Reviewed, UniProtKB/Swiss-Prot P47196 (AKT1_RAT)

Names and origin

Protein names

Recommended name:
    RAC-alpha serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    RAC-PK-alpha
    Protein kinase B
      Short name=PKB

Gene names

Name:

Akt1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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 By similarity. Mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1466', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. 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	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 (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	cell projection organization Inferred from direct assay. Source: MGI glucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW glycogen biosynthetic process Ref.3 Inferred from mutant phenotype. Source: UniProtKB insulin receptor signaling pathway Ref.2 Inferred from mutant phenotype. Source: UniProtKB insulin-like growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of JNK cascade Inferred from direct assay. Source: RGD negative regulation of cell size Inferred from direct assay. Source: MGI negative regulation of protein kinase activity Inferred from direct assay. Source: UniProtKB peptidyl-serine phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of cell growth Inferred from direct assay. Source: RGD regulation of cell migration Inferred from mutant phenotype. Source: RGD regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW translation Ref.2 Ref.3 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: RGD nucleoplasm Inferred from Experiment. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from direct assay. Source: RGD enzyme binding Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

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_0000085607
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 By similarity
	Modified residue	126	1	Phosphoserine By similarity
	Modified residue	129	1	Phosphoserine By similarity
	Modified residue	308	1	Phosphothreonine; by PDPK1 Probable
	Modified residue	473	1	Phosphoserine Probable
	Modified residue	474	1	Phosphotyrosine By similarity
Experimental info
	Mutagenesis	179	1	K → D: Lacks kinase activity. Inhibits insulin-induced activation of glycogen synthase when expressed. Ref.2 Ref.3
	Mutagenesis	308	1	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. Ref.2 Ref.3
	Mutagenesis	473	1	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. Ref.2 Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P47196-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 5DCAAE7134366D04	FASTA	480	55,735
	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

References

[1]	"Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta." Konishi H., Shinomura T., Kuroda S.I., Ono Y., Kikkawa U. Biochem. Biophys. Res. Commun. 205:817-825(1994) [PubMed: 7999118] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport." Kitamura T., Ogawa W., Sakaue H., Hino Y., Kuroda S., Takata M., Matsumoto M., Maeda T., Konishi H., Kikkawa U., Kasuga M. Mol. Cell. Biol. 18:3708-3717(1998) [PubMed: 9632753] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-179; THR-308 AND SER-473.
[3]	"Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1)." Takata M., Ogawa W., Kitamura T., Hino Y., Kuroda S., Kotani K., Klip A., Gingras A.-C., Sonenberg N., Kasuga M. J. Biol. Chem. 274:20611-20618(1999) [PubMed: 10400692] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-308 AND SER-473, MUTAGENESIS OF LYS-179; THR-308 AND SER-473.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D30040 mRNA. Translation: BAA06279.1.
IPI	IPI00212844.
PIR	JC2437.
RefSeq	NP_150233.1.
UniGene	Rn.11422
3D structure databases
HSSP	HSSP built from PDB template 1H10 based on UniProtKB P31749.
SMR	P47196. Positions 3-121.
ModBase	Search...
Protein-protein interaction databases
STRING	P47196.
PTM databases
PhosphoSite	P47196.
Proteomic databases
PRIDE	P47196.
Genome annotation databases
Ensembl	ENSRNOT00000031164; ENSRNOP00000038369; ENSRNOG00000028629; Rattus norvegicus. [Genome view]
GeneID	24185.
KEGG	rno:24185.
UCSC	NM_033230. rat.
Organism-specific databases
CTD	24185.
RGD	2081. Akt1.
Phylogenomic databases
HOVERGEN	P47196.
OMA	KLSPPFK.
Enzyme and pathway databases
BRENDA	2.7.11.1. 248.
Gene expression databases
ArrayExpress	P47196.
Genevestigator	P47196.
GermOnline	ENSRNOG00000028629. Rattus norvegicus.
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
NextBio	602545.

Entry information

Entry name

AKT1_RAT

Accession

Primary (citable) accession number: P47196

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	November 3, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)