EKS-RAN-00136

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00136

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/Akt	503.9	1.2E-151	150	408	259

Status

Reviewed

Ensembl Protein

ENSRNOP00000038369

UniProt Accession

P47196;

Protein Name

RAC-alpha serine/threonine-protein kinase

Protein Synonyms/Alias

Protein kinase B; PKB; Protein kinase B alpha; PKB alpha; RAC-PK-alpha;

Gene Name

Akt1

Gene Synonyms/Alias

Akt1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSRNOG00000028629	ENSRNOP00000038369	ENSRNOT00000031164

Organism

Rattus norvegicus

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 (By similarity). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity (By similarity). 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

480

Protein Sequence
(FASTA)

MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVEQRES PLNNFSVAQC 60

QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KRQEEETMDF 120

RSGSPSDNSG AEEMEVALAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI 180

LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS 240

RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI 300

KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL 360

ILMEEIRFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK EIMQHRFFAN IVWQDVYEKK 420

LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA 480

Nucleotide Sequence
(FASTA)

ATGAACGACG TAGCCATTGT GAAGGAGGGC TGGCTGCACA AACGAGGGGA ATATATTAAA 60

ACCTGGCGGC CACGCTACTT CCTCCTCAAG AATGATGGCA CCTTTATTGG CTACAAGGAA 120

CGGCCTCAGG ATGTGGAGCA GCGCGAGTCC CCACTCAACA ACTTCTCAGT GGCACAATGT 180

CAGCTGATGA AGACAGAGCG GCCGAGGCCC AACACCTTCA TCATCCGCTG CCTGCAGTGG 240

ACCACGGTCA TTGAGCGCAC CTTCCATGTG GAAACGCCTG AGGAGCGGGA AGAGTGGACC 300

ACCGCCATTC AGACTGTGGC TGATGGACTC AAACGGCAGG AGGAGGAGAC GATGGACTTC 360

CGGTCAGGTT CACCCAGTGA CAACTCAGGT GCTGAGGAGA TGGAGGTGGC CCTGGCCAAG 420

CCCAAGCACC GTGTGACCAT GAACGAGTTT GAGTACCTGA AGCTACTGGG CAAGGGCACC 480

TTTGGGAAGG TGATCCTGGT GAAGGAGAAG GCCACAGGTC GCTACTATGC CATGAAGATC 540

CTCAAGAAGG AGGTCATCGT TGCCAAGGAT GAGGTTGCCC ACACGCTTAC TGAGAACCGT 600

GTCCTGCAGA ACTCTAGGCA TCCCTTCCTT ACAGCCCTCA AGTACTCATT CCAGACCCAC 660

GACCGCCTCT GCTTTGTCAT GGAGTACGCC AATGGGGGCG AGCTCTTCTT CCACCTGTCT 720

CGTGAGCGCG TGTTTTCAGA GGACCGGGCC CGCTTCTACG GTGCGGAGAT TGTGTCCGCC 780

CTGGACTACT TGCACTCCGA GAAGAACGTG GTGTACCGGG ACCTCAAGCT GGAGAACCTC 840

ATGCTGGACA AGGACGGGCA CATCAAGATA ACGGACTTCG GGCTGTGCAA GGAGGGTATC 900

AAGGACGGTG CCACCATGAA GACGTTCTGC GGGACACCCG AGTACCTGGC CCCTGAGGTG 960

CTGGAGGACA ACGACTATGG CCGTGCAGTG GACTGGTGGG GGCTGGGCGT GGTCATGTAC 1020

GAGATGATGT GCGGCCGCCT GCCCTTCTAC AACCAGGACC ATGAGAAGCT GTTCGAGCTC 1080

ATCCTAATGG AGGAGATCCG CTTCCCACGC ACACTCGGGC CGGAGGCCAA GTCCCTGCTC 1140

TCGGGGCTGC TCAAGAAGGA CCCTACACAG AGGCTCGGTG GGGGCTCCGA GGACGCCAAG 1200

GAGATCATGC AGCACCGCTT CTTTGCCAAC ATCGTGTGGC AAGATGTGTA TGAGAAGAAG 1260

CTGAGCCCAC CTTTCAAGCC CCAGGTCACC TCTGAGACCG ACACCAGGTA TTTTGATGAG 1320

GAGTTCACAG CTCAGATGAT CACCATCACG CCGCCTGATC AAGATGACAG CATGGAGTGT 1380

GTGGACAGTG AACGGAGGCC GCACTTTCCC CAGTTCTCCT ACTCAGCCAG TGGCACAGCC 1440

TGA 1443

Domain Profile

S: 1     fdllkllGkGtfGkvilvrekatqklyalkilkkevivakdevahtlterrvlkrtkhpf  60

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

Q: 150   FEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPF  209

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

S: 61    lvalkysfqtkeklclvleyvnGGelffhlskervfsedrarfygaeivsaldylhs.kd  119

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

Q: 210   LTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSeKN  269

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

S: 120   vvyrdlklenllldkdGhikitdfGlckeeikdgdktktfcGtpeylapevlededygka  179

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

Q: 270   VVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRA  329

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

S: 180   vdwwglGvvlyemlcGrlpfynkdheklfelilleelkfprklseeaksllsGllkkdpk  239

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

Q: 330   VDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPT  389

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

S: 240   krlGggkddakeireheff  258

         +rlGgg++dakei++h+ff

Q: 390   QRLGGGSEDAKEIMQHRFF  408

         ******************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 LSGLLKKDPT 240

QRLGGGSEDA KEIMQHRFF 259

Keyword

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

Sequence Source

Ensembl

Orthology

Ortholog group

Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Equus caballus"; ?>Gallus gallus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>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"; ?>Petromyzon marinus"; ?>Procavia capensis"; ?>Pteropus vampyrus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0030027	; C:lamellipodium
GO:0005654	; C:nucleoplasm
GO:0005886	; C:plasma membrane
GO:0005819	; C:spindle
GO:0005524	; F:ATP 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:0007568	; P:aging
GO:0042640	; P:anagen
GO:0008637	; P:apoptotic mitochondrial changes
GO:0030030	; P:cell projection organization
GO:0071364	; P:cellular response to epidermal growth factor stimulus
GO:0071456	; P:cellular response to hypoxia
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:0001893	; P:maternal placenta development
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:0001649	; P:osteoblast differentiation
GO:0018105	; P:peptidyl-serine phosphorylation
GO:0032287	; P:peripheral nervous system myelin maintenance
GO:0043065	; P:positive regulation of apoptotic process
GO:0043536	; P:positive regulation of blood vessel endothelial cell migration
GO:0030307	; P:positive regulation of cell growth
GO:0032270	; P:positive regulation of cellular protein metabolic process
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:0045907	; P:positive regulation of vasoconstriction
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:0030334	; P:regulation of cell migration
GO:0010975	; P:regulation of neuron projection development
GO:0032880	; P:regulation of protein localization
GO:0006417	; P:regulation of translation
GO:0034405	; P:response to fluid shear stress
GO:0032094	; P:response to food
GO:0070141	; P:response to UV-A
GO:0051146	; P:striated muscle cell differentiation
GO:0006412	; P:translation

KEGG

rno:24185

;

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