Reactome | UniProt:Q9Y243 AKT3

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UniProt:Q9Y243 AKT3 Show undefined attributes

chain	initiator methionine:1 chain:2-479
checksum	F08BDDE6502E78FB
comment	FUNCTION 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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION 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.BIOPHYSICOCHEMICAL PROPERTIES 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).SUBCELLULAR LOCATION Membrane-associated after cell stimulation leading to its translocation.ALTERNATIVE PRODUCTS 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.DOMAIN Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.PTM Phosphorylation on Thr-305 and Ser-472 is required for full activity (PubMed:12162751, PubMed:9512493). Phosphorylation of the activation loop at Thr-305 by PDPK1/PDK1 is a prerequisite for full activation (PubMed:9512493). Phosphorylation at Ser-472 by mTORC2 in response to growth factors plays a key role in AKT1 activation by facilitating subsequent phosphorylation of the activation loop by PDPK1/PDK1 (By similarity).PTM Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.PTM O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDPK1/PDK1.DISEASE 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.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.
created	[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
crossReference	[DatabaseIdentifier:12136594] Orphanet:AKT3 [DatabaseIdentifier:12817719] ZINC - World Drugs:AKT3_HUMAN [DatabaseIdentifier:12815997] ZINC target:Q9Y243 [DatabaseIdentifier:12812623] ZINC - Substances:AKT3_HUMAN [DatabaseIdentifier:12808135] ZINC - Predictions - Purchasable:AKT3_HUMAN [DatabaseIdentifier:12806266] ZINC - Investigational:AKT3_HUMAN [DatabaseIdentifier:12805215] ZINC - FDA approved:AKT3_HUMAN [DatabaseIdentifier:12803993] ZINC - Biogenic:AKT3_HUMAN [DatabaseIdentifier:12343754] RefSeq:NP_005456.1 [DatabaseIdentifier:12343756] RefSeq:XP_054184598.1 [DatabaseIdentifier:12343757] RefSeq:XP_054189659.1 [DatabaseIdentifier:12343758] RefSeq:NP_001357003.1 [DatabaseIdentifier:12343755] RefSeq:NP_001193658.1 [DatabaseIdentifier:12343759] RefSeq:NP_859029.1 [DatabaseIdentifier:12292650] Pharos - Targets:Q9Y243 [DatabaseIdentifier:12254951] PRO:Q9Y243 [DatabaseIdentifier:12225250] PDB:8ZXW [DatabaseIdentifier:12225249] PDB:2X18 [DatabaseIdentifier:11461640] ENSEMBL:ENSG00000117020 [DatabaseIdentifier:11461641] ENSEMBL:ENSG00000275199 [DatabaseIdentifier:11555079] ENSEMBL:ENSP00000479922 [DatabaseIdentifier:11555081] ENSEMBL:ENSP00000263826 [DatabaseIdentifier:11555074] ENSEMBL:ENSP00000505276 [DatabaseIdentifier:11555075] ENSEMBL:ENSP00000500582 [DatabaseIdentifier:11555080] ENSEMBL:ENSP00000479081 [DatabaseIdentifier:11555077] ENSEMBL:ENSP00000483054 [DatabaseIdentifier:11555076] ENSEMBL:ENSP00000355498 [DatabaseIdentifier:11555078] ENSEMBL:ENSP00000336943 [DatabaseIdentifier:11677776] ENSEMBL:ENST00000336199 [DatabaseIdentifier:11677773] ENSEMBL:ENST00000366540 [DatabaseIdentifier:11677777] ENSEMBL:ENST00000621586 [DatabaseIdentifier:11677780] ENSEMBL:ENST00000619536 [DatabaseIdentifier:11677774] ENSEMBL:ENST00000613395 [DatabaseIdentifier:11677779] ENSEMBL:ENST00000263826 [DatabaseIdentifier:11677778] ENSEMBL:ENST00000680118 [DatabaseIdentifier:11677775] ENSEMBL:ENST00000673466 [DatabaseIdentifier:11778627] Guide to Pharmacology - Targets:2286 [DatabaseIdentifier:11794826] GeneCards:AKT3 [DatabaseIdentifier:11810744] GlyGen:Q9Y243 [DatabaseIdentifier:11831910] HMDB Protein:HMDBP01363 [DatabaseIdentifier:11847796] HPA:ENSG00000117020-AKT3 [DatabaseIdentifier:12132479] OpenTargets:ENSG00000117020
databaseName	UniProt
dbId	415917
description	recommendedName: RAC-gamma serine/threonine-protein kinase ecNumber: 2.7.11.1 alternativeName: Protein kinase Akt-3 alternativeName: Protein kinase B gamma shortName: PKB gamma alternativeName: RAC-PK-gamma alternativeName: STK-2
displayName	UniProt:Q9Y243 AKT3
geneName	AKT3 PKBG
identifier	Q9Y243
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing ATP-binding Cytoplasm Disease variant Disulfide bond Glycoprotein Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	AKT3
otherIdentifier	10000 11739189_at 11739190_a_at 11739191_at 11758336_s_at 11759289_at 11759290_at 16701238 212607_PM_at 212607_at 212609_PM_s_at 212609_s_at 219393_PM_s_at 219393_s_at 222880_PM_at 222880_at 224229_PM_s_at 224229_s_at 242879_PM_x_at 242879_x_at 2464006 2464007 2464008 2464009 2464010 2464011 2464012 2464013 2464014 2464020 2464026 2464027 2464033 2464035 2464036 2464050 2464051 2464052 2464053 2464059 2464061 2464062 2464063 2464065 2464066 2464067 2464068 2464075 2464077 2464081 2464082 2464105 2464106 2464107 2464112 2464113 2464114 2464116 2464118 2464120 2464135 40781_at 7925531 80409_at 83997_r_at 87279_at A_23_P160354 A_24_P110983 A_24_P45481 GE537571 GE56492 GE88420 GO:0000002 GO:0000166 GO:0001938 GO:0003824 GO:0004672 GO:0004674 GO:0005515 GO:0005524 GO:0005634 GO:0005654 GO:0005737 GO:0005794 GO:0005815 GO:0005829 GO:0005886 GO:0005929 GO:0006468 GO:0007165 GO:0008286 GO:0016020 GO:0016301 GO:0016740 GO:0030335 GO:0032008 GO:0035556 GO:0036064 GO:0043066 GO:0043226 GO:0043536 GO:0045766 GO:0045793 GO:0048854 GO:0048873 GO:0090050 GO:0106310 GO:0140096 GO:1903898 GO:1905564 GO:1905653 GO:2000773 HMNXSV003005098 HMNXSV003016224 HMNXSV003022774 Hs.161189.0.A1_3p_at Hs.161189.0.A1_3p_x_at Hs.300642.0.S1_3p_at Hs.300642.0.S1_3p_s_at Hs.300642.0.S2_3p_at ILMN_1733598 ILMN_1757130 ILMN_2325610 ILMN_2325612 PH_hs_0023601 TC01004040.hg TC01006240.hg U79271_at g4574743_3p_at g4885548_3p_a_at g5912042_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-3009365] p-T305,S472-AKT3 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3009367] p-T305,S472-AKT3 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3009363] p-S472-AKT3 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2976006] AKT3 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2976007] AKT3 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3009370] p-T305-AKT3 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000117020] ENSEMBL:ENSG00000117020 AKT3 [ReferenceDNASequence:12679128] UCSC:Q9Y243 AKT3 [ReferenceDNASequence:11326084] BioGPS Gene:10000 AKT3 [ReferenceDNASequence:11392102] COSMIC - genes:AKT3 AKT3 [ReferenceDNASequence:11423658] CTD Gene:10000 AKT3 [ReferenceDNASequence:11427849] dbSNP Gene:10000 AKT3 [ReferenceDNASequence:11826523] HGNC:393 AKT3 [ReferenceDNASequence:11868419] KEGG:hsa:10000 AKT3 [ReferenceDNASequence:11955873] Monarch:10000 AKT3 [ReferenceDNASequence:12039966] NCBI Gene:10000 AKT3 [ReferenceDNASequence:12116835] OMIM:611223 AKT3
referenceTranscript	[ReferenceRNASequence:12525629] RefSeq:NM_005465.7 AKT3 [ReferenceRNASequence:12525634] RefSeq:NM_001206729.2 AKT3 [ReferenceRNASequence:12525633] RefSeq:NM_001370074.1 AKT3 [ReferenceRNASequence:12525631] RefSeq:XM_054333684.1 AKT3 [ReferenceRNASequence:12525630] RefSeq:XM_054328623.1 AKT3 [ReferenceRNASequence:12525632] RefSeq:NM_181690.2 AKT3
schemaClass	ReferenceGeneProduct
secondaryIdentifier	AKT3_HUMAN Q0VAA6 Q5VTI1 Q5VTI2 Q96QV3 Q9UFP5
sequenceLength	479
species	[Species:48887] Homo sapiens
stId	uniprot:Q9Y243
url	http://purl.uniprot.org/uniprot/Q9Y243

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-3009365] p-T305,S472-AKT3 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-3009367] p-T305,S472-AKT3 [cytosol] [EntityWithAccessionedSequence:R-HSA-3009363] p-S472-AKT3 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-2976006] AKT3 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-2976007] AKT3 [cytosol] [EntityWithAccessionedSequence:R-HSA-3009370] p-T305-AKT3 [cytosol]
(referenceSequence)	[ModifiedResidue:3009368] O-phospho-L-threonine at 305 [ModifiedResidue:3009366] O-phospho-L-serine at 472
(interactor)	[UndirectedInteraction:11222845] UniProt:P07900 <-> UniProt:Q9Y243 (IntAct) [UndirectedInteraction:11256155] UniProt:Q9Y243 <-> UniProt:Q16543 (IntAct) [UndirectedInteraction:11256157] UniProt:Q9Y243 <-> UniProt:P42574 (IntAct) [UndirectedInteraction:11256159] UniProt:Q9Y243 <-> UniProt:P53804 (IntAct)

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