Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUVKA6R)

• DOT Name: SUN domain-containing protein 5 (SUN5)
• Synonyms: Sad1 and UNC84 domain-containing protein 5; Sperm-associated antigen 4-like protein; Testis and spermatogenesis-related gene 4 protein
• Gene Name: SUN5
• Related Disease:
  Male infertility
  Narcolepsy
  Spermatogenic failure 16
  Acute myelogenous leukaemia
  Spermatogenic failure 31
• UniProt ID: SUN5_HUMAN
• Pfam ID: PF07738
• Sequence:
  MPRSSRSPGDPGALLEDVAHNPRPRRIAQRGRNTSRMAEDTSPNMNDNILLPVRNNDQAL
  GLTQCMLGCVSWFTCFACSLRTQAQQVLFNTCRCKLLCQKLMEKTGILLLCAFGFWMFSI
  HLPSKMKVWQDDSINGPLQSLRLYQEKVRHHSGEIQDLRGSMNQLIAKLQEMEAMSDEQK
  MAQKIMKMIHGDYIEKPDFALKSIGASIDFEHTSVTYNHEKAHSYWNWIQLWNYAQPPDV
  ILEPNVTPGNCWAFEGDRGQVTIQLAQKVYLSNLTLQHIPKTISLSGSLDTAPKDFVIYG
  MEGSPKEEVFLGAFQFQPENIIQMFPLQNQPARAFSAVKVKISSNWGNPGFTCLYRVRVH
  GSVAPPREQPHQNPYPKRD
• Function: Plays an essential role in anchoring sperm head to the tail. Is responsible for the attachment of the coupling apparatus to the sperm nuclear envelope.
• Tissue Specificity: Sperm (at protein level) . Widely expressed . Conflictingly shown to be specifically expressed in testis .

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[2]
Spermatogenic failure 16	DISJT1VL	Strong	Autosomal recessive	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]
Spermatogenic failure 31	DIS1NFFP	moderate	GermlineCausalMutation	[5]

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 decreases the methylation of SUN domain-containing protein 5 (SUN5).	[6]

References

• [1] SPAG4L/SPAG4L interacts with Nesprin2 to participate in the meiosis of spermatogenesis.Acta Biochim Biophys Sin (Shanghai). 2019 Jul 10;51(7):669-676. doi: 10.1093/abbs/gmz051.
• [2] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [3] [On advanced, productive interpersonal relations]. Sykepleien. 1977 Sep 5;64(14):784-7.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome.Am J Hum Genet. 2016 Oct 6;99(4):942-949. doi: 10.1016/j.ajhg.2016.08.004. Epub 2016 Sep 15.
• [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.