Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEFB87Z)

• DOT Name: PH and SEC7 domain-containing protein 4 (PSD4)
• Synonyms: Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 B; Exchange factor for ARF6 B; Pleckstrin homology and SEC7 domain-containing protein 4; Telomeric of interleukin-1 cluster protein
• Gene Name: PSD4
• Related Disease:
  Glioma
  Nephropathy
  Advanced cancer
  Autism
  Autism spectrum disorder
  Carcinoma
  Melanoma
  Pancreatic tumour
  Serous cystadenocarcinoma
  Spondylometaphyseal dysplasia, Sedaghatian type
  Thrombophilia
  Thyroid gland papillary carcinoma
  Tourette syndrome
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  High blood pressure
  Pancreatic cancer
  Plasma cell myeloma
  facioscapulohumeral muscular dystrophy
  Head-neck squamous cell carcinoma
  Mesothelioma
  Stroke
• UniProt ID: PSD4_HUMAN
• Pfam ID: PF15410 ; PF01369
• Sequence:
  MMGDYRLPDHPQPMEILNLYLGDSLEPHPGECPRETCSHEDPPEPFEEQTWATDPPEPTR
  QNVPPWGSGVELTHLGSWVHQDGLEPCQEQTRATDPPESTRQDAPPWGSGVELTHLGSPS
  AQREHRQNTASPGSPVNSHLPGSPKQNRSTSTQVVFWAGILQAQMCVLDLEEELEKTEGL
  KAGLKCCLPTPPVDLPGDTGLHSSPPENEDSGEDSSEPEGEGQAWLREGTPDSSPQWGAE
  EESMFFSNPLFLASPCSENSASGECFSWGASDSHAGVRTGPESPATLEPPLPEDTVLWEL
  ESEPDLGDGAAISGHCTPPFPVPIYKPHSICWASVAAAEGAPAAPPGHGESEGDRLGPAP
  SAAPCVDEALTWESGCVGSDLGPAAHPVQPWASLSPEGWQRGGPFWPQVTLNSQDRDERE
  GGHPQESLPCTLAPCPWRSPASSPEPSSPESESRGPGPRPSPASSQEGSPQLQHHSSGIL
  PKWTLDASQSSLLETDGEQPSSLKKKEAGEAPKPGEEVKSEGTARPAETGDVQPDIHLTS
  AEHENLRTPMNSSWLPGSPMPQAQSPEEGQRPPAGDKLANGVRNNKVAWNLASRLYRLEG
  FRKSEVAAYLQKNNDFSRAVAEEYLSFFQFGGQSLDRALRSFLQALVLSGETQERERILY
  QFSRRFHHCNPGIFPSVDSVHTLTCAIMLLNTDLHGQNIGKSMSCQEFITNLNGLRDGGN
  FPKELLKALYWSIRSEKLEWAVDEEDTARPEKAQPSLPAGKMSKPFLQLAQDPTVPTYKQ
  GILARKMHQDADGKKTPWGKRGWKMFHTLLRGMVLYFLKQGEDHCLEGESLVGQMVDEPV
  GVHHSLATPATHYTKKPHVFQLRTADWRLYLFQAPTAKEMSSWIARINLAAATHSAPPFP
  AAVGSQRRFVRPILPVGPAQSSLEEQHRSHENCLDAAADDLLDLQRNLPERRGRGRELEE
  HRLRKEYLEYEKTRYETYVQLLVARLHCPSDALDLWEEQLGREAGGTREPKLSLKKSHSS
  PSLHQDEAPTTAKVKRNISERRTYRKIIPKRNRNQL
• Function: Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 4,5-bisphosphate.
• Tissue Specificity: Widely expressed. Highest levels of expression are found in placenta, pancreas, spleen, thymus and peripheral blood.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[7]
Serous cystadenocarcinoma	DISVK716	Strong	Biomarker	[5]
Spondylometaphyseal dysplasia, Sedaghatian type	DISMKJPA	Strong	Biomarker	[8]
Thrombophilia	DISQR7U7	Strong	Biomarker	[9]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[10]
Tourette syndrome	DISX9D54	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	moderate	Biomarker	[12]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[12]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[3]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[13]
Pancreatic cancer	DISJC981	moderate	Biomarker	[14]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[15]
facioscapulohumeral muscular dystrophy	DISSE0H0	Limited	Biomarker	[16]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[17]
Mesothelioma	DISKWK9M	Limited	Biomarker	[18]
Stroke	DISX6UHX	Limited	Biomarker	[19]

3 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 PH and SEC7 domain-containing protein 4 (PSD4).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PH and SEC7 domain-containing protein 4 (PSD4).	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of PH and SEC7 domain-containing protein 4 (PSD4).	[29]

8 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 PH and SEC7 domain-containing protein 4 (PSD4).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[24]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[25]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[28]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of PH and SEC7 domain-containing protein 4 (PSD4).	[30]

References

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• [16] AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD.JCI Insight. 2018 Nov 15;3(22):e123538. doi: 10.1172/jci.insight.123538.
• [17] GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.Oncogene. 2018 Mar;37(10):1340-1353. doi: 10.1038/s41388-017-0038-6. Epub 2017 Dec 19.
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• [22] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [23] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
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