Molecule Information

General Information of the Molecule (ID: Mol04162)

• Name: Sterol regulatory element binding protein 2 (SREBP2) ,Homo sapiens
• Synonyms: Class D basic helix-loop-helix protein 2; Sterol regulatory element-binding transcription factor 2
• Molecule Type: Protein
• Gene ID: 6721
• Location: chr22:41833105-41907306[+]
• Sequence:
  MDDSGELGGLETMETLTELGDELTLGDIDEMLQFVSNQVGEFPDLFSEQLCSSFPGSGGS
  GSSSGSSGSSSSSSNGRGSSSGAVDPSVQRSFTQVTLPSFSPSAASPQAPTLQVKVSPTS
  VPTTPRATPILQPRPQPQPQPQTQLQQQTVMITPTFSTTPQTRIIQQPLIYQNAATSFQV
  LQPQVQSLVTSSQVQPVTIQQQVQTVQAQRVLTQTANGTLQTLAPATVQTVAAPQVQQVP
  VLVQPQIIKTDSLVLTTLKTDGSPVMAAVQNPALTALTTPIQTAALQVPTLVGSSGTILT
  TMPVMMGQEKVPIKQVPGGVKQLEPPKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGT
  DAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNKLLKGIDLGSLVDNEVDLK
  IEDFNQNVLLMSPPASDSGSQAGFSPYSIDSEPGSPLLDDAKVKDEPDSPPVALGMVDRS
  RILLCVLTFLCLSFNPLTSLLQWGGAHDSDQHPHSGSGRSVLSFESGSGGWFDWMMPTLL
  LWLVNGVIVLSVFVKLLVHGEPVIRPHSRSSVTFWRHRKQADLDLARGDFAAAAGNLQTC
  LAVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKKVFQCRRATPATEAGFEDEAK
  TSARDAALAYHRLHQLHITGKLPAGSACSDVHMALCAVNLAECAEEKIPPSTLVEIHLTA
  AMGLKTRCGGKLGFLASYFLSRAQSLCGPEHSAVPDSLRWLCHPLGQKFFMERSWSVKSA
  AKESLYCAQRNPADPIAQVHQAFCKNLLERAIESLVKPQAKKKAGDQEEESCEFSSALEY
  LKLLHSFVDSVGVMSPPLSRSSVLKSALGPDIICRWWTSAITVAISWLQGDDAAVRSHFT
  KVERIPKALEVTESPLVKAIFHACRAMHASLPGKADGQQSSFCHCERASGHLWSSLNVSG
  ATSDPALNHVVQLLTCDLLLSLRTALWQKQASASQAVGETYHASGAELAGFQRDLGSLRR
  LAHSFRPAYRKVFLHEATVRLMAGASPTRTHQLLEHSLRRRTTQSTKHGEVDAWPGQRER
  ATAILLACRHLPLSFLSSPGQRAVLLAEAARTLEKVGDRRSCNDCQQMIVKLGGGTAIAA
  S
• 3D-structure: PDB ID: 1UKL; Classification: Protein transport/dna binding protein; Method: X-ray diffraction; Resolution: 3.00 Å
• 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 (PubMed:32322062). 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 (PubMed:32322062). .; [Processed sterol regulatory element-binding protein 2]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis (PubMed:12177166, PubMed:32322062). 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') (PubMed:12177166, PubMed:7903453). Regulates transcription of genes related to cholesterol synthesis pathway (PubMed:12177166, PubMed:32322062). .
• Uniprot ID: SRBP2_HUMAN
• Ensembl ID: ENSG00000198911
• HGNC ID: HGNC:11290

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Caffine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Neuroblastoma [ICD-11: 2AOO.11] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: Neuroblastoma [ICD-11: 2AOO.11]
• Sensitive Drug: Caffine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Terpenoid backbone biosynthesis; Activation; hsa00900
• In Vivo Model: NOD/SCID mice, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Our data are consistent with a recent study in liver cancer cell lines showing that statin represses FOXM1 expression by blocking geranylgeranylation of RhoA, Rac1 or Cdc42 proteins (46). Together, these findings suggest a molecular mechanism for the long-observed connection between the mevalonate pathway and cell-cycle progression (47).

Simvastatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Neuroblastoma [ICD-11: 2AOO.11] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Neuroblastoma [ICD-11: 2AOO.11]
• Resistant Drug: Simvastatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Terpenoid backbone biosynthesis; Activation; hsa00900
• In Vivo Model: NOD/SCID mice, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Our data are consistent with a recent study in liver cancer cell lines showing that statin represses FOXM1 expression by blocking geranylgeranylation of RhoA, Rac1 or Cdc42 proteins (46). Together, these findings suggest a molecular mechanism for the long-observed connection between the mevalonate pathway and cell-cycle progression (47).

References

• Ref 1: Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma. Cancer Res. 2023 Jul 5;83(13):2248-2261.