Details of Drug Off-Target (DOT)

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

• DOT Name: Sterol regulatory element-binding protein 2 (SREBF2)
• Synonyms: SREBP-2; Class D basic helix-loop-helix protein 2; bHLHd2; Sterol regulatory element-binding transcription factor 2
• Gene Name: SREBF2
• UniProt ID: SRBP2_HUMAN
• PDB ID: 1UKL
• Pfam ID: PF00010
• Sequence:
  MDDSGELGGLETMETLTELGDELTLGDIDEMLQFVSNQVGEFPDLFSEQLCSSFPGSGGS
  GSSSGSSGSSSSSSNGRGSSSGAVDPSVQRSFTQVTLPSFSPSAASPQAPTLQVKVSPTS
  VPTTPRATPILQPRPQPQPQPQTQLQQQTVMITPTFSTTPQTRIIQQPLIYQNAATSFQV
  LQPQVQSLVTSSQVQPVTIQQQVQTVQAQRVLTQTANGTLQTLAPATVQTVAAPQVQQVP
  VLVQPQIIKTDSLVLTTLKTDGSPVMAAVQNPALTALTTPIQTAALQVPTLVGSSGTILT
  TMPVMMGQEKVPIKQVPGGVKQLEPPKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGT
  DAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNKLLKGIDLGSLVDNEVDLK
  IEDFNQNVLLMSPPASDSGSQAGFSPYSIDSEPGSPLLDDAKVKDEPDSPPVALGMVDRS
  RILLCVLTFLCLSFNPLTSLLQWGGAHDSDQHPHSGSGRSVLSFESGSGGWFDWMMPTLL
  LWLVNGVIVLSVFVKLLVHGEPVIRPHSRSSVTFWRHRKQADLDLARGDFAAAAGNLQTC
  LAVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKKVFQCRRATPATEAGFEDEAK
  TSARDAALAYHRLHQLHITGKLPAGSACSDVHMALCAVNLAECAEEKIPPSTLVEIHLTA
  AMGLKTRCGGKLGFLASYFLSRAQSLCGPEHSAVPDSLRWLCHPLGQKFFMERSWSVKSA
  AKESLYCAQRNPADPIAQVHQAFCKNLLERAIESLVKPQAKKKAGDQEEESCEFSSALEY
  LKLLHSFVDSVGVMSPPLSRSSVLKSALGPDIICRWWTSAITVAISWLQGDDAAVRSHFT
  KVERIPKALEVTESPLVKAIFHACRAMHASLPGKADGQQSSFCHCERASGHLWSSLNVSG
  ATSDPALNHVVQLLTCDLLLSLRTALWQKQASASQAVGETYHASGAELAGFQRDLGSLRR
  LAHSFRPAYRKVFLHEATVRLMAGASPTRTHQLLEHSLRRRTTQSTKHGEVDAWPGQRER
  ATAILLACRHLPLSFLSSPGQRAVLLAEAARTLEKVGDRRSCNDCQQMIVKLGGGTAIAA
  S
• Function: [Sterol regulatory element-binding protein 2]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane. Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis ; [Processed sterol regulatory element-binding protein 2]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis. Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). Regulates transcription of genes related to cholesterol synthesis pathway.
• Tissue Specificity: Ubiquitously expressed in adult and fetal tissues.
• Reactome Pathway:
  Cholesterol biosynthesis (R-HSA-191273)
  PPARA activates gene expression (R-HSA-1989781)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)
  Regulation of cholesterol biosynthesis by SREBP (SREBF) (R-HSA-1655829)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ritonavir	DMU764S	Approved	Sterol regulatory element-binding protein 2 (SREBF2) increases the Hepatomegaly ADR of Ritonavir.	[36]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
ANW-32821	DMMJOZD	Phase 2	Sterol regulatory element-binding protein 2 (SREBF2) increases the abundance of ANW-32821.	[37]

2 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 Sterol regulatory element-binding protein 2 (SREBF2).	[1]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Sterol regulatory element-binding protein 2 (SREBF2).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[10]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[11]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[12]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[13]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[14]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[17]
Crizotinib	DM4F29C	Approved	Crizotinib increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[18]
Ezetimibe	DM7A8TW	Approved	Ezetimibe decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[19]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[28]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[29]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[30]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[31]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[32]
Linalool	DMGZQ5P	Investigative	Linalool decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[33]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[34]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Sterol regulatory element-binding protein 2 (SREBF2).	[35]
25-hydroxycholesterol	DMCHAQ7	Investigative	25-hydroxycholesterol decreases the activity of Sterol regulatory element-binding protein 2 (SREBF2).	[11]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the metabolism of Sterol regulatory element-binding protein 2 (SREBF2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the localization of Sterol regulatory element-binding protein 2 (SREBF2).	[16]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the localization of Sterol regulatory element-binding protein 2 (SREBF2).	[16]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the cleavage of Sterol regulatory element-binding protein 2 (SREBF2).	[22]

References

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