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AKT3 AKT serine/threonine kinase 3 [ Homo sapiens (human) ]

Gene ID: 10000, updated on 9-Feb-2020

Summary

Official Symbol
AKT3provided by HGNC
Official Full Name
AKT serine/threonine kinase 3provided by HGNC
Primary source
HGNC:HGNC:393
See related
Ensembl:ENSG00000117020 MIM:611223
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MPPH; PKBG; MPPH2; PRKBG; STK-2; PKB-GAMMA; RAC-gamma; RAC-PK-gamma
Summary
The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in brain (RPKM 16.6), ovary (RPKM 12.6) and 22 other tissues See more
Orthologs

Genomic context

See AKT3 in Genome Data Viewer
Location:
1q43-q44
Exon count:
24
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (243488233..243851079, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (243651535..244014381, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene SHH signaling and ciliogenesis regulator SDCCAG8 Neighboring gene FCF1 pseudogene 7 Neighboring gene microRNA 4677 Neighboring gene uncharacterized LOC105373255 Neighboring gene fatty acid binding protein 7 pseudogene 1 Neighboring gene VISTA enhancer hs545 Neighboring gene Sharpr-MPRA regulatory region 14056 Neighboring gene long intergenic non-protein coding RNA 2774 Neighboring gene uncharacterized LOC105373258

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2
MedGen: C4014738 OMIM: 615937 GeneReviews: MPPH Syndrome
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2016-04-14)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated (2016-04-14)

ClinGen Genome Curation Page

NHGRI GWAS Catalog

Description
A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.
NHGRI GWA Catalog
Biological insights from 108 schizophrenia-associated genetic loci.
NHGRI GWA Catalog
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
NHGRI GWA Catalog
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
NHGRI GWA Catalog
Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder.
NHGRI GWA Catalog
Genome-wide association study of age at menarche in African-American women.
NHGRI GWA Catalog
Genome-wide meta-analysis for severe diabetic retinopathy.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of IL-6 and IL-8 via the p38 signaling pathway and the PI3K/Akt signaling pathway in astrocytes PubMed
env HIV-1 gp120 activates AKT, ERK1/2, and p38 signaling in tonsil CD4+ T cells. Soluble CD4 inhibits AKT and ERK1/2 activation, but enhances phosphorylation of p38 PubMed
env Gp120-mediated activation of caspase-3 is significantly reduced in cells pretreated with PDGF-B. PDGF-mediated protection against gp120 involves the phosphoinositide (PI)3-kinase/Akt pathway PubMed
env Insulin-like growth factor-I (IGF-I) and erythropoietin treatment protect against HIV/gp120-mediated neuronal damage in culture and in vivo, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling PubMed
env HIV-1 gp120 induced cell death is inhibited by a CCR5-mediated neuroprotective pathway that involves protein kinase Akt/PKB as an essential component and can be triggered by the CCR5 agonists MIP-1beta and RANTES PubMed
env CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway PubMed
env Fractalkine (CX3CL1) protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120, and neuronal CX(3)CR1 receptors and Akt activation are responsible for the neuroprotective effects of fractalkine PubMed
env Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways PubMed
env HIV-1 gp120 downregulates expression of c-Myc, Max, and 14-3-3epsilon proteins, and decreases phosphorylation of ATP-dependent tyrosine kinases (Akt) at Ser-473 in human mesangial cells (HMC) PubMed
Nef nef HIV-1 Nef synergizes with KSHV oncoprotein K1 to activate PI3K/AKT/mTOR signaling pathway, and induces cell proliferation and microtubule formation in endothelial cells PubMed
nef Knockdown of AKT2 and AKT3 by siRNA shows significant reduction of CCL5 levels, suggesting that AKT2 and AKT3 proteins are involved in Nef-mediated upregulation of CCL5 PubMed
nef HIV-1 Nef induces phosphorylation of MEK1 at position serine 298, which depends on Pak and Rac activity PubMed
nef HIV-1 Nef synergizes with IL-6 to activate the AKT pathway promoting angiogenesis and tumorigenesis in a chicken chorioallantoic membrane model and nude mice PubMed
nef HIV-1 Nef synergizes with IL-6 to enhance vascular tube formation, cell proliferation, VEGF expression, and phosphorylated AKT activation in human umbilical vein endothelial cells PubMed
nef Incubation of human macrophages with exogenous HIV-1 Nef protein induces phosphorylation of Akt and GSK-3ss, and promotes IL-10 release PubMed
nef HIV-1 Nef decreases levels of AKT phosphorylation in insulin-stimulated adipocytes PubMed
Tat tat HIV-1 Tat-mediated upregulation of CCL5 involves JAK2/3, AKT2/3, p38delta, NF-kappaB (p65/p50), C/EBP alpha/gamma, and AP-1 proteins PubMed
tat Treatment with HIV-Tat and morphine activates extracellular signal-regulated kinase-1/2 (ERK1/2), upregulates p53 and p21 levels, and downregulates cyclin D1 and Akt levels in human fetal brain-derived neural precursor cells PubMed
tat HIV-1 Tat induces phosphorylation of PI3K, AKT, PTEN, and GSK-3beta activating PI3K and AKT and inactivating PTEN and GSK-3beta in vIL-6 expressing cells PubMed
tat PI3K/Akt, TRPC, and GSK3beta signaling pathways are all involved in PDGF-C mediated neuroprotection against HIV-1 Tat in human neuroblastoma cells PubMed
tat HIV-1 Tat activates AKT kinase through activation of PI3 kinase, resulting in the protection of cells from apoptosis PubMed
tat Lancemaside A1 inhibits the movement of Akt to the plasma membrane, a critical step for Akt activation, and Compound K inhibits Akt phosphorylation in Tat-expressing CHME5 cells PubMed
tat PDGF-BB-mediated protection against HIV-1 Tat and morphine-induced neuron apoptosis involves Akt activation PubMed
tat HIV-1 Tat inhibits autophagy in bystander macrophages/monocytic cells through Tat-mediated activation and phosphorylation of Src-Akt signaling PubMed
tat Phosphatidylinositol 3-kinase/Akt signaling pathway is involved in HIV-1 Tat-induced NADPH oxidase stimulation and LTR transactivation PubMed
tat A Coumarin derivative BPRHIV001 modulates Tat function through a reduction of the p300 protein level and a concordant reduction of phosphorylated Akt PubMed
tat Pro-survival effects of intracellular HIV-1 Tat in a microglial cell line is attributed to activation of the PI-3-kinase (PI3K)/Akt pathway via decreasing expression of PTEN, a negative regulator of the PI-3-K pathway PubMed
tat HIV-1 Tat downregulates CREB transcription factor expression in PC12 neuronal cells through activation of a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway PubMed
Vpr vpr HIV-1 Vpr-induced upregulation of CCL5 requires p50 and p65 subunits of NF-kappaB, p38delta MAPK, Akt-2 and Akt-3, and AP-1 transcription factor in HIV-1 Vpr transfected astrocytes PubMed
vpr HIV-1 Vpr inhibits Akt-induced cytoplasmic translocation of Foxo3a, a subtype of the forkhead transcription factors PubMed
matrix gag HIV-1 p17 and its C-terminal truncated form of p17 (p17delta36) differentially regulate Akt phosphorylation by reducing and increasing phosphorylation levels of PTEN, respectively PubMed
gag HIV-1 p17 induces capillary-like structures in human endothelial cells by binding to CXCR1 and CXCR2, which requires activation of the Akt-dependent ERK signaling pathway PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp434N0250

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity TAS
Traceable Author Statement
more info
PubMed 
protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IEA
Inferred from Electronic Annotation
more info
 
membrane IEA
Inferred from Electronic Annotation
more info
 
nucleus IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
RAC-gamma serine/threonine-protein kinase
Names
PKB gamma
RAC-gamma serine/threonine protein kinase
v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)
NP_001193658.1
NP_001357003.1
NP_005456.1
NP_859029.1
XP_011542316.1
XP_016855474.1
XP_024301768.1
XP_024302660.1
XP_024303706.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029764.2 RefSeqGene

    Range
    5837..356356
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1396

mRNA and Protein(s)

  1. NM_001206729.1NP_001193658.1  RAC-gamma serine/threonine-protein kinase isoform 2

    See identical proteins and their annotated locations for NP_001193658.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 3' UTR and 3' coding region, compared to variant 1. The resulting isoform (2) is shorter and has has a distinct C-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AC096539, AL117525
    Consensus CDS
    CCDS31076.1
    UniProtKB/Swiss-Prot
    Q9Y243
    Related
    ENSP00000355498.1, ENST00000366540.5
    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cd05571
    Location:152451
    STKc_PKB; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B
  2. NM_001370074.1NP_001357003.1  RAC-gamma serine/threonine-protein kinase isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC096539, AL591721, AL592151, AL662889
    Related
    ENSP00000263826.5, ENST00000263826.11
    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cd05593
    Location:132479
    STKc_PKB_gamma; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3)
  3. NM_005465.7NP_005456.1  RAC-gamma serine/threonine-protein kinase isoform 1

    See identical proteins and their annotated locations for NP_005456.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC096539, AF135794, AL592151, U79271
    Consensus CDS
    CCDS31077.1
    UniProtKB/Swiss-Prot
    Q9Y243
    Related
    ENSP00000500582.1, ENST00000673466.1
    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cd05593
    Location:132479
    STKc_PKB_gamma; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3)
  4. NM_181690.2NP_859029.1  RAC-gamma serine/threonine-protein kinase isoform 2

    See identical proteins and their annotated locations for NP_859029.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 3' UTR and 3' coding region, compared to variant 1. The resulting isoform (2) is shorter and has has a distinct C-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AL591721, AL592151, AY005799, BC121154
    Consensus CDS
    CCDS31076.1
    UniProtKB/Swiss-Prot
    Q9Y243
    Related
    ENSP00000336943.5, ENST00000336199.9
    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cd05571
    Location:152451
    STKc_PKB; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    243488233..243851079 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_016999985.1XP_016855474.1  RAC-gamma serine/threonine-protein kinase isoform X3

    Related
    ENSP00000500597.1, ENST00000672578.1
    Conserved Domains (2) summary
    cd05593
    Location:71418
    STKc_PKB_gamma; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3)
    cl17171
    Location:149
    PH-like; Pleckstrin homology-like domain
  2. XM_011544014.2XP_011542316.1  RAC-gamma serine/threonine-protein kinase isoform X5

    See identical proteins and their annotated locations for XP_011542316.1

    Conserved Domains (1) summary
    cl21453
    Location:40249
    PKc_like; Protein Kinases, catalytic domain
  3. XM_024446000.1XP_024301768.1  RAC-gamma serine/threonine-protein kinase isoform X2

    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cl21453
    Location:152435
    PKc_like; Protein Kinases, catalytic domain
  4. XM_024446892.1XP_024302660.1  RAC-gamma serine/threonine-protein kinase isoform X4

    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cl21453
    Location:132273
    PKc_like; Protein Kinases, catalytic domain
  5. XM_024447938.1XP_024303706.1  RAC-gamma serine/threonine-protein kinase isoform X6

    Conserved Domains (2) summary
    cd01241
    Location:4110
    PH_PKB; Protein Kinase B-like pleckstrin homology (PH) domain
    cl21453
    Location:132235
    PKc_like; Protein Kinases, catalytic domain

Reference GRCh38.p13 ALT_REF_LOCI_1

Genomic

  1. NT_187519.1 Reference GRCh38.p13 ALT_REF_LOCI_1

    Range
    500341..867542 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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