Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBUZ7KA)

• DOT Name: Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1)
• Synonyms: Katanin p60 subunit A-like 1; EC 5.6.1.1; p60 katanin-like 1
• Gene Name: KATNAL1
• Related Disease:
  Isolated congenital microcephaly
  Male infertility
  Prostate cancer
  Prostate carcinoma
  Intellectual disability
• UniProt ID: KATL1_HUMAN
• PDB ID: 6B5C
• EC Number: 5.6.1.1
• Pfam ID: PF00004 ; PF17862 ; PF21126 ; PF09336
• Sequence:
  MNLAEICDNAKKGREYALLGNYDSSMVYYQGVMQQIQRHCQSVRDPAIKGKWQQVRQELL
  EEYEQVKSIVSTLESFKIDKPPDFPVSCQDEPFRDPAVWPPPVPAEHRAPPQIRRPNREV
  RPLRKEMAGVGARGPVGRAHPISKSEKPSTSRDKDYRARGRDDKGRKNMQDGASDGEMPK
  FDGAGYDKDLVEALERDIVSRNPSIHWDDIADLEEAKKLLREAVVLPMWMPDFFKGIRRP
  WKGVLMVGPPGTGKTMLAKAVATECGTTFFNVSSSTLTSKYRGESEKLVRLLFEMARFYA
  PTTIFIDEIDSICSRRGTSDEHEASRRVKSELLIQMDGVGGALENDDPSKMVMVLAATNF
  PWDIDEALRRRLEKRIYIPLPTAKGRAELLKINLREVELDPDIQLEDIAEKIEGYSGADI
  TNVCRDASLMAMRRRINGLSPEEIRALSKEELQMPVTKGDFELALKKIAKSVSAADLEKY
  EKWMVEFGSA
• Function: Regulates microtubule dynamics in Sertoli cells, a process that is essential for spermiogenesis and male fertility. Severs microtubules in an ATP-dependent manner, promoting rapid reorganization of cellular microtubule arrays. Has microtubule-severing activity in vitro.
• Tissue Specificity: Expressed in testis, restricted to Sertoli cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated congenital microcephaly	DISUXHZ6	Definitive	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Intellectual disability	DISMBNXP	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
OXYQUINOLINE	DMZVS9Y	Investigative	Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1) affects the response to substance of OXYQUINOLINE.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[12]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1).	[14]

References

• [1] A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.Mol Psychiatry. 2018 Mar;23(3):713-722. doi: 10.1038/mp.2017.54. Epub 2017 Apr 4.
• [2] Lack of association of KATNAL1 gene sequence variants and azoospermia in humans.J Assist Reprod Genet. 2014 Aug;31(8):1065-71. doi: 10.1007/s10815-014-0269-1. Epub 2014 Jun 10.
• [3] Circ_KATNAL1 regulates prostate cancer cell growth and invasiveness through the miR-145-3p/WISP1 pathway.Biochem Cell Biol. 2020 Jun;98(3):396-404. doi: 10.1139/bcb-2019-0211. Epub 2019 Dec 4.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [14] 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.
• [15] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.