Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA551F7)

• DOT Name: Polyamine-modulated factor 1-binding protein 1 (PMFBP1)
• Synonyms: PMF-1-binding protein
• Gene Name: PMFBP1
• Related Disease:
  Male infertility
  Spermatogenic failure 16
  Spermatogenic failure 31
• UniProt ID: PMFBP_HUMAN
• Sequence:
  MKDEAGERDREVSSLNSKLLSLQLDIKNLHDVCKRQRKTLQDNQLCMEEAMNSSHDKKQA
  QALAFEESEVEFGSSKQCHLRQLQQLKKKLLVLQQELEFHTEELQTSYYSLRQYQSILEK
  QTSDLVLLHHHCKLKEDEVILYEEEMGNHNENTGEKLHLAQEQLALAGDKIASLERSLNL
  YRDKYQSSLSNIELLECQVKMLQGELGGIMGQEPENKGDHSKVRIYTSPCMIQEHQETQK
  RLSEVWQKVSQQDDLIQELRNKLACSNALVLEREKALIKLQADFASCTATHRYPPSSSEE
  CEDIKKILKHLQEQKDSQCLHVEEYQNLVKDLRVELEAVSEQKRNIMKDMMKLELDLHGL
  REETSAHIERKDKDITILQCRLQELQLEFTETQKLTLKKDKFLQEKDEMLQELEKKLTQV
  QNSLLKKEKELEKQQCMATELEMTVKEAKQDKSKEAECKALQAEVQKLKNSLEEAKQQER
  LAAQQAAQCKEEAALAGCHLEDTQRKLQKGLLLDKQKADTIQELQRELQMLQKESSMAEK
  EQTSNRKRVEELSLELSEALRKLENSDKEKRQLQKTVAEQDMKMNDMLDRIKHQHREQGS
  IKCKLEEDLQEATKLLEDKREQLKKSKEHEKLMEGELEALRQEFKKKDKTLKENSRKLEE
  ENENLRAELQCCSTQLESSLNKYNTSQQVIQDLNKEIALQKESLMSLQAQLDKALQKEKH
  YLQTTITKEAYDALSRKSAACQDDLTQALEKLNHVTSETKSLQQSLTQTQEKKAQLEEEI
  IAYEERMKKLNTELRKLRGFHQESELEVHAFDKKLEEMSCQVLQWQKQHQNDLKMLAAKE
  EQLREFQEEMAALKENLLEDDKEPCCLPQWSVPKDTCRLYRGNDQIMTNLEQWAKQQKVA
  NEKLGNQLREQVKYIAKLSGEKDHLHSVMVHLQQENKKLKKEIEEKKMKAENTRLCTKAL
  GPSRTESTQREKVCGTLGWKGLPQDMGQRMDLTKYIGMPHCPGSSYC
• Function: Required for normal spermatogenesis. It functions as a scaffold protein that attaches the sperm head-tail connecting piece to the nuclear envelope, thus maintaining sperm head and tail integrity. May also be involved in the general organization of cellular cytoskeleton.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Genetic Variation	[1]
Spermatogenic failure 16	DISJT1VL	Strong	Genetic Variation	[1]
Spermatogenic failure 31	DIS1NFFP	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Polyamine-modulated factor 1-binding protein 1 (PMFBP1).	[2]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Polyamine-modulated factor 1-binding protein 1 (PMFBP1).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Polyamine-modulated factor 1-binding protein 1 (PMFBP1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Polyamine-modulated factor 1-binding protein 1 (PMFBP1).	[5]

References

• [1] Mutations in PMFBP1 Cause Acephalic Spermatozoa Syndrome. Am J Hum Genet. 2018 Aug 2;103(2):188-199. doi: 10.1016/j.ajhg.2018.06.010. Epub 2018 Jul 19.
• [2] 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.
• [3] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.