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2.A.6.6.16
Sterol regulatory element-binding protein cleavage-activating protein, SCAP (SLC64 Family), an SSD domain-containing protein of 731 aas and 7 TMSs in a 1 + 5 + 1 TMS arrangement. The cholesterol-sensing protein Scap induces cholesterol synthesis by transporting membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) from the theendoplasmic reticulum (ER) to the Golgi apparatus for proteolytic activation. Transport requires interaction between Scap's two ER luminal loops (L1 and L7), which flank an intramembrane sterol-sensing domain (SSD). Cholesterol inhibits Scap transport by binding to L1, which triggers Scap's binding to Insig, an ER retention protein. Kober et al. 2021 used cryo-EM to elucidate two structures of full-length chicken Scap: (1) a wild-type free of Insigs and (2) mutant Scap bound to chicken Insig without cholesterol.  L1 and L7 intertwine tightly to form a globular domain that acts as a luminal platform connecting the SSD to the rest of Scap. In the presence of Insig, this platform undergoes a large rotation accompanied by rearrangement of Scap's transmembrane helices. This conformational change may halt Scap transport of SREBPs and thereby inhibit cholesterol synthesis (Kober et al. 2021).

Accession Number:Q5F3Q8
Protein Name:SSD domain-containing protein
Length:731
Molecular Weight:81959.00
Species:Gallus gallus (Chicken) [9031]
Number of TMSs:7
Substrate cholesterol, sterol, 25-hydroxycholesterol

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FASTA formatted sequence
1:	MTLTEKLRER ISRAFYNHGL LCASYPIPII LFTGLCILAC CYPLLKLPLP GTGPVEFSTP 
61:	VKDYFPPSPD VVSQQGDLSE RPDWYVGAPV AYIQQIFVKA TVSPWQKNFL AVDVFRSPLS 
121:	RVFQLVEEIR NHALRDSSGV KSLEEVCLQV TDLLPGLKKL RNLLPEHGCL LLSPGNFWQN 
181:	DRERFNADPD IIKTIHQHEP KALQTSATLK DLLFGLPGKY SGVNLYNRKR VVSYTVTLGL 
241:	QRYDSRFLSS LRSRLKLLHP SPNCTLREDS IVHVHFKEEI GIAELIPLVT TYIILFAYIY 
301:	FSTRKIDMVK SKWGLALAAV VTVLSSLLMS VGLCTLFGLT PTLNGGEIFP YLVVVIGLEN 
361:	VLVLTKSVVS TPVDLEVKLR IAQGLSNESW SIMKNMATEL GIILIGYFTL VPAIQEFCLF 
421:	AVVGLVSDFF LQMLFFTTVL SIDIRRMELA DLNKRLPAEA CLPPAKPASR SQRYERQPAV 
481:	RPATPHTITL QPSSFRNLRL PKRLRVIYFF ARTRLAQRLI MAGTVIWIGI LVYTDPAGLR 
541:	TYLTSQVTEQ SPLGEAGLPP MPVPGGVLPA GDPKIDLSVF PSDPIQLSEN QTQQREQQAG 
601:	LEPLGRLETN QHSWAQGPEG RGNGQTELGT EAEVTWGAED EEIWRKLSFR HWPSLFSYYN 
661:	ITLAKRYISI LPAIPVTLYL NPQEALEVRH PQEANRYHPF LSSSGGKLNA EAQPDQTSSR 
721:	LQGHRDVTLY K