Details of Drug Off-Target (DOT)

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

• DOT Name: SH3 and PX domain-containing protein 2A (SH3PXD2A)
• Synonyms: Adapter protein TKS5; Five SH3 domain-containing protein; SH3 multiple domains protein 1; Tyrosine kinase substrate with five SH3 domains
• Gene Name: SH3PXD2A
• Related Disease:
  Alzheimer disease
  Atrial fibrillation
  Brain neoplasm
  Colorectal carcinoma
  Glioma
  Lung adenocarcinoma
  Neoplasm
  Schizophrenia
  Stroke
  Advanced cancer
  Familial atrial fibrillation
  Hepatocellular carcinoma
  Asthma
  Malignant peripheral nerve sheath tumor
  Melanoma
  Rheumatoid arthritis
• UniProt ID: SPD2A_HUMAN
• PDB ID: 2DNU; 2EGA; 2EGC; 2EKH
• Pfam ID: PF00787 ; PF00018 ; PF07653
• Sequence:
  MLAYCVQDATVVDVEKRRNPSKHYVYIINVTWSDSTSQTIYRRYSKFFDLQMQLLDKFPI
  EGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHISQCDEVFRF
  FEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADATAEPMILEQYVVVSNYKKQ
  ENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTRDDSDINTSKTGEV
  SKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEIGFEKGVTVEVIRKNL
  EGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGNIMEISNLLNKKASGDKE
  TPPAEGEGHEAPIAKKEISLPILCNASNGSAVGVPDRTVSRLAQGSPAVARIAPQRAQIS
  SPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEFQSCISDGISFRGGQKAEVIDK
  NSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTLTRPKVPPPAPPSKPKEAEEGPTG
  ASESQDSPRKLKYEEPEYDIPAFGFDSEPELSEEPVEDRASGERRPAQPHRPSPASSLQR
  ARFKVGESSEDVALEEETIYENEGFRPYAEDTLSARGSSGDSDSPGSSSLSLTRKNSPKS
  GSPKSSSLLKLKAEKNAQAEMGKNHSSASFSSSITINTTCCSSSSSSSSSLSKTSGDLKP
  RSASDAGIRGTPKVRAKKDADANAGLTSCPRAKPSVRPKPFLNRAESQSQEKMDISTLRR
  QLRPTGQLRGGLKGSKSEDSELPPQTASEAPSEGSRRSSSDLITLPATTPPCPTKKEWEG
  PATSYMTCSAYQKVQDSEISFPAGVEVQVLEKQESGWWYVRFGELEGWAPSHYLVLDENE
  QPDPSGKELDTVPAKGRQNEGKSDSLEKIERRVQALNTVNQSKKATPPIPSKPPGGFGKT
  SGTPAVKMRNGVRQVAVRPQSVFVSPPPKDNNLSCALRRNESLTATDGLRGVRRNSSFST
  ARSAAAEAKGRLAERAASQGSDSPLLPAQRNSIPVSPVRPKPIEKSQFIHNNLKDVYVSI
  ADYEGDEETAGFQEGVSMEVLERNPNGWWYCQILDGVKPFKGWVPSNYLEKKN
• Function: Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide.
• Tissue Specificity: Found in several cancer cell lines, particularly invasive breast carcinomas and melanomas.
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  Invadopodia formation (R-HSA-8941237)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[2]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Schizophrenia	DISSRV2N	Strong	Biomarker	[7]
Stroke	DISX6UHX	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[9]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[11]
Asthma	DISW9QNS	Limited	Genetic Variation	[12]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Limited	FusionGene	[13]
Melanoma	DIS1RRCY	Limited	Altered Expression	[14]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[22]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[25]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[26]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SH3 and PX domain-containing protein 2A (SH3PXD2A).	[32]

References

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• [33] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.