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2.A.6.6.4
SREBP cleavage-activating protein, Scap of 1279 aas.  Cholesterol homeostasis is mediated by Scap, a polytopic ER protein that transports SREBPs from ER to Golgi where SREBPs are processed to forms that activate cholesterol synthesis. Scap has eight transmembrane helices and two large luminal loops, designated Loop1 and Loop7. Evidence suggests that Loop1 binds to Loop7, allowing Scap to bind COPII proteins for transport in coated vesicles (Zhang et al. 2016). When ER cholesterol rises, it binds to Loop1 causeing dissociation from Loop7, abrogating COPII binding. Direct binding of the two loops causes dissociation from the membrane, allowing the soluble complex to be secreted.  Point mutations that disrupt the Loop1-Loop7 interaction prevented secretion.

Accession Number:P97260
Protein Name:SCAP
Length:1276
Molecular Weight:139514.00
Species:Cricetulus griseus (Chinese hamster) [10029]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate Sterol regulatory element-binding proteins

Cross database links:

Pfam: PF00400   

Gene Ontology

GO:0005789 C:endoplasmic reticulum membrane
GO:0012507 C:ER to Golgi transport vesicle membrane
GO:0000139 C:Golgi membrane
GO:0016021 C:integral to membrane
GO:0008022 F:protein C-terminus binding
GO:0008203 P:cholesterol metabolic process
GO:0006994 P:positive regulation of transcription via st...
GO:0006993 P:sterol regulatory element binding protein n...

References (12)

[1] “Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein.”  Hua X.et.al.   8898195
[2] “Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols.”  Yabe D.et.al.   12482938
[3] “Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies.”  Sakai J.et.al.   9488713
[4] “Topology of SREBP cleavage-activating protein, a polytopic membrane protein with a sterol-sensing domain.”  Nohturfft A.et.al.   9642295
[5] “Failure to cleave sterol regulatory element-binding proteins (SREBPs) causes cholesterol auxotrophy in Chinese hamster ovary cells with genetic absence of SREBP cleavage-activating protein.”  Rawson R.B.et.al.   10497220
[6] “Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi.”  Nohturfft A.et.al.   10500160
[7] “Overexpression of membrane domain of SCAP prevents sterols from inhibiting SCAP.SREBP exit from endoplasmic reticulum.”  Yang T.et.al.   10896675
[8] “Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER.”  Espenshade P.J.et.al.   12193656
[9] “Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain.”  Radhakrishnan A.et.al.   15260976
[10] “Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro.”  Sun L.-P.et.al.   15899885
[11] “Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change.”  Feramisco J.D.et.al.   15728349
[12] “Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins.”  Sun L.-P.et.al.   17428919

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTLTERLREK ISQAFYNHGL LCASYPIPII LFTGLCILAC CYPLLKLPLP GTGPVEFSTP 
61:	VKDYSPPPVD SDHKQGEPSE QPEWYVGAPV AYIQQIFVKS SVSPWHKNLL AVDVFRLPLS 
121:	RAFQLVEEIR NHVLRDSSGT KSLEEVCLQV TDLLPGLRKL RNLLPEHGCL LLSPGNFWQN 
181:	DWERFHADPD IIGTIHQHEP KTLQTSATLK DLLFGVPGKY SGVSLYTRKR TVSYTITLVF 
241:	QRYHAKFLSS LRARLMLLHP SPNCSLRAEN LVHVHFKEEI GIAELIPLVT TYIILFAYIY 
301:	FSTRKIDMVK SKWGLALAAV VTVLSSLLMS VGLCTLFGLT PTLNGGEIFP YLVVVIGLEN 
361:	VLVLTKSVVS TPVDLEVKLR IAQGLSSESW SIMKNVATEL GIILIGYFTL VPAIQEFCLF 
421:	AVVGLVSDFF LQMFFFTTVL SIDIRRMELA DLNKRLPPES CLPSAKPVGR PARYERQLAV 
481:	RPAMPHTITL QPSSFRNLRL PKRLRVIYFL ARTRLAQRLI MAGTVVWIGI LVYTDPAGLR 
541:	TYLAAQVTEQ SPLGEGSLGP MPVPSGVLPA SRPDPAFSIF PPDAPKLPEN QTVPGELPEH 
601:	AAPAEGVHDS RAPEVTWGPE DEELWRRLSF RHWPTLFNYY NITLAKRYIS LLPVIPVTLR 
661:	LNPQEALEGR QPQDGRSAWA PPESLPAGLW EAGPKGPGGT QAHGDITLYK VAALGLAAGI 
721:	VLVLLLLCLY RVLCPRNYGQ PGGGAGRRRR GELPCDDYGY APPETEIVPL VLRGHLMDIE 
781:	CLASDGMLLV SCCLAGQVCV WDAQTGDCLT RIPRPGSRRD SCGGGAFETQ ENWERLSDGG 
841:	KTSPEEPGES PPLRHRPRGP PQPALFGDQP DLTCLIDTNF SVQLPPEPTQ PEPRHRAGCG 
901:	RARDSGYDFS RLVQRVYQEE GLAAVRMPAL RPPSPGSPLP QASQEDGAAP EKGSPPLAWA 
961:	PSTAGSIWSL ELQGNLIVVG RSSGRLEVWD AIEGVLCCSN DEVSSGITAL VFLDRRIVAA 
1021:	RLNGSLDFFS LETHTSLSPL QFRGTPGRGS SPSSSVYSSS NTVACHLTHT VPCAHQKPIT 
1081:	ALRAAAGRLV TGSQDHTLRV FRLEDSCCLF TLQGHSGAIT TVYIDQTMVL ASGGQDGAIC 
1141:	LWDVLTGSRV SHTFAHRGDV TSLTCTTSCV ISSGLDDLIN IWDRSTGIKL YSIQQDLGCG 
1201:	ASLGVISDNL LVTGGQGCVS FWDLNYGDLL QTVYLGKNSE AQPARQILVL DNAAIVCNFG 
1261:	SELSLVYVPS VLEKLD