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Protein

RAC-gamma serine/threonine-protein kinase

Gene

AKT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

AKT3 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. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation (By similarity). IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.By similarity

Kineticsi

  1. KM=87.9 µM for ATP (for purified and in vitro activated AKT3)1 Publication
  2. KM=12.4 µM for peptide substrate (for purified and in vitro activated AKT3)1 Publication
  3. KM=118.7 µM for ATP (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)1 Publication
  4. KM=2.3 µM for peptide substrate (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei177 – 1771ATPPROSITE-ProRule annotation
Active sitei271 – 2711Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi154 – 1629ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. protein kinase activity Source: ProtInc
  3. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. mitochondrial genome maintenance Source: UniProtKB
  2. protein phosphorylation Source: ProtInc
  3. signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_115662. Downregulation of ERBB2:ERBB3 signaling.
REACT_12442. AKT phosphorylates targets in the nucleus.
REACT_12447. Negative regulation of the PI3K/AKT network.
REACT_12564. AKT phosphorylates targets in the cytosol.
REACT_13655. AKT-mediated inactivation of FOXO1A.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_19358. CD28 dependent PI3K/Akt signaling.
REACT_19405. CTLA4 inhibitory signaling.
REACT_263991. VEGFR2 mediated vascular permeability.
REACT_549. Activation of BAD and translocation to mitochondria.
REACT_75829. PIP3 activates AKT signaling.
SignaLinkiQ9Y243.

Names & Taxonomyi

Protein namesi
Recommended name:
RAC-gamma serine/threonine-protein kinase (EC:2.7.11.1)
Alternative name(s):
Protein kinase Akt-3
Protein kinase B gamma
Short name:
PKB gamma
RAC-PK-gamma
STK-2
Gene namesi
Name:AKT3
Synonyms:PKBG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componentsi: Chromosome 1, Unplaced

Organism-specific databases

HGNCiHGNC:393. AKT3.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Membrane-associated after cell stimulation leading to its translocation.

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. Golgi apparatus Source: HPA
  3. nucleoplasm Source: HPA
  4. plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (MPPH2)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.

See also OMIM:615937
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti17 – 171E → K in MPPH2 and melanoma; results in activation of AKT. 3 Publications
VAR_065830
Natural varianti229 – 2291N → S in MPPH2. 1 Publication
VAR_069260
Natural varianti465 – 4651R → W in MPPH2; disease phenotype overlaps with megalencephaly-capillary malformation syndrome. 1 Publication
VAR_069261

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi305 – 3051T → A: No activation after pervanadate treatment. 1 Publication
Mutagenesisi305 – 3051T → D: 2-fold increase of phosphorylation steady state level, no activation after pervanadate treatment. 1 Publication
Mutagenesisi447 – 4471T → A: No effect. 1 Publication
Mutagenesisi447 – 4471T → D: No effect. 1 Publication
Mutagenesisi472 – 4721S → A: 67% decrease of activity after pervanadate treatment. 1 Publication
Mutagenesisi472 – 4721S → D: 1.4-fold increase of phosphorylation steady state level, 50% decrease of activity after pervanadate treatment. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi615937. phenotype.
Orphaneti99802. Hemimegalencephaly.
83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBiPA24686.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 479478RAC-gamma serine/threonine-protein kinasePRO_0000085611Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Disulfide bondi59 ↔ 76By similarity
Disulfide bondi293 ↔ 307By similarity
Glycosylationi302 – 3021O-linked (GlcNAc)By similarity
Modified residuei305 – 3051Phosphothreonine; by PDPK11 Publication
Glycosylationi309 – 3091O-linked (GlcNAc)By similarity
Modified residuei447 – 4471Phosphothreonine1 Publication
Modified residuei472 – 4721Phosphoserine; by PKC/PRKCZ1 Publication

Post-translational modificationi

Phosphorylation on Thr-305 and Ser-472 is required for full activity.By similarity
Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.3 Publications
O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9Y243.
PaxDbiQ9Y243.
PRIDEiQ9Y243.

PTM databases

PhosphoSiteiQ9Y243.

Expressioni

Tissue specificityi

In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.

Gene expression databases

BgeeiQ9Y243.
CleanExiHS_AKT3.
ExpressionAtlasiQ9Y243. baseline and differential.
GenevestigatoriQ9Y243.

Organism-specific databases

HPAiCAB013090.
HPA026441.

Interactioni

Subunit structurei

Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6. Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CASP3P425742EBI-296115,EBI-524064
CDC37Q165432EBI-296115,EBI-295634

Protein-protein interaction databases

BioGridi115318. 11 interactions.
DIPiDIP-32584N.
IntActiQ9Y243. 7 interactions.
MINTiMINT-222821.
STRINGi9606.ENSP00000263826.

Structurei

Secondary structure

1
479
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 1510Combined sources
Beta strandi17 – 3014Combined sources
Beta strandi33 – 419Combined sources
Helixi44 – 463Combined sources
Beta strandi51 – 555Combined sources
Beta strandi60 – 645Combined sources
Beta strandi66 – 683Combined sources
Beta strandi71 – 755Combined sources
Turni80 – 823Combined sources
Beta strandi84 – 885Combined sources
Helixi92 – 11322Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X18X-ray1.46A/B/C/D/E/F/G/H1-118[»]
ProteinModelPortaliQ9Y243.
SMRiQ9Y243. Positions 2-476.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 107103PHPROSITE-ProRule annotationAdd
BLAST
Domaini148 – 405258Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini406 – 47974AGC-kinase C-terminalAdd
BLAST

Domaini

Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI3K) results in its targeting to the plasma membrane.

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120449.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ9Y243.
KOiK04456.
OMAiRGCQIMA.
OrthoDBiEOG7Q5HCW.
PhylomeDBiQ9Y243.
TreeFamiTF102004.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y243-1) [UniParc]FASTAAdd to basket

Also known as: PKB gamma

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSDVTIVKEG WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP
60 70 80 90 100
LNNFSVAKCQ LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE
110 120 130 140 150
AIQAVADRLQ RQEEERMNCS PTSQIDNIGE EEMDASTTHH KRKTMNDFDY
160 170 180 190 200
LKLLGKGTFG KVILVREKAS GKYYAMKILK KEVIIAKDEV AHTLTESRVL
210 220 230 240 250
KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE RVFSEDRTRF
260 270 280 290 300
YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA
310 320 330 340 350
ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD
360 370 380 390 400
HEKLFELILM EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDAKEIM
410 420 430 440 450
RHSFFSGVNW QDVYDKKLVP PFKPQVTSET DTRYFDEEFT AQTITITPPE
460 470
KYDEDGMDCM DNERRPHFPQ FSYSASGRE
Length:479
Mass (Da):55,775
Last modified:November 1, 1999 - v1
Checksum:iF08BDDE6502E78FB
GO
Isoform 2 (identifier: Q9Y243-2) [UniParc]FASTAAdd to basket

Also known as: PKB gamma 1

The sequence of this isoform differs from the canonical sequence as follows:
     452-479: YDEDGMDCMDNERRPHFPQFSYSASGRE → CQQSDCGMLGNWKK

Show »
Length:465
Mass (Da):54,032
Checksum:i592EF88B6937D1E0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti279 – 2791L → R in AAI21155 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti17 – 171E → K in MPPH2 and melanoma; results in activation of AKT. 3 Publications
VAR_065830
Natural varianti171 – 1711G → R in a glioblastoma multiforme sample; somatic mutation. 1 Publication
VAR_040358
Natural varianti229 – 2291N → S in MPPH2. 1 Publication
VAR_069260
Natural varianti465 – 4651R → W in MPPH2; disease phenotype overlaps with megalencephaly-capillary malformation syndrome. 1 Publication
VAR_069261

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei452 – 47928YDEDG…ASGRE → CQQSDCGMLGNWKK in isoform 2. 3 PublicationsVSP_004947Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124141 mRNA. Translation: AAD29089.1.
AF135794 mRNA. Translation: AAD24196.1.
AF085234 mRNA. Translation: AAL40392.1.
AJ245709 mRNA. Translation: CAB53537.1.
AL117525 mRNA. Translation: CAB55977.1. Different termination.
AY005799 mRNA. Translation: AAF91073.1.
AL591721
, AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71866.1.
AL591721
, AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71867.1.
AL592151
, AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72891.1.
AL592151
, AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72892.1.
AL662889
, AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73072.1.
AL662889
, AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73073.1.
CH471148 Genomic DNA. Translation: EAW77093.1.
CH471148 Genomic DNA. Translation: EAW77094.1.
BC121154 mRNA. Translation: AAI21155.1.
CCDSiCCDS31076.1. [Q9Y243-2]
CCDS31077.1. [Q9Y243-1]
PIRiA59380.
T17287.
RefSeqiNP_001193658.1. NM_001206729.1. [Q9Y243-2]
NP_005456.1. NM_005465.4. [Q9Y243-1]
NP_859029.1. NM_181690.2. [Q9Y243-2]
XP_005273051.1. XM_005272994.2. [Q9Y243-1]
XP_005273052.1. XM_005272995.2. [Q9Y243-1]
XP_006711788.1. XM_006711725.1. [Q9Y243-2]
XP_006725022.1. XM_006724959.1. [Q9Y243-1]
XP_006725023.1. XM_006724960.1. [Q9Y243-1]
XP_006725024.1. XM_006724961.1. [Q9Y243-2]
UniGeneiHs.498292.

Genome annotation databases

EnsembliENST00000263826; ENSP00000263826; ENSG00000117020. [Q9Y243-1]
ENST00000336199; ENSP00000336943; ENSG00000117020. [Q9Y243-2]
ENST00000366539; ENSP00000355497; ENSG00000117020. [Q9Y243-1]
ENST00000366540; ENSP00000355498; ENSG00000117020. [Q9Y243-2]
ENST00000613395; ENSP00000479922; ENSG00000275199. [Q9Y243-2]
ENST00000619536; ENSP00000483054; ENSG00000275199. [Q9Y243-2]
ENST00000621586; ENSP00000479081; ENSG00000275199. [Q9Y243-1]
GeneIDi10000.
KEGGihsa:10000.
UCSCiuc001hzz.1. human. [Q9Y243-2]
uc001iab.2. human. [Q9Y243-1]

Polymorphism databases

DMDMi12643943.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124141 mRNA. Translation: AAD29089.1.
AF135794 mRNA. Translation: AAD24196.1.
AF085234 mRNA. Translation: AAL40392.1.
AJ245709 mRNA. Translation: CAB53537.1.
AL117525 mRNA. Translation: CAB55977.1. Different termination.
AY005799 mRNA. Translation: AAF91073.1.
AL591721
, AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71866.1.
AL591721
, AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71867.1.
AL592151
, AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72891.1.
AL592151
, AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72892.1.
AL662889
, AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73072.1.
AL662889
, AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73073.1.
CH471148 Genomic DNA. Translation: EAW77093.1.
CH471148 Genomic DNA. Translation: EAW77094.1.
BC121154 mRNA. Translation: AAI21155.1.
CCDSiCCDS31076.1. [Q9Y243-2]
CCDS31077.1. [Q9Y243-1]
PIRiA59380.
T17287.
RefSeqiNP_001193658.1. NM_001206729.1. [Q9Y243-2]
NP_005456.1. NM_005465.4. [Q9Y243-1]
NP_859029.1. NM_181690.2. [Q9Y243-2]
XP_005273051.1. XM_005272994.2. [Q9Y243-1]
XP_005273052.1. XM_005272995.2. [Q9Y243-1]
XP_006711788.1. XM_006711725.1. [Q9Y243-2]
XP_006725022.1. XM_006724959.1. [Q9Y243-1]
XP_006725023.1. XM_006724960.1. [Q9Y243-1]
XP_006725024.1. XM_006724961.1. [Q9Y243-2]
UniGeneiHs.498292.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X18X-ray1.46A/B/C/D/E/F/G/H1-118[»]
ProteinModelPortaliQ9Y243.
SMRiQ9Y243. Positions 2-476.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115318. 11 interactions.
DIPiDIP-32584N.
IntActiQ9Y243. 7 interactions.
MINTiMINT-222821.
STRINGi9606.ENSP00000263826.

Chemistry

BindingDBiQ9Y243.
ChEMBLiCHEMBL2111353.
GuidetoPHARMACOLOGYi2286.

PTM databases

PhosphoSiteiQ9Y243.

Polymorphism databases

DMDMi12643943.

Proteomic databases

MaxQBiQ9Y243.
PaxDbiQ9Y243.
PRIDEiQ9Y243.

Protocols and materials databases

DNASUi10000.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263826; ENSP00000263826; ENSG00000117020. [Q9Y243-1]
ENST00000336199; ENSP00000336943; ENSG00000117020. [Q9Y243-2]
ENST00000366539; ENSP00000355497; ENSG00000117020. [Q9Y243-1]
ENST00000366540; ENSP00000355498; ENSG00000117020. [Q9Y243-2]
ENST00000613395; ENSP00000479922; ENSG00000275199. [Q9Y243-2]
ENST00000619536; ENSP00000483054; ENSG00000275199. [Q9Y243-2]
ENST00000621586; ENSP00000479081; ENSG00000275199. [Q9Y243-1]
GeneIDi10000.
KEGGihsa:10000.
UCSCiuc001hzz.1. human. [Q9Y243-2]
uc001iab.2. human. [Q9Y243-1]

Organism-specific databases

CTDi10000.
GeneCardsiGC01M243653.
HGNCiHGNC:393. AKT3.
HPAiCAB013090.
HPA026441.
MIMi611223. gene.
615937. phenotype.
neXtProtiNX_Q9Y243.
Orphaneti99802. Hemimegalencephaly.
83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBiPA24686.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120449.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ9Y243.
KOiK04456.
OMAiRGCQIMA.
OrthoDBiEOG7Q5HCW.
PhylomeDBiQ9Y243.
TreeFamiTF102004.

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_115662. Downregulation of ERBB2:ERBB3 signaling.
REACT_12442. AKT phosphorylates targets in the nucleus.
REACT_12447. Negative regulation of the PI3K/AKT network.
REACT_12564. AKT phosphorylates targets in the cytosol.
REACT_13655. AKT-mediated inactivation of FOXO1A.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_19358. CD28 dependent PI3K/Akt signaling.
REACT_19405. CTLA4 inhibitory signaling.
REACT_263991. VEGFR2 mediated vascular permeability.
REACT_549. Activation of BAD and translocation to mitochondria.
REACT_75829. PIP3 activates AKT signaling.
SignaLinkiQ9Y243.

Miscellaneous databases

ChiTaRSiAKT3. human.
GeneWikiiAKT3.
GenomeRNAii10000.
NextBioi37765.
PROiQ9Y243.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y243.
CleanExiHS_AKT3.
ExpressionAtlasiQ9Y243. baseline and differential.
GenevestigatoriQ9Y243.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A human protein kinase B gamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain."
    Brodbeck D., Cron P., Hemmings B.A.
    J. Biol. Chem. 274:9133-9136(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS.
  2. "Identification of a human Akt3 (protein kinase B gamma) which contains the regulatory serine phosphorylation site."
    Nakatani K., Sakaue H., Thompson D.A., Weigel R.J., Roth R.A.
    Biochem. Biophys. Res. Commun. 257:906-910(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3."
    Masure S., Haefner B., Wesselink J.-J., Hoefnagel E., Mortier E., Verhasselt P., Tuytelaars A., Gordon R., Richardson A.
    Eur. J. Biochem. 265:353-360(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  4. "Cloning of a novel human cDNA, STK-2, which encodes a rat serine-threonine protein kinase (STK) homolog."
    Li X., Yu L., Huang H., Zhang M., Zhao Y., Zhao S.
    Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Testis.
  6. "Two splice variants of PKB gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site Ser-472 in the C-terminal hydrophobic domain."
    Brodbeck D., Hill M.M., Hemmings B.A.
    J. Biol. Chem. 276:29550-29558(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF THR-305 AND THR-447.
  7. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  10. "Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha."
    Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.
    Biochem. J. 331:299-308(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, PHOSPHORYLATION AT THR-305 BY PDPK1.
  11. "Characterization of PDK2 activity against protein kinase B gamma."
    Hodgkinson C.P., Sale E.M., Sale G.J.
    Biochemistry 41:10351-10359(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-472.
  12. "Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family."
    Laine J., Kuenstle G., Obata T., Noguchi M.
    J. Biol. Chem. 277:3743-3751(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TCL1A.
  13. "Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1."
    Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F., Roumestand C., Stern M.H., Noguchi M.
    Mol. Cell. Biol. 22:1513-1525(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TCL1A.
  14. Cited for: INVOLVEMENT IN TUMORS.
  15. "A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition."
    Cristiano B.E., Chan J.C., Hannan K.M., Lundie N.A., Marmy-Conus N.J., Campbell I.G., Phillips W.A., Robbie M., Hannan R.D., Pearson R.B.
    Cancer Res. 66:11718-11725(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CANCER.
  16. Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
  17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic kidney.
  18. "VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase."
    Wright G.L., Maroulakou I.G., Eldridge J., Liby T.L., Sridharan V., Tsichlis P.N., Muise-Helmericks R.C.
    FASEB J. 22:3264-3275(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  19. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  20. Cited for: UBIQUITINATION BY TTC3.
  21. Cited for: INTERACTION WITH TRAF6.
  22. "The Akt isoforms are present at distinct subcellular locations."
    Santi S.A., Lee H.
    Am. J. Physiol. 298:C580-C591(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  23. Cited for: INVOLVEMENT IN TUMORS.
  24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  25. "Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts."
    Moriya C., Jinnin M., Yamane K., Maruo K., Muchemwa F.C., Igata T., Makino T., Fukushima S., Ihn H.
    J. Invest. Dermatol. 131:655-661(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  26. Cited for: REVIEW ON FUNCTION.
  27. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-447, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  28. "The crystal structure of the PH domain of human Akt3 protein kinase."
    Vollmar M., Wang J., Zhang Y., Elkins J.M., Burgess-Brown N., Chaikuad A., Pike A.C.W., Von Delft F., Bountra C., Arrowsmith C.H., Weigelt J., Edwards A., Knapp S.
    Submitted (NOV-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 1-118.
  29. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-171.
  30. Cited for: VARIANT MELANOMA LYS-17, CHARACTERIZATION OF VARIANT MELANOMA LYS-17.
  31. Cited for: VARIANTS MPPH2 SER-229 AND TRP-465.
  32. "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly."
    Lee J.H., Huynh M., Silhavy J.L., Kim S., Dixon-Salazar T., Heiberg A., Scott E., Bafna V., Hill K.J., Collazo A., Funari V., Russ C., Gabriel S.B., Mathern G.W., Gleeson J.G.
    Nat. Genet. 44:941-945(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MPPH2 LYS-17.
  33. Cited for: VARIANT MPPH2 LYS-17.

Entry informationi

Entry nameiAKT3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y243
Secondary accession number(s): Q0VAA6
, Q5VTI1, Q5VTI2, Q96QV3, Q9UFP5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: April 1, 2015
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Caution

In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.