dbPTM

AKTS1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	AKTS1_HUMAN
UniProt AC	Q96B36
Protein Name	Proline-rich AKT1 substrate 1
Gene Name	AKT1S1 {ECO:0000312\|EMBL:AAH16043.1}
Organism	Homo sapiens (Human).
Sequence Length	256
Subcellular Localization	Cytoplasm, cytosol. Found in the cytosolic fraction of the brain..
Protein Description	Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection..
Protein Sequence	MASGRPEELWEAVVGAAERFRARTGTELVLLTAAPPPPPRPGPCAYAAHGRGALAEAARRCLHDIALAHRAATAARPPAPPPAPQPPSPTPSPPRPTLAREDNEEDEDEPTETETSGEQLGISDNGGLFVMDEDATLQDLPPFCESDPESTDDGSLSEETPAGPPTCSVPPASALPTQQYAKSLPVSVPVWGFKEKRTEARSSDEENGPPSSPDLDRIAASMRALVLREAEDTQVFGDLPRPRLNTSDFQKLKRKY

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2 (in isoform 3)	Phosphorylation	-	22.23	28188228
32	Phosphorylation	GTELVLLTAAPPPPP CCEEEEEEECCCCCC	19.33	-
40	Methylation	AAPPPPPRPGPCAYA ECCCCCCCCCCCCHH	55.36	115488649
51	Dimethylation	CAYAAHGRGALAEAA CCHHCCCHHHHHHHH	19.83	-
51	Methylation	CAYAAHGRGALAEAA CCHHCCCHHHHHHHH	19.83	24129315
61	Glutathionylation	LAEAARRCLHDIALA HHHHHHHHHHHHHHH	3.09	22555962
73	Phosphorylation	ALAHRAATAARPPAP HHHHHHHHHCCCCCC	21.62	20044836
88	Phosphorylation	PPAPQPPSPTPSPPR CCCCCCCCCCCCCCC	48.35	29255136
90	Phosphorylation	APQPPSPTPSPPRPT CCCCCCCCCCCCCCC	40.51	29255136
92	Phosphorylation	QPPSPTPSPPRPTLA CCCCCCCCCCCCCCC	50.44	29255136
97	Phosphorylation	TPSPPRPTLAREDNE CCCCCCCCCCCCCCC	34.04	29255136
108 (in isoform 3)	Phosphorylation	-	78.48	27251275
110 (in isoform 3)	Phosphorylation	-	48.10	27251275
112 (in isoform 3)	Phosphorylation	-	56.19	27251275
116	Phosphorylation	EPTETETSGEQLGIS CCCCCCCCCCCCCCC	33.82	-
183	Phosphorylation	PTQQYAKSLPVSVPV CHHHHHHHCCCCCEE	29.72	22322096
187	Phosphorylation	YAKSLPVSVPVWGFK HHHHCCCCCEECCCC	20.82	23927012
198	Phosphorylation	WGFKEKRTEARSSDE CCCCCCCCCCCCCCC	45.10	29255136
202	Phosphorylation	EKRTEARSSDEENGP CCCCCCCCCCCCCCC	49.54	29255136
203 (in isoform 3)	Phosphorylation	-	43.41	27251275
203	Phosphorylation	KRTEARSSDEENGPP CCCCCCCCCCCCCCC	43.41	29255136
211	Phosphorylation	DEENGPPSSPDLDRI CCCCCCCCCCHHHHH	58.60	29255136
212	Phosphorylation	EENGPPSSPDLDRIA CCCCCCCCCHHHHHH	28.36	29255136
218 (in isoform 3)	Phosphorylation	-	3.61	27251275
221	Phosphorylation	DLDRIAASMRALVLR HHHHHHHHHHHHHHH	10.36	30576142
222 (in isoform 3)	Phosphorylation	-	2.20	27251275
223 (in isoform 3)	Phosphorylation	-	23.44	27251275
231 (in isoform 3)	Phosphorylation	-	57.76	27251275
232 (in isoform 3)	Phosphorylation	-	49.87	27251275
233	Phosphorylation	VLREAEDTQVFGDLP HHHHCCCCCCCCCCC	20.38	28555341
246	Phosphorylation	LPRPRLNTSDFQKLK CCCCCCCHHHHHHHH	33.97	22322096
247	Phosphorylation	PRPRLNTSDFQKLKR CCCCCCHHHHHHHHH	35.04	27273156
251	Methylation	LNTSDFQKLKRKY-- CCHHHHHHHHHHC--	56.84	115975615
251	Ubiquitination	LNTSDFQKLKRKY-- CCHHHHHHHHHHC--	56.84	-
256	Phosphorylation	FQKLKRKY------- HHHHHHHC-------	28.02	-
266 (in isoform 3)	Phosphorylation	-		27251275

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
183	S	Phosphorylation	Kinase	MTOR	P42345	PSP
183	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
202	S	Phosphorylation	Kinase	PKM	P14618	PSP
203	S	Phosphorylation	Kinase	PKM	P14618	PSP
212	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
221	S	Phosphorylation	Kinase	MTOR	P42345	PSP
221	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
246	T	Phosphorylation	Kinase	AKT1	P31749	Uniprot
246	T	Phosphorylation	Kinase	AKT1	P31750	PSP
246	T	Phosphorylation	Kinase	DYRK3	O43781	Uniprot
246	T	Phosphorylation	Kinase	PIM1	P11309	GPS
246	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
246	T	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
246	T	Phosphorylation		12524439
Phosphorylation at Thr-246 by DYRK3 relieves inhibitory function on mTORC1.

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 AKTS1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MTOR_HUMAN	MTOR	physical	19446321
RPTOR_HUMAN	RPTOR	physical	19446321
NXP20_HUMAN	FAM114A1	physical	22863883
1433Z_HUMAN	YWHAZ	physical	17277771
AKTS1_HUMAN	AKT1S1	physical	26578655
CBY1_HUMAN	CBY1	physical	27173435

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of AKTS1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183;SER-202; SER-212 AND THR-246, AND MASS SPECTROMETRY.	19690332 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183; THR-198; SER-202;SER-203; SER-211; SER-212 AND THR-246, AND MASS SPECTROMETRY.	19413330 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183;SER-202; SER-203; SER-211; SER-212 AND THR-246, AND MASS SPECTROMETRY.	18669648 [Abstract]
"Global proteomic profiling of phosphopeptides using electron transferdissociation tandem mass spectrometry."; Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.; Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88 AND SER-92, AND MASSSPECTROMETRY.	17287340 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND THR-246, ANDMASS SPECTROMETRY.	17081983 [Abstract]
"Identification of a proline-rich Akt substrate as a 14-3-3 bindingpartner."; Kovacina K.S., Park G.Y., Bae S.S., Guzzetta A.W., Schaefer E.,Birnbaum M.J., Roth R.A.; J. Biol. Chem. 278:10189-10194(2003). Cited for: INTERACTION WITH 14-3-3, TISSUE SPECIFICITY, AND PHOSPHORYLATION ATTHR-246.	12524439 [Abstract]

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