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Protein

RAC-gamma serine/threonine-protein kinase

Gene

Akt3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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. IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei177 – 1771ATPPROSITE-ProRule annotation
Active sitei271 – 2711Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi154 – 1629ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: RGD
  • protein kinase C binding Source: RGD
  • protein serine/threonine kinase activity Source: RGD

GO - Biological processi

  • cellular response to insulin stimulus Source: MGI
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of sodium ion transport Source: MGI
  • protein phosphorylation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

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.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Akt3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi62390. Akt3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 479478RAC-gamma serine/threonine-protein kinasePRO_0000085613Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Disulfide bondi59 ↔ 76By similarity
Disulfide bondi293 ↔ 307By similarity
Glycosylationi302 – 3021O-linked (GlcNAc)By similarity
Modified residuei305 – 3051Phosphothreonine; by PDPK1By similarity
Glycosylationi309 – 3091O-linked (GlcNAc)By similarity
Modified residuei447 – 4471PhosphothreonineBy similarity
Modified residuei472 – 4721Phosphoserine; by PKC/PRKCZBy similarity

Post-translational modificationi

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).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

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63484.
PRIDEiQ63484.

PTM databases

iPTMnetiQ63484.
PhosphoSiteiQ63484.

Interactioni

Subunit structurei

Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6 (By similarity). Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity).By similarity

GO - Molecular functioni

  • protein kinase C binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000054688.

Structurei

3D structure databases

ProteinModelPortaliQ63484.
SMRiQ63484. Positions 1-115, 142-476.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 107103PHPROSITE-ProRule annotationAdd
BLAST
Domaini148 – 405258Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini406 – 47974AGC-kinase C-terminalAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi452 – 4554Poly-Asp

Domaini

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

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.
HOVERGENiHBG108317.
InParanoidiQ63484.
KOiK04456.
PhylomeDBiQ63484.

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.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q63484-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDVTIVKED WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP
60 70 80 90 100
LNNFSVAKCQ LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE
110 120 130 140 150
AIQAVADRLQ RQEEERMNCS PTSQIDNIGE EEMDASTTHH KRKTMNDFDY
160 170 180 190 200
LKLLGKGTFG KVILVREKAS GKYYAMKILK KEVIIAKDEV AHTLTESRVL
210 220 230 240 250
KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE RVFSEDRTRF
260 270 280 290 300
YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA
310 320 330 340 350
ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD
360 370 380 390 400
HEKLFELILM EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDPKEIM
410 420 430 440 450
RHSFFSGVNW QDVYDKKLVP PFKPQVTSET DTRYFDEEFT AQTITITPPE
460 470
KDDDDGMDCM DNERRPHFPQ FSYSASGRE
Length:479
Mass (Da):55,796
Last modified:November 28, 2006 - v2
Checksum:iD75D83A027B1A6B9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti452 – 4543DDD → CPL in BAA08637 (PubMed:7488143).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03086280 Genomic DNA. No translation available.
D49836 mRNA. Translation: BAA08637.1.
PIRiJC4345.
RefSeqiNP_113763.1. NM_031575.1.
UniGeneiRn.10506.

Genome annotation databases

GeneIDi29414.
KEGGirno:29414.
UCSCiRGD:62390. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03086280 Genomic DNA. No translation available.
D49836 mRNA. Translation: BAA08637.1.
PIRiJC4345.
RefSeqiNP_113763.1. NM_031575.1.
UniGeneiRn.10506.

3D structure databases

ProteinModelPortaliQ63484.
SMRiQ63484. Positions 1-115, 142-476.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000054688.

PTM databases

iPTMnetiQ63484.
PhosphoSiteiQ63484.

Proteomic databases

PaxDbiQ63484.
PRIDEiQ63484.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29414.
KEGGirno:29414.
UCSCiRGD:62390. rat.

Organism-specific databases

CTDi10000.
RGDi62390. Akt3.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ63484.
KOiK04456.
PhylomeDBiQ63484.

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.
ReactomeiR-RNO-114604. GPVI-mediated activation cascade.
R-RNO-1257604. PIP3 activates AKT signaling.

Miscellaneous databases

PROiQ63484.

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. "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.
    , 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.

Entry informationi

Entry nameiAKT3_RAT
AccessioniPrimary (citable) accession number: Q63484
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 28, 2006
Last modified: June 8, 2016
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.