SCAP_XENLA
ID SCAP_XENLA Reviewed; 1311 AA.
AC A0JPH4; Q6GQ00;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein;
DE Short=SCAP;
DE Short=SREBP cleavage-activating protein;
GN Name=scap {ECO:0000250|UniProtKB:Q12770};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000312|EMBL:AAI27424.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula {ECO:0000312|EMBL:AAH72950.1}, and Tail bud;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
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. Binds cholesterol via its SSD domain.
CC {ECO:0000250|UniProtKB:P97260}.
CC -!- SUBUNIT: Membrane region forms a homotetramer. Component of the SCAP-
CC SREBP complex (composed of SCAP and srebf1/srebp1 or srebf2/srebp2).
CC Forms a ternary complex with insig1 or insig2 through its transmembrane
CC domains at high sterol concentrations. Interacts with the SEC23-SEC24
CC complex. {ECO:0000250|UniProtKB:P97260}.
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.
CC {ECO:0000250|UniProtKB:P97260}.
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 -!- SIMILARITY: Belongs to the WD repeat SCAP family. {ECO:0000305}.
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DR EMBL; BC072950; AAH72950.1; -; mRNA.
DR EMBL; BC127423; AAI27424.1; -; mRNA.
DR RefSeq; NP_001085277.1; NM_001091808.1.
DR AlphaFoldDB; A0JPH4; -.
DR SMR; A0JPH4; -.
DR DNASU; 443598; -.
DR GeneID; 443598; -.
DR KEGG; xla:443598; -.
DR CTD; 443598; -.
DR Xenbase; XB-GENE-996524; scap.S.
DR OrthoDB; 523786at2759; -.
DR Proteomes; UP000186698; Chromosome 6S.
DR Bgee; 443598; Expressed in spleen and 19 other tissues.
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:0032934; F:sterol binding; ISS:UniProtKB.
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: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; 2.
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; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Lipid metabolism; Lipid-binding; Membrane;
KW Reference proteome; Repeat; Steroid metabolism; Sterol metabolism;
KW Transmembrane; Transmembrane helix; WD repeat.
FT CHAIN 1..1311
FT /note="Sterol regulatory element-binding protein cleavage-
FT activating protein"
FT /id="PRO_0000315873"
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..277
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 278..298
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 311..331
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..342
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 343..363
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 364..399
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 400..420
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 421
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 422..442
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 513..533
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 534..723
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 724..744
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 745..1311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT DOMAIN 282..440
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REPEAT 790..827
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 997..1034
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 1037..1076
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 1109..1146
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 1149..1187
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 1190..1227
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 1230..1267
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT REGION 46..282
FT /note="Loop-1"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 529..726
FT /note="Loop-7"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 747..1311
FT /note="Interaction with srebf"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT MOTIF 445..450
FT /note="ER export signal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 583
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1311 AA; 145362 MW; 569453E0A1A7E64A CRC64;
MPLIDKLRER ISRAFYSHGL LCASYPIPII ILTALCILAS CYPLLKLPLP GTGPVEYVTS
VKDYSPPPLE PNPEDHSDQP DWYVGLPVAF IQQVLVKAVV SPWDKDFLAV DVFRSPLSRV
FPLVEEIRNH VLRDKSQEKS LEDVCLQVTD LLPGLKKFRD KLPEHGCLLL SPANFWQNSQ
EQFSSDPDLI RTIHQHEPKT LQTSATLKDL LFGVPGKQSG VSLYNRKRIV SYTVTIALRR
YNATFLDSLR SRLKRQHPST NSSAASQHIV HVHFKEEIGI AELIPLVTTY IILFAYIYFS
TRKIDLVKSK WGLALAAVVT VLSSLLMSVG LCTLFGLTPT LNGGEIFPYL VVVIGLENVL
VLTKSVVSTP VDLEVKLRIA QGLRNESWFI MKNMATELGI ILIGYFTLVP AIQEFCLFAV
VGLVSDFFLQ MFFFTTVLSI DIRRMELADL NKRIPAEACI PPPKPGAKRY DRQPTLRPAT
PHTITLQSLR NLRLPKRLRL VYFFARTRLA QRIIMAGTVV WIGILVYTDP AGLRNYLTVH
VTEQSPLGGA VMPPIPVPVL SASNPHGPLS AVFPTGSSQL LENQSQRDSK EVIDSLSSRI
WEESHPEDKS KERAAKIEDK AHTQVTWGAE DEETWRKLSF RHWPTLFSYY NITLAKKYIS
ILPMIPVTLY LTPQEVSDAR HPQEAQHSHP YLQREGKPDE AWARVEAKGA EKPTENQTPA
DVTLYKVAAL GLASGIFLVL FFFLLYRLLC PKNYGQNGVS HGRRKKGDLP CDDYGYSPPE
TEIVPLVLRG HHMDIECLAS DKMLLVSCCL AGQIRVWDAQ SGDCLTIIPK PSLRRESSGV
FEYQDNWEPT PECKYNPEES LENGYQLKRR TLHPPLFSDQ PDLTSLIDTN FSEQPANEES
GARQRLSCIK QESPPIGYDF SSLVQKVYEE HEVSSFGSFP LVLSPAPYGQ CQLSSGRRSQ
TPAGCVDGSC ARRKSSTEET TGYCNGSSSP APSWTDSFES SVWSLGLQGN LIVVGRSNGN
LEVWDAIEGS LRCSNCDGQS GITSLVFLNH RVVVARLNGS MDFYCLDSQK SSNQLQFRGA
PNRSNVPSSP LYSTDDVIGC QRTHTVACAH RKPITALKAA AGRLVTGSQD HTVRIYRLED
ACCLFTLQGH SGGITAIYID ETMVLASGGQ DGAICLWDVL TGSRVSHMFG HRGDVTSLLC
TASCVISSGL DDVISIWDRS TAIKLYSIQQ DLGCGSSLGL ISDNLLVTGG LGCVSFWDVG
YGDLLQTVYL GKCEDSQPAR HILVLDNSAI VCDFGSELSL VYVPSVLEKL D
