Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4AVU95)

• DOT Name: Protein phosphatase 1 regulatory subunit 12A (PPP1R12A)
• Synonyms: Myosin phosphatase-targeting subunit 1; Myosin phosphatase target subunit 1; Protein phosphatase myosin-binding subunit
• Gene Name: PPP1R12A
• Related Disease:
  Abdominal aortic aneurysm
  Bartter syndrome
  Cardiac failure
  Chagas disease
  Colorectal carcinoma
  Congestive heart failure
  Gastric disease
  Genitourinary and/or brain malformation syndrome
  Holoprosencephaly
  Huntington disease
  Intellectual disability
  Neoplasm
  Retinal vein occlusion
  Advanced cancer
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Influenza
  Neuroendocrine cancer
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Rhabdomyosarcoma
  Asthma
  Gastric cancer
  Gitelman syndrome
  Leiomyosarcoma
  Mesothelioma
  Neuroblastoma
  Stomach cancer
  Type-1/2 diabetes
• UniProt ID: MYPT1_HUMAN
• PDB ID: 2KJY; 5HUZ
• Pfam ID: PF12796 ; PF15898
• Sequence:
  MKMADAKQKRNEQLKRWIGSETDLEPPVVKRQKTKVKFDDGAVFLAACSSGDTDEVLKLL
  HRGADINYANVDGLTALHQACIDDNVDMVKFLVENGANINQPDNEGWIPLHAAASCGYLD
  IAEFLIGQGAHVGAVNSEGDTPLDIAEEEAMEELLQNEVNRQGVDIEAARKEEERIMLRD
  ARQWLNSGHINDVRHAKSGGTALHVAAAKGYTEVLKLLIQAGYDVNIKDYDGWTPLHAAA
  HWGKEEACRILVDNLCDMEMVNKVGQTAFDVADEDILGYLEELQKKQNLLHSEKRDKKSP
  LIESTANMDNNQSQKTFKNKETLIIEPEKNASRIESLEQEKVDEEEEGKKDESSCSSEED
  EEDDSESEAETDKTKPLASVTNANTSSTQAAPVAVTTPTVSSGQATPTSPIKKFPTTATK
  ISPKEEERKDESPATWRLGLRKTGSYGALAEITASKEGQKEKDTAGVTRSASSPRLSSSL
  DNKEKEKDSKGTRLAYVAPTIPRRLASTSDIEEKENRDSSSLRTSSSYTRRKWEDDLKKN
  SSVNEGSTYHKSCSFGRRQDDLISSSVPSTTSTPTVTSAAGLQKSLLSSTSTTTKITTGS
  SSAGTQSSTSNRLWAEDSTEKEKDSVPTAVTIPVAPTVVNAAASTTTLTTTTAGTVSSTT
  EVRERRRSYLTPVRDEESESQRKARSRQARQSRRSTQGVTLTDLQEAEKTIGRSRSTRTR
  EQENEEKEKEEKEKQDKEKQEEKKESETSREDEYKQKYSRTYDETYQRYRPVSTSSSTTP
  SSSLSTMSSSLYASSQLNRPNSLVGITSAYSRGITKENEREGEKREEEKEGEDKSQPKSI
  RERRRPREKRRSTGVSFWTQDSDENEQEQQSDTEEGSNKKETQTDSISRYETSSTSAGDR
  YDSLLGRSGSYSYLEERKPYSSRLEKDDSTDFKKLYEQILAENEKLKAQLHDTNMELTDL
  KLQLEKATQRQERFADRSLLEMEKRERRALERRISEMEEELKMLPDLKADNQRLKDENGA
  LIRVISKLSK
• Function: Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity.
• Tissue Specificity: Expressed in striated muscles, specifically in type 2a fibers (at protein level).
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Vascular smooth muscle contraction (hsa04270)
  Focal adhesion (hsa04510)
  Platelet activation (hsa04611)
  Regulation of actin cytoskeleton (hsa04810)
  Oxytocin sig.ling pathway (hsa04921)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  RHO GTPases activate PKNs (R-HSA-5625740)
  RHO GTPases activate CIT (R-HSA-5625900)
  RHO GTPases Activate ROCKs (R-HSA-5627117)
  RHO GTPases activate PAKs (R-HSA-5627123)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Posttranslational Modification	[1]
Bartter syndrome	DIS7D44B	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Altered Expression	[3]
Chagas disease	DIS8KNVF	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[3]
Gastric disease	DISNZNTG	Strong	Biomarker	[6]
Genitourinary and/or brain malformation syndrome	DISD071D	Strong	Autosomal dominant	[7]
Holoprosencephaly	DISR35EC	Strong	Biomarker	[8]
Huntington disease	DISQPLA4	Strong	Altered Expression	[9]
Intellectual disability	DISMBNXP	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Retinal vein occlusion	DISSVWOE	Strong	Posttranslational Modification	[11]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[12]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[14]
Influenza	DIS3PNU3	moderate	Biomarker	[15]
Neuroendocrine cancer	DISVGJET	moderate	Biomarker	[16]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[13]
Prostate cancer	DISF190Y	moderate	Biomarker	[17]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[17]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[16]
Asthma	DISW9QNS	Limited	Altered Expression	[18]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[19]
Gitelman syndrome	DISEM9V2	Limited	Posttranslational Modification	[20]
Leiomyosarcoma	DIS6COXM	Limited	Posttranslational Modification	[21]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[22]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[23]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[19]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Protein phosphatase 1 regulatory subunit 12A (PPP1R12A) increases the Metabolic disorder ADR of Chlorothiazide.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[25]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[31]
Norepinephrine	DMOUC09	Approved	Norepinephrine increases the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[36]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[31]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[31]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[41]
Forskolin	DM6ITNG	Investigative	Forskolin increases the phosphorylation of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[28]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[30]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the activity of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[32]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[33]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[34]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[35]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein phosphatase 1 regulatory subunit 12A (PPP1R12A).	[40]

References

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