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Q63484 (AKT3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length479 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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 specificity has 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 may also 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 By similarity.

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

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.

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 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 479479RAC-gamma serine/threonine-protein kinase
PRO_0000085613

Regions

Domain5 – 107103PH
Domain148 – 405258Protein kinase
Domain406 – 47974AGC-kinase C-terminal
Nucleotide binding154 – 1629ATP By similarity
Compositional bias452 – 4554Poly-Asp

Sites

Active site2711Proton acceptor By similarity
Binding site1771ATP By similarity

Amino acid modifications

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

Experimental info

Sequence conflict452 – 4543DDD → CPL in BAA08637. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q63484 [UniParc].

Last modified November 28, 2006. Version 2.
Checksum: D75D83A027B1A6B9

FASTA47955,796
        10         20         30         40         50         60 
MSDVTIVKED 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 GGPDDPKEIM RHSFFSGVNW QDVYDKKLVP 

       430        440        450        460        470 
PFKPQVTSET DTRYFDEEFT AQTITITPPE KDDDDGMDCM DNERRPHFPQ FSYSASGRE 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[2]"Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and beta gamma subunits of G proteins."
Konishi H., Kuroda S., Tanaka M., Matsuzaki H., Ono Y., Kameyama K., Haga T., Kikkawa U.
Biochem. Biophys. Res. Commun. 216:526-534(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-454.
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AABR03086280 Genomic DNA. No translation available.
D49836 mRNA. Translation: BAA08637.1.
IPIIPI00209156.
PIRJC4345.
RefSeqNP_113763.1. NM_031575.1.
UniGeneRn.10506.

3D structure databases

ProteinModelPortalQ63484.
SMRQ63484. Positions 1-115, 142-476.
ModBaseSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000031636.

PTM databases

PhosphoSiteQ63484.

Proteomic databases

PRIDEQ63484.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID29414.
KEGGrno:29414.
UCSCRGD:62390. rat.

Organism-specific databases

CTD10000.
RGD62390. Akt3.

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108317.
KOK04456.

Enzyme and pathway databases

BRENDA2.7.11.1. 5301.
ReactomeREACT_109781. Immune System.
REACT_110573. Disease.
REACT_111984. Signal Transduction.
REACT_82403. Hemostasis.

Gene expression databases

GenevestigatorQ63484.

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_cat_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. Kinase_like. 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

NextBio609088.

Entry information

Entry nameAKT3_RAT
AccessionPrimary (citable) accession number: Q63484
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 28, 2006
Last modified: April 3, 2013
This is version 106 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