Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP51XIP)

• DOT Name: Protein shortage in chiasmata 1 ortholog (SHOC1)
• Synonyms: EC 3.6.-.-; Protein ZIP2 homolog; MZIP2
• Gene Name: SHOC1
• Related Disease:
  Carotid artery disease
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carotid stenosis
  Cryptococcosis
  Parkinson disease
  Coronary heart disease
  Pulmonary tuberculosis
  Spermatogenic failure
• UniProt ID: SHOC1_HUMAN
• EC Number: 3.6.-.-
• Pfam ID: PF17825
• Sequence:
  MTDTSVLDQWKASFFVEDFLEKKTITRMVTQINCEFEEVVPSSNPDSQIEVEEVSLYTHM
  DYNEVFTPVSCLEKCSALQNQNQDLFIDDKGILFVSSRKHLPTLPTLLSRLKLFLVKDPL
  LDFKGQIFTEANFSRECFSLQETLEAFVKEDFCMDKVNFCQEKLEDTICLNEPSSFLIEY
  EFLIPPSLKPEIDIPSLSELKELLNPVPEIINYVDEKEKLFERDLTNKHGIEDIGDIKFS
  STEILTIQSQSEPEECSKPGELEMPLTPLFLTCQHSSVNSLRTELQTFPLSPVCKINLLT
  AEESANEYYMMWQLERCRSPLNPFLLTVPRIQEPHSQYSVTDLKKIFSVKEESLVINLEK
  AEWWKQAGLNLKMMETLEHLNTYLCHDNLSSNDTKIEIFLPTKVLQLESCLEHKSHSSPI
  ALIDEKSTNAHLSLPQKSPSLAKEVPDLCFSDDYFSDKGAAKEEKPKNDQEPVNRIIQKK
  ENNDHFELDCTGPSIKSPSSSIIKKASFEHGKKQENDLDLLSDFIMLRNKYKTCTSKTEV
  TNSDEKHDKEACSLTLQEESPIVHINKTLEEINQERGTDSVIEIQASDSQCQAFCLLEAA
  ASPILKNLVSLCTLPTANWKFATVIFDQTRFLLKEQEKVVSDAVRQGTIDEREMTFKHAA
  LLHLLVTIRDVLLTCSLDTALGYLSKAKDIYNSILGPYLGDIWRQLEIVQFIRGKKPETN
  YKIQELQCQILSWMQSQQQIKVLIIIRMDSDGEKHFLIKILNKIEGLTLTVLHSNERKDF
  LESEGVLRGTSSCVVVHNQYIGADFPWSNFSFVVEYNYVEDSCWTKHCKELNIPYMAFKV
  ILPDTVLERSTLLDRFGGFLLEIQIPYVFFASEGLLNTPDILQLLESNYNISLVERGCSE
  SLKLFGSSECYVVVTIDEHTAIILQDLEELNYEKASDNIIMRLMALSLQYRYCWIILYTK
  ETLNSEYLLTEKTLHHLALIYAALVSFGLNSEELDVKLIIAPGVEATALIIRQIADHSLM
  TSKRDPHEWLDKSWLKVSPSEEEMYLLDFPCINPLVAQLMLNKGPSLHWILLATLCQLQE
  LLPEVPEKVLKHFCSITSLFKIGSSSITKSPQISSPQENRNQISTLSSQSSASDLDSVIQ
  EHNEYYQYLGLGETVQEDKTTILNDNSSIMELKEISSFLPPVTSYNQTSYWKDSSCKSNI
  GQNTPFLINIESRRPAYNSFLNHSDSESDVFSLGLTQMNCETIKSPTDTQKRVSVVPRFI
  NSQKRRTHEAKGFINKDVSDPIFSLEGTQSPLHWNFKKNIWEQENHPFNLQYGAQQTACN
  KLYSQKGNLFTDQQKCLSDESEGLTCESSKDETFWRELPSVPSLDLFRASDSNANQKEFN
  SLYFYQRAGKSLGQKRHHESSFNSGDKESLTGFMCSQLPQFKKRRLAYEKVPGRVDGQTR
  LRFF
• Function: ATPase required during meiosis for the formation of crossover recombination intermediates. Binds DNA: preferentially binds to single-stranded DNA and DNA branched structures. Does not show nuclease activity in vitro, but shows ATPase activity, which is stimulated by the presence of single-stranded DNA. Plays a key role in homologous recombination and crossing-over in meiotic prophase I in male and female germ cells. Required for proper synaptonemal complex assembly and homologous chromosome pairing. Requiref for recruitment TEX11 and MSH4 to recombination intermediates.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carotid artery disease	DISLRVLT	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Carotid stenosis	DISZA8D0	Strong	Genetic Variation	[4]
Cryptococcosis	DISDYDTK	Strong	Genetic Variation	[5]
Parkinson disease	DISQVHKL	Strong	Biomarker	[6]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[7]
Pulmonary tuberculosis	DIS6FLUM	moderate	Altered Expression	[8]
Spermatogenic failure	DIS3D1AI	Limited	Autosomal recessive	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein shortage in chiasmata 1 ortholog (SHOC1).	[10]

References

• [1] Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation.Biofactors. 2015 Nov-Dec;41(6):414-23. doi: 10.1002/biof.1247. Epub 2015 Dec 8.
• [2] Reassessment of the Transport Mechanism of the Human Zinc Transporter SLC39A2. Biochemistry. 2018 Jul 3;57(26):3976-3986.
• [3] Over-expression of Zip-13 mRNA in kidney and lung during dietary zinc deficiency in Wistar rats.Mol Biol Rep. 2011 Mar;38(3):1869-74. doi: 10.1007/s11033-010-0304-y. Epub 2010 Sep 22.
• [4] A novel Zip2 Gln/Arg/Leu codon 2 polymorphism is associated with carotid artery disease in aging.Rejuvenation Res. 2008 Apr;11(2):297-300. doi: 10.1089/rej.2008.0671.
• [5] Effects of zinc transporters on Cryptococcus gattii virulence.Sci Rep. 2015 May 7;5:10104. doi: 10.1038/srep10104.
• [6] Functional Characterization of Novel Circular RNA Molecule, circzip-2 and Its Synthesizing Gene zip-2 in C. elegans Model of Parkinson's Disease.Mol Neurobiol. 2018 Aug;55(8):6914-6926. doi: 10.1007/s12035-018-0903-5. Epub 2018 Jan 23.
• [7] A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs.Atherosclerosis. 2016 Feb;245:62-70. doi: 10.1016/j.atherosclerosis.2015.11.019. Epub 2015 Nov 22.
• [8] Up-regulation of Slc39A2(Zip2) mRNA in peripheral blood mononuclear cells from patients with pulmonary tuberculosis.Mol Biol Rep. 2013 Aug;40(8):4979-84. doi: 10.1007/s11033-013-2598-z. Epub 2013 May 18.
• [9] Bi-allelic SHOC1 loss-of-function mutations cause meiotic arrest and non-obstructive azoospermia. J Med Genet. 2021 Oct;58(10):679-686. doi: 10.1136/jmedgenet-2020-107042. Epub 2020 Sep 8.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.