Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLJCZ1U)

• DOT Name: 14-3-3 protein sigma (SFN)
• Synonyms: Epithelial cell marker protein 1; Stratifin
• Gene Name: SFN
• Related Disease:
  Ovarian cancer
  Squamous cell carcinoma
  Benign prostatic hyperplasia
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Cholangiocarcinoma
  Colon cancer
  Colon carcinoma
  Colorectal neoplasm
  Ductal breast carcinoma in situ
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gallbladder cancer
  Gallbladder carcinoma
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Keloid
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Ovarian neoplasm
  Pancreatic tumour
  Plasma cell myeloma
  Prostate neoplasm
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Corpus callosum, agenesis of
  Esophageal cancer
  Melanoma
  Neoplasm of esophagus
  Prostate cancer
  Prostate carcinoma
• UniProt ID: 1433S_HUMAN
• PDB ID: 1YWT ; 1YZ5 ; 3IQJ ; 3IQU ; 3IQV ; 3LW1 ; 3MHR ; 3O8I ; 3P1N ; 3P1O ; 3P1P ; 3P1Q ; 3P1R ; 3P1S ; 3SMK ; 3SML ; 3SMM ; 3SMN ; 3SMO ; 3SP5 ; 3SPR ; 3T0L ; 3T0M ; 3U9X ; 3UX0 ; 4DAT ; 4DAU ; 4DHM ; 4DHN ; 4DHO ; 4DHP ; 4DHQ ; 4DHR ; 4DHS ; 4DHT ; 4DHU ; 4FL5 ; 4FR3 ; 4IEA ; 4JC3 ; 4JDD ; 4QLI ; 4Y32 ; 4Y3B ; 4Y5I ; 5BTV ; 5HF3 ; 5LTW ; 5LU1 ; 5LU2 ; 5MHC ; 5MOC ; 5MXO ; 5MY9 ; 5MYC ; 5N5R ; 5N5T ; 5N5W ; 5N75 ; 5OEG ; 5OEH ; 5OK9 ; 5OKF ; 5OM0 ; 5OMA ; 6FAU ; 6FAV ; 6FAW ; 6FBB ; 6FBW ; 6FBY ; 6FCP ; 6FI4 ; 6FI5 ; 6G6X ; 6G8I ; 6G8J ; 6G8K ; 6G8L ; 6G8P ; 6G8Q ; 6GHP ; 6HHP ; 6HKB ; 6HKF ; 6HMT ; 6HMU ; 6HN2 ; 6NV2 ; 6QDR ; 6QDS ; 6QDT ; 6QDU ; 6QHL ; 6QHM ; 6QIU ; 6QZR ; 6QZS ; 6R5L ; 6RHC ; 6RJL ; 6RJQ ; 6RJZ ; 6RK8 ; 6RKI ; 6RKK ; 6RKM ; 6RL3 ; 6RL4 ; 6RL6 ; 6RM5 ; 6RM7 ; 6RP6 ; 6RWH ; 6RWI ; 6RWS ; 6RWU ; 6RX2 ; 6S39 ; 6S3C ; 6S40 ; 6S9Q ; 6SIN ; 6SIO ; 6SIP ; 6SIQ ; 6SLV ; 6SLW ; 6SLX ; 6T5F ; 6T5H ; 6T80 ; 6TCH ; 6TJM ; 6TL3 ; 6TLF ; 6TLG ; 6TM7 ; 6TWZ ; 6W0L ; 6XWD ; 6XXC ; 6XY5 ; 6Y18 ; 6Y1D ; 6Y1J ; 6Y3M ; 6Y3O ; 6Y3R ; 6Y3S ; 6Y3V ; 6Y3W ; 6Y40 ; 6Y44 ; 6Y58 ; 6Y7T ; 6Y8A ; 6Y8B ; 6Y8D ; 6Y8E ; 6YE9 ; 6YIA ; 6YIB ; 6YIC ; 6YLU ; 6YOW ; 6YOX ; 6YOY ; 6YP2 ; 6YP3 ; 6YP8 ; 6YPL ; 6YPY ; 6YQ2 ; 6YR5 ; 6YR6 ; 6YR7 ; 6ZCJ ; 6ZVB ; 6ZVC ; 6ZVD ; 6ZVE ; 7AEW ; 7AOG ; 7AXN ; 7AYF ; 7AZ1 ; 7AZ2 ; 7B13 ; 7B15 ; 7B9M ; 7B9R ; 7B9T ; 7BA3 ; 7BA5 ; 7BA6 ; 7BA7 ; 7BA8 ; 7BA9 ; 7BAA ; 7BAB ; 7BDP ; 7BDT ; 7BDY ; 7BFW ; 7BG3 ; 7BGQ ; 7BGR ; 7BGV ; 7BGW ; 7BI3 ; 7BIQ ; 7BIW ; 7BIY ; 7BJB ; 7BJF ; 7BJL ; 7BJW ; 7BKH ; 7BM9 ; 7BMC ; 7NFW ; 7NIF ; 7NIG ; 7NIX ; 7NIZ ; 7NJ6 ; 7NJ8 ; 7NJ9 ; 7NJA ; 7NJB ; 7NK3 ; 7NK5 ; 7NLA ; 7NLE ; 7NM1 ; 7NM3 ; 7NM9 ; 7NMA ; 7NMH ; 7NMW ; 7NMX ; 7NN2 ; 7NND ; 7NNE ; 7NP2 ; 7NPB ; 7NPG ; 7NQP ; 7NR7 ; 7NRK ; 7NRL ; 7NSV ; 7NV4 ; 7NVI ; 7NWS ; 7NXS ; 7NXT ; 7NXW ; 7NXY ; 7NY4 ; 7NYE ; 7NYF ; 7NYG ; 7NZ6 ; 7NZG ; 7NZK ; 7NZV ; 7O07 ; 7O34 ; 7O3A ; 7O3F ; 7O3P ; 7O3Q ; 7O3R ; 7O3S ; 7O57 ; 7O59 ; 7O5A ; 7O5C ; 7O5D ; 7O5F ; 7O5G ; 7O5O ; 7O5P ; 7O5S ; 7O5U ; 7O5X ; 7O6F ; 7O6G ; 7O6I ; 7O6J ; 7O6K ; 7O6M ; 7O6O ; 7OB5 ; 7OB8 ; 7OBC ; 7OBD ; 7OBG ; 7OBH ; 7OBK ; 7OBL ; 7OBS ; 7OBT ; 7OBX ; 7OBY ; 7OPW ; 7OQ7 ; 7OQ8 ; 7OQ9 ; 7OQA ; 7OQG ; 7OQJ ; 7OQS ; 7OQU ; 7OQW ; 7OR3 ; 7OR5 ; 7OR7 ; 7OR8 ; 7ORG ; 7ORH ; 7ORS ; 7ORT ; 7PWT ; 7PWZ ; 7QIK ; 7QIP ; 7ZMU ; 7ZMW ; 8A62 ; 8A65 ; 8A68 ; 8A6F ; 8A6H ; 8ADM ; 8AFN ; 8AI0 ; 8ALR ; 8ALT ; 8ALV ; 8ALW ; 8AM7 ; 8ANB ; 8ANC ; 8ANF ; 8AOY ; 8APS ; 8AQ1 ; 8AQC ; 8AQE ; 8AQZ ; 8AR4 ; 8AR5 ; 8ARG ; 8ARO ; 8ARQ ; 8ARR ; 8ARW ; 8ARX ; 8ARY ; 8ARZ ; 8AS1 ; 8AT9 ; 8ATP ; 8ATR ; 8ATS ; 8AU2 ; 8AUS ; 8AUY ; 8AV0 ; 8AV3 ; 8AV4 ; 8AV7 ; 8AV8 ; 8AWG ; 8AXE ; 8AXU ; 8AZE ; 8B2I ; 8B2K ; 8B39 ; 8B4Q ; 8B5P ; 8BFC ; 8BI7 ; 8BJG ; 8BJN ; 8BM5 ; 8BWJ ; 8BWX ; 8BWZ ; 8BX0 ; 8BX3 ; 8BX4 ; 8BXI ; 8BXM ; 8BXN ; 8BXO ; 8BXQ ; 8BXS ; 8BY9 ; 8BYB ; 8BYC ; 8BYD ; 8BYE ; 8BYF ; 8BYG ; 8BYO ; 8BYY ; 8BYZ ; 8BZ0 ; 8BZ9 ; 8BZA ; 8BZB ; 8BZW ; 8C04 ; 8C0K ; 8C2D ; 8C2E ; 8C2F ; 8C2G ; 8C3C ; 8C4F ; 8C4G ; 8Q4L
• Pfam ID: PF00244
• Sequence:
  MERASLIQKAKLAEQAERYEDMAAFMKGAVEKGEELSCEERNLLSVAYKNVVGGQRAAWR
  VLSSIEQKSNEEGSEEKGPEVREYREKVETELQGVCDTVLGLLDSHLIKEAGDAESRVFY
  LKMKGDYYRYLAEVATGDDKKRIIDSARSAYQEAMDISKKEMPPTNPIRLGLALNFSVFH
  YEIANSPEEAISLAKTTFDEAMADLHTLSEDSYKDSTLIMQLLRDNLTLWTADNAGEEGG
  EAPQEPQS
• Function: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response. Also acts as a TP53/p53-regulated inhibitor of G2/M progression. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway. May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53.
• Tissue Specificity: Present mainly in tissues enriched in stratified squamous keratinizing epithelium.
• KEGG Pathway:
  Cell cycle (hsa04110)
  p53 sig.ling pathway (hsa04115)
  Aldosterone-regulated sodium reabsorption (hsa04960)
• Reactome Pathway:
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)
  RHO GTPases activate PKNs (R-HSA-5625740)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035)
  Regulation of localization of FOXO transcription factors (R-HSA-9614399)
  SARS-CoV-1 targets host intracellular signalling and regulatory pathways (R-HSA-9735871)
  SARS-CoV-2 targets host intracellular signalling and regulatory pathways (R-HSA-9755779)
  Activation of BAD and translocation to mitochondria (R-HSA-111447)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ovarian cancer	DISZJHAP	Definitive	Altered Expression	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Altered Expression	[2]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[12]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Biomarker	[13]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[14]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[16]
Gallbladder cancer	DISXJUAF	Strong	Altered Expression	[10]
Gallbladder carcinoma	DISD6ACL	Strong	Altered Expression	[10]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[17]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Keloid	DISV09JY	Strong	Biomarker	[20]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[21]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[22]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[22]
Lung neoplasm	DISVARNB	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[25]
Ovarian neoplasm	DISEAFTY	Strong	Posttranslational Modification	[26]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[27]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[28]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[29]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[17]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[21]
Corpus callosum, agenesis of	DISO9P40	moderate	Posttranslational Modification	[30]
Esophageal cancer	DISGB2VN	Limited	Altered Expression	[8]
Melanoma	DIS1RRCY	Limited	Biomarker	[31]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[8]
Prostate cancer	DISF190Y	Limited	Biomarker	[32]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[32]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	14-3-3 protein sigma (SFN) decreases the response to substance of Arsenic trioxide.	[73]
Cytarabine	DMZD5QR	Approved	14-3-3 protein sigma (SFN) decreases the response to substance of Cytarabine.	[55]
Mitoxantrone	DMM39BF	Approved	14-3-3 protein sigma (SFN) affects the response to substance of Mitoxantrone.	[75]
Sulforaphane	DMQY3L0	Investigative	14-3-3 protein sigma (SFN) affects the binding of Sulforaphane.	[76]

49 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 14-3-3 protein sigma (SFN).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 14-3-3 protein sigma (SFN).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 14-3-3 protein sigma (SFN).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 14-3-3 protein sigma (SFN).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 14-3-3 protein sigma (SFN).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 14-3-3 protein sigma (SFN).	[38]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 14-3-3 protein sigma (SFN).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 14-3-3 protein sigma (SFN).	[40]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of 14-3-3 protein sigma (SFN).	[41]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of 14-3-3 protein sigma (SFN).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 14-3-3 protein sigma (SFN).	[43]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of 14-3-3 protein sigma (SFN).	[44]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of 14-3-3 protein sigma (SFN).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of 14-3-3 protein sigma (SFN).	[46]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of 14-3-3 protein sigma (SFN).	[47]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of 14-3-3 protein sigma (SFN).	[48]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of 14-3-3 protein sigma (SFN).	[49]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of 14-3-3 protein sigma (SFN).	[50]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of 14-3-3 protein sigma (SFN).	[51]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of 14-3-3 protein sigma (SFN).	[52]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of 14-3-3 protein sigma (SFN).	[53]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of 14-3-3 protein sigma (SFN).	[45]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of 14-3-3 protein sigma (SFN).	[54]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of 14-3-3 protein sigma (SFN).	[56]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of 14-3-3 protein sigma (SFN).	[53]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of 14-3-3 protein sigma (SFN).	[54]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of 14-3-3 protein sigma (SFN).	[54]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of 14-3-3 protein sigma (SFN).	[54]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of 14-3-3 protein sigma (SFN).	[57]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of 14-3-3 protein sigma (SFN).	[54]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of 14-3-3 protein sigma (SFN).	[53]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of 14-3-3 protein sigma (SFN).	[58]
Isoniazid	DM5JVS3	Approved	Isoniazid decreases the expression of 14-3-3 protein sigma (SFN).	[59]
Chlorambucil	DMRKE63	Approved	Chlorambucil increases the expression of 14-3-3 protein sigma (SFN).	[60]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 14-3-3 protein sigma (SFN).	[61]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 14-3-3 protein sigma (SFN).	[62]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of 14-3-3 protein sigma (SFN).	[63]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of 14-3-3 protein sigma (SFN).	[64]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of 14-3-3 protein sigma (SFN).	[65]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine increases the expression of 14-3-3 protein sigma (SFN).	[67]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 increases the expression of 14-3-3 protein sigma (SFN).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 14-3-3 protein sigma (SFN).	[68]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of 14-3-3 protein sigma (SFN).	[69]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 14-3-3 protein sigma (SFN).	[70]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of 14-3-3 protein sigma (SFN).	[71]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of 14-3-3 protein sigma (SFN).	[72]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of 14-3-3 protein sigma (SFN).	[59]
Chrysin	DM7V2LG	Investigative	Chrysin increases the expression of 14-3-3 protein sigma (SFN).	[42]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of 14-3-3 protein sigma (SFN).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the methylation of 14-3-3 protein sigma (SFN).	[55]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of 14-3-3 protein sigma (SFN).	[66]

References

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