Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0W9GE7)

• DOT Name: Mitogen-activated protein kinase 13 (MAPK13)
• Synonyms: MAP kinase 13; MAPK 13; EC 2.7.11.24; Mitogen-activated protein kinase p38 delta; MAP kinase p38 delta; Stress-activated protein kinase 4
• Gene Name: MAPK13
• Related Disease:
  Diabetic retinopathy
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cholangiocarcinoma
  Cholestasis
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Neuronal ceroid lipofuscinosis
  Triple negative breast cancer
  Chronic obstructive pulmonary disease
  Kidney cancer
  Malignant pleural mesothelioma
  Peritoneal mesothelioma
  Renal carcinoma
  Rheumatoid arthritis
• UniProt ID: MK13_HUMAN
• PDB ID: 3COI; 4EYJ; 4EYM; 4MYG; 4YNO; 5EKN; 5EKO
• EC Number: 2.7.11.24
• Pfam ID: PF00069
• Sequence:
  MSLIRKKGFYKQDVNKTAWELPKTYVSPTHVGSGAYGSVCSAIDKRSGEKVAIKKLSRPF
  QSEIFAKRAYRELLLLKHMQHENVIGLLDVFTPASSLRNFYDFYLVMPFMQTDLQKIMGM
  EFSEEKIQYLVYQMLKGLKYIHSAGVVHRDLKPGNLAVNEDCELKILDFGLARHADAEMT
  GYVVTRWYRAPEVILSWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTG
  VPGTEFVQKLNDKAAKSYIQSLPQTPRKDFTQLFPRASPQAADLLEKMLELDVDKRLTAA
  QALTHPFFEPFRDPEEETEAQQPFDDSLEHEKLTVDEWKQHIYKEIVNFSPIARKDSRRR
  SGMKL
• Function: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.
• Tissue Specificity: Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  MAPK sig.ling pathway (hsa04010)
  Rap1 sig.ling pathway (hsa04015)
  FoxO sig.ling pathway (hsa04068)
  Sphingolipid sig.ling pathway (hsa04071)
  Oocyte meiosis (hsa04114)
  Efferocytosis (hsa04148)
  Cellular senescence (hsa04218)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  VEGF sig.ling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  C-type lectin receptor sig.ling pathway (hsa04625)
  IL-17 sig.ling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  Fc epsilon RI sig.ling pathway (hsa04664)
  TNF sig.ling pathway (hsa04668)
  Leukocyte transendothelial migration (hsa04670)
  Thermogenesis (hsa04714)
  Neurotrophin sig.ling pathway (hsa04722)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Dopaminergic sy.pse (hsa04728)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  GnRH sig.ling pathway (hsa04912)
  Progesterone-mediated oocyte maturation (hsa04914)
  Prolactin sig.ling pathway (hsa04917)
  Relaxin sig.ling pathway (hsa04926)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Growth hormone synthesis, secretion and action (hsa04935)
  Alcoholic liver disease (hsa04936)
  Amyotrophic lateral sclerosis (hsa05014)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Proteoglycans in cancer (hsa05205)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  p38MAPK events (R-HSA-171007)
  DSCAM interactions (R-HSA-376172)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  NOD1/2 Signaling Pathway (R-HSA-168638)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[4]
Cholestasis	DISDJJWE	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Neuronal ceroid lipofuscinosis	DIS9A4K4	Strong	Biomarker	[8]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[9]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[10]
Kidney cancer	DISBIPKM	Limited	Altered Expression	[2]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[11]
Peritoneal mesothelioma	DISW7W4V	Limited	Genetic Variation	[11]
Renal carcinoma	DISER9XT	Limited	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[12]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Mitogen-activated protein kinase 13 (MAPK13) decreases the response to substance of Afimoxifene.	[35]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Mitogen-activated protein kinase 13 (MAPK13).	[13]
Sulfate	DMW0ZBF	Investigative	Sulfate affects the methylation of Mitogen-activated protein kinase 13 (MAPK13).	[34]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[18]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[21]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitogen-activated protein kinase 13 (MAPK13).	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[23]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[24]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[25]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[26]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Mitogen-activated protein kinase 13 (MAPK13).	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[32]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Mitogen-activated protein kinase 13 (MAPK13).	[33]

References

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