Id: acc2286
Group: 2sens
Protein: RB
Gene Symbol: RB1
Protein Id: P06400
Protein Name: RB_HUMAN
PTM: phosphorylation
Site: Ser811
Site Sequence: GNIYISPLKSPYKISEGLPTP
Disease Category: Cancer
Disease: Breast Cancer
Disease Subtype: EGFR-high/ERBB2-amplified
Disease Cellline: SK-BR-3
Disease Info:
Drug: erlotinib + trastuzumab
Drug Info: "Erlotinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used primarily in the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations, as well as pancreatic cancer in combination with chemotherapy. Trastuzumab is a humanized monoclonal antibody targeting HER2/neu receptors, approved for HER2-positive breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma."
Effect: modulate
Effect Info: "Erlotinib significantly reduced the phosphorylation levels of RPS6 and RB by inhibiting the EGFR signaling pathway, thereby suppressing the growth and proliferation of tumor cells."
Note:
Score: 4.0
Pubmed(PMID): 23552733
Sentence Index:
Sentence:

Sequence & Structure:

MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTALCQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIAAVDLDEMSFTFTELQKNIEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSSISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQLMLCVLDYFIKLSPPMLLKEPYKTAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFMNSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDARLFLDHDKTLQTDSIDSFETQRTPRKSNLDEEVNVIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVKDIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDNIFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEGNLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNHTAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYLRLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLKFKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLSPIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFGTSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQKLAEMTSTRTRMQKQKMNDSMDTSNKEEK

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
RB1-Ser811
Cancer Intensity
BRCA 0.326
COAD -0.737
HGSC 1.982
ccRCC
GBM -0.759
HNSC 0.242
LUAD
LUSC -1.24
non_ccRCC
PDAC 0.434
UCEC -0.248

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
S 811 D Skin cancer Phosphorylation 23888052
S 811 U Intraocular melanoma Phosphorylation 10969768 ;  10969768
S 811 U Bladder cancer Phosphorylation 22787429
S 811 U Neuroendocrine cancer/carcinoma Phosphorylation 24135281
S 811 U Melanoma Phosphorylation 15502804 ;  15502804
S 811 U Pancreatic cancer/carcinoma/adenocarcinoma Phosphorylation 23408967

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
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 AZD8055 6.0392 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Tideglusib 4.8968 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Staursporin 11.4859 -
P06400 RB1 P Ser811 IPGGNIYISPLKS(ph)PYK A549 Pictilisib 8.291 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Pictilisib 10.5849 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 PD325901 9.0766 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Nintedanib 8.0388 -
P06400 RB1 P Ser811 IPGGNIYISPLKS(ph)PYK A549 Dasatinib 2 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Dasatinib 6.2296 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Dasatinib 6.7852 -
P06400 RB1 P Tyr805;Ser811 IPGGNIY(ph)ISPLKS(ph)PYK A549 Dasatinib 10.7569 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A549 Dactolisib 10.8604 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Afatinib 7.2979 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Gefitinib 6.2454 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Gefitinib 8.2708 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Gefitinib 7.7927 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Dasatinib 9.0028 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Dasatinib 8.9649 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Dasatinib 2 -
P06400 RB1 P Ser811 IPGGNIYISPLKS(ph)PYK A431 Dasatinib 5.5362 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Dasatinib 12.3408 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Afatinib 7.9015 -
P06400 RB1 P Ser807;Ser811 IPGGNIYIS(ph)PLKS(ph)PYK A431 Afatinib 8.3885 -

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: