Id: | acc1863 |
Group: | 2sens |
Protein: | HSP70 |
Gene Symbol: | HSPA1A |
Protein Id: | P0DMV8 |
Protein Name: | HS71A_HUMAN |
PTM: | methylation |
Site: | Arg447 |
Site Sequence: | VLIQVYEGERAMTKDNNLLGR |
Disease Category: | Cancer |
Disease: | Pancreas Cancer |
Disease Subtype: | |
Disease Cellline: | MIA PaCa-2 |
Disease Info: | |
Drug: | gemcitabine |
Drug Info: | "Gemcitabine is a pyrimidine nucleoside analog antimetabolite and antineoplastic agent that inhibits DNA synthesis and repair, leading to autophagy and apoptosis, and is used in the treatment of various solid tumors including non-small cell lung cancer, pancreatic cancer, breast cancer, and ovarian cancer. " |
Effect: | resist |
Effect Info: | Overexpression of PRMT1 (which can be inhibited by DB75 and TC - E5003) increases arginine methylation of HSP70 and protects cancer cells from apoptosis induced by cellular stress and the therapeutic drug gemcitabine. |
Note: | |
Score: | 5.0 |
Pubmed(PMID): | 32699135 |
Sentence Index: | 32699135_4-5 |
Sentence: | "In this study, we report that PRMT1 expression is increased in pancreatic cancer tissues and is associated with higher tumor grade, increased aggressiveness, and worse prognosis. PRMT1 overexpression increased arginine methylation of HSPs of 70 kDa (HSP70); this methylation enhanced HSP70 binding and stabilization of BCL2 mRNA through AU-rich elements in 3'-untranslated region and consequentially increased BCL2 protein expression and protected cancer cells from apoptosis induced by cellular stresses and therapeutics." |
Sequence & Structure:
MAKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRLIGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEISSMVLTKMKEIAEAYLGYPVTNAVITVPAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEVKATAGDTHLGGEDFDNRLVNHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGIDFYTSITRARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINPDEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQIFTTYSDNQPGVLIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGRLSKEEIERMVQEAEKYKAEDEVQRERVSAKNALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDANTLAEKDEFEHKRKELEQVCNPIISGLYQGAGGPGPGGFGAQGPKGGSGSGPTIEEVD
Select PDB:
Target | Drug name | MOA | Phase | Status | Disease | Source |
---|---|---|---|---|---|---|
HSPA1A | CD24FC | Heat shock 70 kDa protein 1A/1B inhibitor | 3 | Completed | COVID-19 | ClinicalTrials |
HSPA1A | CD24FC | Heat shock 70 kDa protein 1A/1B inhibitor | 1 | Terminated | neoplasm | ClinicalTrials |
HSPA1A | CD24FC | Heat shock 70 kDa protein 1A/1B inhibitor | 1 | Withdrawn | metastatic melanoma | ClinicalTrials |
Note: Only show clinically investigational or approved drugs with protein targets.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTACNo data.
PTM-Disease Association:
source: PTMDResidue | Position | State | Disease | Class | PMID |
---|---|---|---|---|---|
S | 631 | D | Pulmonary hypertension | Phosphorylation | 30485823 |
K | 126 | U | Breast cancer | Acetylation | 30352233 |
K | 561 | U | Breast cancer/tumor/carcinoma | Methylation | 26448330 |
K | 561 | U | Ovarian cancer/carcinoma | Methylation | 26448330 |
K | 561 | U | Adenocarcinoma | Methylation | 22990868 |
K | 561 | U | Bladder cancer | Methylation | 22990868 |
K | 561 | U | Cancer | Methylation | 22990868 |
K | 561 | U | Cervical cancer/carcinoma | Methylation | 22990868 |
K | 561 | U | Colon cancer/carcinoma | Methylation | 22990868 |
K | 561 | U | Hepatocellular carcinoma/hepatocarcinoma/hepatoma | Methylation | 22990868 |
K | 561 | U | Lung adenocarcinoma | Methylation | 22990868 |
K | 561 | U | Lung cancer/carcinoma | Methylation | 22990868 |
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: DecryptMNo data.
Function score:
source: funscoRNo data.