Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9R78BU)

• DOT Name: FHF complex subunit HOOK-interacting protein 1A (FHIP1A)
• Synonyms: FHIP1A; FTS- and Hook-interacting protein like; FHIP-L
• Gene Name: FHIP1A
• UniProt ID: FHI1A_HUMAN
• Pfam ID: PF19314 ; PF19311 ; PF10257
• Sequence:
  MMSSVSTESKLQQAVSLQGVDPETCMIVFKNHWAQVVKILEKHDPLKNTQAKYGSIPPDE
  ASAVQNYVEHMLFLLIEEQAKDAAMGPILEFVVSENIMEKLFLWSLRREFTDETKIEQLK
  MYEMLVTQSHQPLLHHKPILKPLMMLLSSCSGTTTPTVEEKLVVLLNQLCSILAKDPSIL
  ELFFHTSEDQGAANFLIFSLLIPFIHREGSVGQQARDALLFIMSLSAENTMVAHHIVENT
  YFCPVLATGLSGLYSSLPTKLEEKGEEWHCLLKDDWLLLPSLVQFMNSLEFCNAVIQVAH
  PLIRNQLVNYIYNGFLVPVLAPALHKVTVEEVMTTTAYLDLFLRSISEPALLEIFLRFIL
  LHQHENVHILDTLTSRINTPFRLCVVSLALFRTLIGLHCEDVMLQLVLRYLIPCNHMMLS
  QRWAVKERDCYSVSAAKLLALTPVCCSSGITLTLGNQERDYILWSKCMHDTSGPVERPFP
  EAFSESACIVEYGKALDISYLQYLWEAHTNILRCMRDCRVWSALYDGDSPDPEMFLQSLT
  EEGSVSSACPVFGLPQQLPRKTGPQLAPRKDKSQTELEWDDSYDTGISSGADVGSPGPYD
  DLEVSGPPAPIDPPKHIQEMKKNALLLFKGSYIEESDFQDDVMVYRLCAEKDSEDMKDSQ
  EEAARPPAEAQAEVQSVPINNGPLLSTQPETDSEEEWNRDNSDPFHSEPKEPKQEREPEA
  APESNSELASPAPEAEHSSNLTAAHPESEELIAQYDQIIKELDSGAEGLMEQNYPTPDPL
  LLTKEEEGKEESKGEKEKEGKKELEDEEDDFDSFIAEMPAVETVPSPFVGRDEAAFASRH
  PVRTQSTPFTGPFISVVLSKLENMLENSLHVNLLLIGIITQLASYPQPLLRSFLLNTNMV
  FQPSVRSLYQVLASVKNKIEQFASVERDFPGLLIQAQQYLLFRVDMSDMTPAALTKDPIQ
  EASRTGSGKNLLDGPPRVLQPFLTHRTKVAEAPPNLPLPVRNPMLAAALFPEFLKELAAL
  AQEHSILCYKILGDFEDSCC
• Function: Probable component of the FTS/Hook/FHIP complex (FHF complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of FHF complex subunit HOOK-interacting protein 1A (FHIP1A).	[8]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.