIRFPR TLGPEAKSLL AGLLKKDPKQ 240 | | RLGGGPSDAK EVMEHRFF 258 |
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| Keyword | Apoptosis; ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Disulfide bond; Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Sugar transport; Transferase; Translation regulation; Transport; Ubl conjugation. |
| Sequence Source | Ensembl |
| Orthology | |
| Gene Ontology | | GO:0005829 | ; C:cytosol | | GO:0032593 | ; C:insulin-responsive compartment | | GO:0030027 | ; C:lamellipodium | | GO:0005739 | ; C:mitochondrion | | GO:0005654 | ; C:nucleoplasm | | GO:0005886 | ; C:plasma membrane | | GO:0005524 | ; F:ATP binding | | GO:0005543 | ; F:phospholipid binding | | GO:0004674 | ; F:protein serine/threonine kinase activity | | GO:0032859 | ; P:activation of Ral GTPase activity | | GO:0008643 | ; P:carbohydrate transport | | GO:0006006 | ; P:glucose metabolic process | | GO:0005978 | ; P:glycogen biosynthetic process | | GO:0008286 | ; P:insulin receptor signaling pathway | | GO:0043066 | ; P:negative regulation of apoptotic process | | GO:0043154 | ; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | | GO:0010748 | ; P:negative regulation of plasma membrane long-chain fatty acid transport | | GO:0033119 | ; P:negative regulation of RNA splicing | | GO:0032287 | ; P:peripheral nervous system myelin maintenance | | GO:0030335 | ; P:positive regulation of cell migration | | GO:0032000 | ; P:positive regulation of fatty acid beta-oxidation | | GO:2001275 | ; P:positive regulation of glucose import in response to insulin stimulus | | GO:0045725 | ; P:positive regulation of glycogen biosynthetic process | | GO:0045429 | ; P:positive regulation of nitric oxide biosynthetic process | | GO:0033138 | ; P:positive regulation of peptidyl-serine phosphorylation | | GO:0050927 | ; P:positive regulation of positive chemotaxis | | GO:0009967 | ; P:positive regulation of signal transduction | | GO:0010765 | ; P:positive regulation of sodium ion transport | | GO:0045944 | ; P:positive regulation of transcription from RNA polymerase II promoter | | GO:0043491 | ; P:protein kinase B signaling cascade | | GO:0072659 | ; P:protein localization to plasma membrane | | GO:0046328 | ; P:regulation of JNK cascade | | GO:0006417 | ; P:regulation of translation | | GO:0014850 | ; P:response to muscle activity | | GO:0006970 | ; P:response to osmotic stress |
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| Created Date | 20-Feb-2013 |