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Protein

RAC-alpha serine/threonine-protein kinase

Gene

Akt1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. Phosphorylation of BAD stimulates its pro-apoptotic 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.4 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

  • ATP binding Source: RGD
  • enzyme binding Source: BHF-UCL
  • GTPase activating protein binding Source: RGD
  • nitric-oxide synthase regulator activity Source: Ensembl
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: Ensembl
  • phosphatidylinositol-3,4-bisphosphate binding Source: Ensembl
  • protein kinase activity Source: RGD
  • protein kinase binding Source: RGD
  • protein kinase C binding Source: RGD
  • protein phosphatase 2A binding Source: RGD
  • protein serine/threonine/tyrosine kinase activity Source: Ensembl
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

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. 5301.
ReactomeiR-RNO-114604. GPVI-mediated activation cascade.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-RNO-165159. mTOR signalling.
R-RNO-198323. AKT phosphorylates targets in the cytosol.
R-RNO-198693. AKT phosphorylates targets in the nucleus.
R-RNO-199418. Negative regulation of the PI3K/AKT network.
R-RNO-203615. eNOS activation.
R-RNO-211163. AKT-mediated inactivation of FOXO1A.
R-RNO-354192. Integrin alphaIIb beta3 signaling.
R-RNO-3769402. Deactivation of the beta-catenin transactivating complex.
R-RNO-389357. CD28 dependent PI3K/Akt signaling.
R-RNO-389513. CTLA4 inhibitory signaling.
R-RNO-392451. G beta:gamma signalling through PI3Kgamma.
R-RNO-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
R-RNO-450604. KSRP (KHSRP) binds and destabilizes mRNA.
R-RNO-5218920. VEGFR2 mediated vascular permeability.
R-RNO-5628897. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
RAC-alpha serine/threonine-protein kinase (EC:2.7.11.1)
Alternative name(s):
Protein kinase B
Short name:
PKB
Protein kinase B alpha
Short name:
PKB alpha
RAC-PK-alpha
Gene namesi
Name:Akt1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi2081. Akt1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Cell membrane By similarity

  • Note: Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A (By similarity). 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. Colocalizes with WDFY2 in intracellular vesicles (By similarity).By similarity

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • ciliary basal body Source: Ensembl
  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • mitochondrion Source: Ensembl
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • protein complex Source: Ensembl
  • spindle Source: Ensembl
  • vesicle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi179 – 1791K → D: Lacks kinase activity. Inhibits insulin-induced activation of glycogen synthase when expressed. 2 Publications
Mutagenesisi308 – 3081T → A: Inhibits insulin-induced activation of endogenous Akt1, insulin-stimulated protein synthesis, insulin-induced activation of glycogen synthase and insulin-induced phosphorylation of 4E-BP1 in a dominant negative manner when overexpressed; when associated with A-473. 2 Publications
Mutagenesisi473 – 4731S → A: Inhibits insulin-induced activation of endogenous Akt1, insulin-stimulated protein synthesis, insulin-induced activation of glycogen synthase and insulin-induced phosphorylation of 4E-BP1 in a dominant negative manner when overexpressed; when associated with A-308. 2 Publications

Chemistry

ChEMBLiCHEMBL1075215.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 480480RAC-alpha serine/threonine-protein kinasePRO_0000085607Add
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 – 1241PhosphoserineCombined sources
Modified residuei126 – 1261Phosphoserine; alternateBy similarity
Glycosylationi126 – 1261O-linked (GlcNAc); alternateBy similarity
Modified residuei129 – 1291Phosphoserine; alternateCombined sources
Glycosylationi129 – 1291O-linked (GlcNAc); alternateBy similarity
Modified residuei176 – 1761Phosphotyrosine; by TNK2By similarity
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 TBK1By similarity
Glycosylationi312 – 3121O-linked (GlcNAc)By similarity
Modified residuei448 – 4481PhosphothreonineBy similarity
Modified residuei450 – 4501Phosphothreonine; by MTORBy similarity
Modified residuei473 – 4731Phosphoserine; by IKKE, MTOR and TBK1; alternate1 Publication
Glycosylationi473 – 4731O-linked (GlcNAc); alternate
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.1 Publication
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 cell 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 (By similarity). Ser-473 phosphorylation is enhanced by signaling through activated FLT3 (By similarity). 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. Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation (By similarity).By similarity
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

PaxDbiP47196.
PRIDEiP47196.

PTM databases

iPTMnetiP47196.
PhosphoSiteiP47196.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevisibleiP47196. RN.

Interactioni

Subunit structurei

Interacts (via the C-terminus) with CCDC88A (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding. 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 TNK2 and CLK2. Interacts with RAF1. Interacts (via the C-terminus) with THEM4 (via its C-terminus). Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with and phosphorylated by PDPK1 (By similarity). Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts with PA2G4. Interacts with KIF14; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with WDFY2 (via WD repeats 1-3) (By similarity). Forms a complex with WDFY2 and FOXO1 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GapdhP047973EBI-7204362,EBI-349219
Nfkb1Q633699EBI-7204362,EBI-8498561
Smad2O704362EBI-7204362,EBI-7948047
Smad3P840254EBI-7204362,EBI-7201857

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • GTPase activating protein binding Source: RGD
  • protein kinase binding Source: RGD
  • protein kinase C binding Source: RGD
  • protein phosphatase 2A binding Source: RGD

Protein-protein interaction databases

BioGridi246375. 10 interactions.
DIPiDIP-42185N.
IntActiP47196. 11 interactions.
MINTiMINT-1210360.
STRINGi10116.ENSRNOP00000038369.

Structurei

3D structure databases

ProteinModelPortaliP47196.
SMRiP47196. Positions 3-121, 144-477.
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 (By similarity).By similarity
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

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126961.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP47196.
KOiK04456.
OMAiQDDSMES.
OrthoDBiEOG7Q5HCW.
PhylomeDBiP47196.
TreeFamiTF102004.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. 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.

P47196-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVEQRES
60 70 80 90 100
PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT
110 120 130 140 150
TAIQTVADGL KRQEEETMDF RSGSPSDNSG AEEMEVALAK 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):55,735
Last modified:February 1, 1996 - v1
Checksum:i5DCAAE7134366D04
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30040 mRNA. Translation: BAA06279.1.
PIRiJC2437.
RefSeqiNP_150233.1. NM_033230.2.
XP_006240693.1. XM_006240631.2.
UniGeneiRn.11422.

Genome annotation databases

EnsembliENSRNOT00000031164; ENSRNOP00000038369; ENSRNOG00000028629.
GeneIDi24185.
KEGGirno:24185.
UCSCiRGD:2081. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30040 mRNA. Translation: BAA06279.1.
PIRiJC2437.
RefSeqiNP_150233.1. NM_033230.2.
XP_006240693.1. XM_006240631.2.
UniGeneiRn.11422.

3D structure databases

ProteinModelPortaliP47196.
SMRiP47196. Positions 3-121, 144-477.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246375. 10 interactions.
DIPiDIP-42185N.
IntActiP47196. 11 interactions.
MINTiMINT-1210360.
STRINGi10116.ENSRNOP00000038369.

Chemistry

ChEMBLiCHEMBL1075215.

PTM databases

iPTMnetiP47196.
PhosphoSiteiP47196.

Proteomic databases

PaxDbiP47196.
PRIDEiP47196.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000031164; ENSRNOP00000038369; ENSRNOG00000028629.
GeneIDi24185.
KEGGirno:24185.
UCSCiRGD:2081. rat.

Organism-specific databases

CTDi207.
RGDi2081. Akt1.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126961.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP47196.
KOiK04456.
OMAiQDDSMES.
OrthoDBiEOG7Q5HCW.
PhylomeDBiP47196.
TreeFamiTF102004.

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.
ReactomeiR-RNO-114604. GPVI-mediated activation cascade.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-RNO-165159. mTOR signalling.
R-RNO-198323. AKT phosphorylates targets in the cytosol.
R-RNO-198693. AKT phosphorylates targets in the nucleus.
R-RNO-199418. Negative regulation of the PI3K/AKT network.
R-RNO-203615. eNOS activation.
R-RNO-211163. AKT-mediated inactivation of FOXO1A.
R-RNO-354192. Integrin alphaIIb beta3 signaling.
R-RNO-3769402. Deactivation of the beta-catenin transactivating complex.
R-RNO-389357. CD28 dependent PI3K/Akt signaling.
R-RNO-389513. CTLA4 inhibitory signaling.
R-RNO-392451. G beta:gamma signalling through PI3Kgamma.
R-RNO-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
R-RNO-450604. KSRP (KHSRP) binds and destabilizes mRNA.
R-RNO-5218920. VEGFR2 mediated vascular permeability.
R-RNO-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

NextBioi602545.
PROiP47196.

Gene expression databases

GenevisibleiP47196. RN.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta."
    Konishi H., Shinomura T., Kuroda S.I., Ono Y., Kikkawa U.
    Biochem. Biophys. Res. Commun. 205:817-825(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  2. "Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport."
    Kitamura T., Ogawa W., Sakaue H., Hino Y., Kuroda S., Takata M., Matsumoto M., Maeda T., Konishi H., Kikkawa U., Kasuga M.
    Mol. Cell. Biol. 18:3708-3717(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF LYS-179; THR-308 AND SER-473.
  3. "Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1)."
    Takata M., Ogawa W., Kitamura T., Hino Y., Kuroda S., Kotani K., Klip A., Gingras A.-C., Sonenberg N., Kasuga M.
    J. Biol. Chem. 274:20611-20618(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT THR-308 AND SER-473, MUTAGENESIS OF LYS-179; THR-308 AND SER-473.
  4. "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.
  5. "The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes."
    Berwick D.C., Hers I., Heesom K.J., Moule S.K., Tavare J.M.
    J. Biol. Chem. 277:33895-33900(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF ACLY.
  6. "Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles."
    Berwick D.C., Dell G.C., Welsh G.I., Heesom K.J., Hers I., Fletcher L.M., Cooke F.T., Tavare J.M.
    J. Cell Sci. 117:5985-5993(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PIKFYVE.
  7. "Ebp1 isoforms distinctively regulate cell survival and differentiation."
    Liu Z., Ahn J.Y., Liu X., Ye K.
    Proc. Natl. Acad. Sci. U.S.A. 103:10917-10922(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PA2G4.
  8. Cited for: REVIEW ON FUNCTION.
  9. "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.
  10. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiAKT1_RAT
AccessioniPrimary (citable) accession number: P47196
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: May 11, 2016
This is version 166 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.