Details of Drug Off-Target (DOT)

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

• DOT Name: AP-1 complex subunit sigma-2 (AP1S2)
• Synonyms: Adaptor protein complex AP-1 subunit sigma-1B; Adaptor-related protein complex 1 subunit sigma-1B; Clathrin assembly protein complex 1 sigma-1B small chain; Golgi adaptor HA1/AP1 adaptin sigma-1B subunit; Sigma 1B subunit of AP-1 clathrin; Sigma-adaptin 1B; Sigma1B-adaptin
• Gene Name: AP1S2
• Related Disease:
  Non-syndromic X-linked intellectual disability
  Prostate cancer
  Prostate carcinoma
  Syndromic X-linked intellectual disability 5
  X-linked syndromic intellectual disability
  Autism
  Breast neoplasm
  Congenital hydrocephalus
  Coronary atherosclerosis
  Coronary heart disease
  Dandy-Walker syndrome
  Dystonia
  Intellectual disability
  Neoplasm
  Pulmonary disease
  X-linked intellectual disability
  Hydrocephalus
  Fried syndrome
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Neurodevelopmental disorder
  Osteoarthritis
• UniProt ID: AP1S2_HUMAN
• Pfam ID: PF01217
• Sequence:
  MQFMLLFSRQGKLRLQKWYVPLSDKEKKKITRELVQTVLARKPKMCSFLEWRDLKIVYKR
  YASLYFCCAIEDQDNELITLEIIHRYVELLDKYFGSVCELDIIFNFEKAYFILDEFLLGG
  EVQETSKKNVLKAIEQADLLQEEAETPRSVLEEIGLT
• Function: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Lysosome (hsa04142)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Lysosome Vesicle Biogenesis (R-HSA-432720)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)
  Nef mediated downregulation of MHC class I complex cell surface expression (R-HSA-164940)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-syndromic X-linked intellectual disability	DIS71AI3	Definitive	Biomarker	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Syndromic X-linked intellectual disability 5	DISO5SAY	Definitive	X-linked recessive	[3]
X-linked syndromic intellectual disability	DISG1YOH	Definitive	X-linked	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Congenital hydrocephalus	DIS7O6UL	Strong	Genetic Variation	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[8]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[8]
Dandy-Walker syndrome	DIS4HC6W	Strong	Genetic Variation	[9]
Dystonia	DISJLFGW	Strong	Biomarker	[9]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Pulmonary disease	DIS6060I	Strong	Genetic Variation	[11]
X-linked intellectual disability	DISYJBY3	Strong	Genetic Variation	[10]
Hydrocephalus	DISIZUF7	moderate	Genetic Variation	[12]
Fried syndrome	DIS990VP	Supportive	X-linked	[12]
Autism spectrum disorder	DISXK8NV	Limited	X-linked	[13]
Breast cancer	DIS7DPX1	Limited	Biomarker	[14]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[14]
Neurodevelopmental disorder	DIS372XH	Limited	Genetic Variation	[10]
Osteoarthritis	DIS05URM	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	AP-1 complex subunit sigma-2 (AP1S2) affects the response to substance of DTI-015.	[32]

19 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 AP-1 complex subunit sigma-2 (AP1S2).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[21]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[22]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[23]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[24]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[25]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[26]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[28]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[26]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of AP-1 complex subunit sigma-2 (AP1S2).	[31]

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 AP-1 complex subunit sigma-2 (AP1S2).	[30]

References

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