Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT560QR5)

• DOT Name: Hornerin (HRNR)
• Gene Name: HRNR
• Related Disease:
  Anaplastic large cell lymphoma
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic cancer
  Pancreatic tumour
  Allergic contact dermatitis
  Hepatocellular carcinoma
• UniProt ID: HORN_HUMAN
• Pfam ID: PF01023
• Sequence:
  MPKLLQGVITVIDVFYQYATQHGEYDTLNKAELKELLENEFHQILKNPNDPDTVDIILQS
  LDRDHNKKVDFTEYLLMIFKLVQARNKIIGKDYCQVSGSKLRDDTHQHQEEQEETEKEEN
  KRQESSFSHSSWSAGENDSYSRNVRGSLKPGTESISRRLSFQRDFSGQHNSYSGQSSSYG
  EQNSDSHQSSGRGQCGSGSGQSPNYGQHGSGSGQSSSNDTHGSGSGQSSGFSQHKSSSGQ
  SSGYSQHGSGSGHSSGYGQHGSRSGQSSRGERHRSSSGSSSSYGQHGSGSRQSLGHGRQG
  SGSRQSPSHVRHGSGSGHSSSHGQHGSGSSYSYSRGHYESGSGQTSGFGQHESGSGQSSG
  YSKHGSGSGHSSSQGQHGSTSGQASSSGQHGSSSRQSSSYGQHESASRHSSGRGQHSSGS
  GQSPGHGQRGSGSGQSPSSGQHGTGFGRSSSSGPYVSGSGYSSGFGHHESSSEHSSGYTQ
  HGSGSGHSSGHGQHGSRSGQSSRGERQGSSAGSSSSYGQHGSGSRQSLGHSRHGSGSGQS
  PSPSRGRHESGSRQSSSYGPHGYGSGRSSSRGPYESGSGHSSGLGHQESRSGQSSGYGQH
  GSSSGHSSTHGQHGSTSGQSSSCGQHGATSGQSSSHGQHGSGSSQSSRYGQQGSGSGQSP
  SRGRHGSDFGHSSSYGQHGSGSGWSSSNGPHGSVSGQSSGFGHKSGSGQSSGYSQHGSGS
  SHSSGYRKHGSRSGQSSRSEQHGSSSGLSSSYGQHGSGSHQSSGHGRQGSGSGHSPSRVR
  HGSSSGHSSSHGQHGSGTSCSSSCGHYESGSGQASGFGQHESGSGQGYSQHGSASGHFSS
  QGRHGSTSGQSSSSGQHDSSSGQSSSYGQHESASHHASGRGRHGSGSGQSPGHGQRGSGS
  GQSPSYGRHGSGSGRSSSSGRHGSGSGQSSGFGHKSSSGQSSGYTQHGSGSGHSSSYEQH
  GSRSGQSSRSEQHGSSSGSSSSYGQHGSGSRQSLGHGQHGSGSGQSPSPSRGRHGSGSGQ
  SSSYGPYRSGSGWSSSRGPYESGSGHSSGLGHRESRSGQSSGYGQHGSSSGHSSTHGQHG
  STSGQSSSCGQHGASSGQSSSHGQHGSGSSQSSGYGRQGSGSGQSPGHGQRGSGSRQSPS
  YGRHGSGSGRSSSSGQHGSGLGESSGFGHHESSSGQSSSYSQHGSGSGHSSGYGQHGSRS
  GQSSRGERHGSSSGSSSHYGQHGSGSRQSSGHGRQGSGSGHSPSRGRHGSGLGHSSSHGQ
  HGSGSGRSSSRGPYESRSGHSSVFGQHESGSGHSSAYSQHGSGSGHFCSQGQHGSTSGQS
  STFDQEGSSTGQSSSYGHRGSGSSQSSGYGRHGAGSGQSPSRGRHGSGSGHSSSYGQHGS
  GSGWSSSSGRHGSGSGQSSGFGHHESSSWQSSGCTQHGSGSGHSSSYEQHGSRSGQSSRG
  ERHGSSSGSSSSYGQHGSGSRQSLGHGQHGSGSGQSPSPSRGRHGSGSGQSSSYSPYGSG
  SGWSSSRGPYESGSSHSSGLGHRESRSGQSSGYGQHGSSSGHSSTHGQHGSTSGQSSSCG
  QHGASSGQSSSHGQHGSGSSQSSGYGRQGSGSGQSPGHGQRGSGSRQSPSYGRHGSGSGR
  SSSSGQHGSGLGESSGFGHHESSSGQSSSYSQHGSGSGHSSGYGQHGSRSGQSSRGERHG
  SSSRSSSRYGQHGSGSRQSSGHGRQGSGSGQSPSRGRHGSGLGHSSSHGQHGSGSGRSSS
  RGPYESRSGHSSVFGQHESGSGHSSAYSQHGSGSGHFCSQGQHGSTSGQSSTFDQEGSST
  GQSSSHGQHGSGSSQSSSYGQQGSGSGQSPSRGRHGSGSGHSSSYGQHGSGSGWSSSSGR
  HGSGSGQSSGFGHHESSSWQSSGYTQHGSGSGHSSSYEQHGSRSGQSSRGEQHGSSSGSS
  SSYGQHGSGSRQSLGHGQHGSGSGQSPSPSRGRHGSGSGQSSSYGPYGSGSGWSSSRGPY
  ESGSGHSSGLGHRESRSGQSSGYGQHGSSSGHSSTHGQHGSASGQSSSCGQHGASSGQSS
  SHGQHGSGSSQSSGYGRQGSGSGQSPGHGQRGSGSRQSPSYGRHGSGSGRSSSSGQHGPG
  LGESSGFGHHESSSGQSSSYSQHGSGSGHSSGYGQHGSRSGQSSRGERHGSSSGSSSRYG
  QHGSGSRQSSGHGRQGSGSGHSPSRGRHGSGSGHSSSHGQHGSGSGRSSSRGPYESRSGH
  SSVFGQHESGSGHSSAYSQHGSGSGHFCSQGQHGSTSGQSSTFDQEGSSTGQSSSHGQHG
  SGSSQSSSYGQQGSGSGQSPSRGRHGSGSGHSSSYGQHGSGSGWSSSSGRHGSGSGQSSG
  FGHHESSSWQSSGYTQHGSGSGHSSSYEQHGSRSGQSSRGERHGSSSGSSSSYGQHGSGS
  RQSLGHGQHGSGSGQSPSPSRGRHGSGSGQSSSYSPYGSGSGWSSSRGPYESGSGHSSGL
  GHRESRSGQSSGYGQHGSSSGHSSTHGQHGSTSGQSSSCGQHGASSGQSSSHGQHGSGSS
  QSSGYGRQGSGSGQSPGHGQRGSGSRQSPSYGRHGSGSGRSSSSGQHGSGLGESSGFGHH
  ESSSGQSSSYSQHGSGSGHSSGYGQHGSRSGQSSRGERHGSSSGSSSHYGQHGSGSRQSS
  GHGRQGSGSGQSPSRGRHGSGLGHSSSHGQHGSGSGRSSSRGPYESRLGHSSVFGQHESG
  SGHSSAYSQHGSGSGHFCSQGQHGSTSGQSSTFDQEGSSTGQSSSYGHRGSGSSQSSGYG
  RHGAGSGQSLSHGRHGSGSGQSSSYGQHGSGSGQSSGYSQHGSGSGQDGYSYCKGGSNHD
  GGSSGSYFLSFPSSTSPYEYVQEQRCYFYQ
• Function: Component of the epidermal cornified cell envelopes.
• Tissue Specificity: Expressed in cornified epidermis, psoriatic and regenerating skin after wounding. Found in the upper granular layer and in the entire cornified layer of epidermis.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anaplastic large cell lymphoma	DISP4D1R	Strong	Altered Expression	[1]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[4]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Pancreatic cancer	DISJC981	Strong	Biomarker	[5]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[5]
Allergic contact dermatitis	DISFFVF9	Limited	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hornerin (HRNR).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Hornerin (HRNR).	[10]

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 Hornerin (HRNR).	[9]

References

• [1] Expression of the novel intermediate filament-associated protein restin in Hodgkin's disease and anaplastic large-cell lymphoma.Blood. 1992 Dec 1;80(11):2891-6.
• [2] Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr(-/-) ) double-deficient mice.Allergy. 2019 Jul;74(7):1327-1339. doi: 10.1111/all.13756. Epub 2019 Apr 15.
• [3] Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer.BMC Cancer. 2012 Jun 22;12:266. doi: 10.1186/1471-2407-12-266.
• [4] Restin in Hodgkin's disease and anaplastic large cell lymphoma.Leuk Lymphoma. 1993 Dec;12(1-2):21-6. doi: 10.3109/10428199309059567.
• [5] Identification of the S100 fused-type protein hornerin as a regulator of tumor vascularity.Nat Commun. 2017 Sep 15;8(1):552. doi: 10.1038/s41467-017-00488-6.
• [6] Mutational landscape of penile squamous cell carcinoma in a Chinese population.Int J Cancer. 2019 Sep 1;145(5):1280-1289. doi: 10.1002/ijc.32373. Epub 2019 May 8.
• [7] Hornerin promotes tumor progression and is associated with poor prognosis in hepatocellular carcinoma.BMC Cancer. 2018 Aug 13;18(1):815. doi: 10.1186/s12885-018-4719-5.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.