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UniProtKB/Swiss-Prot entry P47196


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name AKT1_RAT
Primary accession number P47196
Secondary accession numbers None
Integrated into Swiss-Prot on February 1, 1996
Sequence was last modified on February 1, 1996 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 80)
Name and origin of the protein
Protein name RAC-alpha serine/threonine-protein kinase
Synonyms EC 2.7.11.1
RAC-PK-alpha
Protein kinase B
PKB
Gene name
Name: Akt1
From
Rattus norvegicus (Rat) [TaxID: 10116] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Rattus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Testis;
DOI=10.1006/bbrc.1994.2738; PubMed=7999118 [NCBI, ExPASy, EBI, Israel, Japan]
Konishi H., Shinomura T., Kuroda S.I., Ono Y., Kikkawa U.;
"Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta.";
Biochem. Biophys. Res. Commun. 205:817-825(1994).
[2]
FUNCTION, AND MUTAGENESIS OF LYS-179; THR-308 AND SER-473.
PubMed=9632753 [NCBI, ExPASy, EBI, Israel, Japan]
Kitamura T., Ogawa W., Sakaue H., Hino Y., Kuroda S., Takata M., Matsumoto M., Maeda T., Konishi H., Kikkawa U., Kasuga M.;
"Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.";
Mol. Cell. Biol. 18:3708-3717(1998).
[3]
FUNCTION, PHOSPHORYLATION AT THR-308 AND SER-473, AND MUTAGENESIS OF LYS-179; THR-308 AND SER-473.
DOI=10.1074/jbc.274.29.20611; PubMed=10400692 [NCBI, ExPASy, EBI, Israel, Japan]
Takata M., Ogawa W., Kitamura T., Hino Y., Kuroda S., Kotani K., Klip A., Gingras A.-C., Sonenberg N., Kasuga M.;
"Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).";
J. Biol. Chem. 274:20611-20618(1999).
Comments
  • FUNCTION: General protein kinase capable of phosphorylating several known proteins. Phosphorylates TBC1D4. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) 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). Plays a role in glucose transport by mediating insulin-induced translocation of the GLUT4 glucose transporter to the cell surface. Mediates the antiapoptotic effects of IGF-I (By similarity). Mediates insulin-stimulated protein synthesis, partly by playing a role in both insulin-induced phosphorylation of 4E-BP1 and in insulin-induced activation of p70 S6 kinase. Promotes glycogen synthesis by mediating the insulin-induced activation of glycogen synthase.
  • 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: The C-terminus interacts with the C-terminus of CCDC88A/GRDN and THEM4. Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B (By similarity).
  • SUBCELLULAR LOCATION: 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).
  • TISSUE SPECIFICITY: Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis.
  • DOMAIN: Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.
  • DOMAIN: The AGC-kinase C-terminal mediates interaction with THEM4 (By similarity).
  • PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Ser-473 phosphorylation favors Thr-308 phosphorylation.
  • SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
  • SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
  • SIMILARITY: Contains 1 PH domain.
  • SIMILARITY: Contains 1 protein kinase domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
D30040; BAA06279.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR JC2437; JC2437.
RefSeq NP_150233.1; -.
UniGene Rn.11422
3D structure databases
HSSP P31749; 1H10. [HSSP ENTRY / PDB]
SMR P47196; 3-121.
ModBase P47196.
PTM databases
PhosphoSite P47196; -.
Organism-specific databases
RGD 2081; Akt1.
Gene expression databases
ArrayExpress P47196; -.
GermOnline ENSRNOG00000028629; Rattus norvegicus.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005654; Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0004674; Molecular function: protein serine/threonine kinase activity (inferred from sequence or structural similarity from UniProtKB).
GO:0030030; Biological process: cell projection organization and biogenesis (inferred from direct assay from MGI).
GO:0005978; Biological process: glycogen biosynthetic process (inferred from mutant phenotype from UniProtKB).
GO:0008286; Biological process: insulin receptor signaling pathway (inferred from mutant phenotype from UniProtKB).
GO:0048009; Biological process: insulin-like growth factor receptor signaling pathway (inferred from sequence or structural similarity from UniProtKB).
GO:0045792; Biological process: negative regulation of cell size (inferred from direct assay from MGI).
GO:0006468; Biological process: protein amino acid phosphorylation (inferred from sequence or structural similarity from UniProtKB).
GO:0006412; Biological process: translation (inferred from mutant phenotype from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR015744; Akt.
IPR001849; PH.
IPR011993; PH_type.
IPR000961; Pkinase_C.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.
Gene3D G3DSA:2.30.29.30; PH_type; 1.
PANTHER PTHR22985:SF69; Akt; 1.
Pfam PF00169; PH; 1.
PF00069; Pkinase; 1.
PF00433; Pkinase_C; 1.
Pfam graphical view of domain structure.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00233; PH; 1.
SM00133; S_TK_X; 1.
SM00220; S_TKc; 1.
SMART graphical view of domain structure.
PROSITE PS51285; AGC_KINASE_CTER; 1.
PS50003; PH_DOMAIN; 1.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P47196.
Genome annotation databases
Ensembl ENSRNOG00000028629; Rattus norvegicus. [Contig view]
GeneID 24185; -.
KEGG rno:24185; -.
Phylogenomic databases
HOVERGEN P47196; -.
Other
ProtoNet P47196.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Apoptosis; ATP-binding; Carbohydrate metabolism; Cell membrane; Cytoplasm; Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Serine/threonine-protein kinase; Sugar transport; Transferase; Translation regulation; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   480  480     RAC-alpha serine/threonine-protein kinase. PRO_0000085607
DOMAIN   5   108  104     PH. 
DOMAIN   150   408  259     Protein kinase. 
DOMAIN   409   480  72     AGC-kinase C-terminal. 
NP_BIND   156   164  9     ATP (By similarity). 
ACT_SITE   274   274        Proton acceptor (By similarity). 
BINDING   179   179        ATP. 
MOD_RES   124   124        Phosphoserine (By similarity). 
MOD_RES   126   126        Phosphoserine (By similarity). 
MOD_RES   129   129        Phosphoserine (By similarity). 
MOD_RES   308   308        Phosphothreonine; by PDPK1 (Probable). 
MOD_RES   473   473        Phosphoserine (Probable). 
MOD_RES   474   474        Phosphotyrosine (By similarity). 
MUTAGEN   179   179        K->D: Lacks kinase activity. Inhibits insulin-induced activation of glycogen synthase when expressed. 
MUTAGEN   308   308        T->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. 
MUTAGEN   473   473        S->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. 
Sequence information
Length: 480 AA [This is the length of the unprocessed precursor] Molecular weight: 55735 Da [This is the MW of the unprocessed precursor] CRC64: 5DCAAE7134366D04 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVEQRES PLNNFSVAQC 

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

       130        140        150        160        170        180 
RSGSPSDNSG AEEMEVALAK 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 

P47196 in FASTA format

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