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P31750 (AKT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Akt1
Synonyms:Akt, Rac
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length480 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 specificityhas 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 ofcyclic 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. Ref.2 Ref.8 Ref.9 Ref.12 Ref.13 Ref.15 Ref.20 Ref.21 Ref.24 Ref.26

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 hasa more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation. Ref.2 Ref.8 Ref.9 Ref.12 Ref.13 Ref.15 Ref.20 Ref.21 Ref.24 Ref.26

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 structure

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. Ref.14 Ref.16 Ref.17 Ref.22 Ref.24

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. Ref.11 Ref.24

Tissue specificity

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

Developmental stage

Expressed in trophoblast and vessel endothelial cells of the placenta and in the brain at 14.5 dpc (at protein level). Ref.2

Domain

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.

Post-translational modification

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.

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 By similarity. Ref.2 Ref.10 Ref.16 Ref.20 Ref.23 Ref.24 Ref.25

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. Ref.2 Ref.10 Ref.16 Ref.20 Ref.23 Ref.24 Ref.25

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.

Disruption phenotype

Show fetal growth impairment and reduced vascularization in the placenta; majority of pups died within 10 days. Ref.2

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 PH domain.

Contains 1 protein kinase domain.

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 specificfunctions 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.

Ontologies

Keywords
   Biological processApoptosis
Carbohydrate metabolism
Glucose metabolism
Glycogen biosynthesis
Glycogen metabolism
Neurogenesis
Sugar transport
Translation regulation
Transport
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Disulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation-induced cell death of T cells

Inferred from sequence orthology PubMed 14749367. Source: MGI

aging

Inferred from electronic annotation. Source: Ensembl

anagen

Inferred from mutant phenotype PubMed 15713628. Source: MGI

apoptotic mitochondrial changes

Inferred from direct assay PubMed 12869584. Source: MGI

cell projection organization

Inferred from sequence orthology PubMed 16286931. Source: MGI

cellular response to epidermal growth factor stimulus

Inferred from direct assay PubMed 21712384. Source: UniProtKB

cellular response to growth factor stimulus

Inferred from direct assay PubMed 19744960. Source: MGI

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from direct assay PubMed 19139280. Source: UniProtKB

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

cytoskeleton organization

Traceable author statement Ref.26. Source: UniProtKB

endocrine pancreas development

Traceable author statement. Source: Reactome

execution phase of apoptosis

Inferred from direct assay PubMed 12124386. Source: MGI

germ cell development

Inferred from direct assay PubMed 12140361. Source: MGI

glucose homeostasis

Inferred from mutant phenotype PubMed 19897600. Source: MGI

glucose metabolic process

Inferred from mutant phenotype PubMed 19897600. Source: MGI

glucose transport

Inferred from mutant phenotype Ref.8. Source: UniProtKB

glycogen biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

glycogen cell differentiation involved in embryonic placenta development

Inferred from mutant phenotype Ref.2. Source: MGI

glycogen metabolic process

Inferred from mutant phenotype Ref.2. Source: MGI

hyaluronan metabolic process

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Inferred from direct assay PubMed 14730361. Source: MGI

insulin receptor signaling pathway

Inferred from mutant phenotype Ref.12Ref.8. Source: UniProtKB

insulin-like growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from sequence orthology PubMed 14749367. Source: MGI

labyrinthine layer blood vessel development

Inferred from mutant phenotype Ref.2. Source: MGI

maternal placenta development

Inferred from mutant phenotype Ref.2. Source: MGI

negative regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.12. Source: UniProtKB

negative regulation of autophagy

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell size

Inferred from sequence orthology PubMed 16286931. Source: MGI

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 18977203. Source: UniProtKB

negative regulation of fatty acid beta-oxidation

Inferred from electronic annotation. Source: Ensembl

negative regulation of plasma membrane long-chain fatty acid transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

negative regulation of release of cytochrome c from mitochondria

Inferred from direct assay PubMed 18977203. Source: UniProtKB

osteoblast differentiation

Inferred from genetic interaction PubMed 19208758. Source: MGI

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 16513828. Source: MGI

peripheral nervous system myelin maintenance

Inferred from mutant phenotype PubMed 20448149. Source: MGI

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from electronic annotation. Source: Ensembl

positive regulation of fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

positive regulation of glycogen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of lipid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric-oxide synthase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 15937334. Source: MGI

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of sodium ion transport

Inferred from direct assay PubMed 17715136. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 18762576. Source: MGI

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

protein catabolic process

Inferred from direct assay PubMed 12145204. Source: MGI

protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

protein kinase B signaling

Inferred from genetic interaction PubMed 15249583. Source: MGI

protein phosphorylation

Inferred from direct assay Ref.24. Source: UniProtKB

protein ubiquitination

Inferred from direct assay PubMed 12145204. Source: MGI

regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neuron projection development

Inferred from direct assay Ref.21. Source: UniProtKB

regulation of protein localization

Inferred from direct assay PubMed 17715136. Source: MGI

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

response to UV-A

Inferred from electronic annotation. Source: Ensembl

response to fluid shear stress

Inferred from electronic annotation. Source: Ensembl

response to food

Inferred from direct assay PubMed 16513828. Source: MGI

response to hormone

Inferred from direct assay PubMed 16357133. Source: UniProtKB

striated muscle cell differentiation

Inferred from genetic interaction PubMed 18762576. Source: MGI

translation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12124386. Source: MGI

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 16116448. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.24. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.24. Source: UniProtKB

spindle

Inferred from direct assay PubMed 15509711. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

kinase activity

Inferred from sequence orthology PubMed 14749367. Source: MGI

nitric-oxide synthase regulator activity

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-3,4,5-trisphosphate binding

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-3,4-bisphosphate binding

Inferred from electronic annotation. Source: Ensembl

protein kinase activity

Inferred from direct assay PubMed 16357133. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.26. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.26. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 480480RAC-alpha serine/threonine-protein kinase
PRO_0000085606

Regions

Domain5 – 108104PH
Domain150 – 408259Protein kinase
Domain409 – 48072AGC-kinase C-terminal
Nucleotide binding156 – 1649ATP By similarity
Region14 – 196Inositol-(1,3,4,5)-tetrakisphosphate binding By similarity
Region23 – 253Inositol-(1,3,4,5)-tetrakisphosphate binding By similarity
Region228 – 2303Inhibitor binding By similarity

Sites

Active site2741Proton acceptor By similarity
Binding site531Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding site861Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding site1611Inhibitor; via amide nitrogen By similarity
Binding site1791ATP
Binding site2301Inhibitor; via amide nitrogen By similarity
Binding site2341Inhibitor By similarity
Binding site2921Inhibitor By similarity

Amino acid modifications

Modified residue141N6-acetyllysine By similarity
Modified residue201N6-acetyllysine By similarity
Modified residue1241Phosphoserine
Modified residue1261Phosphoserine; alternate
Modified residue1291Phosphoserine; alternate Ref.18
Modified residue1761Phosphotyrosine; by TNK2 Ref.24
Modified residue2841N6-acetyllysine; by MUL1 By similarity
Modified residue3081Phosphothreonine; by IKKE, PDPK1 and TBK1 Ref.16 Ref.20 Ref.24
Modified residue4501Phosphothreonine; by MTOR Ref.23
Modified residue4731Phosphoserine; by IKKE, MTOR and TBK1; alternate Probable
Modified residue4741Phosphotyrosine By similarity
Glycosylation1261O-linked (GlcNAc); alternate By similarity
Glycosylation1291O-linked (GlcNAc); alternate By similarity
Glycosylation3051O-linked (GlcNAc) By similarity
Glycosylation3121O-linked (GlcNAc) By similarity
Glycosylation4731O-linked (GlcNAc); alternate By similarity
Disulfide bond60 ↔ 77 By similarity
Disulfide bond296 ↔ 310 By similarity

Experimental info

Mutagenesis1761Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. Ref.24
Mutagenesis1791K → A: Lacks kinase activity. Overexpression inhibits insulin-stimulated translocation of SLC2A4/GLUT4 in a dominant negative manner. Ref.8
Mutagenesis3081T → A: Does not affect ubiquitination by ZNRF1. Ref.26
Mutagenesis4731S → A: Does not affect ubiquitination by ZNRF1. Ref.26
Sequence conflict3671R → A in AAA18254. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P31750 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 98DF28E5EFE03730

FASTA48055,707
        10         20         30         40         50         60 
MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQRES PLNNFSVAQC 

        70         80         90        100        110        120 
QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWA TAIQTVADGL KRQEEETMDF 

       130        140        150        160        170        180 
RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI 

       190        200        210        220        230        240 
LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS 

       250        260        270        280        290        300 
RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI 

       310        320        330        340        350        360 
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL 

       370        380        390        400        410        420 
ILMEEIRFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK EIMQHRFFAN IVWQDVYEKK 

       430        440        450        460        470        480 
LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"Tcl1 enhances Akt kinase activity and mediates its nuclear translocation."
Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S., Russo G., Tsichlis P., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000) [PubMed] [Europe PMC] [Abstract]
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]"A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis."
Anai M., Shojima N., Katagiri H., Ogihara T., Sakoda H., Onishi Y., Ono H., Fujishiro M., Fukushima Y., Horike N., Viana A., Kikuchi M., Noguchi N., Takahashi S., Takata K., Oka Y., Uchijima Y., Kurihara H., Asano T.
J. Biol. Chem. 280:18525-18535(2005) [PubMed] [Europe PMC] [Abstract]
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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[19]"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.
[20]"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.
[21]"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.
[22]"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.
[23]"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.
[24]"Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation."
Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W., Lopez A.S., Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S., Cheng J.Q., Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.
PLoS ONE 5:E9646-E9646(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2.
[25]"Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling."
Arora D., Stopp S., Bohmer S.A., Schons J., Godfrey R., Masson K., Razumovskaya E., Ronnstrand L., Tanzer S., Bauer R., Bohmer F.D., Muller J.P.
J. Biol. Chem. 286:10918-10929(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
[26]"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.
[27]"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.
[28]"Akt signalling in health and disease."
Hers I., Vincent E.E., Tavare J.M.
Cell. Signal. 23:1515-1527(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[29]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS33364.
RefSeqNP_001159366.1. NM_001165894.1.
NP_033782.1. NM_009652.3.
XP_006515478.1. XM_006515415.1.
XP_006515479.1. XM_006515416.1.
UniGeneMm.6645.

3D structure databases

ProteinModelPortalP31750.
SMRP31750. Positions 1-477.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198056. 15 interactions.
DIPDIP-736N.
IntActP31750. 24 interactions.
MINTMINT-4049532.

Chemistry

BindingDBP31750.
ChEMBLCHEMBL5859.

PTM databases

PhosphoSiteP31750.

Proteomic databases

PaxDbP31750.
PRIDEP31750.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001780; ENSMUSP00000001780; ENSMUSG00000001729.
GeneID11651.
KEGGmmu:11651.
UCSCuc007pex.2. mouse.

Organism-specific databases

CTD207.
MGIMGI:87986. Akt1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000114960.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidQ6GSA6.
KOK04456.
OMASRERVFP.
OrthoDBEOG7Q5HCW.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.
ReactomeREACT_13641. Regulation of Beta-Cell Development.
REACT_147847. Translocation of Glut4 to the Plasma Membrane.
REACT_188257. Signal Transduction.
REACT_77193. Inhibition of HSL.

Gene expression databases

ArrayExpressP31750.
BgeeP31750.
CleanExMM_AKT1.
GenevestigatorP31750.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

ChiTaRSAKT1. mouse.
NextBio279257.
PROP31750.
SOURCESearch...

Entry information

Entry nameAKT1_MOUSE
AccessionPrimary (citable) accession number: P31750
Secondary accession number(s): Q62274, Q6GSA6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot