Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSXYVW1)

• DOT Name: Rho-associated protein kinase 1 (ROCK1)
• Synonyms: EC 2.7.11.1; Renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing protein kinase 1; Rho-associated, coiled-coil-containing protein kinase I; ROCK-I; p160 ROCK-1; p160ROCK
• Gene Name: ROCK1
• UniProt ID: ROCK1_HUMAN
• PDB ID: 1S1C; 2ESM; 2ETK; 2ETR; 2V55; 3D9V; 3NCZ; 3NDM; 3O0Z; 3TV7; 3TWJ; 3V8S; 4L2W; 4W7P; 4YVC; 4YVE; 5BML; 5F5P; 5HVU; 5KKS; 5KKT; 5UZJ; 5WNE; 5WNF; 5WNG; 5WNH; 6E9W; 7JOU; 7S25; 7S26; 8P0S
• EC Number: 2.7.11.1
• Pfam ID: PF00069 ; PF08912
• Sequence:
  MSTGDSFETRFEKMDNLLRDPKSEVNSDCLLDGLDALVYDLDFPALRKNKNIDNFLSRYK
  DTINKIRDLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAF
  FWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTA
  EVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTAVGTPDY
  ISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFP
  DDNDISKEAKNLICAFLTDREVRLGRNGVEEIKRHLFFKNDQWAWETLRDTVAPVVPDLS
  SDIDTSNFDDLEEDKGEEETFPIPKAFVGNQLPFVGFTYYSNRRYLSSANPNDNRTSSNA
  DKSLQESLQKTIYKLEEQLHNEMQLKDEMEQKCRTSNIKLDKIMKELDEEGNQRRNLEST
  VSQIEKEKMLLQHRINEYQRKAEQENEKRRNVENEVSTLKDQLEDLKKVSQNSQLANEKL
  SQLQKQLEEANDLLRTESDTAVRLRKSHTEMSKSISQLESLNRELQERNRILENSKSQTD
  KDYYQLQAILEAERRDRGHDSEMIGDLQARITSLQEEVKHLKHNLEKVEGERKEAQDMLN
  HSEKEKNNLEIDLNYKLKSLQQRLEQEVNEHKVTKARLTDKHQSIEEAKSVAMCEMEKKL
  KEEREAREKAENRVVQIEKQCSMLDVDLKQSQQKLEHLTGNKERMEDEVKNLTLQLEQES
  NKRLLLQNELKTQAFEADNLKGLEKQMKQEINTLLEAKRLLEFELAQLTKQYRGNEGQMR
  ELQDQLEAEQYFSTLYKTQVKELKEEIEEKNRENLKKIQELQNEKETLATQLDLAETKAE
  SEQLARGLLEEQYFELTQESKKAASRNRQEITDKDHTVSRLEEANSMLTKDIEILRRENE
  ELTEKMKKAEEEYKLEKEEEISNLKAAFEKNINTERTLKTQAVNKLAEIMNRKDFKIDRK
  KANTQDLRKKEKENRKLQLELNQEREKFNQMVVKHQKELNDMQAQLVEECAHRNELQMQL
  ASKESDIEQLRAKLLDLSDSTSVASFPSADETDGNLPESRIEGWLSVPNRGNIKRYGWKK
  QYVVVSSKKILFYNDEQDKEQSNPSMVLDIDKLFHVRPVTQGDVYRAETEEIPKIFQILY
  ANEGECRKDVEMEPVQQAEKTNFQNHKGHEFIPTLYHFPANCDACAKPLWHVFKPPPALE
  CRRCHVKCHRDHLDKKEDLICPCKVSYDVTSARDMLLLACSQDEQKKWVTHLVKKIPKNP
  PSGFVRASPRTLSTRSTANQSFRKVVKNTSGKTS
• Function: Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles.
• Tissue Specificity: Detected in blood platelets.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Chemokine sig.ling pathway (hsa04062)
  Sphingolipid sig.ling pathway (hsa04071)
  Vascular smooth muscle contraction (hsa04270)
  TGF-beta sig.ling pathway (hsa04350)
  Axon guidance (hsa04360)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Platelet activation (hsa04611)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Oxytocin sig.ling pathway (hsa04921)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Yersinia infection (hsa05135)
  Human cytomegalovirus infection (hsa05163)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  EPHB-mediated forward signaling (R-HSA-3928662)
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  G alpha (12/13) signalling events (R-HSA-416482)
  Sema4D induced cell migration and growth-cone collapse (R-HSA-416572)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RHO GTPases Activate ROCKs (R-HSA-5627117)
  Neutrophil degranulation (R-HSA-6798695)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  Potential therapeutics for SARS (R-HSA-9679191)
  RND3 GTPase cycle (R-HSA-9696264)
  Apoptotic cleavage of cellular proteins (R-HSA-111465)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Leptin	DM5LY1H	Investigative	Rho-associated protein kinase 1 (ROCK1) increases the Ovarian cancer ADR of Leptin.	[27]

4 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 Rho-associated protein kinase 1 (ROCK1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rho-associated protein kinase 1 (ROCK1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Rho-associated protein kinase 1 (ROCK1).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Rho-associated protein kinase 1 (ROCK1).	[19]

26 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 Rho-associated protein kinase 1 (ROCK1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Rho-associated protein kinase 1 (ROCK1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho-associated protein kinase 1 (ROCK1).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[10]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Rho-associated protein kinase 1 (ROCK1).	[11]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Rho-associated protein kinase 1 (ROCK1).	[12]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Rho-associated protein kinase 1 (ROCK1).	[9]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the activity of Rho-associated protein kinase 1 (ROCK1).	[14]
Pamidronate	DMB4AVP	Approved	Pamidronate decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[15]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[16]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Rho-associated protein kinase 1 (ROCK1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Rho-associated protein kinase 1 (ROCK1).	[18]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rho-associated protein kinase 1 (ROCK1).	[21]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Rho-associated protein kinase 1 (ROCK1).	[18]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Rho-associated protein kinase 1 (ROCK1).	[23]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Rho-associated protein kinase 1 (ROCK1).	[24]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Rho-associated protein kinase 1 (ROCK1).	[18]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Rho-associated protein kinase 1 (ROCK1).	[25]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Rho-associated protein kinase 1 (ROCK1).	[26]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Rho-associated protein kinase 1 (ROCK1).	[18]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acocantherin	DM7JT24	Approved	Acocantherin increases the cleavage of Rho-associated protein kinase 1 (ROCK1).	[13]

References

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