Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4KS2UU)

• DOT Name: Gelsolin (GSN)
• Synonyms: AGEL; Actin-depolymerizing factor; ADF; Brevin
• Gene Name: GSN
• Related Disease: Finnish type amyloidosis
• UniProt ID: GELS_HUMAN
• PDB ID: 1C0F ; 1C0G ; 1D4X ; 1DEJ ; 1EQY ; 1ESV ; 1H1V ; 1KCQ ; 1MDU ; 1NLV ; 1NM1 ; 1NMD ; 1P8X ; 1P8Z ; 1SOL ; 1T44 ; 1YAG ; 1YVN ; 2FF3 ; 2FF6 ; 2FH1 ; 2FH2 ; 2FH3 ; 2FH4 ; 3A5L ; 3A5M ; 3A5N ; 3A5O ; 3CI5 ; 3CIP ; 3CJB ; 3CJC ; 3FFK ; 3FFN ; 3TU5 ; 4PKG ; 4PKH ; 4PKI ; 4S10 ; 4Z94 ; 5FAE ; 5FAF ; 5H3M ; 5H3N ; 5O2Z ; 5UBO ; 5ZZ0 ; 6H1F ; 6JCO ; 6JEG ; 6JEH ; 6LJE ; 6LJF ; 6Q9R ; 6Q9Z ; 6QBF ; 6QW3 ; 7P2B
• Pfam ID: PF00626
• Sequence:
  MAPHRPAPALLCALSLALCALSLPVRAATASRGASQAGAPQGRVPEARPNSMVVEHPEFL
  KAGKEPGLQIWRVEKFDLVPVPTNLYGDFFTGDAYVILKTVQLRNGNLQYDLHYWLGNEC
  SQDESGAAAIFTVQLDDYLNGRAVQHREVQGFESATFLGYFKSGLKYKKGGVASGFKHVV
  PNEVVVQRLFQVKGRRVVRATEVPVSWESFNNGDCFILDLGNNIHQWCGSNSNRYERLKA
  TQVSKGIRDNERSGRARVHVSEEGTEPEAMLQVLGPKPALPAGTEDTAKEDAANRKLAKL
  YKVSNGAGTMSVSLVADENPFAQGALKSEDCFILDHGKDGKIFVWKGKQANTEERKAALK
  TASDFITKMDYPKQTQVSVLPEGGETPLFKQFFKNWRDPDQTDGLGLSYLSSHIANVERV
  PFDAATLHTSTAMAAQHGMDDDGTGQKQIWRIEGSNKVPVDPATYGQFYGGDSYIILYNY
  RHGGRQGQIIYNWQGAQSTQDEVAASAILTAQLDEELGGTPVQSRVVQGKEPAHLMSLFG
  GKPMIIYKGGTSREGGQTAPASTRLFQVRANSAGATRAVEVLPKAGALNSNDAFVLKTPS
  AAYLWVGTGASEAEKTGAQELLRVLRAQPVQVAEGSEPDGFWEALGGKAAYRTSPRLKDK
  KMDAHPPRLFACSNKIGRFVIEEVPGELMQEDLATDDVMLLDTWDQVFVWVGKDSQEEEK
  TEALTSAKRYIETDPANRDRRTPITVVKQGFEPPSFVGWFLGWDDDYWSVDPLDRAMAEL
  AA
• Function: Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis.
• Tissue Specificity: Phagocytic cells, platelets, fibroblasts, nonmuscle cells, smooth and skeletal muscle cells.
• KEGG Pathway:
  Fc gamma R-mediated phagocytosis (hsa04666)
  Regulation of actin cytoskeleton (hsa04810)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Amyloid fiber formation (R-HSA-977225)
  Caspase-mediated cleavage of cytoskeletal proteins (R-HSA-264870)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Finnish type amyloidosis	DISWU9AH	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Menadione	DMSJDTY	Approved	Gelsolin (GSN) affects the response to substance of Menadione.	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Gelsolin (GSN).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Gelsolin (GSN).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Gelsolin (GSN).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Gelsolin (GSN).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Gelsolin (GSN).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Gelsolin (GSN).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gelsolin (GSN).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Gelsolin (GSN).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Gelsolin (GSN).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Gelsolin (GSN).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Gelsolin (GSN).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Gelsolin (GSN).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Gelsolin (GSN).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Gelsolin (GSN).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Gelsolin (GSN).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Gelsolin (GSN).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Gelsolin (GSN).	[17]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Gelsolin (GSN).	[18]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Gelsolin (GSN).	[19]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Gelsolin (GSN).	[20]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Gelsolin (GSN).	[21]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Gelsolin (GSN).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Gelsolin (GSN).	[23]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Gelsolin (GSN).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Gelsolin (GSN).	[15]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Gelsolin (GSN).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Gelsolin (GSN).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Gelsolin (GSN).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Gelsolin (GSN).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Gelsolin (GSN).	[30]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Gelsolin (GSN).	[33]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Gelsolin (GSN).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
ABT-263	DMNE56X	Phase 3	ABT-263 increases the cleavage of Gelsolin (GSN).	[24]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the secretion of Gelsolin (GSN).	[32]
toxaphene	DM4R657	Investigative	toxaphene increases the degradation of Gelsolin (GSN).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gelsolin (GSN).	[29]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of Gelsolin (GSN).	[31]

References

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