Id: acc1362
Group: 2sens
Protein: TSC-2
Gene Symbol: TSC2
Protein Id: P49815
Protein Name: TSC2_HUMAN
PTM: phosphorylation
Site: Ser1387
Site Sequence: PSQPLSKSSSSPELQTLQDIL
Disease Category: Cancer
Disease: Prostate Cancer
Disease Subtype: CRPC
Disease Cellline: C4-2
Disease Info:
Drug: salinomycin
Drug Info: "Salinomycin is a polyether ionophore antibiotic primarily used as an anticoccidial agent in poultry and as a growth promoter in livestock, with emerging research interest in its potential anticancer properties. "
Effect: modulate
Effect Info: "Salinomycin inhibits AR phosphorylation and promotes AMPK phosphorylation. AMPK activation leads to an increase in the phosphorylation of Raptor and TSC2 at Ser1387. Meanwhile, salinomycin also blocks the inhibitory phosphorylation of TSC2 (Ser939/Thr1462) by AKT, thereby inhibiting both AR and mTORC1."
Note:
Score: 4.0
Pubmed(PMID): 27557496
Sentence Index:
Sentence:

Sequence & Structure:

MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

No data.

Protein Tractability:

source: Open Targets
Small molecule
Antibody
PROTAC
Other modalities
Approved Drug
Advanced Clinical
Phase 1 Clinical
Structure with Ligand
High-Quality Ligand
High-Quality Pocket
Med-Quality Pocket
Druggable Family
Approved Drug
Advanced Clinical
Phase 1 Clinical
UniProt loc high conf
GO CC high conf
UniProt loc med conf
UniProt SigP or TMHMM
GO CC med conf
Human Protein Atlas loc
Approved Drug
Advanced Clinical
Phase 1 Clinical
Literature
UniProt Ubiquitination
Database Ubiquitination
Half-life Data
Small Molecule Binder
Approved Drug
Advanced Clinical
Phase 1 Clinical

PTM Intensity:

source: CPTAC
TSC2-Ser1387
Cancer Intensity
BRCA
COAD 0.691
HGSC -1.147
ccRCC 0.456
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
S 664 U Tuberous sclerosis complex Phosphorylation 17671177
S 939 U Tuberous sclerosis complex Phosphorylation 12150915
S 939 U Tuberous sclerosis Phosphorylation 12150915
S 939 U Tuberous sclerosis Phosphorylation 12150915
T 1462 U Tuberous sclerosis Phosphorylation 12150915 ;  12150915

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM
Protein Gene PTM Position Modified sequence Cell Drug pEC50 Regulation Experiment
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK Ramos Rituximab -2.2364 down
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK Ramos Rituximab -3.0145 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR KYSE-520 SHP099 5.2517 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR MDA-MB-175 Lapatinib 6.2348 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK MDA-MB-175 Pertuzumab -2.2478 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK MDA-MB-175 Trastuzumab 1.6988 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR MDA-MB-175 Trastuzumab -1.6694 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR PC-9 AZD4547 7.1383 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR PC-9 AZD4547 5.1225 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR PC-9 Gefitinib 8.3488 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR PC-9 GeftinibAZD4547-1to80 6.2615 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR PC-9 Lapatinib 4.7579 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR PC-9 LapatinibAZD4547 8.3608 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK Ramos Rituximab -3.7364 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR Ramos Rituximab -2.553 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK KYSE-520 SHP099 6.3738 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR Ramos Rituximab -0.8019 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK Ramos Rituximab -1.4253 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK Ramos Rituximab -2.3243 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR Ramos Rituximab -7.1684 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SK-BR-3 Pertuzumab -1.7563 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SK-BR-3 Trastuzumab -4.5457 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SU-DHL-4 Rituximab 2.5898 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SU-DHL-4 Rituximab -2.2295 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SU-DHL-4 Rituximab -1.4894 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SU-DHL-4 Rituximab -7.4771 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR SU-DHL-4 Rituximab -1.4632 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK A549 Refametinib 6.7808 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A431 Dasatinib 9.9319 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK A431 Dasatinib 6.842 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK A431 Gefitinib 5.8143 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A459 MK2206 4.7634 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A459 Selumetinib 6.8703 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A459 SelumetinibMK2206-1to2 8.5419 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A459 SelumetinibMK2206-3to1 8.7638 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK A549 Dasatinib 8.9933 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A549 Dasatinib 5.6508 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK A549 PD325901 4 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A549 Refametinib 9.126 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDK A549 Refametinib 7.1766 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK A431 Dasatinib 5.4173 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR A549 Staursporin 8.251 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR ARH-77 Rituximab -0.4653 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK ARH-77 Rituximab -0.5684 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR ARH-77 Rituximab -3.7377 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR BT-474 Lapatinib 6.7743 -
P49815 TSC2 P Ser1387;Ser1411 SSS(ph)SPELQTLQDILGDPGDKADVGRLS(ph)PEVK BT-474 Pertuzumab -1.7433 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR BT-474 Pertuzumab -2.4175 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR BT-474 Trastuzumab -2.3293 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR HeLa CUDC101 5.1664 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR K562 Dasatinib 10.4856 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR K562 Dasatinib 7.0598 -
P49815 TSC2 P Ser1387 SSS(ph)SPELQTLQDILGDPGDKADVGR K562 Paclitaxel 6.2968 -

pEC50 Note: pEC50 is the negative logarithm of EC50 (half-maximal effective concentration, dosage unit Mol), calculated as pEC50 = -log10(EC50), which quantifies the potency of a drug or compound.

Function score:

source: funscoR

No data.

Cross Links: