SRBP1_MOUSE
ID SRBP1_MOUSE Reviewed; 1134 AA.
AC Q9WTN3; Q3U458; Q3UDJ3; Q5SRX5; Q8C733; Q99JK7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 4.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Sterol regulatory element-binding protein 1 {ECO:0000303|PubMed:10052151, ECO:0000303|PubMed:9062340};
DE Short=SREBP-1 {ECO:0000303|PubMed:10052151, ECO:0000303|PubMed:9062340};
DE AltName: Full=Sterol regulatory element-binding transcription factor 1 {ECO:0000303|PubMed:10052151, ECO:0000303|PubMed:9062340};
DE Contains:
DE RecName: Full=Processed sterol regulatory element-binding protein 1 {ECO:0000305};
DE AltName: Full=Transcription factor SREBF1 {ECO:0000305};
GN Name=Srebf1 {ECO:0000312|MGI:MGI:107606};
GN Synonyms=Srebp1 {ECO:0000303|PubMed:10052151, ECO:0000303|PubMed:9062340};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SREBP-1A).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Kidney, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SREBP-1A).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary gland;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-41 (ISOFORMS SREBP-1A AND SREBP-1C), AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=9062340; DOI=10.1172/jci119247;
RA Shimomura I., Shimano H., Horton J.D., Goldstein J.L., Brown M.S.;
RT "Differential expression of exons 1a and 1c in mRNAs for sterol regulatory
RT element binding protein-1 in human and mouse organs and cultured cells.";
RL J. Clin. Invest. 99:838-845(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-444 (ISOFORMS SREBP-1A-W42 AND
RP SREBP-1C-W42).
RX PubMed=10052151; DOI=10.1271/bbb.63.243;
RA Inoue J., Sato R.;
RT "A novel splicing isoform of mouse sterol regulatory element-binding
RT protein-1 (SREBP-1).";
RL Biosci. Biotechnol. Biochem. 63:243-245(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-1134.
RA Lloyd D.J., Shackleton S., Trembath R.C.;
RT "Mouse Srebp1.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION (ISOFORM SREBP-1A), AND SUBCELLULAR LOCATION.
RX PubMed=8833906; DOI=10.1172/jci118951;
RA Shimano H., Horton J.D., Hammer R.E., Shimomura I., Brown M.S.,
RA Goldstein J.L.;
RT "Overproduction of cholesterol and fatty acids causes massive liver
RT enlargement in transgenic mice expressing truncated SREBP-1a.";
RL J. Clin. Invest. 98:1575-1584(1996).
RN [8]
RP FUNCTION (ISOFORM SREBP-1C), AND SUBCELLULAR LOCATION.
RX PubMed=9062341; DOI=10.1172/jci119248;
RA Shimano H., Horton J.D., Shimomura I., Hammer R.E., Brown M.S.,
RA Goldstein J.L.;
RT "Isoform 1c of sterol regulatory element binding protein is less active
RT than isoform 1a in livers of transgenic mice and in cultured cells.";
RL J. Clin. Invest. 99:846-854(1997).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9329978; DOI=10.1172/jci119746;
RA Shimano H., Shimomura I., Hammer R.E., Herz J., Goldstein J.L., Brown M.S.,
RA Horton J.D.;
RT "Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice
RT homozygous for a targeted disruption of the SREBP-1 gene.";
RL J. Clin. Invest. 100:2115-2124(1997).
RN [10]
RP FUNCTION.
RX PubMed=9784493; DOI=10.1101/gad.12.20.3182;
RA Shimomura I., Hammer R.E., Richardson J.A., Ikemoto S., Bashmakov Y.,
RA Goldstein J.L., Brown M.S.;
RT "Insulin resistance and diabetes mellitus in transgenic mice expressing
RT nuclear SREBP-1c in adipose tissue: model for congenital generalized
RT lipodystrophy.";
RL Genes Dev. 12:3182-3194(1998).
RN [11]
RP INTERACTION WITH LMNA.
RX PubMed=11929849; DOI=10.1093/hmg/11.7.769;
RA Lloyd D.J., Trembath R.C., Shackleton S.;
RT "A novel interaction between lamin A and SREBP1: implications for partial
RT lipodystrophy and other laminopathies.";
RL Hum. Mol. Genet. 11:769-777(2002).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11782483; DOI=10.1074/jbc.m111421200;
RA Liang G., Yang J., Horton J.D., Hammer R.E., Goldstein J.L., Brown M.S.;
RT "Diminished hepatic response to fasting/refeeding and liver X receptor
RT agonists in mice with selective deficiency of sterol regulatory element-
RT binding protein-1c.";
RL J. Biol. Chem. 277:9520-9528(2002).
RN [13]
RP FUNCTION.
RX PubMed=12855691; DOI=10.1074/jbc.m306540200;
RA Horton J.D., Shimomura I., Ikemoto S., Bashmakov Y., Hammer R.E.;
RT "Overexpression of sterol regulatory element-binding protein-1a in mouse
RT adipose tissue produces adipocyte hypertrophy, increased fatty acid
RT secretion, and fatty liver.";
RL J. Biol. Chem. 278:36652-36660(2003).
RN [14]
RP FUNCTION.
RX PubMed=16100574; DOI=10.1172/jci25614;
RA Engelking L.J., Liang G., Hammer R.E., Takaishi K., Kuriyama H.,
RA Evers B.M., Li W.P., Horton J.D., Goldstein J.L., Brown M.S.;
RT "Schoenheimer effect explained--feedback regulation of cholesterol
RT synthesis in mice mediated by Insig proteins.";
RL J. Clin. Invest. 115:2489-2498(2005).
RN [15]
RP FUNCTION, AND INTERACTION WITH CEBPA.
RX PubMed=17290224; DOI=10.1038/sj.emboj.7601563;
RA Pedersen T.A., Bereshchenko O., Garcia-Silva S., Ermakova O., Kurz E.,
RA Mandrup S., Porse B.T., Nerlov C.;
RT "Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene
RT expression in vivo.";
RL EMBO J. 26:1081-1093(2007).
RN [16]
RP FUNCTION, PHOSPHORYLATION AT SER-331; SER-332 AND SER-395, AND MUTAGENESIS
RP OF SER-331; SER-332 AND SER-395.
RX PubMed=19244231; DOI=10.1074/jbc.m900096200;
RA Yoon Y.S., Seo W.Y., Lee M.W., Kim S.T., Koo S.H.;
RT "Salt-inducible kinase regulates hepatic lipogenesis by controlling SREBP-
RT 1c phosphorylation.";
RL J. Biol. Chem. 284:10446-10452(2009).
RN [17]
RP INDUCTION.
RX PubMed=19786558; DOI=10.1124/mol.109.057000;
RA Cho Y., Noshiro M., Choi M., Morita K., Kawamoto T., Fujimoto K., Kato Y.,
RA Makishima M.;
RT "The basic helix-loop-helix proteins differentiated embryo chondrocyte
RT (DEC) 1 and DEC2 function as corepressors of retinoid X receptors.";
RL Mol. Pharmacol. 76:1360-1369(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
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 [19]
RP FUNCTION, PHOSPHORYLATION AT SER-389, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF SER-354 AND SER-389.
RX PubMed=21459323; DOI=10.1016/j.cmet.2011.03.009;
RA Li Y., Xu S., Mihaylova M.M., Zheng B., Hou X., Jiang B., Park O., Luo Z.,
RA Lefai E., Shyy J.Y., Gao B., Wierzbicki M., Verbeuren T.J., Shaw R.J.,
RA Cohen R.A., Zang M.;
RT "AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic
RT steatosis and atherosclerosis in diet-induced insulin-resistant mice.";
RL Cell Metab. 13:376-388(2011).
RN [20]
RP FUNCTION (ISOFORM SREBP-1A), TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE
RP (ISOFORM SREBP-1A).
RX PubMed=21531336; DOI=10.1016/j.cmet.2011.04.001;
RA Im S.S., Yousef L., Blaschitz C., Liu J.Z., Edwards R.A., Young S.G.,
RA Raffatellu M., Osborne T.F.;
RT "Linking lipid metabolism to the innate immune response in macrophages
RT through sterol regulatory element binding protein-1a.";
RL Cell Metab. 13:540-549(2011).
RN [21]
RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE.
RX PubMed=21987372; DOI=10.1002/hep.24733;
RA Jourdan T., Demizieux L., Gresti J., Djaouti L., Gaba L., Verges B.,
RA Degrace P.;
RT "Antagonism of peripheral hepatic cannabinoid receptor-1 improves liver
RT lipid metabolism in mice: evidence from cultured explants.";
RL Hepatology 55:790-799(2012).
RN [22]
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: [Sterol regulatory element-binding protein 1]: Precursor of
CC the transcription factor form (Processed sterol regulatory element-
CC binding protein 1), which is embedded in the endoplasmic reticulum
CC membrane (PubMed:11782483, PubMed:12855691, PubMed:19244231). Low
CC sterol concentrations promote processing of this form, releasing the
CC transcription factor form that translocates into the nucleus and
CC activates transcription of genes involved in cholesterol biosynthesis
CC and lipid homeostasis (PubMed:11782483, PubMed:12855691,
CC PubMed:16100574, PubMed:19244231). {ECO:0000269|PubMed:11782483,
CC ECO:0000269|PubMed:12855691, ECO:0000269|PubMed:16100574,
CC ECO:0000269|PubMed:19244231}.
CC -!- FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key
CC transcription factor that regulates expression of genes involved in
CC cholesterol biosynthesis and lipid homeostasis (PubMed:19244231,
CC PubMed:17290224, PubMed:9329978, PubMed:9784493, PubMed:21459323).
CC Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') (By
CC similarity). Has dual sequence specificity binding to both an E-box
CC motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (By
CC similarity). Regulates the promoters of genes involved in cholesterol
CC biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation
CC (PubMed:19244231, PubMed:17290224, PubMed:9329978, PubMed:9784493,
CC PubMed:21459323). {ECO:0000250|UniProtKB:P36956,
CC ECO:0000269|PubMed:17290224, ECO:0000269|PubMed:19244231,
CC ECO:0000269|PubMed:21459323, ECO:0000269|PubMed:9329978,
CC ECO:0000269|PubMed:9784493}.
CC -!- FUNCTION: [Isoform SREBP-1A]: Isoform expressed only in select tissues,
CC which has higher transcriptional activity compared to SREBP-1C
CC (PubMed:12855691, PubMed:21531336). Able to stimulate both lipogenic
CC and cholesterogenic gene expression (PubMed:8833906). Has a role in the
CC nutritional regulation of fatty acids and triglycerides in lipogenic
CC organs such as the liver (PubMed:9062341, PubMed:12855691). Required
CC for innate immune response in macrophages by regulating lipid
CC metabolism (PubMed:21531336). {ECO:0000269|PubMed:12855691,
CC ECO:0000269|PubMed:21531336, ECO:0000269|PubMed:8833906,
CC ECO:0000269|PubMed:9062341}.
CC -!- FUNCTION: [Isoform SREBP-1C]: Predominant isoform expressed in most
CC tissues, which has weaker transcriptional activity compared to isoform
CC SREBP-1A (PubMed:12855691, PubMed:21531336). Primarily controls
CC expression of lipogenic gene (PubMed:8833906, PubMed:9062341). Strongly
CC activates global lipid synthesis in rapidly growing cells
CC (PubMed:8833906, PubMed:9062341). {ECO:0000269|PubMed:12855691,
CC ECO:0000269|PubMed:21531336, ECO:0000269|PubMed:8833906,
CC ECO:0000269|PubMed:9062341}.
CC -!- SUBUNIT: [Sterol regulatory element-binding protein 1]: Forms a tight
CC complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum
CC membrane. {ECO:0000250|UniProtKB:P36956}.
CC -!- SUBUNIT: [Processed sterol regulatory element-binding protein 1]:
CC Efficient DNA binding of the soluble transcription factor fragment
CC requires dimerization with another bHLH protein (By similarity).
CC Interacts with CEBPA, the interaction produces a transcriptional
CC synergy (PubMed:17290224). Interacts with LMNA (PubMed:11929849).
CC {ECO:0000250|UniProtKB:P36956, ECO:0000269|PubMed:11929849,
CC ECO:0000269|PubMed:17290224}.
CC -!- INTERACTION:
CC Q9WTN3; Q923E4: Sirt1; NbExp=2; IntAct=EBI-5273743, EBI-1802585;
CC -!- SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 1]:
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:21459323}; Multi-
CC pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:21459323}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, COPII-coated vesicle membrane
CC {ECO:0000269|PubMed:21459323}; Multi-pass membrane protein
CC {ECO:0000255}. Note=At high sterol concentrations, the SCAP-SREBP is
CC retained in the endoplasmic reticulum (PubMed:21459323). Low sterol
CC concentrations promote recruitment into COPII-coated vesicles and
CC transport of the SCAP-SREBP to the Golgi, where it is processed
CC (PubMed:21459323). {ECO:0000269|PubMed:21459323}.
CC -!- SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding
CC protein 1]: Nucleus {ECO:0000269|PubMed:21459323,
CC ECO:0000269|PubMed:8833906, ECO:0000269|PubMed:9062341}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=SREBP-1A {ECO:0000303|PubMed:21531336,
CC ECO:0000303|PubMed:8833906};
CC IsoId=Q9WTN3-1; Sequence=Displayed;
CC Name=SREBP-1A-W42;
CC IsoId=Q9WTN3-2; Sequence=VSP_002152;
CC Name=SREBP-1C {ECO:0000303|PubMed:9062341};
CC IsoId=Q9WTN3-3; Sequence=VSP_002151;
CC Name=SREBP-1C-W42;
CC IsoId=Q9WTN3-4; Sequence=VSP_002151, VSP_002152;
CC -!- TISSUE SPECIFICITY: [Isoform SREBP-1C]: Predominant isoform expressed
CC in most tissues (PubMed:21531336). Predominates in liver, adrenal
CC gland, brain and adipose tissue (PubMed:9062340). Also found in kidney,
CC thymus, testis, muscle, jejunum, and ileum (PubMed:9062340).
CC {ECO:0000269|PubMed:21531336, ECO:0000269|PubMed:9062340}.
CC -!- TISSUE SPECIFICITY: [Isoform SREBP-1A]: Expressed only in select
CC tissues, such as intestinal epithelial, heart, macrophage and bone
CC marrow dendritic cells (PubMed:9062340, PubMed:21531336). Also found in
CC kidney, thymus, testis, muscle, jejunum, and ileum (PubMed:9062340).
CC {ECO:0000269|PubMed:21531336, ECO:0000269|PubMed:9062340}.
CC -!- INDUCTION: [Isoform SREBP-1C]: Expressed in a circadian manner in the
CC liver with a peak at ZT16 (PubMed:19786558).
CC {ECO:0000269|PubMed:19786558}.
CC -!- INDUCTION: Up-regulated by endocannabinoid anandamide/AEA.
CC {ECO:0000269|PubMed:21987372}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P36956}.
CC -!- PTM: [Sterol regulatory element-binding protein 1]: Processed in the
CC Golgi apparatus, releasing the protein from the membrane. At low
CC cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for
CC export from the endoplasmic reticulum. In the Golgi, complex SREBPs are
CC cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P)
CC proteases (By similarity). The first cleavage by site-1 protease occurs
CC within the luminal loop, the second cleavage by site-2 protease occurs
CC within the first transmembrane domain, releasing the transcription
CC factor from the Golgi membrane (By similarity).
CC {ECO:0000250|UniProtKB:P36956, ECO:0000250|UniProtKB:Q12772}.
CC -!- PTM: Phosphorylated by AMPK, leading to suppress protein processing and
CC nuclear translocation, and repress target gene expression.
CC Phosphorylation at Ser-389 by SIK1 represses activity possibly by
CC inhibiting DNA-binding. {ECO:0000269|PubMed:19244231,
CC ECO:0000269|PubMed:21459323}.
CC -!- PTM: [Processed sterol regulatory element-binding protein 1]:
CC Ubiquitinated; the nuclear form has a rapid turnover and is rapidly
CC ubiquitinated and degraded by the proteasome in the nucleus.
CC {ECO:0000250|UniProtKB:P36956}.
CC -!- DISRUPTION PHENOTYPE: Mice show high embryonic lethality around day 11
CC dpc (PubMed:9329978). Surviving mice show a 2-3-fold increase in
CC processed Srebpf2 protein in liver nuclei, 3-fold increase in
CC cholesterol synthesis and 50% increase in cholesterol content of the
CC liver (PubMed:9329978). {ECO:0000269|PubMed:9329978}.
CC -!- DISRUPTION PHENOTYPE: [Isoform SREBP-1A]: Mice lacking isoform SREBP-1A
CC are resistant to pro-inflammatory toxic shock (PubMed:21531336).
CC Macrophages challenged with bacterial lipopolysaccharide fail to
CC activate lipogenesis as well as hallmarks of inflammasome functions,
CC activation of caspase-1 and secretion of IL1B (PubMed:21531336).
CC {ECO:0000269|PubMed:21531336}.
CC -!- DISRUPTION PHENOTYPE: [Isoform SREBP-1C]: Mice lacking isoform SREBP-1C
CC show a lack of up-regulation of several lipogenic enzymes in response
CC to high insulin or LXR activation. {ECO:0000269|PubMed:11782483}.
CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}.
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DR EMBL; AK052628; BAC35068.1; -; mRNA.
DR EMBL; AK150052; BAE29268.1; -; mRNA.
DR EMBL; AK154424; BAE32576.1; -; mRNA.
DR EMBL; AK169607; BAE41256.1; -; mRNA.
DR EMBL; AL669954; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006051; AAH06051.1; -; mRNA.
DR EMBL; BC056922; AAH56922.1; -; mRNA.
DR EMBL; AB017337; BAA74795.1; -; mRNA.
DR EMBL; AF374266; AAK54762.1; -; mRNA.
DR CCDS; CCDS24785.1; -. [Q9WTN3-1]
DR PIR; PD0035; PD0035.
DR RefSeq; NP_001300908.1; NM_001313979.1.
DR RefSeq; NP_035610.1; NM_011480.4. [Q9WTN3-1]
DR RefSeq; XP_006532778.1; XM_006532715.2.
DR AlphaFoldDB; Q9WTN3; -.
DR SMR; Q9WTN3; -.
DR BioGRID; 203495; 8.
DR IntAct; Q9WTN3; 6.
DR MINT; Q9WTN3; -.
DR STRING; 10090.ENSMUSP00000020846; -.
DR ChEMBL; CHEMBL3616359; -.
DR iPTMnet; Q9WTN3; -.
DR PhosphoSitePlus; Q9WTN3; -.
DR MaxQB; Q9WTN3; -.
DR PaxDb; Q9WTN3; -.
DR PRIDE; Q9WTN3; -.
DR ProteomicsDB; 254555; -. [Q9WTN3-1]
DR ProteomicsDB; 254556; -. [Q9WTN3-2]
DR ProteomicsDB; 254557; -. [Q9WTN3-3]
DR ProteomicsDB; 254558; -. [Q9WTN3-4]
DR Antibodypedia; 3952; 651 antibodies from 39 providers.
DR DNASU; 20787; -.
DR Ensembl; ENSMUST00000020846; ENSMUSP00000020846; ENSMUSG00000020538. [Q9WTN3-1]
DR GeneID; 20787; -.
DR KEGG; mmu:20787; -.
DR UCSC; uc007jfn.1; mouse. [Q9WTN3-1]
DR CTD; 6720; -.
DR MGI; MGI:107606; Srebf1.
DR VEuPathDB; HostDB:ENSMUSG00000020538; -.
DR eggNOG; KOG2588; Eukaryota.
DR GeneTree; ENSGT00940000159156; -.
DR InParanoid; Q9WTN3; -.
DR OMA; QLCQHIP; -.
DR OrthoDB; 330300at2759; -.
DR PhylomeDB; Q9WTN3; -.
DR TreeFam; TF313894; -.
DR Reactome; R-MMU-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF). [Q9WTN3-1]
DR Reactome; R-MMU-191273; Cholesterol biosynthesis. [Q9WTN3-1]
DR BioGRID-ORCS; 20787; 5 hits in 76 CRISPR screens.
DR ChiTaRS; Srebf1; mouse.
DR PRO; PR:Q9WTN3; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9WTN3; protein.
DR Bgee; ENSMUSG00000020538; Expressed in white adipose tissue and 136 other tissues.
DR ExpressionAtlas; Q9WTN3; baseline and differential.
DR Genevisible; Q9WTN3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
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:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:HGNC-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0032810; F:sterol response element binding; ISS:HGNC-UCL.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0009267; P:cellular response to starvation; IDA:HGNC-UCL.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:MGI.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0030073; P:insulin secretion; IMP:MGI.
DR GO; GO:0008610; P:lipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0010876; P:lipid localization; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; TAS:BHF-UCL.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IDA:MGI.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IDA:UniProtKB.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; ISO:MGI.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IMP:MGI.
DR GO; GO:0003062; P:regulation of heart rate by chemical signal; IMP:MGI.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:MGI.
DR GO; GO:0010883; P:regulation of lipid storage; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032094; P:response to food; IEA:Ensembl.
DR GO; GO:0033762; P:response to glucagon; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IMP:MGI.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0032933; P:SREBP signaling pathway; ISS:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cholesterol metabolism;
KW Cytoplasmic vesicle; DNA-binding; Endoplasmic reticulum; Golgi apparatus;
KW Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..1134
FT /note="Sterol regulatory element-binding protein 1"
FT /id="PRO_0000127448"
FT CHAIN 1..480
FT /note="Processed sterol regulatory element-binding protein
FT 1"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT /id="PRO_0000314030"
FT TOPO_DOM 1..477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..536
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 537..557
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 558..1134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 317..367
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..60
FT /note="Transcriptional activation (acidic)"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT REGION 46..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 170..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..487
FT /note="Interaction with LMNA"
FT /evidence="ECO:0000269|PubMed:11929849"
FT REGION 367..388
FT /note="Leucine-zipper"
FT REGION 415..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 27..35
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT COMPBIAS 422..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 451..452
FT /note="Cleavage; by caspase-3 and caspase-7"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 480..481
FT /note="Cleavage; by MBTPS2"
FT /evidence="ECO:0000250|UniProtKB:Q12772"
FT SITE 519..520
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56720"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT MOD_RES 331
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000269|PubMed:19244231"
FT MOD_RES 332
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000269|PubMed:19244231"
FT MOD_RES 389
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:21459323"
FT MOD_RES 395
FT /note="Phosphoserine; by SIK1"
FT /evidence="ECO:0000269|PubMed:19244231"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1047
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36956"
FT VAR_SEQ 1..29
FT /note="MDELAFGEAALEQTLAEMCELDTAVLNDI -> MDCTF (in isoform
FT SREBP-1C and isoform SREBP-1C-W42)"
FT /evidence="ECO:0000303|PubMed:10052151,
FT ECO:0000303|PubMed:9062340"
FT /id="VSP_002151"
FT VAR_SEQ 90..131
FT /note="Missing (in isoform SREBP-1A-W42 and isoform SREBP-
FT 1C-W42)"
FT /evidence="ECO:0000303|PubMed:10052151"
FT /id="VSP_002152"
FT MUTAGEN 331
FT /note="S->A: Weakly affects phosphorylation by SIK1."
FT /evidence="ECO:0000269|PubMed:19244231"
FT MUTAGEN 332
FT /note="S->A: Weakly affects phosphorylation by SIK1."
FT /evidence="ECO:0000269|PubMed:19244231"
FT MUTAGEN 354
FT /note="S->A: Does not affect AMPK-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:21459323"
FT MUTAGEN 389
FT /note="S->A: Abolishes AMPK-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:21459323"
FT MUTAGEN 395
FT /note="S->A: Strongly impairs affects phosphorylation by
FT SIK1."
FT /evidence="ECO:0000269|PubMed:19244231"
FT CONFLICT 272..276
FT /note="Missing (in Ref. 1; BAE32576 and 6; AAK54762)"
FT /evidence="ECO:0000305"
FT CONFLICT 795
FT /note="R -> P (in Ref. 1; BAE29268)"
FT /evidence="ECO:0000305"
FT CONFLICT 1003
FT /note="H -> N (in Ref. 3; AAH06051)"
FT /evidence="ECO:0000305"
FT CONFLICT 1061
FT /note="T -> A (in Ref. 3; AAH06051)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1134 AA; 120537 MW; 3D7422406E07A376 CRC64;
MDELAFGEAA LEQTLAEMCE LDTAVLNDIE DMLQLINNQD SDFPGLFDAP YAGGETGDTG
PSSPGANSPE SFSSASLASS LEAFLGGPKV TPAPLSPPPS APAALKMYPS VSPFSPGPGI
KEEPVPLTIL QPAAPQPSPG TLLPPSFPAP PVQLSPAPVL GYSSLPSGFS GTLPGNTQQP
PSSLPLAPAP GVLPTPALHT QVQSLASQQP LPASAAPRTN TVTSQVQQVP VVLQPHFIKA
DSLLLTAVKT DAGATVKTAG ISTLAPGTAV QAGPLQTLVS GGTILATVPL VVDTDKLPIH
RLAAGSKALG SAQSRGEKRT AHNAIEKRYR SSINDKIVEL KDLVVGTEAK LNKSAVLRKA
IDYIRFLQHS NQKLKQENLT LRSAHKSKSL KDLVSACGSG GGTDVSMEGM KPEVVETLTP
PPSDAGSPSQ SSPLSFGSRA SSSGGSDSEP DSPAFEDSQV KAQRLPSHSR GMLDRSRLAL
CVLAFLCLTC NPLASLFGWG ILTPSDATGT HRSSGRSMLE AESRDGSNWT QWLLPPLVWL
ANGLLVLACL ALLFVYGEPV TRPHSGPAVH FWRHRKQADL DLARGDFPQA AQQLWLALQA
LGRPLPTSNL DLACSLLWNL IRHLLQRLWV GRWLAGQAGG LLRDRGLRKD ARASARDAAV
VYHKLHQLHA MGKYTGGHLA ASNLALSALN LAECAGDAIS MATLAEIYVA AALRVKTSLP
RALHFLTRFF LSSARQACLA QSGSVPLAMQ WLCHPVGHRF FVDGDWAVHG APPESLYSVA
GNPVDPLAQV TRLFREHLLE RALNCIAQPS PGAADGDREF SDALGYLQLL NSCSDAAGAP
ACSFSVSSSM AATTGPDPVA KWWASLTAVV IHWLRRDEEA AERLYPLVEH IPQVLQDTER
PLPRAALYSF KAARALLDHR KVESSPASLA ICEKASGYLR DSLASTPTGS SIDKAMQLLL
CDLLLVARTS LWQRQQSPAS VQVAHGTSNG PQASALELRG FQHDLSSLRR LAQSFRPAMR
RVFLHEATAR LMAGASPART HQLLDRSLRR RAGSSGKGGT TAELEPRPTW REHTEALLLA
SCYLPPAFLS APGQRMSMLA EAARTVEKLG DHRLLLDCQQ MLLRLGGGTT VTSS
