SCAP_MOUSE
ID SCAP_MOUSE Reviewed; 1276 AA.
AC Q6GQT6; Q6A0A6; Q6NS67; Q7TNG7; Q80UI6;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein {ECO:0000303|PubMed:9854040};
DE Short=SCAP {ECO:0000303|PubMed:9854040};
DE Short=SREBP cleavage-activating protein {ECO:0000303|PubMed:9854040};
GN Name=Scap {ECO:0000303|PubMed:9854040, ECO:0000312|MGI:MGI:2135958};
GN Synonyms=Kiaa0199 {ECO:0000303|PubMed:15368895};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:BAD32190.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain {ECO:0000312|EMBL:BAD32190.1};
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2] {ECO:0000312|EMBL:BAE27338.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE27338.1};
RC TISSUE=Embryonic heart {ECO:0000312|EMBL:BAE27338.1}, and
RC Macrophage {ECO:0000312|EMBL:BAE29431.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000312|EMBL:AAH72633.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH72633.1}, and
RC FVB/N {ECO:0000312|EMBL:AAH55472.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH72633.1},
RC Colon {ECO:0000312|EMBL:AAH55472.1}, and
RC Mammary gland {ECO:0000312|EMBL:AAH51066.1};
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).
RN [4] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF ASP-443.
RX PubMed=9854040; DOI=10.1172/jci5341;
RA Korn B.S., Shimomura I., Bashmakov Y., Hammer R.E., Horton J.D.,
RA Goldstein J.L., Brown M.S.;
RT "Blunted feedback suppression of SREBP processing by dietary cholesterol in
RT transgenic mice expressing sterol-resistant SCAP(D443N).";
RL J. Clin. Invest. 102:2050-2060(1998).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11358865; DOI=10.1101/gad.891301;
RA Matsuda M., Korn B.S., Hammer R.E., Moon Y.-A., Komuro R., Horton J.D.,
RA Goldstein J.L., Brown M.S., Shimomura I.;
RT "SREBP cleavage-activating protein (SCAP) is required for increased lipid
RT synthesis in liver induced by cholesterol deprivation and insulin
RT elevation.";
RL Genes Dev. 15:1206-1216(2001).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821 AND SER-934, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821; SER-843 AND SER-850, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1048, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [9]
RP FUNCTION, UBIQUITINATION AT LYS-454 AND LYS-466, AND MUTAGENESIS OF LYS-454
RP AND LYS-466.
RX PubMed=29068315; DOI=10.7554/elife.28766;
RA Zhang L., Rajbhandari P., Priest C., Sandhu J., Wu X., Temel R.,
RA Castrillo A., de Aguiar Vallim T.Q., Sallam T., Tontonoz P.;
RT "Inhibition of cholesterol biosynthesis through RNF145-dependent
RT ubiquitination of SCAP.";
RL Elife 6:0-0(2017).
RN [10]
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).
CC -!- FUNCTION: Escort protein required for cholesterol as well as lipid
CC homeostasis (PubMed:11358865, PubMed:9854040). Regulates export of the
CC SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low
CC cholesterol, thereby regulating the processing of sterol regulatory
CC element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2
CC (PubMed:11358865, PubMed:9854040, PubMed:29068315). 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 (By similarity). Low sterol
CC concentrations trigger release of INSIG, a conformational change in the
CC SSD domain of SCAP, unmasking of the ER export signal, promoting
CC recruitment into COPII-coated vesicles and transport of the SCAP-SREBP
CC to the Golgi: in the Golgi, SREBPs are then processed, releasing the
CC transcription factor fragment of SREBPs from the membrane, its import
CC into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate
CC pathway (By similarity). Binds cholesterol via its SSD domain (By
CC similarity). {ECO:0000250|UniProtKB:P97260,
CC ECO:0000269|PubMed:11358865, ECO:0000269|PubMed:29068315,
CC ECO:0000269|PubMed:9854040}.
CC -!- SUBUNIT: Membrane region forms a homotetramer. Component of the SCAP-
CC SREBP complex (composed of SCAP and SREBF1/SREBP1 or SREBF2/SREBP2);
CC interacts with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal
CC cytoplasmic domain. Forms a ternary complex with INSIG1 or INSIG2
CC through its transmembrane domains at high sterol concentrations.
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. Interacts with SPRING1 (By similarity).
CC {ECO:0000250|UniProtKB:P97260, 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:0000269|PubMed:29068315}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Scap in their liver show an 80%
CC reduction in cholesterol and fatty acid synthesis in the liver as well
CC as a lack of regulation of target gene expression in response to
CC cholesterol deprivation or insulin elevation. Mice expressing dominant
CC negative mutant Scap in their liver show higher levels of mature Srebf1
CC and Srebf2 as well as transcripts encoding proteins involved in uptake
CC and synthesis of cholesterol and fatty acids. They show an 1.6-fold
CC increase in liver size as well as a six-fold increase in cholesterol
CC and a nine-fold increase in triglyceride content of the liver. Their
CC plasma levels of cholesterol and triglycerides are reduced by 50%. They
CC show reduced down-regulation of mature Srebf1/2 when fed a high
CC cholesterol diet. {ECO:0000269|PubMed:11358865}.
CC -!- SIMILARITY: Belongs to the WD repeat SCAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32190.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK172912; BAD32190.1; ALT_INIT; Transcribed_RNA.
DR EMBL; AK146658; BAE27338.1; -; mRNA.
DR EMBL; AK150275; BAE29431.1; -; mRNA.
DR EMBL; AK152478; BAE31252.1; -; mRNA.
DR EMBL; AK153330; BAE31909.1; -; mRNA.
DR EMBL; BC051066; AAH51066.1; -; mRNA.
DR EMBL; BC055472; AAH55472.1; -; mRNA.
DR EMBL; BC069955; AAH69955.1; -; mRNA.
DR EMBL; BC070437; AAH70437.1; -; mRNA.
DR EMBL; BC072633; AAH72633.1; -; mRNA.
DR CCDS; CCDS23564.1; -.
DR RefSeq; NP_001001144.2; NM_001001144.3.
DR RefSeq; NP_001096632.1; NM_001103162.2.
DR RefSeq; XP_006512146.1; XM_006512083.2.
DR RefSeq; XP_006512147.1; XM_006512084.3.
DR RefSeq; XP_006512148.1; XM_006512085.3.
DR AlphaFoldDB; Q6GQT6; -.
DR SMR; Q6GQT6; -.
DR BioGRID; 231694; 2.
DR DIP; DIP-61666N; -.
DR IntAct; Q6GQT6; 1.
DR STRING; 10090.ENSMUSP00000095953; -.
DR GlyConnect; 2740; 3 N-Linked glycans (2 sites).
DR GlyGen; Q6GQT6; 3 sites, 3 N-linked glycans (2 sites).
DR iPTMnet; Q6GQT6; -.
DR PhosphoSitePlus; Q6GQT6; -.
DR SwissPalm; Q6GQT6; -.
DR EPD; Q6GQT6; -.
DR jPOST; Q6GQT6; -.
DR MaxQB; Q6GQT6; -.
DR PaxDb; Q6GQT6; -.
DR PeptideAtlas; Q6GQT6; -.
DR PRIDE; Q6GQT6; -.
DR ProteomicsDB; 255480; -.
DR Antibodypedia; 1330; 236 antibodies from 26 providers.
DR DNASU; 235623; -.
DR Ensembl; ENSMUST00000098350; ENSMUSP00000095953; ENSMUSG00000032485.
DR GeneID; 235623; -.
DR KEGG; mmu:235623; -.
DR UCSC; uc009rtw.3; mouse.
DR CTD; 22937; -.
DR MGI; MGI:2135958; Scap.
DR VEuPathDB; HostDB:ENSMUSG00000032485; -.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000158130; -.
DR HOGENOM; CLU_006510_0_0_1; -.
DR InParanoid; Q6GQT6; -.
DR OMA; IMKQYNV; -.
DR OrthoDB; 523786at2759; -.
DR PhylomeDB; Q6GQT6; -.
DR TreeFam; TF315236; -.
DR Reactome; R-MMU-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR BioGRID-ORCS; 235623; 29 hits in 76 CRISPR screens.
DR ChiTaRS; Scap; mouse.
DR PRO; PR:Q6GQT6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q6GQT6; protein.
DR Bgee; ENSMUSG00000032485; Expressed in pigmented layer of retina and 251 other tissues.
DR ExpressionAtlas; Q6GQT6; baseline and differential.
DR Genevisible; Q6GQT6; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0032936; C:SREBP-SCAP complex; IBA:GO_Central.
DR GO; GO:0015485; F:cholesterol binding; TAS:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0032934; F:sterol binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0044255; P:cellular lipid metabolic process; IMP:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:MGI.
DR GO; GO:0090110; P:COPII-coated vesicle cargo loading; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IMP:MGI.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISO:MGI.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; IMP:MGI.
DR GO; GO:0042304; P:regulation of fatty acid biosynthetic process; IMP:MGI.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IDA:MGI.
DR GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR GO; GO:0032868; P:response to insulin; IMP:MGI.
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 1: Evidence at protein 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_0000315870"
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 669..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 927..960
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:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 837
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 843
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 850
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12770"
FT MOD_RES 934
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 1048
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
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:0000269|PubMed:29068315"
FT CROSSLNK 466
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:29068315"
FT MUTAGEN 443
FT /note="D->N: Higher level of processed SREBF1 and SREBF2
FT when expressed in liver."
FT /evidence="ECO:0000269|PubMed:9854040"
FT MUTAGEN 454
FT /note="K->R: Loss of ubiquitination; when associated with
FT R-466."
FT /evidence="ECO:0000269|PubMed:29068315"
FT MUTAGEN 466
FT /note="K->R: Loss of ubiquitination; when associated with
FT R-454."
FT /evidence="ECO:0000269|PubMed:29068315"
FT CONFLICT 247
FT /note="Missing (in Ref. 1; BAD32190)"
FT /evidence="ECO:0000305"
FT CONFLICT 619
FT /note="P -> L (in Ref. 3; AAH70437)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1276 AA; 139611 MW; 4EE7DDCEEB6F3331 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 SIMKNAATEL GIILIGYFTL VPAIQEFCLF
AVVGLVSDFF LQMLFFTTVL SIDIRRMELA DLNKRLPPES CLPSAKPVGR PARYERQQAV
RPSTPHTITL QPSSFRNLRL PKRLRVIYFL ARTRLAQRLI MAGTVVWIGI LVYTDPAGLR
TYLAAQVTEQ SPLGEGSLGP MPVPSGVLPA SHPDPAFSIF PPDAPKLPEN QTLPGELPEH
AGPAEGVHDS RAPEVTWGPE DEELWRKLSF RHWPTLFNYY NITLAKRYIS LLPVIPVTLH
LNPREALEGR HPQDGRSAWA PQEPLPAGLW ESGPKGPGGT QTHGDITLYK VAALGLAAGI
VLVLLLLCLY RVLCPRNYGQ PGGGPGRRRR GELPCDDYGY APPETEIVPL VLRGHLMDIE
CLASDGMLLV SCCLAGQVCV WDAQTGDCLT RIPRPGPRRD SCGGGAFETQ ENWERLSDGG
KASPEEPGDS PPLRRRPRGP PPPSLFGDQP DLTCLIDTNF SVQLPPEPTQ PEPRHRVGCG
RSRDSGYDFS RLVQRVYQEE GLAAMRMPAL RPPSPGPPLP QASQEEGTAP EKGSPPLAWT
PSTAGSIWSL ELQGNLIVVG RSSGRLEVWD AIEGVLCCSN EEISSGITAL VFLDRRIVAA
RLNGSLDFFS LETHTSLSPL QFRGTPGRGS SPSSSVYSSS NTVTCHRTHT VPCAHQKPIT
ALRAAAGRLV TGSQDHTLRV FRLDDSCCLF TLKGHSGAIT AVYIDQTMVL ASGGQDGAIC
LWDVLTGSRV SQTFAHRGDV TSLTCTASCV ISSGLDDFIS IWDRSTGIKL YSIQQDLGCG
ASLGVISDNL LVTGGQGCVS FWDLNYGDLL QTVYLGKNSE AQPARQILVL DNAAIVCNFG
SELSLVYVPS VLEKLD
