Details of Drug Off-Target (DOT)

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

• DOT Name: Far upstream element-binding protein 2 (KHSRP)
• Synonyms: FUSE-binding protein 2; KH type-splicing regulatory protein; KSRP; p75
• Gene Name: KHSRP
• Related Disease:
  Glioma
  Adenocarcinoma
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Arthritis
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Classic Hodgkin lymphoma
  Cystic fibrosis
  Depression
  Epilepsy
  Esophageal squamous cell carcinoma
  Huntington disease
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Matthew-Wood syndrome
  Neuroblastoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Osteoarthritis
  Pancreatic ductal carcinoma
  Parkinson disease
  Retinoblastoma
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Triple negative breast cancer
  Type-1/2 diabetes
  Hepatocellular carcinoma
  Medulloblastoma
  Thyroid gland papillary carcinoma
  Acute myelogenous leukaemia
  Bone osteosarcoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Hyperglycemia
  Melanoma
  Myeloid leukaemia
  Nervous system disease
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  Small-cell lung cancer
• UniProt ID: FUBP2_HUMAN
• PDB ID: 2HH2; 2HH3; 2JVZ; 2OPU; 2OPV; 4B8T
• Pfam ID: PF09005 ; PF00013
• Sequence:
  MSDYSTGGPPPGPPPPAGGGGGAGGAGGGPPPGPPGAGDRGGGGPGGGGPGGGSAGGPSQ
  PPGGGGPGIRKDAFADAVQRARQIAAKIGGDAATTVNNSTPDFGFGGQKRQLEDGDQPES
  KKLASQGDSISSQLGPIHPPPRTSMTEEYRVPDGMVGLIIGRGGEQINKIQQDSGCKVQI
  SPDSGGLPERSVSLTGAPESVQKAKMMLDDIVSRGRGGPPGQFHDNANGGQNGTVQEIMI
  PAGKAGLVIGKGGETIKQLQERAGVKMILIQDGSQNTNVDKPLRIIGDPYKVQQACEMVM
  DILRERDQGGFGDRNEYGSRIGGGIDVPVPRHSVGVVIGRSGEMIKKIQNDAGVRIQFKQ
  DDGTGPEKIAHIMGPPDRCEHAARIINDLLQSLRSGPPGPPGGPGMPPGGRGRGRGQGNW
  GPPGGEMTFSIPTHKCGLVIGRGGENVKAINQQTGAFVEISRQLPPNGDPNFKLFIIRGS
  PQQIDHAKQLIEEKIEGPLCPVGPGPGGPGPAGPMGPFNPGPFNQGPPGAPPHAGGPPPH
  QYPPQGWGNTYPQWQPPAPHDPSKAAAAAADPNAAWAAYYSHYYQQPPGPVPGPAPAPAA
  PPAQGEPPQPPPTGQSDYTKAWEEYYKKIGQQPQQPGAPPQQDYTKAWEEYYKKQAQVAT
  GGGPGAPPGSQPDYSAAWAEYYRQQAAYYGQTPGPGGPQPPPTQQGQQQAQ
• Function: Binds to the dendritic targeting element and may play a role in mRNA trafficking. Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.
• Tissue Specificity: Detected in neural and non-neural cell lines.
• Reactome Pathway:
  KSRP (KHSRP) binds and destabilizes mRNA (R-HSA-450604)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[4]
Arthritis	DIST1YEL	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[11]
Depression	DIS3XJ69	Strong	Genetic Variation	[12]
Epilepsy	DISBB28L	Strong	Altered Expression	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[17]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[18]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[21]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[18]
Parkinson disease	DISQVHKL	Strong	Biomarker	[22]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[23]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[21]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[25]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[26]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[27]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[28]
Medulloblastoma	DISZD2ZL	moderate	Biomarker	[29]
Thyroid gland papillary carcinoma	DIS48YMM	Disputed	Altered Expression	[30]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[31]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[32]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[33]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[34]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[35]
Melanoma	DIS1RRCY	Limited	Biomarker	[36]
Myeloid leukaemia	DISMN944	Limited	Biomarker	[37]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[38]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[32]
Prostate cancer	DISF190Y	Limited	Altered Expression	[39]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[39]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Far upstream element-binding protein 2 (KHSRP).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Far upstream element-binding protein 2 (KHSRP).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Far upstream element-binding protein 2 (KHSRP).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Far upstream element-binding protein 2 (KHSRP).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Far upstream element-binding protein 2 (KHSRP).	[45]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Far upstream element-binding protein 2 (KHSRP).	[47]
Marinol	DM70IK5	Approved	Marinol increases the expression of Far upstream element-binding protein 2 (KHSRP).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Far upstream element-binding protein 2 (KHSRP).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Far upstream element-binding protein 2 (KHSRP).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Far upstream element-binding protein 2 (KHSRP).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Far upstream element-binding protein 2 (KHSRP).	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Far upstream element-binding protein 2 (KHSRP).	[53]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Far upstream element-binding protein 2 (KHSRP).	[49]

References

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