Molecule Information

General Information of the Molecule (ID: Mol04154)

• Name: SREBP cleavage activating protein (SCAP) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: SCAP
• Gene ID: 22937
• Location: chr3:47413681-47477126[-]
• Sequence:
  MTLTERLREKISRAFYNHGLLCASYPIPIILFTGFCILACCYPLLKLPLPGTGPVEFTTP
  VKDYSPPPVDSDRKQGEPTEQPEWYVGAPVAYVQQIFVKSSVFPWHKNLLAVDVFRSPLS
  RAFQLVEEIRNHVLRDSSGIRSLEELCLQVTDLLPGLRKLRNLLPEHGCLLLSPGNFWQN
  DWERFHADPDIIGTIHQHEPKTLQTSATLKDLLFGVPGKYSGVSLYTRKRMVSYTITLVF
  QHYHAKFLGSLRARLMLLHPSPNCSLRAESLVHVHFKEEIGVAELIPLVTTYIILFAYIY
  FSTRKIDMVKSKWGLALAAVVTVLSSLLMSVGLCTLFGLTPTLNGGEIFPYLVVVIGLEN
  VLVLTKSVVSTPVDLEVKLRIAQGLSSESWSIMKNMATELGIILIGYFTLVPAIQEFCLF
  AVVGLVSDFFLQMLFFTTVLSIDIRRMELADLNKRLPPEACLPSAKPVGQPTRYERQLAV
  RPSTPHTITLQPSSFRNLRLPKRLRVVYFLARTRLAQRLIMAGTVVWIGILVYTDPAGLR
  NYLAAQVTEQSPLGEGALAPMPVPSGMLPPSHPDPAFSIFPPDAPKLPENQTSPGESPER
  GGPAEVVHDSPVPEVTWGPEDEELWRKLSFRHWPTLFSYYNITLAKRYISLLPVIPVTLR
  LNPREALEGRHPQDGRSAWPPPGPIPAGHWEAGPKGPGGVQAHGDVTLYKVAALGLATGI
  VLVLLLLCLYRVLCPRNYGQLGGGPGRRRRGELPCDDYGYAPPETEIVPLVLRGHLMDIE
  CLASDGMLLVSCCLAGHVCVWDAQTGDCLTRIPRPGRQRRDSGVGSGLEAQESWERLSDG
  GKAGPEEPGDSPPLRHRPRGPPPPSLFGDQPDLTCLIDTNFSAQPRSSQPTQPEPRHRAV
  CGRSRDSPGYDFSCLVQRVYQEEGLAAVCTPALRPPSPGPVLSQAPEDEGGSPEKGSPSL
  AWAPSAEGSIWSLELQGNLIVVGRSSGRLEVWDAIEGVLCCSSEEVSSGITALVFLDKRI
  VAARLNGSLDFFSLETHTALSPLQFRGTPGRGSSPASPVYSSSDTVACHLTHTVPCAHQK
  PITALKAAAGRLVTGSQDHTLRVFRLEDSCCLFTLQGHSGAITTVYIDQTMVLASGGQDG
  AICLWDVLTGSRVSHVFAHRGDVTSLTCTTSCVISSGLDDLISIWDRSTGIKFYSIQQDL
  GCGASLGVISDNLLVTGGQGCVSFWDLNYGDLLQTVYLGKNSEAQPARQILVLDNAAIVC
  NFGSELSLVYVPSVLEKLD
• 3D-structure: PDB ID: 7ETW; Classification: Membrane protein; Method: Electron microscopy; Resolution: 4.10 Å
• Function: Escort protein required for cholesterol as well as lipid homeostasis (By similarity). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:26311497). At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (By similarity). Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (PubMed:26311497). Binds cholesterol via its SSD domain (By similarity). .
• Uniprot ID: SCAP_HUMAN
• Ensembl ID: ENSG00000114650
• HGNC ID: HGNC:30634

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) 1 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Non-small cell lung carcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.24E-08; Fold-change: 3.83E-01; Z-score: 5.97E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Alcoholic liver disease; Activation; hsa04936
• Cell Pathway Regulation: Fatty acid metabolism; Activation; hsa01212
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H441 cells; Pericardial effusion; Homo sapiens (Human); CVCL_1561
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: We demonstrated that SREBP-1 and SCAP are highly expressed in NSCLC and are positively correlated with the aggressive phenotypes of NSCLC cells. In addition, downregulation of the expression of tumor-suppressing hsa-miR-497-5p, which predictively targets SREBP-1, was observed. We also demonstrated that SREBP-1/SCAP/FASN lipogenic signaling plays a key role in CSCs-like and chemoresistant NSCLC phenotypes, especially because the fatostatin or shRNA targeting of SREBP-1 significantly suppressed the viability, cisplatin resistance, and cancer stemness of NSCLC cells and because treatment induced the expression of hsa-miR-497.

References

• Ref 1: Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN Oncometabolic Axis Inhibits the Cancer Stem-like and Chemoresistant Phenotype of Non-Small Cell Lung Carcinoma Cells. Int J Mol Sci. 2022 Jun 30;23(13):7283.