SREBP cleavage-activating protein

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SCAP
Identifiers
AliasesSCAP, entrez:22937, SREBF chaperone
External IDsOMIM: 601510 MGI: 2135958 HomoloGene: 8160 GeneCards: SCAP
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for SCAP
Genomic location for SCAP
Band3p21.31Start47,413,694 bp[1]
End47,477,126 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012235
NM_001320044

NM_001001144
NM_001103162

RefSeq (protein)

NP_001306973
NP_036367

NP_001001144
NP_001096632

Location (UCSC)Chr 3: 47.41 – 47.48 MbChr 9: 110.33 – 110.38 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7][8]

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.[5]

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.[9]

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.[10]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000114650 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032485 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b "Entrez Gene: SREBF chaperone". 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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 1851663Freely accessible. PMID 17428919. 
  10. ^ 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 34238Freely accessible. PMID 10500120. 

Further reading[edit]

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