EKS-HOS-00143

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00143

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/Akt	504.9	2.4E-151	88	346	259

Status

Reviewed

Ensembl Protein

ENSP00000443897

UniProt Accession

P31749; B2RAM5; Q9BWB6;

Protein Name

RAC-alpha serine/threonine-protein kinase

Protein Synonyms/Alias

Protein kinase B; PKB; Protein kinase B alpha; PKB alpha; Proto-oncogene c-Akt; RAC-PK-alpha;

Gene Name

AKT1

Gene Synonyms/Alias

AKT1; PKB, RAC;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000142208	ENSP00000443897	ENST00000544168
ENSG00000142208	ENSP00000451290	ENST00000555380
ENSG00000142208	ENSP00000451166	ENST00000554848
ENSG00000142208	ENSP00000385326	ENST00000402615
ENSG00000142208	ENSP00000451828	ENST00000554581
ENSG00000142208	ENSP00000450681	ENST00000554192
ENSG00000142208	ENSP00000451470	ENST00000555458
ENSG00000142208	ENSP00000270202	ENST00000349310
ENSG00000142208	ENSP00000384293	ENST00000407796
ENSG00000142208	ENSP00000450688	ENST00000555528
ENSG00000142208	ENSP00000451824	ENST00000555926

Organism

Homo sapiens

Functional Description

AKT1 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. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)- response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. 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). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr- 117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro- apoptotic activity. AKT1-specific substrates have been recently identified,including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation.

Protein Length

418

Protein Sequence
(FASTA)

MKTERPRPNT FIIRCLQWTT VIERTFHVET PEEREEWTTA IQTVADGLKK QEEEEMDFRS 60

GSPSDNSGAE EMEVSLAKPK HRVTMNEFEY LKLLGKGTFG KVILVKEKAT GRYYAMKILK 120

KEVIVAKDEV AHTLTENRVL QNSRHPFLTA LKYSFQTHDR LCFVMEYANG GELFFHLSRE 180

RVFSEDRARF YGAEIVSALD YLHSEKNVVY RDLKLENLML DKDGHIKITD FGLCKEGIKD 240

GATMKTFCGT PEYLAPEVLE DNDYGRAVDW WGLGVVMYEM MCGRLPFYNQ DHEKLFELIL 300

MEEIRFPRTL GPEAKSLLSG LLKKDPKQRL GGGSEDAKEI MQHRFFAGIV WQHVYEKKLS 360

PPFKPQVTSE TDTRYFDEEF TAQMITITPP DQDDSMECVD SERRPHFPQF SYSASGTA 418

Nucleotide Sequence
(FASTA)

ATGAAGACGG AGCGGCCCCG GCCCAACACC TTCATCATCC GCTGCCTGCA GTGGACCACT 60

GTCATCGAAC GCACCTTCCA TGTGGAGACT CCTGAGGAGC GGGAGGAGTG GACAACCGCC 120

ATCCAGACTG TGGCTGACGG CCTCAAGAAG CAGGAGGAGG AGGAGATGGA CTTCCGGTCG 180

GGCTCACCCA GTGACAACTC AGGGGCTGAA GAGATGGAGG TGTCCCTGGC CAAGCCCAAG 240

CACCGCGTGA CCATGAACGA GTTTGAGTAC CTGAAGCTGC TGGGCAAGGG CACTTTCGGC 300

AAGGTGATCC TGGTGAAGGA GAAGGCCACA GGCCGCTACT ACGCCATGAA GATCCTCAAG 360

AAGGAAGTCA TCGTGGCCAA GGACGAGGTG GCCCACACAC TCACCGAGAA CCGCGTCCTG 420

CAGAACTCCA GGCACCCCTT CCTCACAGCC CTGAAGTACT CTTTCCAGAC CCACGACCGC 480

CTCTGCTTTG TCATGGAGTA CGCCAACGGG GGCGAGCTGT TCTTCCACCT GTCCCGGGAG 540

CGTGTGTTCT CCGAGGACCG GGCCCGCTTC TATGGCGCTG AGATTGTGTC AGCCCTGGAC 600

TACCTGCACT CGGAGAAGAA CGTGGTGTAC CGGGACCTCA AGCTGGAGAA CCTCATGCTG 660

GACAAGGACG GGCACATTAA GATCACAGAC TTCGGGCTGT GCAAGGAGGG GATCAAGGAC 720

GGTGCCACCA TGAAGACCTT TTGCGGCACA CCTGAGTACC TGGCCCCCGA GGTGCTGGAG 780

GACAATGACT ACGGCCGTGC AGTGGACTGG TGGGGGCTGG GCGTGGTCAT GTACGAGATG 840

ATGTGCGGTC GCCTGCCCTT CTACAACCAG GACCATGAGA AGCTTTTTGA GCTCATCCTC 900

ATGGAGGAGA TCCGCTTCCC GCGCACGCTT GGTCCCGAGG CCAAGTCCTT GCTTTCAGGG 960

CTGCTCAAGA AGGACCCCAA GCAGAGGCTT GGCGGGGGCT CCGAGGACGC CAAGGAGATC 1020

ATGCAGCATC GCTTCTTTGC CGGTATCGTG TGGCAGCACG TGTACGAGAA GAAGCTCAGC 1080

CCACCCTTCA AGCCCCAGGT CACGTCGGAG ACTGACACCA GGTATTTTGA TGAGGAGTTC 1140

ACGGCCCAGA TGATCACCAT CACACCACCT GACCAAGATG ACAGCATGGA GTGTGTGGAC 1200

AGCGAGCGCA GGCCCCACTT CCCCCAGTTC TCCTACTCGG CCAGCGGCAC GGCCTGA 1257

Domain Profile

S: 1     fdllkllGkGtfGkvilvrekatqklyalkilkkevivakdevahtlterrvlkrtkhpf  60

         f++lkllGkGtfGkvilv+ekat+++ya+kilkkevivakdevahtlte+rvl++++hpf

Q: 88    FEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPF  147

         9***********************************************************

S: 61    lvalkysfqtkeklclvleyvnGGelffhlskervfsedrarfygaeivsaldylhs.kd  119

         l+alkysfqt+++lc+v+ey+nGGelffhls+ervfsedrarfygaeivsaldylhs k+

Q: 148   LTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSeKN  207

         ********************************************************9789

S: 120   vvyrdlklenllldkdGhikitdfGlckeeikdgdktktfcGtpeylapevlededygka  179

         vvyrdlklenl+ldkdGhikitdfGlcke+ikdg+++ktfcGtpeylapevled+dyg+a

Q: 208   VVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRA  267

         ************************************************************

S: 180   vdwwglGvvlyemlcGrlpfynkdheklfelilleelkfprklseeaksllsGllkkdpk  239

         vdwwglGvv+yem+cGrlpfyn+dheklfelil+ee++fpr+l++eaksllsGllkkdpk

Q: 268   VDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPK  327

         ************************************************************

S: 240   krlGggkddakeireheff  258

         +rlGgg++dakei++h+ff

Q: 328   QRLGGGSEDAKEIMQHRFF  346

         ******************9

Domain Sequence
(FASTA)

FEYLKLLGKG TFGKVILVKE KATGRYYAMK ILKKEVIVAK DEVAHTLTEN RVLQNSRHPF 60

LTALKYSFQT HDRLCFVMEY ANGGELFFHL SRERVFSEDR ARFYGAEIVS ALDYLHSEKN 120

VVYRDLKLEN LMLDKDGHIK ITDFGLCKEG IKDGATMKTF CGTPEYLAPE VLEDNDYGRA 180

VDWWGLGVVM YEMMCGRLPF YNQDHEKLFE LILMEEIRFP RTLGPEAKSL LSGLLKKDPK 240

QRLGGGSEDA KEIMQHRFF 259

Keyword

3D-structure; Acetylation; Apoptosis; ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Disease mutation; Disulfide bond; Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Sugar transport; Transferase; Translation regulation; Transport; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Anolis carolinensis"; ?>Bos taurus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Gallus gallus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pelodiscus sinensis"; ?>Procavia capensis"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0030027	; C:lamellipodium
GO:0015630	; C:microtubule cytoskeleton
GO:0005654	; C:nucleoplasm
GO:0005886	; C:plasma membrane
GO:0005819	; C:spindle
GO:0005524	; F:ATP binding
GO:0019899	; F:enzyme binding
GO:0030235	; F:nitric-oxide synthase regulator activity
GO:0005547	; F:phosphatidylinositol-3,4,5-trisphosphate binding
GO:0043325	; F:phosphatidylinositol-3,4-bisphosphate binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0006924	; P:activation-induced cell death of T cells
GO:0042640	; P:anagen
GO:0008637	; P:apoptotic mitochondrial changes
GO:0030030	; P:cell projection organization
GO:0008283	; P:cell proliferation
GO:0071364	; P:cellular response to epidermal growth factor stimulus
GO:0031018	; P:endocrine pancreas development
GO:0007173	; P:epidermal growth factor receptor signaling pathway
GO:0008543	; P:fibroblast growth factor receptor signaling pathway
GO:0007186	; P:G-protein coupled receptor signaling pathway
GO:0010467	; P:gene expression
GO:0007281	; P:germ cell development
GO:0042593	; P:glucose homeostasis
GO:0006006	; P:glucose metabolic process
GO:0015758	; P:glucose transport
GO:0005978	; P:glycogen biosynthetic process
GO:0060709	; P:glycogen cell differentiation involved in embryonic placenta development
GO:0006954	; P:inflammatory response
GO:0008286	; P:insulin receptor signaling pathway
GO:0048009	; P:insulin-like growth factor receptor signaling pathway
GO:0060716	; P:labyrinthine layer blood vessel development
GO:0060644	; P:mammary gland epithelial cell differentiation
GO:0001893	; P:maternal placenta development
GO:0016071	; P:mRNA metabolic process
GO:0043066	; P:negative regulation of apoptotic process
GO:0045792	; P:negative regulation of cell size
GO:0043154	; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0031999	; P:negative regulation of fatty acid beta-oxidation
GO:0046329	; P:negative regulation of JNK cascade
GO:0010748	; P:negative regulation of plasma membrane long-chain fatty acid transport
GO:0006469	; P:negative regulation of protein kinase activity
GO:0090201	; P:negative regulation of release of cytochrome c from mitochondria
GO:0048011	; P:nerve growth factor receptor signaling pathway
GO:0006809	; P:nitric oxide biosynthetic process
GO:0001649	; P:osteoblast differentiation
GO:0018105	; P:peptidyl-serine phosphorylation
GO:0032287	; P:peripheral nervous system myelin maintenance
GO:0048015	; P:phosphatidylinositol-mediated signaling
GO:0030168	; P:platelet activation
GO:0043536	; P:positive regulation of blood vessel endothelial cell migration
GO:0030307	; P:positive regulation of cell growth
GO:0031659	; P:positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0090004	; P:positive regulation of establishment of protein localization to plasma membrane
GO:0045600	; P:positive regulation of fat cell differentiation
GO:0046326	; P:positive regulation of glucose import
GO:0045725	; P:positive regulation of glycogen biosynthetic process
GO:0046889	; P:positive regulation of lipid biosynthetic process
GO:0045429	; P:positive regulation of nitric oxide biosynthetic process
GO:0051000	; P:positive regulation of nitric-oxide synthase activity
GO:0033138	; P:positive regulation of peptidyl-serine phosphorylation
GO:0032436	; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0051091	; P:positive regulation of sequence-specific DNA binding transcription factor activity
GO:0010765	; P:positive regulation of sodium ion transport
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter
GO:0046777	; P:protein autophosphorylation
GO:0030163	; P:protein catabolic process
GO:0000060	; P:protein import into nucleus, translocation
GO:0043491	; P:protein kinase B signaling cascade
GO:0016567	; P:protein ubiquitination
GO:2001047	; P:regulation of G1/S transition checkpoint
GO:0010975	; P:regulation of neuron projection development
GO:0006417	; P:regulation of translation
GO:0034405	; P:response to fluid shear stress
GO:0032094	; P:response to food
GO:0009408	; P:response to heat
GO:0070141	; P:response to UV-A
GO:0044281	; P:small molecule metabolic process
GO:0051146	; P:striated muscle cell differentiation
GO:0031295	; P:T cell costimulation
GO:0006412	; P:translation

KEGG

hsa:207

;

InterPros

IPR000961	; AGC-kinase_C.
IPR011009	; Kinase-like_dom.
IPR011993	; PH_like_dom.
IPR017892	; Pkinase_C.
IPR001849	; Pleckstrin_homology.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00169	; PH; 1.
PF00069	; Pkinase; 1.
PF00433	; Pkinase_C; 1.

SMARTs

SM00233	; PH; 1.
SM00133	; S_TK_X; 1.
SM00220	; S_TKc; 1.

Prosites

PS51285	; AGC_KINASE_CTER; 1.
PS50003	; PH_DOMAIN; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013