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P31750

- AKT1_MOUSE

UniProt

P31750 - AKT1_MOUSE

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Protein

RAC-alpha serine/threonine-protein kinase

Gene

Akt1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

AKT1 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 PI3P-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 (PI3K) 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. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (By similarity). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (By similarity). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (By similarity).By similarity
AKT1-specific substrates have been recently identified, including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation.10 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei53 – 531Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
Binding sitei86 – 861Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
Binding sitei161 – 1611Inhibitor; via amide nitrogenBy similarity
Binding sitei179 – 1791ATP
Binding sitei230 – 2301Inhibitor; via amide nitrogenBy similarity
Binding sitei234 – 2341InhibitorBy similarity
Active sitei274 – 2741Proton acceptorPROSITE-ProRule annotation
Binding sitei292 – 2921InhibitorBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi156 – 1649ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. kinase activity Source: MGI
  3. nitric-oxide synthase regulator activity Source: Ensembl
  4. phosphatidylinositol-3,4,5-trisphosphate binding Source: Ensembl
  5. phosphatidylinositol-3,4-bisphosphate binding Source: Ensembl
  6. protein kinase activity Source: UniProtKB
  7. protein kinase binding Source: UniProtKB
  8. protein serine/threonine/tyrosine kinase activity Source: MGI
  9. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. activation-induced cell death of T cells Source: MGI
  2. aging Source: Ensembl
  3. anagen Source: MGI
  4. apoptotic mitochondrial changes Source: MGI
  5. cell projection organization Source: MGI
  6. cellular response to epidermal growth factor stimulus Source: UniProtKB
  7. cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: MGI
  8. cellular response to growth factor stimulus Source: MGI
  9. cellular response to hypoxia Source: Ensembl
  10. cellular response to insulin stimulus Source: UniProtKB
  11. cellular response to mechanical stimulus Source: Ensembl
  12. cellular response to peptide Source: MGI
  13. cytoskeleton organization Source: UniProtKB
  14. endocrine pancreas development Source: Reactome
  15. execution phase of apoptosis Source: MGI
  16. germ cell development Source: MGI
  17. glucose homeostasis Source: MGI
  18. glucose metabolic process Source: MGI
  19. glucose transport Source: UniProtKB
  20. glycogen biosynthetic process Source: UniProtKB-KW
  21. glycogen cell differentiation involved in embryonic placenta development Source: MGI
  22. glycogen metabolic process Source: MGI
  23. hyaluronan metabolic process Source: Ensembl
  24. inflammatory response Source: MGI
  25. insulin-like growth factor receptor signaling pathway Source: UniProtKB
  26. insulin receptor signaling pathway Source: UniProtKB
  27. intracellular signal transduction Source: MGI
  28. labyrinthine layer blood vessel development Source: MGI
  29. maternal placenta development Source: MGI
  30. negative regulation of apoptotic process Source: UniProtKB
  31. negative regulation of autophagy Source: Ensembl
  32. negative regulation of cell size Source: MGI
  33. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  34. negative regulation of fatty acid beta-oxidation Source: Ensembl
  35. negative regulation of JNK cascade Source: Ensembl
  36. negative regulation of plasma membrane long-chain fatty acid transport Source: Ensembl
  37. negative regulation of protein kinase activity Source: Ensembl
  38. negative regulation of proteolysis Source: Ensembl
  39. negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  40. osteoblast differentiation Source: MGI
  41. peptidyl-serine phosphorylation Source: MGI
  42. peripheral nervous system myelin maintenance Source: MGI
  43. positive regulation of apoptotic process Source: Ensembl
  44. positive regulation of blood vessel endothelial cell migration Source: Ensembl
  45. positive regulation of cell growth Source: Ensembl
  46. positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: Ensembl
  47. positive regulation of endothelial cell proliferation Source: UniProtKB
  48. positive regulation of establishment of protein localization to plasma membrane Source: Ensembl
  49. positive regulation of fat cell differentiation Source: Ensembl
  50. positive regulation of glucose import Source: Ensembl
  51. positive regulation of glycogen biosynthetic process Source: Ensembl
  52. positive regulation of lipid biosynthetic process Source: Ensembl
  53. positive regulation of nitric oxide biosynthetic process Source: Ensembl
  54. positive regulation of nitric-oxide synthase activity Source: Ensembl
  55. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  56. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  57. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  58. positive regulation of sodium ion transport Source: MGI
  59. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  60. positive regulation of vasoconstriction Source: Ensembl
  61. protein catabolic process Source: MGI
  62. protein import into nucleus, translocation Source: Ensembl
  63. protein kinase B signaling Source: MGI
  64. protein phosphorylation Source: UniProtKB
  65. protein ubiquitination Source: MGI
  66. regulation of cell migration Source: UniProtKB
  67. regulation of myelination Source: MGI
  68. regulation of neuron projection development Source: UniProtKB
  69. regulation of protein localization Source: MGI
  70. regulation of translation Source: UniProtKB-KW
  71. response to fluid shear stress Source: Ensembl
  72. response to food Source: MGI
  73. response to hormone Source: UniProtKB
  74. response to UV-A Source: Ensembl
  75. striated muscle cell differentiation Source: MGI
  76. translation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Carbohydrate metabolism, Glucose metabolism, Glycogen biosynthesis, Glycogen metabolism, Neurogenesis, Sugar transport, Translation regulation, Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.
ReactomeiREACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198695. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
REACT_198696. KSRP destabilizes mRNA.
REACT_199047. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_199054. Translocation of GLUT4 to the plasma membrane.
REACT_199061. Downregulation of ERBB2:ERBB3 signaling.
REACT_214733. Negative regulation of the PI3K/AKT network.
REACT_218211. AKT phosphorylates targets in the nucleus.
REACT_219771. deactivation of the beta-catenin transactivating complex.
REACT_220092. GPVI-mediated activation cascade.
REACT_220918. AKT phosphorylates targets in the cytosol.
REACT_221264. eNOS activation.
REACT_221926. AKT-mediated inactivation of FOXO1A.
REACT_223974. G beta:gamma signalling through PI3Kgamma.
REACT_226151. CD28 dependent PI3K/Akt signaling.
REACT_226341. PIP3 activates AKT signaling.
REACT_239644. PDE3B signalling.
REACT_246176. Integrin alphaIIb beta3 signaling.
REACT_261568. CTLA4 inhibitory signaling.
REACT_261840. VEGFR2 mediated vascular permeability.

Names & Taxonomyi

Protein namesi
Recommended name:
RAC-alpha serine/threonine-protein kinase (EC:2.7.11.1)
Alternative name(s):
AKT1 kinase
Protein kinase B
Short name:
PKB
Protein kinase B alpha
Short name:
PKB alpha
Proto-oncogene c-Akt
RAC-PK-alpha
Thymoma viral proto-oncogene
Gene namesi
Name:Akt1
Synonyms:Akt, Rac
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 12

Organism-specific databases

MGIiMGI:87986. Akt1.

Subcellular locationi

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.By similarity

GO - Cellular componenti

  1. cell-cell junction Source: MGI
  2. ciliary basal body Source: MGI
  3. cytoplasm Source: MGI
  4. cytosol Source: Reactome
  5. mitochondrion Source: MGI
  6. nucleoplasm Source: Reactome
  7. nucleus Source: UniProtKB
  8. plasma membrane Source: UniProtKB
  9. spindle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Show fetal growth impairment and reduced vascularization in the placenta; majority of pups died within 10 days.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi176 – 1761Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. 1 Publication
Mutagenesisi179 – 1791K → A: Lacks kinase activity. Overexpression inhibits insulin-stimulated translocation of SLC2A4/GLUT4 in a dominant negative manner. 1 Publication
Mutagenesisi308 – 3081T → A: Does not affect ubiquitination by ZNRF1. 1 Publication
Mutagenesisi473 – 4731S → A: Does not affect ubiquitination by ZNRF1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 480480RAC-alpha serine/threonine-protein kinasePRO_0000085606Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141N6-acetyllysineBy similarity
Modified residuei20 – 201N6-acetyllysineBy similarity
Disulfide bondi60 ↔ 77By similarity
Modified residuei124 – 1241Phosphoserine
Modified residuei126 – 1261Phosphoserine; alternate
Glycosylationi126 – 1261O-linked (GlcNAc); alternateBy similarity
Modified residuei129 – 1291Phosphoserine; alternate1 Publication
Glycosylationi129 – 1291O-linked (GlcNAc); alternateBy similarity
Modified residuei176 – 1761Phosphotyrosine; by TNK21 Publication
Cross-linki284 – 284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Disulfide bondi296 ↔ 310By similarity
Glycosylationi305 – 3051O-linked (GlcNAc)By similarity
Modified residuei308 – 3081Phosphothreonine; by IKKE, PDPK1 and TBK13 Publications
Glycosylationi312 – 3121O-linked (GlcNAc)By similarity
Modified residuei450 – 4501Phosphothreonine; by MTOR1 Publication
Modified residuei473 – 4731Phosphoserine; by IKKE, MTOR and TBK1; alternate3 Publications
Glycosylationi473 – 4731O-linked (GlcNAc); alternateBy similarity
Modified residuei474 – 4741PhosphotyrosineBy similarity

Post-translational modificationi

O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction between AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site (By similarity).By similarity
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. Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1. Ser-473 phosphorylation is enhanced by signaling through activated FLT3. Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase. The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase. Ser-473 is dephosphorylated by CPPED1, leading to termination of signaling (By similarity).By similarity
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. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation.9 Publications
Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the inhibition (By similarity).By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP31750.
PaxDbiP31750.
PRIDEiP31750.

PTM databases

PhosphoSiteiP31750.

Expressioni

Tissue specificityi

Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis.1 Publication

Developmental stagei

Expressed in trophoblast and vessel endothelial cells of the placenta and in the brain at 14.5 dpc (at protein level).1 Publication

Gene expression databases

BgeeiP31750.
CleanExiMM_AKT1.
ExpressionAtlasiP31750. baseline and differential.
GenevestigatoriP31750.

Interactioni

Subunit structurei

Interacts with and phosphorylated by PDPK1 (By similarity). Interacts with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the presence of guanine nucleotides. Interacts with AKTIP. 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 MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3 and STK4. Interacts (via PH domain) with SIRT1. Interacts with SRPK2 in a phosphorylation-dependent manner. Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with RAF1 (By similarity). Interacts (via the C-terminus) with CCDC88A (via its C-terminus) and THEM4 (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding. Interacts with KCTD20 (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRB2P321213EBI-298707,EBI-714559From a different organism.
FAM110CQ1W6H93EBI-298707,EBI-3942563From a different organism.
Hsp90aa1P079016EBI-298707,EBI-78930
PREX1Q8TCU62EBI-298707,EBI-1046542From a different organism.
Trib3Q8K4K25EBI-298707,EBI-448962
UbcP629913EBI-298707,EBI-413074
XP031652EBI-298707,EBI-7683985From a different organism.

Protein-protein interaction databases

BioGridi198056. 21 interactions.
DIPiDIP-736N.
IntActiP31750. 24 interactions.
MINTiMINT-4049532.

Structurei

3D structure databases

ProteinModelPortaliP31750.
SMRiP31750. Positions 1-477.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 108104PHPROSITE-ProRule annotationAdd
BLAST
Domaini150 – 408259Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini409 – 48072AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni14 – 196Inositol-(1,3,4,5)-tetrakisphosphate bindingBy similarity
Regioni23 – 253Inositol-(1,3,4,5)-tetrakisphosphate bindingBy similarity
Regioni228 – 2303Inhibitor bindingBy similarity

Domaini

Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction.
The AGC-kinase C-terminal mediates interaction with THEM4.By similarity

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120449.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP31750.
KOiK04456.
OMAiSRERVFP.
OrthoDBiEOG7Q5HCW.
TreeFamiTF102004.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequencei

Sequence statusi: Complete.

P31750-1 [UniParc]FASTAAdd to Basket

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        10         20         30         40         50
MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQRES
60 70 80 90 100
PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWA
110 120 130 140 150
TAIQTVADGL KRQEEETMDF RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF
160 170 180 190 200
EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR
210 220 230 240 250
VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA
260 270 280 290 300
RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI
310 320 330 340 350
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY
360 370 380 390 400
NQDHEKLFEL ILMEEIRFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK
410 420 430 440 450
EIMQHRFFAN IVWQDVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT
460 470 480
PPDQDDSMEC VDSERRPHFP QFSYSASGTA
Length:480
Mass (Da):55,707
Last modified:July 27, 2011 - v2
Checksum:i98DF28E5EFE03730
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti367 – 3671R → A in AAA18254. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X65687 mRNA. Translation: CAA46620.1.
AF534134 Genomic DNA. Translation: AAN04036.1.
M94335 mRNA. Translation: AAA18254.1.
AK154936 mRNA. Translation: BAE32937.1.
CH466549 Genomic DNA. Translation: EDL18586.1.
BC066018 mRNA. Translation: AAH66018.1.
CCDSiCCDS26194.1.
PIRiS33364.
RefSeqiNP_001159366.1. NM_001165894.1.
NP_033782.1. NM_009652.3.
XP_006515478.1. XM_006515415.1.
XP_006515479.1. XM_006515416.1.
UniGeneiMm.6645.

Genome annotation databases

EnsembliENSMUST00000001780; ENSMUSP00000001780; ENSMUSG00000001729.
GeneIDi11651.
KEGGimmu:11651.
UCSCiuc007pex.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X65687 mRNA. Translation: CAA46620.1 .
AF534134 Genomic DNA. Translation: AAN04036.1 .
M94335 mRNA. Translation: AAA18254.1 .
AK154936 mRNA. Translation: BAE32937.1 .
CH466549 Genomic DNA. Translation: EDL18586.1 .
BC066018 mRNA. Translation: AAH66018.1 .
CCDSi CCDS26194.1.
PIRi S33364.
RefSeqi NP_001159366.1. NM_001165894.1.
NP_033782.1. NM_009652.3.
XP_006515478.1. XM_006515415.1.
XP_006515479.1. XM_006515416.1.
UniGenei Mm.6645.

3D structure databases

ProteinModelPortali P31750.
SMRi P31750. Positions 1-477.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198056. 21 interactions.
DIPi DIP-736N.
IntActi P31750. 24 interactions.
MINTi MINT-4049532.

Chemistry

BindingDBi P31750.
ChEMBLi CHEMBL5859.

PTM databases

PhosphoSitei P31750.

Proteomic databases

MaxQBi P31750.
PaxDbi P31750.
PRIDEi P31750.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000001780 ; ENSMUSP00000001780 ; ENSMUSG00000001729 .
GeneIDi 11651.
KEGGi mmu:11651.
UCSCi uc007pex.2. mouse.

Organism-specific databases

CTDi 207.
MGIi MGI:87986. Akt1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00770000120449.
HOGENOMi HOG000233033.
HOVERGENi HBG108317.
InParanoidi P31750.
KOi K04456.
OMAi SRERVFP.
OrthoDBi EOG7Q5HCW.
TreeFami TF102004.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 3474.
Reactomei REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198695. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
REACT_198696. KSRP destabilizes mRNA.
REACT_199047. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_199054. Translocation of GLUT4 to the plasma membrane.
REACT_199061. Downregulation of ERBB2:ERBB3 signaling.
REACT_214733. Negative regulation of the PI3K/AKT network.
REACT_218211. AKT phosphorylates targets in the nucleus.
REACT_219771. deactivation of the beta-catenin transactivating complex.
REACT_220092. GPVI-mediated activation cascade.
REACT_220918. AKT phosphorylates targets in the cytosol.
REACT_221264. eNOS activation.
REACT_221926. AKT-mediated inactivation of FOXO1A.
REACT_223974. G beta:gamma signalling through PI3Kgamma.
REACT_226151. CD28 dependent PI3K/Akt signaling.
REACT_226341. PIP3 activates AKT signaling.
REACT_239644. PDE3B signalling.
REACT_246176. Integrin alphaIIb beta3 signaling.
REACT_261568. CTLA4 inhibitory signaling.
REACT_261840. VEGFR2 mediated vascular permeability.

Miscellaneous databases

ChiTaRSi Akt1. mouse.
NextBioi 279257.
PROi P31750.
SOURCEi Search...

Gene expression databases

Bgeei P31750.
CleanExi MM_AKT1.
ExpressionAtlasi P31750. baseline and differential.
Genevestigatori P31750.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
InterProi IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view ]
SMARTi SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications."
    Bellacosa A., Franke T.F., Gonzalez-Portal M.E., Datta K., Taguchi T., Gardner J., Cheng J.Q., Testa J.R., Tsichlis P.N.
    Oncogene 8:745-754(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: AKR/J.
    Tissue: Thymus.
  2. "Protein kinase B alpha/Akt1 regulates placental development and fetal growth."
    Yang Z.Z., Tschopp O., Hemmings-Mieszczak M., Feng J., Brodbeck D., Perentes E., Hemmings B.A.
    J. Biol. Chem. 278:32124-32131(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PHOSPHORYLATION AT SER-473, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
    Strain: 129/SvJ.
  3. "Complete nucleotide coding sequence for murine rac (related to A and C kinases) protein kinase."
    Bousquets X., Powell C.T.
    Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NOD.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: 129/SvJ.
  6. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  8. "Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells."
    Cong L.N., Chen H., Li Y., Zhou L., McGibbon M.A., Taylor S.I., Quon M.J.
    Mol. Endocrinol. 11:1881-1890(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF LYS-179.
  9. "Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt."
    Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K., Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., Kasuga M.
    Mol. Cell. Biol. 19:6286-6296(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PDE3B.
  10. "Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways."
    Mizuki M., Fenski R., Halfter H., Matsumura I., Schmidt R., Muller C., Gruning W., Kratz-Albers K., Serve S., Steur C., Buchner T., Kienast J., Kanakura Y., Berdel W.E., Serve H.
    Blood 96:3907-3914(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
  11. Cited for: SUBCELLULAR LOCATION.
  12. "Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1."
    Yamashita K., Kajstura J., Discher D.J., Wasserlauf B.J., Bishopric N.H., Anversa P., Webster K.A.
    Circ. Res. 88:609-614(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor."
    Ravichandran L.V., Chen H., Li Y., Quon M.J.
    Mol. Endocrinol. 15:1768-1780(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PTPN1.
  14. "Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane."
    Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M., Hemmings B.A.
    Science 294:374-380(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH THEM4.
  15. "A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain."
    Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E.
    J. Biol. Chem. 277:22115-22118(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF TBC1D4.
  16. Cited for: INTERACTION WITH CCDC88A, PHOSPHORYLATION AT THR-308 AND SER-473.
  17. "Phosphorylation of grb10 regulates its interaction with 14-3-3."
    Urschel S., Bassermann F., Bai R.Y., Munch S., Peschel C., Duyster J.
    J. Biol. Chem. 280:16987-16993(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GRB10.
  18. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  19. "A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB."
    Nawa M., Kanekura K., Hashimoto Y., Aiso S., Matsuoka M.
    Cell. Signal. 20:493-505(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BTBD10.
  20. "O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic beta cells."
    Kang E.S., Han D., Park J., Kwak T.K., Oh M.A., Lee S.A., Choi S., Park Z.Y., Kim Y., Lee J.W.
    Exp. Cell Res. 314:2238-2248(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT SER-473.
  21. "Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance."
    Yang X., Ongusaha P.P., Miles P.D., Havstad J.C., Zhang F., So W.V., Kudlow J.E., Michell R.H., Olefsky J.M., Field S.J., Evans R.M.
    Nature 451:964-969(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, GLYCOSYLATION AT SER-473, PHOSPHORYLATION AT THR-308.
  22. "DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212."
    Kim J.Y., Duan X., Liu C.Y., Jang M.H., Guo J.U., Pow-anpongkul N., Kang E., Song H., Ming G.L.
    Neuron 63:761-773(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  23. "Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis."
    Rodgers J.T., Haas W., Gygi S.P., Puigserver P.
    Cell Metab. 11:23-34(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CLK2.
  24. "mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide."
    Oh W.J., Wu C.C., Kim S.J., Facchinetti V., Julien L.A., Finlan M., Roux P.P., Su B., Jacinto E.
    EMBO J. 29:3939-3951(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-450.
  25. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2.
  26. Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
  27. "ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation."
    Wakatsuki S., Saitoh F., Araki T.
    Nat. Cell Biol. 13:1415-1423(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, UBIQUITINATION BY ZNRF1, MUTAGENESIS OF THR-308 AND SER-473.
  28. "The protein kinase B/Akt signalling pathway in human malignancy."
    Nicholson K.M., Anderson N.G.
    Cell. Signal. 14:381-395(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  29. Cited for: REVIEW ON FUNCTION.
  30. "Akt1 and Akt2: differentiating the aktion."
    Heron-Milhavet L., Khouya N., Fernandez A., Lamb N.J.
    Histol. Histopathol. 26:651-662(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  31. "KCTD20, a relative of BTBD10, is a positive regulator of Akt."
    Nawa M., Matsuoka M.
    BMC Biochem. 14:27-27(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KCTD20.

Entry informationi

Entry nameiAKT1_MOUSE
AccessioniPrimary (citable) accession number: P31750
Secondary accession number(s): Q62274, Q6GSA6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: November 26, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3