SCAP_PIG
ID SCAP_PIG Reviewed; 1279 AA.
AC Q5MNU5; Q0R5S1; Q0R5S2; Q3SBD2; Q5I387; Q5MJG7; Q5QCZ6; Q6VFU0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein {ECO:0000303|PubMed:16705418};
DE Short=SCAP {ECO:0000303|PubMed:16705418};
DE Short=SREBP cleavage-activating protein {ECO:0000303|PubMed:16705418};
GN Name=SCAP {ECO:0000303|PubMed:16705418};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAW19058.2}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 1-44 AND 70-1279, NUCLEOTIDE SEQUENCE [MRNA] OF 817-1114 (ISOFORMS 2 AND
RP 3), AND TISSUE SPECIFICITY.
RX PubMed=16705418; DOI=10.1007/s00438-006-0134-8;
RA Qiu H., Xia T., Chen X., Zhao X., Gan L., Feng S., Lei T., Yang Z.;
RT "Cloning, comparative characterization of porcine SCAP gene, and
RT identification of its two splice variants.";
RL Mol. Genet. Genomics 276:187-196(2006).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAW51130.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1026-1107 (ISOFORM 1).
RC TISSUE=Adipose tissue {ECO:0000312|EMBL:AAQ24843.1};
RA Thacker S.S., Bergen W.G.;
RT "Sequences of transcripts of porcine SREBP cleavage-activating protein
RT (SCAP) and adiponectin.";
RL Submitted (JUL-2003) 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 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000303|PubMed:16705418};
CC IsoId=Q5MNU5-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:16705418};
CC IsoId=Q5MNU5-2; Sequence=VSP_052641, VSP_052642;
CC Name=3 {ECO:0000303|PubMed:16705418};
CC IsoId=Q5MNU5-3; Sequence=VSP_052639, VSP_052640;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Widely expressed with higher levels in
CC lung, kidney, gut, brain and adipose tissue.
CC {ECO:0000269|PubMed:16705418}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in liver and muscle. Isoform
CC 3 expressed in testis. {ECO:0000269|PubMed:16705418}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in testis.
CC {ECO:0000269|PubMed:16705418}.
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; AY705447; AAV84285.1; -; mRNA.
DR EMBL; AY705448; AAW19058.2; -; mRNA.
DR EMBL; AY858690; AAW51130.1; -; Genomic_DNA.
DR EMBL; DQ076089; AAZ31543.1; -; Genomic_DNA.
DR EMBL; DQ076090; AAW19080.2; -; Genomic_DNA.
DR EMBL; DQ076091; AAZ31544.1; -; mRNA.
DR EMBL; DQ076092; AAZ31545.1; -; mRNA.
DR EMBL; AY340938; AAQ24843.1; -; mRNA.
DR RefSeq; NP_001185623.2; NM_001198694.2. [Q5MNU5-1]
DR AlphaFoldDB; Q5MNU5; -.
DR SMR; Q5MNU5; -.
DR STRING; 9823.ENSSSCP00000026028; -.
DR PaxDb; Q5MNU5; -.
DR PeptideAtlas; Q5MNU5; -.
DR PRIDE; Q5MNU5; -.
DR GeneID; 494015; -.
DR KEGG; ssc:494015; -.
DR CTD; 22937; -.
DR eggNOG; KOG1933; Eukaryota.
DR InParanoid; Q5MNU5; -.
DR OrthoDB; 523786at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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:0032936; C:SREBP-SCAP complex; IBA:GO_Central.
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:0045540; P:regulation of cholesterol biosynthetic process; IBA:GO_Central.
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; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cholesterol metabolism; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Isopeptide bond;
KW Lipid metabolism; Lipid-binding; Membrane; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; Steroid metabolism; Sterol metabolism;
KW Transmembrane; Transmembrane helix; Ubl conjugation; WD repeat.
FT CHAIN 1..1279
FT /note="Sterol regulatory element-binding protein cleavage-
FT activating protein"
FT /id="PRO_0000315871"
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..1279
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 770..810
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 952..1002
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 1005..1042
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 1077..1114
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 1117..1155
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 1158..1195
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 1197..1235
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 588..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 668..696
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 730..1279
FT /note="Interaction with SREBF2"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 834..868
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 883..903
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 925..959
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 COMPBIAS 884..903
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 928..948
FT /note="Pro 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 936
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 1051
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"
FT VAR_SEQ 898..909
FT /note="SGCRRTQDCTGY -> CGTPLKACCAVA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16705418"
FT /id="VSP_052639"
FT VAR_SEQ 910..1279
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16705418"
FT /id="VSP_052640"
FT VAR_SEQ 931..938
FT /note="APRPPSPG -> LKACCAVA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16705418"
FT /id="VSP_052641"
FT VAR_SEQ 939..1279
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16705418"
FT /id="VSP_052642"
FT CONFLICT 434
FT /note="P -> L (in Ref. 1; AAW19080)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="A -> V (in Ref. 1; AAW51130)"
FT /evidence="ECO:0000305"
FT CONFLICT 779
FT /note="E -> G (in Ref. 1; AAW19080)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1279 AA; 140058 MW; AAAD115F907E7F82 CRC64;
MTLTERLREK ISQAFYNHGL LCASYPIPII LFTGLCILAC CYPLLKLPLP GTGPVEFTTP
VKDYSPPPSA SDHKPGEPSE QPEWYVGAPV AYIQQIFVKS SVSPWHKNLL AVDVFRSPLS
RAFQLVEEIR NHVLRDSSGT RSLEEVCLQV TDLLPGLRKL RNILPEHGCL LLSPGNFWQN
DRERFHADPD IIGTIHQHEP KTLQTSATLK DLLFGVPGKH SGVSLYTRKR LVSYTITLVF
QHYHAKFLGS LRARLMLLHP SPNCSLRAES LVHVHFKEEI GIAELIPLVT TYIILFAYIY
FSTRKIDMVK SKWGLALAAV VTVLSSLLMS VGLCTLFGLT PTLNGGEIFP YLVVVIGLEN
VLVLTKSVVS TPVDLEVKLR IAQGLSSESW SIMKNMATEL GIILIGYFTL VPAIQEFCLF
AVVGLVSDFF LQMPFFTTVL SIDIRRMELA DLNKRLPPEA CLPPAKPVGR SARFERQLAV
RPATPHTITL QPSSFRNLRL PKRLRVIYFL ARTRLAQRLI MAGTVVWIGI LAYTDPAGLR
TYLAAQVTEQ SPLGEGALAP MPVPSGVLPA SHPDPAFSIF PPEAPKLLEN QTLPGEPPEP
GGQAEGVHDS PAPEVTWGPE DEELWRKLSF RHWPTLFSYY NITLAKRYIS LLPVIPVTLR
LNPREALEGR HPQDSRSAWS PPQPAQGGLW DAGPKGPGVA QAHRDVTLYK VAALGLATGI
LLVLLLCLYR VLCPRNYGQP GAGPGRRRRG ELPCDDYGYA PPETEIVPLV LRGHLMDIEC
LASDGMLLVS CCLAGHVCVW DAQTGDCLTR IPHPGRQRRD SGVGSVLEAQ ENWERLSDGG
KASPEEPGDS PPLRHRPRGT PLPSLFGDQP DLTCLIDTNF SAHPRLPELD HPEPRHRSGC
RRTQDCTGYD FSRLVQRAYQ EEGMVPMHTP APRPPSPGPT PPQTPEDEGS FPPEKGSPSF
TWAPSADGSI WSLELQGNLI VVGRSSGRLE VWDAIEGMLR CSSEEVASGI TALVFLDKRI
VAARLNGSLD FFSLETHTAL SPLQFRGAPG RGSSPTSPVY SSSDTVVCHL THTVPCAHQK
PITALKAAAG RLVTGSQDHT LRVFRLEDSC CLFTLQGHSG AITTVYIDQT MVLASGGQDG
AICLWDVLTG SRVSHMFAHR GDVTSLTCTT SCVISSGLDD LISIWDRSTG IKLYSIQQDL
GCGASLGVIS DNLLVTGGQG CVSFWDLNYG DLLQTVYLGK DSEAQPARQI LVLDNAAIVC
NFGSELSLVY VPSVLEKLD
