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Q9WUA6 (AKT3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
RAC-gamma serine/threonine-protein kinase

EC=2.7.11.1
Alternative name(s):
Protein kinase Akt-3
Protein kinase B gamma
Short name=PKB gamma
RAC-PK-gamma
Gene names
Name:Akt3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length479 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

AKT3 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. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform mayalso be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Ref.3 Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation By similarity. IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival By similarity.

Subunit structure

Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6 By similarity.

Subcellular location

Nucleus By similarity. Cytoplasm. Membrane; Peripheral membrane protein. Note: Membrane-associated after cell stimulation leading to its translocation.

Tissue specificity

Isoform 1 is expressed in prostate, testis, uterus and mammary gland and isoform 2 is expressed in prostate, testis and mammary gland.

Domain

Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI3K) results in its targeting to the plasma membrane.

Post-translational modification

Phosphorylation on Thr-305 and Ser-472 is required for full activity.

Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome By similarity.

O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1 By similarity.

Disruption phenotype

Results in the cytoplasmic accumulation of the master regulator of mitochondrial biogenesis, Ppargc1a, and a reduction in known Ppargc1a target genes, which leads to an abnormal mitochondrial phenotype in the brain tissue. Ref.4

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9WUA6-1)

Also known as: PKB gamma;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9WUA6-2)

Also known as: PKB gamma 1;

The sequence of this isoform differs from the canonical sequence as follows:
     452-479: YDDDGMDGMDNERRPHFPQFSYSASGRE → CQQSDCGMLGNWKKNDNKK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 479478RAC-gamma serine/threonine-protein kinase
PRO_0000085612

Regions

Domain5 – 107103PH
Domain148 – 405258Protein kinase
Domain406 – 47974AGC-kinase C-terminal
Nucleotide binding154 – 1629ATP By similarity

Sites

Active site2711Proton acceptor By similarity
Binding site1771ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue3051Phosphothreonine; by PDPK1 By similarity
Modified residue4721Phosphoserine; by PKC/PRKCZ By similarity
Glycosylation3021O-linked (GlcNAc) By similarity
Glycosylation3091O-linked (GlcNAc) By similarity
Disulfide bond59 ↔ 76 By similarity
Disulfide bond293 ↔ 307 By similarity

Natural variations

Alternative sequence452 – 47928YDDDG…ASGRE → CQQSDCGMLGNWKKNDNKK in isoform 2.
VSP_004948

Experimental info

Mutagenesis2191D → V: Enhances kinase activity and causes low seizure threshold, sporadic tonic-clonic seizures, brain enlargement and ectopic neurons in the dentate hilus and molecular layer of the hippocampus. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PKB gamma) [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: F08ACDF75743B8FB

FASTA47955,714
        10         20         30         40         50         60 
MSDVTIVKEG WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP LNNFSVAKCQ 

        70         80         90        100        110        120 
LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE AIQAVADRLQ RQEEERMNCS 

       130        140        150        160        170        180 
PTSQIDNIGE EEMDASTTHH KRKTMNDFDY LKLLGKGTFG KVILVREKAS GKYYAMKILK 

       190        200        210        220        230        240 
KEVIIAKDEV AHTLTESRVL KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE 

       250        260        270        280        290        300 
RVFSEDRTRF YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA 

       310        320        330        340        350        360 
ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD HEKLFELILM 

       370        380        390        400        410        420 
EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDAKEIM RHSFFSGVNW QDVYDKKLVP 

       430        440        450        460        470 
PFKPQVTSET DTRYFDEEFT AQTITITPPE KYDDDGMDGM DNERRPHFPQ FSYSASGRE 

« Hide

Isoform 2 (PKB gamma 1) [UniParc].

Checksum: B4352DF496792EF8
Show »

FASTA47054,631

References

[1]"A human protein kinase B gamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain."
Brodbeck D., Cron P., Hemmings B.A.
J. Biol. Chem. 274:9133-9136(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Two splice variants of PKB gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site Ser-472 in the C-terminal hydrophobic domain."
Brodbeck D., Hill M.M., Hemmings B.A.
J. Biol. Chem. 276:29550-29558(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain.
[3]"Role for Akt3/protein kinase Bgamma in attainment of normal brain size."
Easton R.M., Cho H., Roovers K., Shineman D.W., Mizrahi M., Forman M.S., Lee V.M., Szabolcs M., de Jong R., Oltersdorf T., Ludwig T., Efstratiadis A., Birnbaum M.J.
Mol. Cell. Biol. 25:1869-1878(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase."
Wright G.L., Maroulakou I.G., Eldridge J., Liby T.L., Sridharan V., Tsichlis P.N., Muise-Helmericks R.C.
FASEB J. 22:3264-3275(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice."
Tokuda S., Mahaffey C.L., Monks B., Faulkner C.R., Birnbaum M.J., Danzer S.C., Frankel W.N.
Hum. Mol. Genet. 20:988-999(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-219, FUNCTION.
[6]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF124142 mRNA. Translation: AAD29090.1.
CCDSCCDS35799.1. [Q9WUA6-1]
RefSeqNP_035915.3. NM_011785.3. [Q9WUA6-1]
XP_006496881.1. XM_006496818.1. [Q9WUA6-1]
XP_006496882.1. XM_006496819.1. [Q9WUA6-1]
UniGeneMm.235194.

3D structure databases

ProteinModelPortalQ9WUA6.
SMRQ9WUA6. Positions 3-476.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204720. 2 interactions.
IntActQ9WUA6. 1 interaction.
MINTMINT-4087479.
STRING10090.ENSMUSP00000106790.

PTM databases

PhosphoSiteQ9WUA6.

Proteomic databases

MaxQBQ9WUA6.
PaxDbQ9WUA6.
PRIDEQ9WUA6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000019843; ENSMUSP00000019843; ENSMUSG00000019699. [Q9WUA6-2]
ENSMUST00000111159; ENSMUSP00000106789; ENSMUSG00000019699. [Q9WUA6-1]
ENSMUST00000111160; ENSMUSP00000106790; ENSMUSG00000019699. [Q9WUA6-1]
GeneID23797.
KEGGmmu:23797.
UCSCuc007duk.2. mouse. [Q9WUA6-1]

Organism-specific databases

CTD10000.
MGIMGI:1345147. Akt3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000114960.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidQ9WUA6.
KOK04456.
OMAMRHSFFA.
OrthoDBEOG7Q5HCW.
PhylomeDBQ9WUA6.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

BgeeQ9WUA6.
CleanExMM_AKT3.
GenevestigatorQ9WUA6.

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

NextBio303415.
PROQ9WUA6.
SOURCESearch...

Entry information

Entry nameAKT3_MOUSE
AccessionPrimary (citable) accession number: Q9WUA6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 133 of the entry and version 1 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