dbPTM

LST8_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	LST8_HUMAN
UniProt AC	Q9BVC4
Protein Name	Target of rapamycin complex subunit LST8
Gene Name	MLST8
Organism	Homo sapiens (Human).
Sequence Length	326
Subcellular Localization	Cytoplasm.
Protein Description	Subunit of both mTORC1 and mTORC2, 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, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'..
Protein Sequence	MNTSPGTVGSDPVILATAGYDHTVRFWQAHSGICTRTVQHQDSQVNALEVTPDRSMIAAAGYQHIRMYDLNSNNPNPIISYDGVNKNIASVGFHEDGRWMYTGGEDCTARIWDLRSRNLQCQRIFQVNAPINCVCLHPNQAELIVGDQSGAIHIWDLKTDHNEQLIPEPEVSITSAHIDPDASYMAAVNSTGNCYVWNLTGGIGDEVTQLIPKTKIPAHTRYALQCRFSPDSTLLATCSADQTCKIWRTSNFSLMTELSIKSGNPGESSRGWMWGCAFSGDSQYIVTASSDNLARLWCVETGEIKREYGGHQKAVVCLAFNDSVLG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1 (in isoform 4)	Acetylation	-	12.77	19369195
1	Acetylation	-------MNTSPGTV -------CCCCCCCC	12.77	19369195
3	Phosphorylation	-----MNTSPGTVGS -----CCCCCCCCCC	34.69	25159151
4	Phosphorylation	----MNTSPGTVGSD ----CCCCCCCCCCC	19.14	25159151
7	Phosphorylation	-MNTSPGTVGSDPVI -CCCCCCCCCCCCEE	25.69	30108239
7 (in isoform 4)	Phosphorylation	-	25.69	17192257
10	Phosphorylation	TSPGTVGSDPVILAT CCCCCCCCCCEEEEE	34.11	30108239
12 (in isoform 4)	Phosphorylation	-	19.42	24247654
17	Phosphorylation	SDPVILATAGYDHTV CCCEEEEECCCCCHH	19.71	26074081
19 (in isoform 4)	Phosphorylation	-	24.85	18691976
20	Phosphorylation	VILATAGYDHTVRFW EEEEECCCCCHHEEH	11.33	26074081
20 (in isoform 3)	Ubiquitination	-	11.33	21906983
23	Phosphorylation	ATAGYDHTVRFWQAH EECCCCCHHEEHHHC	15.52	24425749
37	Phosphorylation	HSGICTRTVQHQDSQ CCCCCEEEEECCCCC	13.33	20873877
43	Phosphorylation	RTVQHQDSQVNALEV EEEECCCCCCCEEEE	29.47	20873877
51	Phosphorylation	QVNALEVTPDRSMIA CCCEEEECCCHHHHH	15.31	26091039
55	Phosphorylation	LEVTPDRSMIAAAGY EEECCCHHHHHHHCC	23.17	-
62	Phosphorylation	SMIAAAGYQHIRMYD HHHHHHCCCEEEEEE	7.68	29496907
85	Ubiquitination	IISYDGVNKNIASVG CEEECCCCCCEEEEE	36.87	21963094
86 (in isoform 1)	Ubiquitination	-	47.53	21906983
86	Ubiquitination	ISYDGVNKNIASVGF EEECCCCCCEEEEEE	47.53	2190698
92	Ubiquitination	NKNIASVGFHEDGRW CCCEEEEEEEECCCE	18.72	21963094
101	Phosphorylation	HEDGRWMYTGGEDCT EECCCEEEECCCCCC	8.69	29496907
105 (in isoform 4)	Ubiquitination	-	51.78	21906983
111	Ubiquitination	GEDCTARIWDLRSRN CCCCCEEHHHHHHCC	2.88	21963094
141	Ubiquitination	VCLHPNQAELIVGDQ EEECCCCEEEEEECC	21.87	21963094
149	Ubiquitination	ELIVGDQSGAIHIWD EEEEECCCCCEEEEE	34.63	21963094
157	Ubiquitination	GAIHIWDLKTDHNEQ CCEEEEECCCCCCCC	3.75	21963094
163	Ubiquitination	DLKTDHNEQLIPEPE ECCCCCCCCCCCCCC	43.26	21963094
179	Ubiquitination	SITSAHIDPDASYMA EEEEEEECCCCCCEE	25.76	21963094
195	Ubiquitination	VNSTGNCYVWNLTGG EECCCCEEEEECCCC	16.70	21963094
201	Ubiquitination	CYVWNLTGGIGDEVT EEEEECCCCCCHHHH	28.96	21963094
214	Phosphorylation	VTQLIPKTKIPAHTR HHHCCCCCCCCCCCE	28.93	20068231
214	Ubiquitination	VTQLIPKTKIPAHTR HHHCCCCCCCCCCCE	28.93	21963094
215	Ubiquitination	TQLIPKTKIPAHTRY HHCCCCCCCCCCCEE	53.47	21963094
221	Ubiquitination	TKIPAHTRYALQCRF CCCCCCCEEEEEEEC	12.59	21963094
222	Phosphorylation	KIPAHTRYALQCRFS CCCCCCEEEEEEECC	16.90	-
239	Ubiquitination	STLLATCSADQTCKI CEEEEECCCCCCCEE	30.44	21963094
240	Ubiquitination	TLLATCSADQTCKIW EEEEECCCCCCCEEE	18.31	21963094
244	Ubiquitination	TCSADQTCKIWRTSN ECCCCCCCEEEEECC	2.21	21963094
245	Ubiquitination	CSADQTCKIWRTSNF CCCCCCCEEEEECCC	49.00	21963094
249	Phosphorylation	QTCKIWRTSNFSLMT CCCEEEEECCCEEEE	17.02	28509920
250	Phosphorylation	TCKIWRTSNFSLMTE CCEEEEECCCEEEEE	27.57	28509920
251	Ubiquitination	CKIWRTSNFSLMTEL CEEEEECCCEEEEEE	29.88	21963094
259	Phosphorylation	FSLMTELSIKSGNPG CEEEEEEEECCCCCC	23.03	29083192
260	Ubiquitination	SLMTELSIKSGNPGE EEEEEEEECCCCCCC	6.86	21963094
261	Ubiquitination	LMTELSIKSGNPGES EEEEEEECCCCCCCC	49.27	21963094
267	Ubiquitination	IKSGNPGESSRGWMW ECCCCCCCCCCCEEE	46.96	21963094
270	Ubiquitination	GNPGESSRGWMWGCA CCCCCCCCCEEEEEE	52.66	21963094
286	Ubiquitination	SGDSQYIVTASSDNL CCCCCEEEEECCCCE	2.89	21963094
304	Ubiquitination	WCVETGEIKREYGGH EEEECCCEEHHHCCC	5.58	21963094
305	Ubiquitination	CVETGEIKREYGGHQ EEECCCEEHHHCCCC	34.57	21963094
305	Sumoylation	CVETGEIKREYGGHQ EEECCCEEHHHCCCC	34.57	-
311	Ubiquitination	IKREYGGHQKAVVCL EEHHHCCCCCEEEEE	22.93	21963094
330	Ubiquitination	SVLG----------- CCCC-----------		21963094

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
-	K	Ubiquitination	E3 ubiquitin ligase	TANK	Q92844	PMID:28489822

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of LST8_HUMAN !!

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 LST8_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MTOR_HUMAN	MTOR	physical	20562859
RPTOR_HUMAN	RPTOR	physical	20562859
KRT85_HUMAN	KRT85	physical	20562859
TCPB_HUMAN	CCT2	physical	20562859
SQSTM_HUMAN	SQSTM1	physical	21981924
MTOR_HUMAN	MTOR	physical	12718876
ANM1_HUMAN	PRMT1	physical	23455924
4EBP1_HUMAN	EIF4EBP1	physical	18955708
RPTOR_HUMAN	RPTOR	physical	12408816
MTOR_HUMAN	MTOR	physical	12408816
TCPH_HUMAN	CCT7	physical	26186194
MTOR_HUMAN	MTOR	physical	26186194
TCPW_HUMAN	CCT6B	physical	26186194
TCPB_HUMAN	CCT2	physical	26186194
THIC_HUMAN	ACAT2	physical	26186194
SETX_HUMAN	SETX	physical	26186194
PRAME_HUMAN	PRAME	physical	26186194
TBA1A_HUMAN	TUBA1A	physical	26186194
PFD5_HUMAN	PFDN5	physical	26186194
FOXF2_HUMAN	FOXF2	physical	26186194
ETV3_HUMAN	ETV3	physical	26186194
LYPA2_HUMAN	LYPLA2	physical	26186194
KEAP1_HUMAN	KEAP1	physical	26186194
MELK_HUMAN	MELK	physical	26186194
WDR60_HUMAN	WDR60	physical	26186194
UBP54_HUMAN	USP54	physical	26186194
MTOR_HUMAN	MTOR	physical	28514442
LYPA2_HUMAN	LYPLA2	physical	28514442
PRAME_HUMAN	PRAME	physical	28514442
TCPH_HUMAN	CCT7	physical	28514442
THIC_HUMAN	ACAT2	physical	28514442
FOXF2_HUMAN	FOXF2	physical	28514442
TCPB_HUMAN	CCT2	physical	28514442
TBA4A_HUMAN	TUBA4A	physical	28514442
TCPG_HUMAN	CCT3	physical	28514442
TCPW_HUMAN	CCT6B	physical	28514442
MELK_HUMAN	MELK	physical	28514442
RICTR_HUMAN	RICTOR	physical	28514442

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 LST8_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-4 AND THR-7,PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7 (ISOFORM 3), AND MASSSPECTROMETRY.	19369195 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, PHOSPHORYLATION[LARGE SCALE ANALYSIS] AT SER-7 (ISOFORM 3), AND MASS SPECTROMETRY.	18691976 [Abstract]