UniProtKB - P31751 (AKT2_HUMAN)
RAC-beta serine/threonine-protein kinase
AKT2
Functioni
AKT2 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 PI3P-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 (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). 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.
One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'.
Miscellaneous
Caution
Catalytic activityi
Activity regulationi
Kineticsi
- KM=358.4 µM for ATP (for purified and in vitro activated AKT2)1 Publication
- KM=3.4 µM for peptide substrate (for purified and in vitro activated AKT2)1 Publication
- KM=564 µM for ATP (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)1 Publication
- KM=2.3 µM for peptide substrate (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 181 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 200 | 4-[2-(4-amino-2,5-dihydro-1,2,5-oxadiazol-3-yl)-6-{[(1S)-3-amino-1-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol; inhibitorCombined sources1 Publication | 1 | |
Binding sitei | 232 | 4-[2-(4-amino-2,5-dihydro-1,2,5-oxadiazol-3-yl)-6-{[(1S)-3-amino-1-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol; inhibitor; via amide nitrogenCombined sources1 Publication | 1 | |
Active sitei | 275 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Metal bindingi | 280 | Manganese1 Publication | 1 | |
Binding sitei | 282 | 4-[2-(4-amino-2,5-dihydro-1,2,5-oxadiazol-3-yl)-6-{[(1S)-3-amino-1-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol; inhibitorCombined sources1 Publication | 1 | |
Metal bindingi | 293 | Manganese1 Publication | 1 | |
Binding sitei | 293 | 4-[2-(4-amino-2,5-dihydro-1,2,5-oxadiazol-3-yl)-6-{[(1S)-3-amino-1-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol; inhibitorCombined sources1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 158 – 166 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- activation of GTPase activity Source: Ensembl
- carbohydrate transport Source: UniProtKB-KW
- cellular protein modification process Source: ProtInc
- cellular response to high light intensity Source: Ensembl
- cellular response to insulin stimulus Source: BHF-UCL
- fat cell differentiation Source: UniProtKB
- glucose metabolic process Source: UniProtKB-KW
- glycogen biosynthetic process Source: UniProtKB-KW
- insulin receptor signaling pathway Source: BHF-UCL
- intracellular protein transmembrane transport Source: UniProtKB
- intracellular signal transduction Source: GO_Central
- mammary gland epithelial cell differentiation Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of long-chain fatty acid import across plasma membrane Source: BHF-UCL
- peptidyl-serine phosphorylation Source: GO_Central
- peripheral nervous system myelin maintenance Source: Ensembl
- positive regulation of cell migration Source: BHF-UCL
- positive regulation of cell motility Source: BHF-UCL
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of fatty acid beta-oxidation Source: BHF-UCL
- positive regulation of glucose import Source: BHF-UCL
- positive regulation of glucose metabolic process Source: BHF-UCL
- positive regulation of glycogen biosynthetic process Source: BHF-UCL
- positive regulation of mitochondrial membrane potential Source: UniProtKB
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of protein targeting to membrane Source: UniProtKB
- positive regulation of vesicle fusion Source: UniProtKB
- protein localization to plasma membrane Source: Ensembl
- regulation of cell cycle Source: UniProtKB
- regulation of cell migration Source: UniProtKB
- regulation of translation Source: UniProtKB-KW
- retinal rod cell apoptotic process Source: Ensembl
- signal transduction Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Apoptosis, Carbohydrate metabolism, Glucose metabolism, Glycogen biosynthesis, Glycogen metabolism, Sugar transport, Translation regulation, Transport |
Ligand | ATP-binding, Manganese, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 2681 |
PathwayCommonsi | P31751 |
Reactomei | R-HSA-111447, Activation of BAD and translocation to mitochondria R-HSA-1257604, PIP3 activates AKT signaling R-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling R-HSA-1445148, Translocation of SLC2A4 (GLUT4) to the plasma membrane R-HSA-165158, Activation of AKT2 R-HSA-165160, PDE3B signalling R-HSA-165181, Inhibition of TSC complex formation by PKB R-HSA-198323, AKT phosphorylates targets in the cytosol R-HSA-198693, AKT phosphorylates targets in the nucleus R-HSA-199418, Negative regulation of the PI3K/AKT network R-HSA-211163, AKT-mediated inactivation of FOXO1A R-HSA-3769402, Deactivation of the beta-catenin transactivating complex R-HSA-389357, CD28 dependent PI3K/Akt signaling R-HSA-389513, CTLA4 inhibitory signaling R-HSA-392451, G beta:gamma signalling through PI3Kgamma R-HSA-5218920, VEGFR2 mediated vascular permeability R-HSA-5628897, TP53 Regulates Metabolic Genes R-HSA-5674400, Constitutive Signaling by AKT1 E17K in Cancer R-HSA-6804757, Regulation of TP53 Degradation R-HSA-6804758, Regulation of TP53 Activity through Acetylation R-HSA-6804759, Regulation of TP53 Activity through Association with Co-factors R-HSA-69202, Cyclin E associated events during G1/S transition R-HSA-69656, Cyclin A:Cdk2-associated events at S phase entry R-HSA-8876198, RAB GEFs exchange GTP for GDP on RABs R-HSA-8941332, RUNX2 regulates genes involved in cell migration R-HSA-8948751, Regulation of PTEN stability and activity R-HSA-9607240, FLT3 Signaling R-HSA-9614399, Regulation of localization of FOXO transcription factors R-HSA-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SABIO-RKi | P31751 |
SignaLinki | P31751 |
SIGNORi | P31751 |
Names & Taxonomyi
Protein namesi | Recommended name: RAC-beta serine/threonine-protein kinase (EC:2.7.11.1)Alternative name(s): Protein kinase Akt-2 Protein kinase B beta Short name: PKB beta RAC-PK-beta |
Gene namesi | Name:AKT2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:392, AKT2 |
MIMi | 164731, gene |
neXtProti | NX_P31751 |
VEuPathDBi | HostDB:ENSG00000105221 |
Subcellular locationi
Plasma membrane
Cytoplasm and Cytosol
Endosome
- Early endosome By similarity
Nucleus
Note: Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5)P3 or PI(3,4)P2, cell membrane targeting is also facilitared by interaction with CLIP3. Colocalizes with WDFY2 in early endosomes (By similarity).By similarity
Cytosol
- cytosol Source: HPA
Endosome
- early endosome Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
- ruffle membrane Source: UniProtKB
Other locations
- cell cortex Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Endosome, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Diabetes mellitus, non-insulin-dependent (NIDDM)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067310 | 274 | R → H in NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject. 1 PublicationCorresponds to variant dbSNP:rs121434593EnsemblClinVar. | 1 |
Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067309 | 17 | E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. 1 PublicationCorresponds to variant dbSNP:rs387906659EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 309 | T → A: Impairs interaction with TTC3; when associated with A-474. 2 Publications | 1 | |
Mutagenesisi | 309 | T → E: Constitutively active; when associated with D-474. 2 Publications | 1 | |
Mutagenesisi | 474 | S → A: Impairs interaction with TTC3; when associated with A-309. 2 Publications | 1 | |
Mutagenesisi | 474 | S → D: Constitutively active; when associated with E-309. 2 Publications | 1 |
Keywords - Diseasei
Diabetes mellitus, Disease variant, Proto-oncogeneOrganism-specific databases
DisGeNETi | 208 |
MalaCardsi | AKT2 |
MIMi | 125853, phenotype 240900, phenotype |
OpenTargetsi | ENSG00000105221 |
Orphaneti | 79085, AKT2-related familial partial lipodystrophy 293964, Hypoinsulinemic hypoglycemia and body hemihypertrophy |
PharmGKBi | PA24685 |
Miscellaneous databases
Pharosi | P31751, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2431 |
DrugBanki | DB08073, (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE DB07859, 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE DB07947, ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE DB07812, N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide |
DrugCentrali | P31751 |
GuidetoPHARMACOLOGYi | 1480 |
Genetic variation databases
BioMutai | AKT2 |
DMDMi | 1170703 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085608 | 1 – 481 | RAC-beta serine/threonine-protein kinaseAdd BLAST | 481 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 34 | PhosphoserineCombined sources | 1 | |
Disulfide bondi | 60 ↔ 77 | By similarity | ||
Modified residuei | 126 | PhosphoserineCombined sources | 1 | |
Glycosylationi | 128 | O-linked (GlcNAc) serineBy similarity | 1 | |
Glycosylationi | 131 | O-linked (GlcNAc) serineBy similarity | 1 | |
Disulfide bondi | 297 ↔ 311 | 1 Publication | ||
Glycosylationi | 306 | O-linked (GlcNAc) threonineBy similarity | 1 | |
Modified residuei | 309 | Phosphothreonine; by PDPK14 Publications | 1 | |
Glycosylationi | 313 | O-linked (GlcNAc) threonineBy similarity | 1 | |
Modified residuei | 447 | PhosphoserineCombined sources | 1 | |
Modified residuei | 451 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 474 | PhosphoserineCombined sources2 Publications | 1 | |
Modified residuei | 478 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-788 CPTAC-789 |
EPDi | P31751 |
jPOSTi | P31751 |
MassIVEi | P31751 |
MaxQBi | P31751 |
PaxDbi | P31751 |
PeptideAtlasi | P31751 |
PRIDEi | P31751 |
ProteomicsDBi | 54801 [P31751-1] 58804 |
PTM databases
GlyGeni | P31751, 5 sites, 1 O-linked glycan (1 site) |
iPTMneti | P31751 |
PhosphoSitePlusi | P31751 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000105221, Expressed in right hemisphere of cerebellum and 222 other tissues |
ExpressionAtlasi | P31751, baseline and differential |
Genevisiblei | P31751, HS |
Organism-specific databases
HPAi | ENSG00000105221, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with BTBD10 (By similarity).
Interacts with KCTD20 (By similarity).
Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B.
Interacts with CLK2, PBH2 and TRAF6.
Interacts (when phosphorylated) with CLIP3, the interaction promotes cell membrane localization (PubMed:19139280).
Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).
By similarity7 PublicationsBinary interactionsi
P31751
Isoform 1 [P31751-1]
With | #Exp. | IntAct |
---|---|---|
PDK1 - isoform 1 [Q15118-1] | 2 | EBI-12562336,EBI-12562315 |
Protein-protein interaction databases
BioGRIDi | 106711, 96 interactors |
CORUMi | P31751 |
DIPi | DIP-32583N |
ELMi | P31751 |
IntActi | P31751, 45 interactors |
MINTi | P31751 |
STRINGi | 9606.ENSP00000375892 |
Chemistry databases
BindingDBi | P31751 |
Miscellaneous databases
RNActi | P31751, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | P31751 |
SMRi | P31751 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P31751 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 5 – 108 | PHPROSITE-ProRule annotationAdd BLAST | 104 | |
Domaini | 152 – 409 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 | |
Domaini | 410 – 481 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 72 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0690, Eukaryota |
GeneTreei | ENSGT00940000157189 |
InParanoidi | P31751 |
OrthoDBi | 442523at2759 |
PhylomeDBi | P31751 |
TreeFami | TF102004 |
Family and domain databases
CDDi | cd01241, PH_PKB, 1 hit cd05595, STKc_PKB_beta, 1 hit |
DisProti | DP00304 |
Gene3Di | 2.30.29.30, 1 hit |
IDEALi | IID00037 |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR034677, Akt2 IPR011009, Kinase-like_dom_sf IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR039026, PH_PKB IPR017892, Pkinase_C IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF00069, Pkinase, 1 hit PF00433, Pkinase_C, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in 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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 23 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNEVSVIKEG WLHKRGEYIK TWRPRYFLLK SDGSFIGYKE RPEAPDQTLP
60 70 80 90 100
PLNNFSVAEC QLMKTERPRP NTFVIRCLQW TTVIERTFHV DSPDEREEWM
110 120 130 140 150
RAIQMVANSL KQRAPGEDPM DYKCGSPSDS STTEEMEVAV SKARAKVTMN
160 170 180 190 200
DFDYLKLLGK GTFGKVILVR EKATGRYYAM KILRKEVIIA KDEVAHTVTE
210 220 230 240 250
SRVLQNTRHP FLTALKYAFQ THDRLCFVME YANGGELFFH LSRERVFTEE
260 270 280 290 300
RARFYGAEIV SALEYLHSRD VVYRDIKLEN LMLDKDGHIK ITDFGLCKEG
310 320 330 340 350
ISDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF
360 370 380 390 400
YNQDHERLFE LILMEEIRFP RTLSPEAKSL LAGLLKKDPK QRLGGGPSDA
410 420 430 440 450
KEVMEHRFFL SINWQDVVQK KLLPPFKPQV TSEVDTRYFD DEFTAQSITI
460 470 480
TPPDRYDSLG LLELDQRTHF PQFSYSASIR E
Computationally mapped potential isoform sequencesi
There are 23 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R0P9 | M0R0P9_HUMAN | Non-specific serine/threonine prote... | AKT2 | 450 | Annotation score: | ||
C9JHS6 | C9JHS6_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 184 | Annotation score: | ||
J3QLS6 | J3QLS6_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 157 | Annotation score: | ||
M0QZK3 | M0QZK3_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 151 | Annotation score: | ||
J3QKW1 | J3QKW1_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 396 | Annotation score: | ||
M0R275 | M0R275_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 129 | Annotation score: | ||
A8MX96 | A8MX96_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 133 | Annotation score: | ||
E7EVP8 | E7EVP8_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 134 | Annotation score: | ||
J3KRI8 | J3KRI8_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 130 | Annotation score: | ||
M0R283 | M0R283_HUMAN | RAC-beta serine/threonine-protein k... | AKT2 | 117 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 478 – 481 | SIRE → FREEKDLLMSLFVSLILFSD FSSLKSHSFSSNFILLSFSS LKK in AAA36585 (PubMed:1801921).Curated | 4 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067309 | 17 | E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. 1 PublicationCorresponds to variant dbSNP:rs387906659EnsemblClinVar. | 1 | |
Natural variantiVAR_040356 | 188 | I → V1 PublicationCorresponds to variant dbSNP:rs55859611Ensembl. | 1 | |
Natural variantiVAR_040357 | 208 | R → K1 PublicationCorresponds to variant dbSNP:rs35817154Ensembl. | 1 | |
Natural variantiVAR_067310 | 274 | R → H in NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject. 1 PublicationCorresponds to variant dbSNP:rs121434593EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056930 | 278 – 320 | Missing in isoform 2. 1 PublicationAdd BLAST | 43 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M77198 mRNA Translation: AAA36585.1 M95936 mRNA Translation: AAA58364.1 AK314619 mRNA Translation: BAG37185.1 AC118344 Genomic DNA No translation available. BC032709 mRNA Translation: AAH32709.1 BC120995 mRNA Translation: AAI20996.1 BC120994 mRNA Translation: AAI20995.1 AY708392 Genomic DNA Translation: AAT97984.1 |
CCDSi | CCDS12552.1 [P31751-1] CCDS82350.1 [P31751-2] |
PIRi | A46288 |
RefSeqi | NP_001317440.1, NM_001330511.1 [P31751-2] NP_001617.1, NM_001626.5 [P31751-1] XP_011524916.1, XM_011526614.1 [P31751-1] XP_011524917.1, XM_011526615.1 [P31751-1] XP_011524918.1, XM_011526616.1 [P31751-1] XP_011524920.1, XM_011526618.1 [P31751-1] XP_011524921.1, XM_011526619.1 [P31751-1] XP_011524922.1, XM_011526620.1 [P31751-1] XP_016881959.1, XM_017026470.1 [P31751-1] |
Genome annotation databases
Ensembli | ENST00000311278; ENSP00000309428; ENSG00000105221 [P31751-2] ENST00000392038; ENSP00000375892; ENSG00000105221 ENST00000424901; ENSP00000399532; ENSG00000105221 [P31751-2] |
GeneIDi | 208 |
KEGGi | hsa:208 |
MANE-Selecti | ENST00000392038.7; ENSP00000375892.2; NM_001626.6; NP_001617.1 |
UCSCi | uc002onf.3, human [P31751-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M77198 mRNA Translation: AAA36585.1 M95936 mRNA Translation: AAA58364.1 AK314619 mRNA Translation: BAG37185.1 AC118344 Genomic DNA No translation available. BC032709 mRNA Translation: AAH32709.1 BC120995 mRNA Translation: AAI20996.1 BC120994 mRNA Translation: AAI20995.1 AY708392 Genomic DNA Translation: AAT97984.1 |
CCDSi | CCDS12552.1 [P31751-1] CCDS82350.1 [P31751-2] |
PIRi | A46288 |
RefSeqi | NP_001317440.1, NM_001330511.1 [P31751-2] NP_001617.1, NM_001626.5 [P31751-1] XP_011524916.1, XM_011526614.1 [P31751-1] XP_011524917.1, XM_011526615.1 [P31751-1] XP_011524918.1, XM_011526616.1 [P31751-1] XP_011524920.1, XM_011526618.1 [P31751-1] XP_011524921.1, XM_011526619.1 [P31751-1] XP_011524922.1, XM_011526620.1 [P31751-1] XP_016881959.1, XM_017026470.1 [P31751-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1GZK | X-ray | 2.30 | A | 146-460 | [»] | |
1GZN | X-ray | 2.50 | A | 146-480 | [»] | |
1GZO | X-ray | 2.75 | A | 146-460 | [»] | |
1MRV | X-ray | 2.80 | A | 143-481 | [»] | |
1MRY | X-ray | 2.80 | A | 143-481 | [»] | |
1O6K | X-ray | 1.70 | A | 146-481 | [»] | |
1O6L | X-ray | 1.60 | A | 146-467 | [»] | |
1P6S | NMR | - | A | 1-111 | [»] | |
2JDO | X-ray | 1.80 | A | 146-467 | [»] | |
2JDR | X-ray | 2.30 | A | 146-467 | [»] | |
2UW9 | X-ray | 2.10 | A | 146-467 | [»] | |
2X39 | X-ray | 1.93 | A | 146-467 | [»] | |
2XH5 | X-ray | 2.72 | A | 146-479 | [»] | |
3D0E | X-ray | 2.00 | A/B | 146-480 | [»] | |
3E87 | X-ray | 2.30 | A/B | 146-480 | [»] | |
3E88 | X-ray | 2.50 | A/B | 146-480 | [»] | |
3E8D | X-ray | 2.70 | A/B | 146-480 | [»] | |
BMRBi | P31751 | |||||
SMRi | P31751 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106711, 96 interactors |
CORUMi | P31751 |
DIPi | DIP-32583N |
ELMi | P31751 |
IntActi | P31751, 45 interactors |
MINTi | P31751 |
STRINGi | 9606.ENSP00000375892 |
Chemistry databases
BindingDBi | P31751 |
ChEMBLi | CHEMBL2431 |
DrugBanki | DB08073, (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE DB07859, 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE DB07947, ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE DB07812, N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide |
DrugCentrali | P31751 |
GuidetoPHARMACOLOGYi | 1480 |
PTM databases
GlyGeni | P31751, 5 sites, 1 O-linked glycan (1 site) |
iPTMneti | P31751 |
PhosphoSitePlusi | P31751 |
Genetic variation databases
BioMutai | AKT2 |
DMDMi | 1170703 |
Proteomic databases
CPTACi | CPTAC-788 CPTAC-789 |
EPDi | P31751 |
jPOSTi | P31751 |
MassIVEi | P31751 |
MaxQBi | P31751 |
PaxDbi | P31751 |
PeptideAtlasi | P31751 |
PRIDEi | P31751 |
ProteomicsDBi | 54801 [P31751-1] 58804 |
Protocols and materials databases
Antibodypediai | 3775, 1619 antibodies from 50 providers |
CPTCi | P31751, 6 antibodies |
DNASUi | 208 |
Genome annotation databases
Ensembli | ENST00000311278; ENSP00000309428; ENSG00000105221 [P31751-2] ENST00000392038; ENSP00000375892; ENSG00000105221 ENST00000424901; ENSP00000399532; ENSG00000105221 [P31751-2] |
GeneIDi | 208 |
KEGGi | hsa:208 |
MANE-Selecti | ENST00000392038.7; ENSP00000375892.2; NM_001626.6; NP_001617.1 |
UCSCi | uc002onf.3, human [P31751-1] |
Organism-specific databases
CTDi | 208 |
DisGeNETi | 208 |
GeneCardsi | AKT2 |
HGNCi | HGNC:392, AKT2 |
HPAi | ENSG00000105221, Low tissue specificity |
MalaCardsi | AKT2 |
MIMi | 125853, phenotype 164731, gene 240900, phenotype |
neXtProti | NX_P31751 |
OpenTargetsi | ENSG00000105221 |
Orphaneti | 79085, AKT2-related familial partial lipodystrophy 293964, Hypoinsulinemic hypoglycemia and body hemihypertrophy |
PharmGKBi | PA24685 |
VEuPathDBi | HostDB:ENSG00000105221 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0690, Eukaryota |
GeneTreei | ENSGT00940000157189 |
InParanoidi | P31751 |
OrthoDBi | 442523at2759 |
PhylomeDBi | P31751 |
TreeFami | TF102004 |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 2681 |
PathwayCommonsi | P31751 |
Reactomei | R-HSA-111447, Activation of BAD and translocation to mitochondria R-HSA-1257604, PIP3 activates AKT signaling R-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling R-HSA-1445148, Translocation of SLC2A4 (GLUT4) to the plasma membrane R-HSA-165158, Activation of AKT2 R-HSA-165160, PDE3B signalling R-HSA-165181, Inhibition of TSC complex formation by PKB R-HSA-198323, AKT phosphorylates targets in the cytosol R-HSA-198693, AKT phosphorylates targets in the nucleus R-HSA-199418, Negative regulation of the PI3K/AKT network R-HSA-211163, AKT-mediated inactivation of FOXO1A R-HSA-3769402, Deactivation of the beta-catenin transactivating complex R-HSA-389357, CD28 dependent PI3K/Akt signaling R-HSA-389513, CTLA4 inhibitory signaling R-HSA-392451, G beta:gamma signalling through PI3Kgamma R-HSA-5218920, VEGFR2 mediated vascular permeability R-HSA-5628897, TP53 Regulates Metabolic Genes R-HSA-5674400, Constitutive Signaling by AKT1 E17K in Cancer R-HSA-6804757, Regulation of TP53 Degradation R-HSA-6804758, Regulation of TP53 Activity through Acetylation R-HSA-6804759, Regulation of TP53 Activity through Association with Co-factors R-HSA-69202, Cyclin E associated events during G1/S transition R-HSA-69656, Cyclin A:Cdk2-associated events at S phase entry R-HSA-8876198, RAB GEFs exchange GTP for GDP on RABs R-HSA-8941332, RUNX2 regulates genes involved in cell migration R-HSA-8948751, Regulation of PTEN stability and activity R-HSA-9607240, FLT3 Signaling R-HSA-9614399, Regulation of localization of FOXO transcription factors R-HSA-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SABIO-RKi | P31751 |
SignaLinki | P31751 |
SIGNORi | P31751 |
Miscellaneous databases
BioGRID-ORCSi | 208, 30 hits in 1080 CRISPR screens |
ChiTaRSi | AKT2, human |
EvolutionaryTracei | P31751 |
GeneWikii | AKT2 |
GenomeRNAii | 208 |
Pharosi | P31751, Tchem |
PROi | PR:P31751 |
RNActi | P31751, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000105221, Expressed in right hemisphere of cerebellum and 222 other tissues |
ExpressionAtlasi | P31751, baseline and differential |
Genevisiblei | P31751, HS |
Family and domain databases
CDDi | cd01241, PH_PKB, 1 hit cd05595, STKc_PKB_beta, 1 hit |
DisProti | DP00304 |
Gene3Di | 2.30.29.30, 1 hit |
IDEALi | IID00037 |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR034677, Akt2 IPR011009, Kinase-like_dom_sf IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR039026, PH_PKB IPR017892, Pkinase_C IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF00069, Pkinase, 1 hit PF00433, Pkinase_C, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | AKT2_HUMAN | |
Accessioni | P31751Primary (citable) accession number: P31751 Secondary accession number(s): B2RBD8 Q68GC0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1993 |
Last sequence update: | November 1, 1995 | |
Last modified: | February 23, 2022 | |
This is version 226 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- UniProtKB entry view manual
User manual for the UniProtKB entry view - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families