[1]	NUCLEOTIDE SEQUENCE [MRNA]. Bousquets X., Powell C.T.; "Complete nucleotide coding sequence for murine rac (related to A and C kinases) protein kinase."; Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases.
[2]	NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. STRAIN=AKR/J; TISSUE=Thymus; PubMed=8437858 [NCBI, ExPASy, EBI, Israel, Japan] Bellacosa A., Franke T.F., Gonzalez-Portal M.E., Datta K., Taguchi T., Gardner J., Cheng J.Q., Testa J.R., Tsichlis P.N.; "Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications."; Oncogene 8:745-754(1993).
[3]	FUNCTION, AND MUTAGENESIS OF LYS-179. DOI=10.1210/me.11.13.1881; PubMed=9415393 [NCBI, ExPASy, EBI, Israel, Japan] Cong L.N., Chen H., Li Y., Zhou L., McGibbon M.A., Taylor S.I., Quon M.J.; "Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells."; Mol. Endocrinol. 11:1881-1890(1997).
[4]	SUBCELLULAR LOCATION. DOI=10.1073/pnas.040557697; PubMed=10716693 [NCBI, ExPASy, EBI, Israel, Japan] Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S., Russo G., Tsichlis P., Croce C.M.; "Tcl1 enhances Akt kinase activity and mediates its nuclear translocation."; Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000).
[5]	FUNCTION. PubMed=11282895 [NCBI, ExPASy, EBI, Israel, Japan] Yamashita K., Kajstura J., Discher D.J., Wasserlauf B.J., Bishopric N.H., Anversa P., Webster K.A.; "Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1."; Circ. Res. 88:609-614(2001).
[6]	INTERACTION WITH THEM4. DOI=10.1126/science.1062030; PubMed=11598301 [NCBI, ExPASy, EBI, Israel, Japan] Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M., Hemmings B.A.; "Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane."; Science 294:374-380(2001).
[7]	FUNCTION IN PHOSPHORYLATION OF TBC1D4. DOI=10.1074/jbc.C200198200; PubMed=11994271 [NCBI, ExPASy, EBI, Israel, Japan] Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E.; "A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain."; J. Biol. Chem. 277:22115-22118(2002).
[8]	INTERACTION WITH CCDC88A, AND PHOSPHORYLATION AT THR-308 AND SER-473. DOI=10.1074/jbc.M500586200; PubMed=15753085 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis."; J. Biol. Chem. 280:18525-18535(2005).
[9]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 AND SER-129, AND MASS SPECTROMETRY. TISSUE=Liver; DOI=10.1073/pnas.0609836104; PubMed=17242355 [NCBI, ExPASy, EBI, Israel, Japan] Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; "Large-scale phosphorylation analysis of mouse liver."; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).

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. 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: Interacts with CENTG1 isoform 2 (PIKE-A) in the presence of guanine nucleotides. The C-terminus interacts with CCDC88A/GRDN and THEM4. Interacts with AKTIP (By similarity). 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 (By similarity).
INTERACTION:
O35099:Map3k5; NbExp=1; IntAct=EBI-298707, EBI-777493;
Q8K4K2:Trib3; NbExp=5; IntAct=EBI-298707, EBI-448962;
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.
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 (By similarity).
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

M94335; AAA18254.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X65687; CAA46620.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S33364; S33364.

UniGene

Mm.6645

3D structure databases

HSSP

P31749; 1H10. [HSSP ENTRY / PDB]

SMR

P31750; 3-121.

ModBase

P31750.

Protein-protein interaction databases

DIP

DIP:736N; -.

IntAct

P31750; -.

PTM databases

PhosphoSite

P31750; -.

Organism-specific databases

MGI

MGI:87986; Akt1.

Gene expression databases

ArrayExpress

P31750; -.

CleanEx

MM_AKT1; -.

GermOnline

ENSMUSG00000001729; Mus musculus.

Ontologies

GO:0005829;	Cellular component: cytosol (inferred from experiment from Reactome).
GO:0030027;	Cellular component: lamellipodium (inferred from direct assay from MGI).
GO:0005634;	Cellular component: nucleus (inferred from electronic annotation from UniProtKB-KW).
GO:0005886;	Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005819;	Cellular component: spindle (inferred from direct assay from MGI).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0004674;	Molecular function: protein serine/threonine kinase activity (inferred from sequence or structural similarity from UniProtKB).
GO:0005351;	Molecular function: sugar:hydrogen symporter activity (inferred from electronic annotation from UniProtKB-KW).
GO:0042640;	Biological process: anagen (inferred from mutant phenotype from MGI).
GO:0008637;	Biological process: apoptotic mitochondrial changes (inferred from direct assay from MGI).
GO:0001568;	Biological process: blood vessel development (inferred from mutant phenotype from MGI).
GO:0007281;	Biological process: germ cell development (inferred from direct assay from MGI).
GO:0006006;	Biological process: glucose metabolic process (inferred from electronic annotation from UniProtKB-KW).
GO:0015758;	Biological process: glucose transport (inferred from mutant phenotype from UniProtKB).
GO:0005978;	Biological process: glycogen biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0006954;	Biological process: inflammatory response (inferred from direct assay from MGI).
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:0018105;	Biological process: peptidyl-serine phosphorylation (inferred from direct assay from MGI).
GO:0001890;	Biological process: placenta development (inferred from mutant phenotype from MGI).
GO:0040018;	Biological process: positive regulation of multicellular organism growth (inferred from mutant phenotype from MGI).
GO:0032436;	Biological process: positive regulation of proteasomal ubiquitin-dependent protein catabolic process (inferred from mutant phenotype from MGI).
GO:0043491;	Biological process: protein kinase B signaling cascade (inferred from genetic interaction from MGI).
GO:0016567;	Biological process: protein ubiquitination (inferred from direct assay from MGI).
GO:0045884;	Biological process: regulation of survival gene product expression (inferred from direct assay from MGI).
GO:0006417;	Biological process: regulation of translation (inferred from electronic annotation from UniProtKB-KW).
GO:0032094;	Biological process: response to food (inferred from direct assay from MGI).
GO:0009725;	Biological process: response to hormone stimulus (inferred from direct assay 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).

Genome annotation databases

Ensembl

ENSMUSG00000001729; Mus musculus. [Contig view]

Phylogenomic databases

HOGENOM

P31750; -.

HOVERGEN

P31750; -.

Other

SOURCE

Akt1; Mus musculus.

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

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 480`	`480`	`RAC-alpha serine/threonine-protein kinase.`	`PRO_0000085606`
`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.`
`MOD_RES`	`126 126`		`Phosphoserine.`
`MOD_RES`	`129 129`		`Phosphoserine.`
`MOD_RES`	`308 308`		`Phosphothreonine; by PDPK1.`
`MOD_RES`	`473 473`		`Phosphoserine.`
`MOD_RES`	`474 474`		`Phosphotyrosine (By similarity).`
`MUTAGEN`	`179 179`		`K->A: Lacks kinase activity. Overexpression inhibits insulin-stimulated translocation of GLUT4 in a dominant negative manner.`
`CONFLICT`	`367 367`		`A -> R (in Ref. 2; CAA46620).`

Sequence information

Length: 480 AA [This is the length of the unprocessed precursor]

Molecular weight: 55622 Da [This is the MW of the unprocessed precursor]

CRC64: 18D21018593B5A98 [This is a checksum on the sequence]

        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 
ILMEEIAFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK EIMQHRFFAN IVWQDVYEKK 

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

P31750 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools