SCAP_RAT
ID SCAP_RAT Reviewed; 1276 AA.
AC A2RRU4;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein {ECO:0000250|UniProtKB:Q12770};
DE Short=SCAP {ECO:0000250|UniProtKB:Q12770};
DE Short=SREBP cleavage-activating protein {ECO:0000250|UniProtKB:Q12770};
GN Name=Scap {ECO:0000312|RGD:1309378};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:AAI31853.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart {ECO:0000312|EMBL:AAI31853.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Escort protein required for cholesterol as well as lipid
CC homeostasis. Regulates export of the SCAP-SREBP complex from the
CC endoplasmic reticulum to the Golgi upon low cholesterol, thereby
CC regulating the processing of sterol regulatory element-binding proteins
CC (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. At high sterol
CC concentrations, formation of a ternary complex with INSIG (INSIG1 or
CC INSIG2) leads to mask the ER export signal in SCAP, promoting retention
CC of the complex in the endoplasmic reticulum. Low sterol concentrations
CC trigger release of INSIG, a conformational change in the SSD domain of
CC SCAP, unmasking of the ER export signal, promoting recruitment into
CC COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in
CC the Golgi, SREBPs are then processed, releasing the transcription
CC factor fragment of SREBPs from the membrane, its import into the
CC nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway.
CC Binds cholesterol via its SSD domain. {ECO:0000250|UniProtKB:P97260}.
CC -!- SUBUNIT: Membrane region forms a homotetramer (By similarity). Forms a
CC stable complex with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-
CC terminal cytoplasmic domain (By similarity). Forms a ternary complex
CC with INSIG1 or INSIG2 through its transmembrane domains at high sterol
CC concentrations (By similarity). Interacts with the SEC23-SEC24 complex
CC in a SAR1-GTP-dependent manner through an ER export signal in its third
CC cytoplasmic loop (By similarity). Binds cholesterol through its SSD
CC domain (By similarity). Component of SCAP-SREBP complex composed of
CC SREBF2, SCAP and RNF139; the complex hampers the interaction between
CC SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing (By
CC similarity). Interacts with RNF139; the interaction inhibits the
CC interaction of SCAP with SEC24B and hampering the ER to Golgi transport
CC of the SCAP-SREBP complex (By similarity). Interacts with SPRING1 (By
CC similarity). {ECO:0000250|UniProtKB:P97260,
CC ECO:0000250|UniProtKB:Q12770}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P97260}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:P97260};
CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, COPII-
CC coated vesicle membrane {ECO:0000250|UniProtKB:P97260}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Moves from the endoplasmic
CC reticulum to the Golgi in the absence of sterols. Requires the presence
CC of SPRING for proper localization to endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:P97260, ECO:0000250|UniProtKB:Q12770}.
CC -!- DOMAIN: Loop-1 binds to loop-7, enabling interaction with COPII-coated
CC vesicles. When levels of cholesterol in the endoplasmic reticulum
CC increase, Loop-1 binds to cholesterol instead, thereby disrupting
CC direct binding between the two loops and preventing the SCAP-SREBP
CC complex from exiting the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:P97260}.
CC -!- DOMAIN: Cholesterol bound to SSD domain of SCAP or oxysterol bound to
CC INSIG (INSIG1 or INSIG2) leads to masking of an ER export signal (also
CC named MELADL motif) on SCAP possibly by moving the signal further away
CC from the ER membrane. {ECO:0000250|UniProtKB:P97260}.
CC -!- PTM: Ubiquitinated at Lys-454 and Lys-466. RNF145 triggers
CC ubiquitination of SCAP, likely inhibiting SCAP-SREBP complex transport
CC to the Golgi apparatus and the subsequent processing/maturation of
CC SREBF2/SREBP2. {ECO:0000250|UniProtKB:Q6GQT6}.
CC -!- SIMILARITY: Belongs to the WD repeat SCAP family. {ECO:0000305}.
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DR EMBL; BC131852; AAI31853.1; -; mRNA.
DR RefSeq; NP_001094436.1; NM_001100966.1.
DR RefSeq; XP_006243984.1; XM_006243922.3.
DR RefSeq; XP_006243985.1; XM_006243923.3.
DR RefSeq; XP_006243986.1; XM_006243924.3.
DR RefSeq; XP_006243987.1; XM_006243925.3.
DR RefSeq; XP_017451085.1; XM_017595596.1.
DR AlphaFoldDB; A2RRU4; -.
DR SMR; A2RRU4; -.
DR STRING; 10116.ENSRNOP00000028295; -.
DR GlyGen; A2RRU4; 3 sites.
DR iPTMnet; A2RRU4; -.
DR PhosphoSitePlus; A2RRU4; -.
DR PaxDb; A2RRU4; -.
DR PeptideAtlas; A2RRU4; -.
DR PRIDE; A2RRU4; -.
DR Ensembl; ENSRNOT00000028295; ENSRNOP00000028295; ENSRNOG00000020853.
DR GeneID; 301024; -.
DR KEGG; rno:301024; -.
DR CTD; 22937; -.
DR RGD; 1309378; Scap.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000158130; -.
DR HOGENOM; CLU_006510_0_0_1; -.
DR InParanoid; A2RRU4; -.
DR OMA; IMKQYNV; -.
DR OrthoDB; 523786at2759; -.
DR PhylomeDB; A2RRU4; -.
DR TreeFam; TF315236; -.
DR Reactome; R-RNO-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR PRO; PR:A2RRU4; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000020853; Expressed in ovary and 19 other tissues.
DR Genevisible; A2RRU4; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0032936; C:SREBP-SCAP complex; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0032934; F:sterol binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0044255; P:cellular lipid metabolic process; ISO:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0090110; P:COPII-coated vesicle cargo loading; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; ISO:RGD.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISO:RGD.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; ISO:RGD.
DR GO; GO:0042304; P:regulation of fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:0032933; P:SREBP signaling pathway; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR030225; SCAP.
DR InterPro; IPR000731; SSD.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR46378; PTHR46378; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50156; SSD; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Isopeptide bond; Lipid metabolism;
KW Lipid-binding; Membrane; Methylation; Phosphoprotein; Reference proteome;
KW Repeat; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Ubl conjugation; WD repeat.
FT CHAIN 1..1276
FT /note="Sterol regulatory element-binding protein cleavage-
FT activating protein"
FT /id="PRO_0000315872"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 19..39
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..279
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 280..300
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 301..312
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 313..333
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 334..344
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 345..365
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 366..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 402..422
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 423
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 424..444
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 445..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 519..539
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..707
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 708..728
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 729..1276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT DOMAIN 284..442
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REPEAT 771..811
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 949..999
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 1002..1039
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 1074..1111
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 1114..1152
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 1155..1192
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 1194..1232
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT REGION 46..284
FT /note="Loop-1"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 60..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 535..710
FT /note="Loop-7"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 731..1276
FT /note="Interaction with SREBF2"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 834..903
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 928..958
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 447..452
FT /note="ER export signal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT COMPBIAS 834..853
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 821
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 837
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 843
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6GQT6"
FT MOD_RES 850
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 934
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 1048
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q6GQT6"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 590
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 454
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q6GQT6"
FT CROSSLNK 466
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q6GQT6"
SQ SEQUENCE 1276 AA; 139499 MW; 12278757C1BDA3C6 CRC64;
MTLTERLREK ISQAFYNHGL LCASYPIPII LFTGLCILAC CYPLLKLPLP GTGPVEFSTP
VKGYSPPPAD SDHKQGEPSE QPEWYVGAPV AYIQQIFVKS SVSPWHRNLL AVDVFRSPLS
RAFQLVEEIR NHVLRDSSGT KSLEEVCLQV TDLLPGLRKL RSLLPEHGCL LLSPGNFWQN
DWERFHADPD IIGTIHQHEP KTLQTSATLK DLLFGVPGKY SGVSLYTRKR MVSYTITLVF
QRYHAKFLSS LRARLMLLHP SPNCSLRAEN LVHVHFKEEI GIAELIPLVT TYIILFAYIY
FSTRKIDMVK SKWGLALAAV VTVLSSLLMS VGLCTLFGLT PTLNGGEIFP YLVVVIGLEN
VLVLTKSVVS TPVDLEVKLR IAQGLSSESW SIMKNVATEL GIILIGYFTL VPAIQEFCLF
AVVGLVSDFF LQMLFFTTVL SIDIRRMELA DLNKRLPPES CLPSAKPVGR PARYERQLAV
RPSTPHTITL QPSSFRNLRL PKRLRVIYFL ARTRLAQRLI MAGTVVWIGI LVYTDPAGLR
TYLAAQVTEQ SPLGEGSLGP MPVPSGVLPA SHPDPAFSIF PPDAPKLPEN QTLPGELPEH
AVPAEGVQDS RAPEVTWGPE DEELWRKLSF RHWPTLFNYY NITLAKRYIS LLPVIPVTLH
LNPREALEGR HPQDGRTAWA PPEPLPAGLW ETGPKGPGGT QTHGDITLYK VAALGLAAGI
VLVLLLLCLY RVLCPRNYGQ PGGGAGRRRR GELPCDDYGY APPETEIVPL VLRGHLMDIE
CLASDGMLLV SCCLAGQVCV WDAQTGDCLT RIPRPGPRRD SCGGGAFEAQ ENWERLSDGG
KASPEEPGDS PPLRRRPRGP PPPSLFGDQP DLTCLIDTNF SVQLPPEPTQ PEPRHRAGCG
RSRDSGYDFS RLVQRVYQEE GLAAVHMSAL RPPSPGPPLP QASQEEGTAP EKGSPPLAWA
PSTAGSIWSL ELQGSLIVVG RSSGRLEVWD AIEGVLCCSN EEISSGITAL VFLDRRIVAA
RLNGSLDFFS LETHTSLSPL QFRGTPGRGS SPSSPVYSSS NTVACHLTHT VPCAHQKPIT
ALRAAAGRLV TGSQDHTLRV FRLEDSCCLF TLQGHSGAIT TVYIDQTMVL ASGGQDGAIC
LWDVLTGSRV SHTFAHRGDV TSLTCTTSCV ISSGLDDFIN IWDRSTGIKL YSIQQDLGCG
ASLGVISDNL LVTGGQGCVS FWDLNYGDLL QTVYLGKNSE AQPARQILVL DNAAIVCNFG
SELSLVYVPS VLEKLD
