dbPTM

AKT3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	AKT3_HUMAN
UniProt AC	Q9Y243
Protein Name	RAC-gamma serine/threonine-protein kinase
Gene Name	AKT3
Organism	Homo sapiens (Human).
Sequence Length	479
Subcellular Localization	Nucleus . Cytoplasm . Membrane Peripheral membrane protein . Membrane-associated after cell stimulation leading to its translocation.
Protein Description	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..
Protein Sequence	MSDVTIVKEGWVQKRGEYIKNWRPRYFLLKTDGSFIGYKEKPQDVDLPYPLNNFSVAKCQLMKTERPKPNTFIIRCLQWTTVIERTFHVDTPEEREEWTEAIQAVADRLQRQEEERMNCSPTSQIDNIGEEEMDASTTHHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFPRTLSSDAKSLLSGLLIKDPNKRLGGGPDDAKEIMRHSFFSGVNWQDVYDKKLVPPFKPQVTSETDTRYFDEEFTAQTITITPPEKYDEDGMDCMDNERRPHFPQFSYSASGRE

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	O-linked_Glycosylation	------MSDVTIVKE ------CCCCEEEEC	40.56	30379171
2	Acetylation	------MSDVTIVKE ------CCCCEEEEC	40.56	19413330
14	Ubiquitination	VKEGWVQKRGEYIKN EECCEEECCCCCCCC	53.39	-
31	Phosphorylation	PRYFLLKTDGSFIGY CCEEEEECCCCCCCC	45.63	29083192
34	Phosphorylation	FLLKTDGSFIGYKEK EEEECCCCCCCCCCC	19.25	174875
38	Phosphorylation	TDGSFIGYKEKPQDV CCCCCCCCCCCCCCC	15.91	18083107
120	Phosphorylation	EEERMNCSPTSQIDN HHHHHCCCCCHHCCC	26.63	17525332
122	Phosphorylation	ERMNCSPTSQIDNIG HHHCCCCCHHCCCCC	19.57	23403867
123	Phosphorylation	RMNCSPTSQIDNIGE HHCCCCCHHCCCCCC	28.64	17525332
136	Phosphorylation	GEEEMDASTTHHKRK CCCCCCCCCCCCCCC	29.58	27080861
137	Phosphorylation	EEEMDASTTHHKRKT CCCCCCCCCCCCCCC	31.69	27080861
138	Phosphorylation	EEMDASTTHHKRKTM CCCCCCCCCCCCCCC	21.35	27080861
156	Ubiquitination	DYLKLLGKGTFGKVI HHHHHHCCCCCCEEE	55.54	-
181	Ubiquitination	YAMKILKKEVIIAKD EEEEECCCEEEEECH	54.49	-
193	Phosphorylation	AKDEVAHTLTESRVL ECHHHHHHHHHHHHH	26.15	29255136
195	Phosphorylation	DEVAHTLTESRVLKN HHHHHHHHHHHHHCC	32.82	29255136
197	Phosphorylation	VAHTLTESRVLKNTR HHHHHHHHHHHCCCC	23.58	29255136
273 (in isoform 1)	Ubiquitination	-	59.03	21890473
273	Sumoylation	KIVYRDLKLENLMLD CEEEEEECHHHCEEC	59.03	-
273 (in isoform 2)	Ubiquitination	-	59.03	21890473
273	Sumoylation	KIVYRDLKLENLMLD CEEEEEECHHHCEEC	59.03	-
273	Ubiquitination	KIVYRDLKLENLMLD CEEEEEECHHHCEEC	59.03	-
281	2-Hydroxyisobutyrylation	LENLMLDKDGHIKIT HHHCEECCCCCEEEC	62.74	-
281	Ubiquitination	LENLMLDKDGHIKIT HHHCEECCCCCEEEC	62.74	-
286	Ubiquitination	LDKDGHIKITDFGLC ECCCCCEEECCCCCC	33.60	-
288	Phosphorylation	KDGHIKITDFGLCKE CCCCEEECCCCCCCC	21.92	-
298	Phosphorylation	GLCKEGITDAATMKT CCCCCCCCCHHHHHH	30.37	22322096
302	O-linked_Glycosylation	EGITDAATMKTFCGT CCCCCHHHHHHHCCC	22.41	UniProtKB CARBOHYD
302	Phosphorylation	EGITDAATMKTFCGT CCCCCHHHHHHHCCC	22.41	28857561
305	Phosphorylation	TDAATMKTFCGTPEY CCHHHHHHHCCCHHH	17.21	22322096
307	Glutathionylation	AATMKTFCGTPEYLA HHHHHHHCCCHHHHC	7.79	22555962
309	Phosphorylation	TMKTFCGTPEYLAPE HHHHHCCCHHHHCHH	17.71	30206219
309	O-linked_Glycosylation	TMKTFCGTPEYLAPE HHHHHCCCHHHHCHH	17.71	UniProtKB CARBOHYD
312	Phosphorylation	TFCGTPEYLAPEVLE HHCCCHHHHCHHHHC	14.90	131883
323	Phosphorylation	EVLEDNDYGRAVDWW HHHCCCCCCCCHHHH	18.11	142487
428	Phosphorylation	PFKPQVTSETDTRYF CCCCCCCCCCCCCCC	39.37	26657352
432	Phosphorylation	QVTSETDTRYFDEEF CCCCCCCCCCCCCCE	34.39	-
434	Phosphorylation	TSETDTRYFDEEFTA CCCCCCCCCCCCEEE	19.92	119581
440	Phosphorylation	RYFDEEFTAQTITIT CCCCCCEEEEEEEEC	22.57	46161807
443	Phosphorylation	DEEFTAQTITITPPE CCCEEEEEEEECCCH	20.02	26657352
445 (in isoform 2)	Phosphorylation	-	23.37	22210691
445	Phosphorylation	EFTAQTITITPPEKY CEEEEEEEECCCHHC	23.37	29255136
447 (in isoform 2)	Phosphorylation	-	24.92	22210691
447	Phosphorylation	TAQTITITPPEKYDE EEEEEEECCCHHCCC	24.92	29255136
452	Phosphorylation	TITPPEKYDEDGMDC EECCCHHCCCCCCCC	23.93	27251275
455 (in isoform 2)	Phosphorylation	-	55.61	22210691
472	Phosphorylation	RPHFPQFSYSASGRE CCCCCCCCCCCCCCC	16.96	22322096
473	Phosphorylation	PHFPQFSYSASGRE- CCCCCCCCCCCCCC-	15.00	22322096
474	Phosphorylation	HFPQFSYSASGRE-- CCCCCCCCCCCCC--	18.11	22322096
476	Phosphorylation	PQFSYSASGRE---- CCCCCCCCCCC----	32.23	22322096

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
305	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
305	T	Phosphorylation	Kinase	PDK1	O15530	PSP
472	S	Phosphorylation	Kinase	PRKCZ	Q05513	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	TTC3	P53804	PMID:20059950
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4	P46934	PMID:23195959

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
48	K	Phosphorylation	12162751
When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.
48	K	ubiquitylation	12162751
When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.
302	T	Phosphorylation	-
O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.
305	T	Phosphorylation	11387345
O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.
305	T	Phosphorylation	11387345
Phosphorylation on Thr-305 and Ser-472 is required for full activity.
309	T	Phosphorylation	-
O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.
472	S	Phosphorylation	12162751
Phosphorylation on Thr-305 and Ser-472 is required for full activity.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of AKT3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KPCZ_HUMAN	PRKCZ	physical	12162751
TTC3_HUMAN	TTC3	physical	20059950
BTBDA_MOUSE	Btbd10	physical	18160256
GSK3B_HUMAN	GSK3B	physical	15678105
KCD20_MOUSE	Kctd20	physical	24156551
PKHO1_HUMAN	PLEKHO1	physical	17942896
4EBP1_HUMAN	EIF4EBP1	physical	26344197
RPE_HUMAN	RPE	physical	26344197
AKT1_HUMAN	AKT1	physical	28514442
HS90B_HUMAN	HSP90AB1	physical	28514442
FKBP5_HUMAN	FKBP5	physical	28514442
HS90A_HUMAN	HSP90AA1	physical	28514442
CDC37_HUMAN	CDC37	physical	28514442
SNX8_HUMAN	SNX8	physical	28514442
ANM6_HUMAN	PRMT6	physical	28514442
GSK3B_HUMAN	GSK3B	physical	27563096

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
	Note=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.
615937
Kegg Drug
D10381	Afuresertib (USAN)
D10382	Afuresertib hydrochloride (USAN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of AKT3_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage."; Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; Science 316:1160-1166(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120 AND SER-123, ANDMASS SPECTROMETRY.	17525332 [Abstract]
"Characterization of PDK2 activity against protein kinase B gamma."; Hodgkinson C.P., Sale E.M., Sale G.J.; Biochemistry 41:10351-10359(2002). Cited for: PHOSPHORYLATION AT SER-472.	12162751 [Abstract]
"Activation of protein kinase B beta and gamma isoforms by insulin invivo 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(1998). Cited for: CHARACTERIZATION, AND PHOSPHORYLATION AT THR-305 BY PDPK1.	9512493 [Abstract]

show

show

show

show

show

show

show