SCAP_HUMAN
ID SCAP_HUMAN Reviewed; 1279 AA.
AC Q12770; Q8N2E0; Q8WUA1;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 4.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein {ECO:0000303|PubMed:10570913};
DE Short=SCAP {ECO:0000303|PubMed:10570913};
DE Short=SREBP cleavage-activating protein {ECO:0000303|PubMed:10570913};
GN Name=SCAP {ECO:0000303|PubMed:10570913, ECO:0000312|HGNC:HGNC:30634};
GN Synonyms=KIAA0199 {ECO:0000303|PubMed:8724849};
GN ORFNames=PSEC0227 {ECO:0000303|PubMed:16303743};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Hepatoma;
RX PubMed=10570913; DOI=10.1007/s100380050187;
RA Nakajima T., Hamakubo T., Kodama T., Inazawa J., Emi M.;
RT "Genomic structure and chromosomal mapping of the human sterol regulatory
RT element binding protein (SREBP) cleavage-activating protein (SCAP) gene.";
RL J. Hum. Genet. 44:402-407(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
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).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 350-1278 (ISOFORM 3).
RC TISSUE=Embryo;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [7]
RP INDUCTION.
RX PubMed=15133039; DOI=10.1074/jbc.m401615200;
RA Heemers H., Verrijdt G., Organe S., Claessens F., Heyns W., Verhoeven G.,
RA Swinnen J.V.;
RT "Identification of an androgen response element in intron 8 of the sterol
RT regulatory element-binding protein cleavage-activating protein gene
RT allowing direct regulation by the androgen receptor.";
RL J. Biol. Chem. 279:30880-30887(2004).
RN [8]
RP INTERACTION WITH INSIG2.
RX PubMed=17428920; DOI=10.1073/pnas.0700899104;
RA Radhakrishnan A., Ikeda Y., Kwon H.J., Brown M.S., Goldstein J.L.;
RT "Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi:
RT oxysterols block transport by binding to Insig.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:6511-6518(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-907, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INTERACTION WITH INSIG2.
RX PubMed=26160948; DOI=10.1126/science.aab1091;
RA Ren R., Zhou X., He Y., Ke M., Wu J., Liu X., Yan C., Wu Y., Gong X.,
RA Lei X., Yan S.F., Radhakrishnan A., Yan N.;
RT "Crystal structure of a mycobacterial Insig homolog provides insight into
RT how these sensors monitor sterol levels.";
RL Science 349:187-191(2015).
RN [11]
RP INTERACTION WITH RNF139.
RX PubMed=19706601; DOI=10.1074/jbc.m109.041376;
RA Irisawa M., Inoue J., Ozawa N., Mori K., Sato R.;
RT "The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8
RT hampers ER to Golgi transport of sterol regulatory element-binding protein-
RT 2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2
RT cleavage.";
RL J. Biol. Chem. 284:28995-29004(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-822; SER-838; SER-851 AND
RP SER-907, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-822 AND SER-937, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP REVIEW.
RX PubMed=28849786; DOI=10.1038/nrendo.2017.91;
RA Shimano H., Sato R.;
RT "SREBP-regulated lipid metabolism: convergent physiology - divergent
RT pathophysiology.";
RL Nat. Rev. Endocrinol. 13:710-730(2017).
RN [16]
RP INTERACTION WITH SPRING1, AND SUBCELLULAR LOCATION.
RX PubMed=32111832; DOI=10.1038/s41467-020-14811-1;
RA Loregger A., Raaben M., Nieuwenhuis J., Tan J.M.E., Jae L.T.,
RA van den Hengel L.G., Hendrix S., van den Berg M., Scheij S., Song J.Y.,
RA Huijbers I.J., Kroese L.J., Ottenhoff R., van Weeghel M., van de Sluis B.,
RA Brummelkamp T., Zelcer N.;
RT "Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP
RT signaling and cholesterol metabolism.";
RL Nat. Commun. 11:1128-1128(2020).
RN [17]
RP VARIANT ILE-798.
RX PubMed=10570919; DOI=10.1007/s100380050193;
RA Iwaki K., Nakajima T., Ota N., Emi M.;
RT "A common Ile796Val polymorphism of the human SREBP cleavage-activating
RT protein (SCAP) gene.";
RL J. Hum. Genet. 44:421-422(1999).
CC -!- FUNCTION: Escort protein required for cholesterol as well as lipid
CC homeostasis (By similarity). Regulates export of the SCAP-SREBP complex
CC from the endoplasmic reticulum to the Golgi upon low cholesterol,
CC thereby regulating the processing of sterol regulatory element-binding
CC proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (By similarity). At
CC high sterol concentrations, formation of a ternary complex with INSIG
CC (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP,
CC promoting retention of the complex in the endoplasmic reticulum (By
CC similarity). Low sterol concentrations trigger release of INSIG, a
CC conformational change in the SSD domain of SCAP, unmasking of the ER
CC export signal, promoting recruitment into COPII-coated vesicles and
CC transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then
CC processed, releasing the transcription factor fragment of SREBPs from
CC the membrane, its import into the nucleus and up-regulation of LDLR,
CC INSIG1 and the mevalonate pathway (By similarity). Binds cholesterol
CC via its SSD domain (By similarity). {ECO:0000250|UniProtKB:P97260}.
CC -!- SUBUNIT: Membrane region forms a homotetramer (By similarity).
CC Component of the SCAP-SREBP complex (composed of SCAP and SREBF1/SREBP1
CC or SREBF2/SREBP2); interacts with SREBF1/SREBP1 or SREBF2/SREBP2
CC through its C-terminal cytoplasmic domain (By similarity). Forms a
CC ternary complex with INSIG1 or INSIG2 through its transmembrane domains
CC at high sterol concentrations (PubMed:17428920, PubMed:26160948).
CC Interacts with the SEC23-SEC24 complex in a SAR1-GTP-dependent manner
CC through an ER export signal in its third cytoplasmic loop (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 (PubMed:19706601). Interacts with SPRING1
CC (PubMed:32111832). {ECO:0000250|UniProtKB:P97260,
CC ECO:0000269|PubMed:17428920, ECO:0000269|PubMed:19706601,
CC ECO:0000269|PubMed:26160948, ECO:0000269|PubMed:32111832}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:32111832}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:32111832};
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 (By similarity).
CC Requires the presence of SPRING1 for proper localization to endoplasmic
CC reticulum (PubMed:32111832). {ECO:0000250|UniProtKB:P97260,
CC ECO:0000269|PubMed:32111832}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q12770-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12770-2; Sequence=VSP_007451, VSP_021106;
CC Name=3;
CC IsoId=Q12770-3; Sequence=VSP_007452;
CC Name=4;
CC IsoId=Q12770-4; Sequence=VSP_021105, VSP_021106;
CC -!- INDUCTION: By androgen-bound AR and glucocorticoid-bound NR3C1 in a
CC prostate cancer cell line (LNCaP). {ECO:0000269|PubMed:15133039}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA12111.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC11673.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D83782; BAA12111.2; ALT_INIT; mRNA.
DR EMBL; AK027402; BAB55088.1; -; mRNA.
DR EMBL; BC020987; AAH20987.1; -; mRNA.
DR EMBL; AK075528; BAC11673.1; ALT_INIT; mRNA.
DR CCDS; CCDS2755.2; -. [Q12770-1]
DR RefSeq; NP_036367.2; NM_012235.3. [Q12770-1]
DR RefSeq; XP_011531803.1; XM_011533501.1. [Q12770-1]
DR RefSeq; XP_016861407.1; XM_017005918.1. [Q12770-1]
DR RefSeq; XP_016861410.1; XM_017005921.1. [Q12770-4]
DR PDB; 6M49; EM; 3.70 A; B=1-735.
DR PDB; 7ETW; EM; 4.10 A; B=1-735.
DR PDBsum; 6M49; -.
DR PDBsum; 7ETW; -.
DR AlphaFoldDB; Q12770; -.
DR SMR; Q12770; -.
DR BioGRID; 116596; 128.
DR CORUM; Q12770; -.
DR IntAct; Q12770; 11.
DR MINT; Q12770; -.
DR STRING; 9606.ENSP00000265565; -.
DR GlyGen; Q12770; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q12770; -.
DR PhosphoSitePlus; Q12770; -.
DR BioMuta; SCAP; -.
DR DMDM; 116242783; -.
DR EPD; Q12770; -.
DR jPOST; Q12770; -.
DR MassIVE; Q12770; -.
DR MaxQB; Q12770; -.
DR PaxDb; Q12770; -.
DR PeptideAtlas; Q12770; -.
DR PRIDE; Q12770; -.
DR ProteomicsDB; 58915; -. [Q12770-1]
DR ProteomicsDB; 58916; -. [Q12770-2]
DR ProteomicsDB; 58917; -. [Q12770-3]
DR ProteomicsDB; 58918; -. [Q12770-4]
DR TopDownProteomics; Q12770-2; -. [Q12770-2]
DR Antibodypedia; 1330; 236 antibodies from 26 providers.
DR DNASU; 22937; -.
DR Ensembl; ENST00000265565.10; ENSP00000265565.5; ENSG00000114650.21. [Q12770-1]
DR Ensembl; ENST00000648151.1; ENSP00000497087.1; ENSG00000114650.21. [Q12770-1]
DR GeneID; 22937; -.
DR KEGG; hsa:22937; -.
DR MANE-Select; ENST00000265565.10; ENSP00000265565.5; NM_012235.4; NP_036367.2.
DR UCSC; uc003crh.2; human. [Q12770-1]
DR CTD; 22937; -.
DR DisGeNET; 22937; -.
DR GeneCards; SCAP; -.
DR HGNC; HGNC:30634; SCAP.
DR HPA; ENSG00000114650; Tissue enhanced (adrenal).
DR MIM; 601510; gene.
DR neXtProt; NX_Q12770; -.
DR OpenTargets; ENSG00000114650; -.
DR PharmGKB; PA162402461; -.
DR VEuPathDB; HostDB:ENSG00000114650; -.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000158130; -.
DR HOGENOM; CLU_006510_0_0_1; -.
DR InParanoid; Q12770; -.
DR OMA; IMKQYNV; -.
DR OrthoDB; 523786at2759; -.
DR PhylomeDB; Q12770; -.
DR TreeFam; TF315236; -.
DR PathwayCommons; Q12770; -.
DR Reactome; R-HSA-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR SignaLink; Q12770; -.
DR SIGNOR; Q12770; -.
DR BioGRID-ORCS; 22937; 554 hits in 1098 CRISPR screens.
DR ChiTaRS; SCAP; human.
DR GeneWiki; SREBP_cleavage_activating_protein; -.
DR GenomeRNAi; 22937; -.
DR Pharos; Q12770; Tbio.
DR PRO; PR:Q12770; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q12770; protein.
DR Bgee; ENSG00000114650; Expressed in adrenal tissue and 203 other tissues.
DR ExpressionAtlas; Q12770; baseline and differential.
DR Genevisible; Q12770; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; NAS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0032936; C:SREBP-SCAP complex; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0032934; F:sterol binding; ISS:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; NAS:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0044255; P:cellular lipid metabolic process; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; NAS:UniProtKB.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0042304; P:regulation of fatty acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0032933; P:SREBP signaling pathway; IDA: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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cholesterol metabolism;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Isopeptide bond; Lipid metabolism; Lipid-binding; Membrane; Methylation;
KW Phosphoprotein; Reference proteome; Repeat; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation;
KW WD repeat.
FT CHAIN 1..1279
FT /note="Sterol regulatory element-binding protein cleavage-
FT activating protein"
FT /id="PRO_0000051208"
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..709
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 710..730
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 731..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 771..811
FT /note="WD 1"
FT REPEAT 952..1002
FT /note="WD 2"
FT REPEAT 1005..1042
FT /note="WD 3"
FT REPEAT 1077..1114
FT /note="WD 4"
FT REPEAT 1117..1155
FT /note="WD 5"
FT REPEAT 1158..1195
FT /note="WD 6"
FT REPEAT 1197..1235
FT /note="WD 7"
FT REGION 46..284
FT /note="Loop-1"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 60..80
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 579..615
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 731..1279
FT /note="Interaction with SREBF2"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT REGION 811..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 931..962
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 835..854
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 875..894
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 822
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 838
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 851
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 907
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 937
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
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 1..392
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021105"
FT VAR_SEQ 29..401
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007451"
FT VAR_SEQ 476..983
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16303743"
FT /id="VSP_007452"
FT VAR_SEQ 817
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021106"
FT VARIANT 798
FT /note="V -> I (in dbSNP:rs12487736)"
FT /evidence="ECO:0000269|PubMed:10570919"
FT /id="VAR_012203"
FT CONFLICT 350
FT /note="P -> G (in Ref. 6; BAC11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="S -> T (in Ref. 6; BAC11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="W -> R (in Ref. 4; BAB55088)"
FT /evidence="ECO:0000305"
FT CONFLICT 753
FT /note="L -> Q (in Ref. 4; BAB55088)"
FT /evidence="ECO:0000305"
FT CONFLICT 941
FT /note="V -> A (in Ref. 4; BAB55088)"
FT /evidence="ECO:0000305"
FT CONFLICT 994
FT /note="A -> S (in Ref. 6; BAC11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 1019
FT /note="R -> G (in Ref. 6; BAC11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 1035
FT /note="E -> G (in Ref. 4; BAB55088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1080
FT /note="K -> E (in Ref. 4; BAB55088)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1279 AA; 139729 MW; 4CD73543B7D2ACB4 CRC64;
MTLTERLREK ISRAFYNHGL LCASYPIPII LFTGFCILAC CYPLLKLPLP GTGPVEFTTP
VKDYSPPPVD SDRKQGEPTE QPEWYVGAPV AYVQQIFVKS SVFPWHKNLL AVDVFRSPLS
RAFQLVEEIR NHVLRDSSGI RSLEELCLQV TDLLPGLRKL RNLLPEHGCL LLSPGNFWQN
DWERFHADPD IIGTIHQHEP KTLQTSATLK DLLFGVPGKY SGVSLYTRKR MVSYTITLVF
QHYHAKFLGS LRARLMLLHP SPNCSLRAES LVHVHFKEEI GVAELIPLVT TYIILFAYIY
FSTRKIDMVK SKWGLALAAV VTVLSSLLMS VGLCTLFGLT PTLNGGEIFP YLVVVIGLEN
VLVLTKSVVS TPVDLEVKLR IAQGLSSESW SIMKNMATEL GIILIGYFTL VPAIQEFCLF
AVVGLVSDFF LQMLFFTTVL SIDIRRMELA DLNKRLPPEA CLPSAKPVGQ PTRYERQLAV
RPSTPHTITL QPSSFRNLRL PKRLRVVYFL ARTRLAQRLI MAGTVVWIGI LVYTDPAGLR
NYLAAQVTEQ SPLGEGALAP MPVPSGMLPP SHPDPAFSIF PPDAPKLPEN QTSPGESPER
GGPAEVVHDS PVPEVTWGPE DEELWRKLSF RHWPTLFSYY NITLAKRYIS LLPVIPVTLR
LNPREALEGR HPQDGRSAWP PPGPIPAGHW EAGPKGPGGV QAHGDVTLYK VAALGLATGI
VLVLLLLCLY RVLCPRNYGQ LGGGPGRRRR GELPCDDYGY APPETEIVPL VLRGHLMDIE
CLASDGMLLV SCCLAGHVCV WDAQTGDCLT RIPRPGRQRR DSGVGSGLEA QESWERLSDG
GKAGPEEPGD SPPLRHRPRG PPPPSLFGDQ PDLTCLIDTN FSAQPRSSQP TQPEPRHRAV
CGRSRDSPGY DFSCLVQRVY QEEGLAAVCT PALRPPSPGP VLSQAPEDEG GSPEKGSPSL
AWAPSAEGSI WSLELQGNLI VVGRSSGRLE VWDAIEGVLC CSSEEVSSGI TALVFLDKRI
VAARLNGSLD FFSLETHTAL SPLQFRGTPG RGSSPASPVY SSSDTVACHL THTVPCAHQK
PITALKAAAG RLVTGSQDHT LRVFRLEDSC CLFTLQGHSG AITTVYIDQT MVLASGGQDG
AICLWDVLTG SRVSHVFAHR GDVTSLTCTT SCVISSGLDD LISIWDRSTG IKFYSIQQDL
GCGASLGVIS DNLLVTGGQG CVSFWDLNYG DLLQTVYLGK NSEAQPARQI LVLDNAAIVC
NFGSELSLVY VPSVLEKLD
