InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: AKT1

Summary

InnateDB Gene

IDBG-22709.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

AKT1

Gene Name

v-akt murine thymoma viral oncogene homolog 1

Synonyms

AKT; CWS6; PKB; PKB-ALPHA; PRKBA; RAC; RAC-ALPHA

Species

Homo sapiens

Ensembl Gene

ENSG00000142208

Encoded Proteins

IDBP-22711

v-akt murine thymoma viral oncogene homolog 1

IDBP-295278

v-akt murine thymoma viral oncogene homolog 1

IDBP-295275

v-akt murine thymoma viral oncogene homolog 1

IDBP-603563

v-akt murine thymoma viral oncogene homolog 1

IDBP-587349

v-akt murine thymoma viral oncogene homolog 1

IDBP-595186

v-akt murine thymoma viral oncogene homolog 1

IDBP-590714

v-akt murine thymoma viral oncogene homolog 1

IDBP-590335

v-akt murine thymoma viral oncogene homolog 1

IDBP-807562

v-akt murine thymoma viral oncogene homolog 1

IDBP-584486

v-akt murine thymoma viral oncogene homolog 1

IDBP-598470

v-akt murine thymoma viral oncogene homolog 1

IDBP-588995

v-akt murine thymoma viral oncogene homolog 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21196185

AKT1 is a Ser/Thr protein kinase that plays a pivotal role in functional activation in macrophages. AKT1 specifically functions in phagocytosis, intracellular bacterial infection, LPS tolerance, production of inflammatory cytokines/mediators, and migration during macrophage-mediate innate immunity.

PMID 21683629

AKT1 activation is blocked by Bacillus anthracis, resulting in the opening of a connexin ATP release channel and induction of macrophage death. Constitutive activation of AKT1 interferes with inflammasome activation and IL1B production, which compromises antimicrobial immunity. (Demonstrated in murine model)

PMID 22218715

AKT1 functions downstream of TLR2-stimulation to induce the expression of the monocyte chemoattractant protein 1, CCL2. (Demonstrated in mice)

PMID 23060458

AKT1 is important for establishing the inflammatory microenvironment in the airway upon exposure to rhinovirus.

InnateDB Annotation from Orthologs

Summary

PMID 21196185

[Mus musculus] Akt1 is a Ser/Thr protein kinase that plays a pivotal role in functional activation in macrophages. Akt1 specifically functions in phagocytosis, intracellular bacterial infection, LPS tolerance, production of inflammatory cytokines/mediators, and migration during macrophage-mediate innate immunity.

PMID 21683629

[Mus musculus] Akt1 activation is blocked by Bacillus anthracis, resulting in the opening of a connexin ATP release channel and induction of macrophage death. Constitutive activation of Akt1 interferes with inflammasome activation and Il1b production, which compromises antimicrobial immunity.

PMID 22218715

[Mus musculus] Akt1 functions downstream of Tlr2-stimulation to induce the expression of the monocyte chemoattractant protein 1, Ccl2.

PMID 25783839

[Mus musculus] Lysophosphatidic acid plays an anti-inflammatory role in macrophages by diminishing lipopolysaccharide-induced phosphorylation of Mapk14 and Akt1, as well as Rela nuclear translocation.

PMID 25665524

[Mus musculus] The Akt1/Mir199a/Cav1 pathway is a regulator of innate immunity that is dysfunctional in cystic fibrosis macrophages contributing to lung hyper-inflammation.

Entrez Gene

Summary

The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 14:104769349-104795751

Strand

Reverse strand

Band

q32.33

Transcripts

ENST00000349310	ENSP00000270202
ENST00000402615	ENSP00000385326
ENST00000407796	ENSP00000384293
ENST00000554581	ENSP00000451828
ENST00000553506
ENST00000557552
ENST00000555528	ENSP00000450688
ENST00000555458	ENSP00000451470
ENST00000554192	ENSP00000450681
ENST00000544168	ENSP00000443897
ENST00000554585	ENSP00000481526
ENST00000554848	ENSP00000451166
ENST00000554826
ENST00000556836
ENST00000555380	ENSP00000451290
ENST00000555926	ENSP00000451824
ENST00000557494
ENST00000553797
ENST00000610370

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 482 experimentally validated interaction(s) in this database.
They are also associated with 26 interaction(s) predicted by orthology.

Experimentally validated
Total	482 [view]
Protein-Protein	477 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	26 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005080	protein kinase C binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0005547	phosphatidylinositol-3,4,5-trisphosphate binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0030235	nitric-oxide synthase regulator activity
GO:0042802	identical protein binding
GO:0043325	phosphatidylinositol-3,4-bisphosphate binding
GO:0071889	14-3-3 protein binding

Biological Process

GO:0000060	protein import into nucleus, translocation
GO:0001649	osteoblast differentiation
GO:0001893	maternal placenta development
GO:0001934	positive regulation of protein phosphorylation
GO:0001938	positive regulation of endothelial cell proliferation
GO:0005977	glycogen metabolic process
GO:0005978	glycogen biosynthetic process
GO:0005979	regulation of glycogen biosynthetic process
GO:0006006	glucose metabolic process
GO:0006412	translation
GO:0006417	regulation of translation
GO:0006464	cellular protein modification process
GO:0006468	protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0006809	nitric oxide biosynthetic process
GO:0006915	apoptotic process
GO:0006924	activation-induced cell death of T cells
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007281	germ cell development
GO:0007568	aging
GO:0007596	blood coagulation
GO:0008283	cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0008637	apoptotic mitochondrial changes
GO:0009408	response to heat
GO:0009725	response to hormone
GO:0010467	gene expression
GO:0010507	negative regulation of autophagy
GO:0010748	negative regulation of plasma membrane long-chain fatty acid transport
GO:0010765	positive regulation of sodium ion transport
GO:0010907	positive regulation of glucose metabolic process
GO:0010951	negative regulation of endopeptidase activity
GO:0010975	regulation of neuron projection development
GO:0015758	glucose transport
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0016310	phosphorylation
GO:0016567	protein ubiquitination
GO:0018105	peptidyl-serine phosphorylation
GO:0030030	cell projection organization
GO:0030154	cell differentiation
GO:0030163	protein catabolic process
GO:0030168	platelet activation
GO:0030212	hyaluronan metabolic process
GO:0030307	positive regulation of cell growth
GO:0030334	regulation of cell migration
GO:0031018	endocrine pancreas development
GO:0031295	T cell costimulation
GO:0031659	positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0031999	negative regulation of fatty acid beta-oxidation
GO:0032094	response to food
GO:0032270	positive regulation of cellular protein metabolic process
GO:0032287	peripheral nervous system myelin maintenance
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032869	cellular response to insulin stimulus
GO:0032880	regulation of protein localization
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0034405	response to fluid shear stress
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042593	glucose homeostasis
GO:0042640	anagen
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043491	protein kinase B signaling
GO:0043536	positive regulation of blood vessel endothelial cell migration
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0045600	positive regulation of fat cell differentiation
GO:0045725	positive regulation of glycogen biosynthetic process
GO:0045792	negative regulation of cell size
GO:0045861	negative regulation of proteolysis
GO:0045907	positive regulation of vasoconstriction
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046209	nitric oxide metabolic process
GO:0046326	positive regulation of glucose import
GO:0046329	negative regulation of JNK cascade
GO:0046777	protein autophosphorylation
GO:0046889	positive regulation of lipid biosynthetic process
GO:0048009	insulin-like growth factor receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050999	regulation of nitric-oxide synthase activity
GO:0051000	positive regulation of nitric-oxide synthase activity
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051146	striated muscle cell differentiation
GO:0060644	mammary gland epithelial cell differentiation
GO:0060709	glycogen cell differentiation involved in embryonic placenta development
GO:0060716	labyrinthine layer blood vessel development
GO:0061024	membrane organization
GO:0070141	response to UV-A
GO:0071260	cellular response to mechanical stimulus
GO:0071363	cellular response to growth factor stimulus
GO:0071364	cellular response to epidermal growth factor stimulus
GO:0071407	cellular response to organic cyclic compound
GO:0071456	cellular response to hypoxia
GO:0090004	positive regulation of establishment of protein localization to plasma membrane
GO:0090201	negative regulation of release of cytochrome c from mitochondria
GO:0097011	cellular response to granulocyte macrophage colony-stimulating factor stimulus
GO:0097193	intrinsic apoptotic signaling pathway
GO:0097194	execution phase of apoptosis
GO:1900740	positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:1901653	cellular response to peptide
GO:1901976	regulation of cell cycle checkpoint
GO:1902176	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:2001240	negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005819	spindle
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0015630	microtubule cytoskeleton
GO:0036064	ciliary basal body

Orthologs

Species

Mus musculus

Bos taurus

Gene ID

Gene Order

ENSMUSG00000001729

View Gene Order

ENSBTAG00000017636

Not yet available

Pathways

NETPATH

NetPath_1

Alpha6Beta4Integrin pathway

NetPath_2

AndrogenReceptor pathway

Notch pathway

EGFR1 pathway

KitReceptor pathway

TGF_beta_Receptor pathway

Wnt pathway

TNFalpha pathway

Hedgehog pathway

TCR pathway

BCR pathway

IL1 pathway

IL2 pathway

IL3 pathway

IL4 pathway

IL5 pathway

IL6 pathway

IL-7 pathway

IL9 pathway

RANKL pathway

Leptin pathway

TSH pathway

TSLP pathway

FSH pathway

TWEAK pathway

Prolactin pathway

IL11 pathway

Oncostatin_M pathway

REACTOME

REACT_12442

AKT phosphorylates targets in the nucleus pathway

REACT_12447

Negative regulation of the PI3K/AKT network pathway

REACT_12564

AKT phosphorylates targets in the cytosol pathway

REACT_75829

PIP3 activates AKT signaling pathway

REACT_147814

DAP12 signaling pathway

REACT_147694

DAP12 interactions pathway

REACT_19405

CTLA4 inhibitory signaling pathway

REACT_19358

CD28 dependent PI3K/Akt signaling pathway

REACT_19183

CD28 co-stimulation pathway

REACT_19344

Costimulation by the CD28 family pathway

REACT_15523

Integrin alphaIIb beta3 signaling pathway

REACT_278

Platelet Aggregation (Plug Formation) pathway

REACT_1695

GPVI-mediated activation cascade pathway

REACT_12464

PI3K/AKT activation pathway

REACT_12578

GAB1 signalosome pathway

REACT_9417

Signaling by EGFR pathway

REACT_19290

G beta:gamma signalling through PI3Kgamma pathway

REACT_115961

PI3K events in ERBB4 signaling pathway

REACT_115596

Signaling by ERBB4 pathway

REACT_115662

Downregulation of ERBB2:ERBB3 signaling pathway

REACT_116008

PI3K events in ERBB2 signaling pathway

REACT_115755

Signaling by ERBB2 pathway

REACT_21270

PI-3K cascade pathway

REACT_9470

Signaling by FGFR pathway

REACT_111040

Signaling by SCF-KIT pathway

REACT_17025

Downstream signal transduction pathway

REACT_16888

Signaling by PDGF pathway

REACT_24915

Butyrate Response Factor 1 (BRF1) destabilizes mRNA pathway

REACT_25042

KSRP destabilizes mRNA pathway

REACT_549

Activation of BAD and translocation to mitochondria pathway

REACT_111176

Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation pathway

REACT_12477

eNOS activation pathway

REACT_147727

Constitutive PI3K/AKT Signaling in Cancer pathway

REACT_147867

Translocation of GLUT4 to the plasma membrane pathway

REACT_13655

AKT-mediated inactivation of FOXO1A pathway

REACT_13819

Regulation of gene expression in beta cells pathway

REACT_120736

Signaling by FGFR in disease pathway

REACT_111045

Developmental Biology pathway

REACT_11061

Signalling by NGF pathway

REACT_115871

Signaling by EGFR in Cancer pathway

REACT_21272

Downstream signaling of activated FGFR pathway

REACT_228096

misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling pathway

REACT_228331

Signaling by WNT in cancer pathway

REACT_12389

eNOS activation and regulation pathway

REACT_11045

Signaling by Wnt pathway

REACT_12529

Signaling by VEGF pathway

REACT_163769

Role of LAT2/NTAL/LAB on calcium mobilization pathway

REACT_14797

Signaling by GPCR pathway

REACT_6802

Innate Immune System pathway

REACT_13698

Regulation of beta-cell development pathway

REACT_12508

Metabolism of nitric oxide pathway

REACT_798

Platelet activation, signaling and aggregation pathway

REACT_228016

VEGFR2 mediated vascular permeability pathway

REACT_19388

G-protein beta:gamma signalling pathway

REACT_200731

deactivation of the beta-catenin transactivating complex pathway

REACT_163936

Fc epsilon receptor (FCERI) signaling pathway

REACT_578

Apoptosis pathway

REACT_111102

Signal Transduction pathway

REACT_19184

GPCR downstream signaling pathway

REACT_75774

Adaptive Immune System pathway

REACT_697

Activation of BH3-only proteins pathway

REACT_6900

Immune System pathway

REACT_200777

TCF dependent signaling in response to WNT pathway

REACT_228166

VEGFA-VEGFR2 Pathway pathway

REACT_12056

NGF signalling via TRKA from the plasma membrane pathway

REACT_24994

Regulation of mRNA stability by proteins that bind AU-rich elements pathway

REACT_228188

RNF mutants show enhanced WNT signaling and proliferation pathway

REACT_147723

PI3K/AKT Signaling in Cancer pathway

REACT_964

Intrinsic Pathway for Apoptosis pathway

REACT_111217

Metabolism pathway

REACT_228279

XAV939 inhibits tankyrase, stabilizing AXIN pathway

REACT_118773

Signaling by the B Cell Receptor (BCR) pathway

REACT_118638

Downstream signaling events of B Cell Receptor (BCR) pathway

REACT_71

Gene Expression pathway

REACT_116125

Disease pathway

REACT_604

Hemostasis pathway

REACT_11123

Membrane Trafficking pathway

KEGG

hsa04150

mTOR signaling pathway pathway

hsa05221

Acute myeloid leukemia pathway

hsa04370

VEGF signaling pathway pathway

hsa04664

Fc epsilon RI signaling pathway pathway

hsa05210

Colorectal cancer pathway

hsa05223

Non-small cell lung cancer pathway

hsa04012

ErbB signaling pathway pathway

hsa05211

Renal cell carcinoma pathway

hsa04210

Apoptosis pathway

hsa04010

MAPK signaling pathway pathway

hsa05218

Melanoma pathway

hsa05213

Endometrial cancer pathway

hsa04530

Tight junction pathway

hsa05214

Glioma pathway

hsa05222

Small cell lung cancer pathway

hsa04910

Insulin signaling pathway pathway

hsa04662

B cell receptor signaling pathway pathway

hsa05215

Prostate cancer pathway

hsa04510

Focal adhesion pathway

hsa04660

T cell receptor signaling pathway pathway

hsa04620

Toll-like receptor signaling pathway pathway

hsa04630

Jak-STAT signaling pathway pathway

hsa05220

Chronic myeloid leukemia pathway

hsa04920

Adipocytokine signaling pathway pathway

hsa05212

Pancreatic cancer pathway

hsa04666

Fc gamma R-mediated phagocytosis pathway

hsa04722

Neurotrophin signaling pathway pathway

hsa04062

Chemokine signaling pathway pathway

hsa05200

Pathways in cancer pathway

hsa04914

Progesterone-mediated oocyte maturation pathway

hsa05142

Chagas disease (American trypanosomiasis) pathway

hsa04380

Osteoclast differentiation pathway

hsa05145

Toxoplasmosis pathway

hsa04973

Carbohydrate digestion and absorption pathway

hsa05160

Hepatitis C pathway

INOH

INOH website

CD4 T cell receptor signaling pathway

INOH website

IL-7 signaling pathway

INOH website

JAK STAT pathway and regulation pathway

INOH website

EPO signaling pathway pathway

INOH website

Insulin receptor signaling pathway

INOH website

VEGF signaling pathway pathway

INOH website

IGF1 signaling pathway pathway

INOH website

PDGF signaling pathway pathway

PID NCI

pi3kplctrkpathway

Trk receptor signaling mediated by PI3K and PLC-gamma

nephrin_neph1_pathway

Nephrin/Neph1 signaling in the kidney podocyte

hnf3bpathway

FOXA2 and FOXA3 transcription factor networks

cd40_pathway

CD40/CD40L signaling

ar_nongenomic_pathway

Nongenotropic Androgen signaling

ceramide_pathway

Ceramide signaling pathway

cd8tcrpathway

TCR signaling in na�ve CD8+ T cells

txa2pathway

Thromboxane A2 receptor signaling

ecadherin_nascentaj_pathway

E-cadherin signaling in the nascent adherens junction

il8cxcr2_pathway

IL8- and CXCR2-mediated signaling events

caspase_pathway

Caspase Cascade in Apoptosis

lysophospholipid_pathway

LPA receptor mediated events

pi3kciaktpathway

Class I PI3K signaling events mediated by Akt

aurora_a_pathway

Aurora A signaling

cxcr4_pathway

CXCR4-mediated signaling events

reelinpathway

Reelin signaling pathway

il8cxcr1_pathway

IL8- and CXCR1-mediated signaling events

ar_pathway

Coregulation of Androgen receptor activity

tcr_pathway

TCR signaling in na�ve CD4+ T cells

avb3_integrin_pathway

Integrins in angiogenesis

lymphangiogenesis_pathway

VEGFR3 signaling in lymphatic endothelium

ptp1bpathway

Signaling events mediated by PTP1B

erbb1_downstream_pathway

ErbB1 downstream signaling

mtor_4pathway

mTOR signaling pathway

a6b1_a6b4_integrin_pathway

a6b1 and a6b4 Integrin signaling

igf1_pathway

IGF1 pathway

foxopathway

FoxO family signaling

p53regulationpathway

p53 pathway

ilk_pathway

Integrin-linked kinase signaling

reg_gr_pathway

Glucocorticoid receptor regulatory network

p75ntrpathway

p75(NTR)-mediated signaling

fgf_pathway

FGF signaling pathway

endothelinpathway

Endothelins

bcr_5pathway

BCR signaling pathway

angiopoietinreceptor_pathway

Angiopoietin receptor Tie2-mediated signaling

kitpathway

Signaling events mediated by Stem cell factor receptor (c-Kit)

retinoic_acid_pathway

Retinoic acid receptors-mediated signaling

il4_2pathway

IL4-mediated signaling events

erbb2erbb3pathway

ErbB2/ErbB3 signaling events

s1p_s1p3_pathway

S1P3 pathway

smad2_3nuclearpathway

Regulation of nuclear SMAD2/3 signaling

vegfr1_2_pathway

Signaling events mediated by VEGFR1 and VEGFR2

hif1_tfpathway

HIF-1-alpha transcription factor network

er_nongenomic_pathway

Plasma membrane estrogen receptor signaling

hedgehog_2pathway

Signaling events mediated by the Hedgehog family

hedgehog_glipathway

Hedgehog signaling events mediated by Gli proteins

cxcr3pathway

CXCR3-mediated signaling events

fcer1pathway

Fc-epsilon receptor I signaling in mast cells

vegfr1_pathway

VEGFR1 specific signals

il2_pi3kpathway

IL2 signaling events mediated by PI3K

il6_7pathway

IL6-mediated signaling events

insulin_pathway

Insulin Pathway

insulin_glucose_pathway

Insulin-mediated glucose transport

telomerasepathway

Regulation of Telomerase

ifngpathway

IFN-gamma pathway

faspathway

FAS (CD95) signaling pathway

Cross-References

SwissProt

TrEMBL

UniProt Splice Variant

Entrez Gene

UniGene

Hs.525622 Hs.690497 Hs.732482

RefSeq

NM_001014431 NM_001014432 NM_005163 XM_005267401

HUGO

OMIM

CCDS

CCDS9994

HPRD

01261

IMGT

EMBL

GenPept

RNA Seq Atlas