Reviewed, UniProtKB/Swiss-Prot P31750 (AKT1_MOUSE)

Names and origin

Protein names

Recommended name:
    RAC-alpha serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    RAC-PK-alpha
    AKT1 kinase
    C-AKT
    Protein kinase B
      Short name=PKB
    Thymoma viral proto-oncogene

Gene names

Name:	Akt1
Synonyms:	Akt, Rac

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	480 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	General protein kinase capable of phosphorylating several known proteins. Phosphorylates TBC1D4. Signals downstream of phosphatidylinositol 3-kinase (PI3K) 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 by phosphorylating TSC2 at 'Ser-939' and 'Thr-1465', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 By similarity. 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 structure	Interacts with AGAP2 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.
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. Ref.2
Domain	Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI3K) results in its targeting to the plasma membrane. The AGC-kinase C-terminal mediates interaction with THEM4 By similarity.
Post-translational modification	Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1 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.

Ontologies

Keywords
Biological process	Apoptosis Carbohydrate metabolism Glucose metabolism Glycogen biosynthesis Glycogen metabolism Sugar transport Translation regulation Transport
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	anagen Inferred from mutant phenotype. Source: MGI apoptotic mitochondrial changes Inferred from direct assay. Source: MGI germ cell development Inferred from direct assay. Source: MGI glucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW glucose transport Ref.3 Inferred from mutant phenotype. Source: UniProtKB glycogen biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW glycogen cell development involved in embryonic placenta development Inferred from mutant phenotype. Source: MGI inflammatory response Inferred from direct assay. Source: MGI insulin receptor signaling pathway Ref.3 Ref.5 Inferred from mutant phenotype. Source: UniProtKB insulin-like growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB labyrinthine layer blood vessel development Inferred from mutant phenotype. Source: MGI maternal placenta development Inferred from mutant phenotype. Source: MGI peptidyl-serine phosphorylation Inferred from direct assay. Source: MGI positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype. Source: MGI positive regulation of sodium ion transport Inferred from direct assay. Source: MGI protein catabolic process Inferred from direct assay. Source: MGI protein kinase B signaling cascade Inferred from genetic interaction. Source: MGI protein ubiquitination Inferred from direct assay. Source: MGI regulation of protein localization Inferred from direct assay. Source: MGI regulation of survival gene product expression Inferred from direct assay. Source: MGI regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW response to food Inferred from direct assay. Source: MGI
Cellular component	cytosol Inferred from Experiment. Source: Reactome lamellipodium Inferred from direct assay. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell spindle Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Map3k5	O35099	1	EBI-298707,EBI-777493
Trib3	Q8K4K2	5	EBI-298707,EBI-448962

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 480	480	RAC-alpha serine/threonine-protein kinase		PRO_0000085606
Regions
	Domain	5 – 108	104	PH
	Domain	150 – 408	259	Protein kinase
	Domain	409 – 480	72	AGC-kinase C-terminal
	Nucleotide binding	156 – 164	9	ATP By similarity
Sites
	Active site	274	1	Proton acceptor By similarity
	Binding site	179	1	ATP
Amino acid modifications
	Modified residue	124	1	Phosphoserine Ref.9
	Modified residue	126	1	Phosphoserine Ref.9
	Modified residue	129	1	Phosphoserine Ref.9 Ref.10
	Modified residue	308	1	Phosphothreonine; by PDPK1 Ref.8
	Modified residue	473	1	Phosphoserine Ref.8
	Modified residue	474	1	Phosphotyrosine By similarity
Experimental info
	Mutagenesis	179	1	K → A: Lacks kinase activity. Overexpression inhibits insulin-stimulated translocation of GLUT4 in a dominant negative manner. Ref.3
	Sequence conflict	367	1	A → R in CAA46620. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P31750-1 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 18D21018593B5A98	FASTA	480	55,622
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete nucleotide coding sequence for murine rac (related to A and C kinases) protein kinase." Bousquets X., Powell C.T. Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications." Bellacosa A., Franke T.F., Gonzalez-Portal M.E., Datta K., Taguchi T., Gardner J., Cheng J.Q., Testa J.R., Tsichlis P.N. Oncogene 8:745-754(1993) [PubMed: 8437858] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Strain: AKR/J. Tissue: Thymus.
[3]	"Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells." Cong L.N., Chen H., Li Y., Zhou L., McGibbon M.A., Taylor S.I., Quon M.J. Mol. Endocrinol. 11:1881-1890(1997) [PubMed: 9415393] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-179.
[4]	"Tcl1 enhances Akt kinase activity and mediates its nuclear translocation." Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S., Russo G., Tsichlis P., Croce C.M. Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000) [PubMed: 10716693] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1." Yamashita K., Kajstura J., Discher D.J., Wasserlauf B.J., Bishopric N.H., Anversa P., Webster K.A. Circ. Res. 88:609-614(2001) [PubMed: 11282895] [Abstract] Cited for: FUNCTION.
[6]	"Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane." Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M., Hemmings B.A. Science 294:374-380(2001) [PubMed: 11598301] [Abstract] Cited for: INTERACTION WITH THEM4.
[7]	"A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain." Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E. J. Biol. Chem. 277:22115-22118(2002) [PubMed: 11994271] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF TBC1D4.
[8]	"A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis." 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. J. Biol. Chem. 280:18525-18535(2005) [PubMed: 15753085] [Abstract] Cited for: INTERACTION WITH CCDC88A, PHOSPHORYLATION AT THR-308 AND SER-473.
[9]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 AND SER-129, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 18973353] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M94335 mRNA. Translation: AAA18254.1. X65687 mRNA. Translation: CAA46620.1.
IPI	IPI00323969.
PIR	S33364.
RefSeq	NP_033782.1. XP_001479205.1.
UniGene	Mm.6645
3D structure databases
HSSP	HSSP built from PDB template 1H10 based on UniProtKB P31749.
SMR	P31750. Positions 3-121.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:736N.
IntAct	P31750. 4 interactions.
STRING	P31750.
PTM databases
PhosphoSite	P31750.
Proteomic databases
PRIDE	P31750.
Genome annotation databases
Ensembl	ENSMUST00000001780; ENSMUSP00000001780; ENSMUSG00000001729; Mus musculus. [Genome view] ENSMUST00000109749; ENSMUSP00000105371; ENSMUSG00000001729; Mus musculus. [Genome view] ENSMUST00000121171; ENSMUSP00000113658; ENSMUSG00000001729; Mus musculus. [Genome view]
GeneID	100047666. 11651.
KEGG	mmu:100047666. mmu:11651.
Organism-specific databases
MGI	MGI:87986. Akt1.
Phylogenomic databases
HOGENOM	P31750.
HOVERGEN	P31750.
Enzyme and pathway databases
BRENDA	2.7.11.1. 244.
Reactome	REACT_13641. Regulation of Beta-Cell Development.
Gene expression databases
ArrayExpress	P31750.
Bgee	P31750.
CleanEx	MM_AKT1.
Genevestigator	P31750.
GermOnline	ENSMUSG00000001729. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011993. PH_type. IPR017892. Pkinase_C. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. IPR015744. Serine/threonine_Kinase_Rac. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
PANTHER	PTHR22985:SF69. Akt. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS51285. 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]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

AKT1_MOUSE

Accession

Primary (citable) accession number: P31750
Secondary accession number(s): Q62274

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	November 3, 2009
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)