SREBP cleavage activating protein

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SREBF chaperone
Identifiers
Symbols SCAP ; KIAA0199
External IDs OMIM601510 MGI2135958 HomoloGene8160 GeneCards: SCAP Gene
Orthologs
Species Human Mouse
Entrez 22937 235623
Ensembl ENSG00000114650 ENSMUSG00000032485
UniProt Q12770 Q6GQT6
RefSeq (mRNA) NM_012235 NM_001001144
RefSeq (protein) NP_036367 NP_001001144
Location (UCSC) Chr 3:
47.46 – 47.52 Mb
Chr 9:
110.33 – 110.38 Mb
PubMed search [1] [2]

Sterol regulatory element-binding protein cleavage-activating protein, also known as SREBP cleavage-activating protein or SCAP is a protein that in humans is encoded by the SCAP gene.[1][2][3][4]

SCAP contains a sterol sensing domain (SSD) and seven WD domains. In cholesterol-depleted cells, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi apparatus. The SREBPs are then proteolytically cleaved and stimulate sterol biosynthesis.[1]

Function[edit]

SCAP is a regulatory protein that is required for the proteolytic cleavage of the sterol regulatory element-binding protein (SREBP). SCAP is an integral membrane protein located in the endoplasmic reticulum (ER). One of the cytosolic regions of SCAP contains a hexapeptide amino acid sequence, MELADL, that functions to detect cellular cholesterol. When cholesterol is present, SCAP undergoes a conformational change that prevents it from activating SREBP and cholesterol synthesis does not occur.[5]

Structure[edit]

Scap has 8 transmembrane domains and both the N-terminal and C-terminal face the cytoplasm. Also, it binds SREBP by a series of consecutive WD repeats on its C-terminus.[6]

References[edit]

  1. ^ a b "Entrez Gene: SREBF chaperone". 
  2. ^ Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N (February 1996). "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 3 (1): 17–24. doi:10.1093/dnares/3.1.17. PMID 8724849. 
  3. ^ Hua X, Nohturfft A, Goldstein JL, Brown MS (November 1996). "Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein". Cell 87 (3): 415–26. doi:10.1016/S0092-8674(00)81362-8. PMID 8898195. 
  4. ^ Nakajima T, Hamakubo T, Kodama T, Inazawa J, Emi M (1999). "Genomic structure and chromosomal mapping of the human sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) gene". J. Hum. Genet. 44 (6): 402–7. doi:10.1007/s100380050187. PMID 10570913. 
  5. ^ Sun LP, Seemann J, Goldstein JL, Brown MS (2007). "Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins". Proc. Natl. Acad. Sci. U.S.A. 104 (16): 6519–26. doi:10.1073/pnas.0700907104. PMC 1851663. PMID 17428919. 
  6. ^ Brown MS, Goldstein JL (1999). "A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11041–8. doi:10.1073/pnas.96.20.11041. PMC 34238. PMID 10500120. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.