Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXFCK1B)

• DOT Name: Ferroxidase HEPHL1 (HEPHL1)
• Synonyms: EC 1.16.3.1; Hephaestin-like protein 1
• Gene Name: HEPHL1
• Related Disease: Pili torti-developmental delay-neurological abnormalities syndrome
• UniProt ID: HPHL1_HUMAN
• EC Number: 1.16.3.1
• Pfam ID: PF07731 ; PF07732
• Sequence:
  MPRKQPAGCIFLLTFLGLSGLVGTVTRTYYIGIVEEYWNYVPQGKNVITGKSFTEDKLAT
  LFLERGPNRIGSIYKKAVYRRFTDGTYSIEIPKPPWLGFLGPILRAEVGDVIVIHLKNFA
  SRPYSLHPHGVFYNKDSEGALYPDGTSGRNKNDDMVPPGKNYTYVWPVREEYAPTPADAN
  CLTWVYHSHIDAPKDICSGLIGPLLVCKEGILNRYSGTRNDVDREFVIMFTLVDENQSWY
  LNENIKHFCTNPDSVDKKDAVFQRSNKMHALNGYLFGNFPEPDMCVGESVSWHLFGMGNE
  IDIHSIYFYGNTFISRGHRTDVVNLFPATFLTTEMIAENPGKWMITCQVSDHLQAGMLGQ
  YNVDNCKSDIFYPKMKGQQRRYFIAAEKILWDYAPQGYNKFSGLPLNASGSDSDLYFTQG
  DNRIGGKYWKVRYTEFVDATFTKRKRLSAEEAHLGILGPVIKAEVGDTLLVTFANKADKV
  YSILPHGVIYDKASDAAPNLDGFVKPGAHVKPGETFTYKWTVPESVSPTAGDPPCLTYLY
  FSAVDPIKDTSSGLVGPLLVCKKGVLNADGTQKGIDKEFYLLFTVFDENLSRYFDENIQK
  FIWHPFSIDKEDKEFVKSNRMHAVNGYMYGNQPGLNMCKRDRVSWHLIGLGTDTDMHGIV
  FQGNTIHLRGTHRDSLALFPHMATTAFMQPDHAGIFRVFCATMPHLSRGMGQIYEVSSCD
  NRDPSEQRYGMIRTFYIAAEEVEWDYAPNKNWEFEKQHVDARGERHGDIFMNRTENWIGS
  QYKKVVYREYTDGEFVEIKARPPREEHLELLGPMIHAEVGNTVLIIFKNKASRPYSISAQ
  GVEEMDSGKQFQVPMTKPGEVKTYRWNIPKRSGPGPSDPNCIPWVYYSTVNFVKDTYSGL
  MGPLITCRKGVLNEKGRRSDVDYEFALLFLVFNENESWYLDDNIKKYLNKDPRDFKRTDD
  FEESNRMHAINGKIFGNLHGLIMNEDTMTNWYLLGIGSEVDIHTIHYHAESFLFKIDKSY
  REDVYDLFPGTFQTIELFADHPGTWLLHCHVSDHIHAGMETTYTVLRNIDNRIPYSTTSP
  GVASHPATVPSNERPGKEQLYFFGKNLGPTGAKAALVILFIIGLLLLITTVILSLRLCSA
  MKQTDYQQVQSCALPTDAL
• Function: Is a copper-binding glycoprotein with ferroxidase activity. It oxidizes Fe(2+) to Fe(3+) without releasing radical oxygen species. May be involved in the regulation of intracellular iron content.
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Mineral absorption (hsa04978)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pili torti-developmental delay-neurological abnormalities syndrome	DISA0YS0	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ferroxidase HEPHL1 (HEPHL1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ferroxidase HEPHL1 (HEPHL1).	[3]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Ferroxidase HEPHL1 (HEPHL1).	[4]

References

• [1] Biallelic HEPHL1 variants impair ferroxidase activity and cause an abnormal hair phenotype. PLoS Genet. 2019 May 24;15(5):e1008143. doi: 10.1371/journal.pgen.1008143. eCollection 2019 May.
• [2] 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.
• [3] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [4] Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells. Toxicol Lett. 2018 Jun 1;289:42-53. doi: 10.1016/j.toxlet.2018.03.003. Epub 2018 Mar 5.