Id: acc1363
Group: 2sens
Protein: TSC-2
Gene Symbol: TSC2
Protein Id: P49815
Protein Name: TSC2_HUMAN
PTM: phosphorylation
Site: Ser939
Site Sequence: KDSFRARSTSLNERPKSLRIA
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. The activation of AMPK 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-Ser939
Cancer Intensity
BRCA 1.663
COAD
HGSC
ccRCC 0.197
GBM
HNSC
LUAD
LUSC -0.576
non_ccRCC
PDAC -0.785
UCEC -0.498

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
S 939 U Tuberous sclerosis complex Phosphorylation 12150915
S 939 U Tuberous sclerosis Phosphorylation 12150915
S 939 U Tuberous sclerosis Phosphorylation 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 Ser939 STS(ph)LNERPK A549 Staursporin 6.8192 down
P49815 TSC2 P Ser939 STS(ph)LNERPK BT-474 Lapatinib 5.9606 down
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Pictilisib 6.9957 down
P49815 TSC2 P Ser939 STS(ph)LNERPK MDA-MB-175 Pertuzumab -4.7286 down
P49815 TSC2 P Ser939 STS(ph)LNERPK MDA-MB-175 Lapatinib 6.808 down
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 AZD8055 5.7348 down
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Dactolisib 7.1906 down
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Nintedanib 5.3946 down
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 MK2206 6.5826 down
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab -1.2453 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab -1.4011 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab -3.2384 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab 1.5587 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab 1.4812 -
P49815 TSC2 P Ser939 STS(ph)LNERPK BT-474 Pertuzumab -1.7713 -
P49815 TSC2 P Ser939 STS(ph)LNERPK BT-474 Trastuzumab -1.6391 -
P49815 TSC2 P Ser939 STS(ph)LNERPK HeLa CUDC101 6.4565 -
P49815 TSC2 P Ser939 STS(ph)LNERPK KYSE-520 SHP099 5.0682 -
P49815 TSC2 P Ser939 STS(ph)LNERPK MDA-MB-175 Trastuzumab 0.1851 -
P49815 TSC2 P Ser939 STS(ph)LNERPK Ramos Rituximab -2.0335 -
P49815 TSC2 P Ser939 STS(ph)LNERPK Ramos Rituximab -2.4428 -
P49815 TSC2 P Ser939 STS(ph)LNERPK Ramos Rituximab -0.4644 -
P49815 TSC2 P Ser939 STS(ph)LNERPK Ramos Rituximab -2.8846 -
P49815 TSC2 P Ser939 STS(ph)LNERPK Ramos Rituximab -1.7006 -
P49815 TSC2 P Ser939 STS(ph)LNERPK Ramos Rituximab -1.5435 -
P49815 TSC2 P Ser939 STS(ph)LNERPK SK-BR-3 Pertuzumab -3.2427 -
P49815 TSC2 P Ser939 STS(ph)LNERPK SU-DHL-4 Rituximab -1.921 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Gefitinib 6.7404 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Afatinib 8.0745 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Afatinib 7.7804 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Afatinib 7.2435 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Dasatinib 6.154 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Dasatinib 5.815 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Dasatinib 5.2634 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Dasatinib 5.4571 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Gefitinib 6.1548 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Gefitinib 6.3656 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Gefitinib 6.2828 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab -1.2228 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Dasatinib 6.8252 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Dasatinib 6.5207 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 PD325901 10.8089 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 PD325901 8.5481 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Refametinib 7.1285 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A549 Tideglusib 7.7594 -
P49815 TSC2 P Ser939 STS(ph)LNERPK A431 Afatinib 7.8447 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab -1.2038 -
P49815 TSC2 P Ser939 STS(ph)LNERPK ARH-77 Rituximab -0.5646 -

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: