ID SRBP2_HUMAN Reviewed; 1141 AA. AC Q12772; Q05BD5; Q6GTH7; Q86V36; Q9UH04; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 09-APR-2025, entry version 230. DE RecName: Full=Sterol regulatory element-binding protein 2 {ECO:0000303|PubMed:15461802}; DE Short=SREBP-2 {ECO:0000303|PubMed:15461802}; DE AltName: Full=Class D basic helix-loop-helix protein 2; DE Short=bHLHd2; DE AltName: Full=Sterol regulatory element-binding transcription factor 2 {ECO:0000303|PubMed:15461802}; DE Contains: DE RecName: Full=Processed sterol regulatory element-binding protein 2 {ECO:0000305}; DE AltName: Full=Transcription factor SREBF2 {ECO:0000305}; GN Name=SREBF2 {ECO:0000303|PubMed:32322062, ECO:0000312|HGNC:HGNC:11290}; GN Synonyms=BHLHD2, SREBP2 {ECO:0000303|PubMed:15461802}; 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), FUNCTION, TISSUE SPECIFICITY, AND RP VARIANT ALA-595. RX PubMed=7903453; DOI=10.1073/pnas.90.24.11603; RA Hua X., Yokoyama C., Wu J., Briggs M.R., Brown M.S., Goldstein J.L., RA Wang X.; RT "SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that RT stimulates transcription by binding to a sterol regulatory element."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11603-11607(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lymph, and Skin; 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 [5] RP PROTEIN SEQUENCE OF 91-109. RX PubMed=8402897; DOI=10.1016/s0092-8674(05)80095-9; RA Yokoyama C., Wang X., Briggs M.R., Admon A., Wu J., Hua X., Goldstein J.L., RA Brown M.S.; RT "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls RT transcription of the low density lipoprotein receptor gene."; RL Cell 75:187-197(1993). RN [6] RP SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=11477106; DOI=10.1074/jbc.m105200200; RA Hirano Y., Yoshida M., Shimizu M., Sato R.; RT "Direct demonstration of rapid degradation of nuclear sterol regulatory RT element-binding proteins by the ubiquitin-proteasome pathway."; RL J. Biol. Chem. 276:36431-36437(2001). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=12202038; DOI=10.1016/s0092-8674(02)00872-3; RA Yang T., Espenshade P.J., Wright M.E., Yabe D., Gong Y., Aebersold R., RA Goldstein J.L., Brown M.S.; RT "Crucial step in cholesterol homeostasis: sterols promote binding of SCAP RT to INSIG-1, a membrane protein that facilitates retention of SREBPs in RT ER."; RL Cell 110:489-500(2002). RN [8] RP FUNCTION, AND MUTAGENESIS OF TYR-342. RX PubMed=12177166; RA Amemiya-Kudo M., Shimano H., Hasty A.H., Yahagi N., Yoshikawa T., RA Matsuzaka T., Okazaki H., Tamura Y., Iizuka Y., Ohashi K., Osuga J., RA Harada K., Gotoda T., Sato R., Kimura S., Ishibashi S., Yamada N.; RT "Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different RT target promoters of lipogenic and cholesterogenic genes."; RL J. Lipid Res. 43:1220-1235(2002). RN [9] RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-478; ARG-519 AND RP 478-ASP--ARG-481. RX PubMed=8626610; DOI=10.1074/jbc.271.17.10379; RA Hua X., Sakai J., Brown M.S., Goldstein J.L.; RT "Regulated cleavage of sterol regulatory element binding proteins requires RT sequences on both sides of the endoplasmic reticulum membrane."; RL J. Biol. Chem. 271:10379-10384(1996). RN [10] RP PROTEOLYTIC CLEAVAGE AT ASP-468 BY CASPASES. RX PubMed=8643593; DOI=10.1073/pnas.93.11.5437; RA Pai J.-T., Brown M.S., Goldstein J.L.; RT "Purification and cDNA cloning of a second apoptosis-related cysteine RT protease that cleaves and activates sterol regulatory element binding RT proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 93:5437-5442(1996). RN [11] RP PROTEOLYTIC CLEAVAGE AT LEU-484 BY S2P, AND MUTAGENESIS OF ARG-479; RP ARG-481; LEU-484; CYS-485; 478-ASP--ARG-481; 479-ARG--ARG-481 AND RP 484-LEU-CYS-485. RX PubMed=9651382; DOI=10.1074/jbc.273.28.17801; RA Duncan E.A., Dave U.P., Sakai J., Goldstein J.L., Brown M.S.; RT "Second-site cleavage in sterol regulatory element-binding protein occurs RT at transmembrane junction as determined by cysteine panning."; RL J. Biol. Chem. 273:17801-17809(1998). RN [12] RP PROTEOLYTIC CLEAVAGE AT LEU-484 BY S2P, PROTEOLYTIC CLEAVAGE AT LEU-522 BY RP S1P, AND MUTAGENESIS OF ASN-495; PRO-496; 490-LEU-CYS-491 AND RP 495-ASN-PRO-496. RX PubMed=10805775; DOI=10.1073/pnas.97.10.5123; RA Ye J., Dave U.P., Grishin N.V., Goldstein J.L., Brown M.S.; RT "Asparagine-proline sequence within membrane-spanning segment of SREBP RT triggers intramembrane cleavage by site-2 protease."; RL Proc. Natl. Acad. Sci. U.S.A. 97:5123-5128(2000). RN [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-855 AND SER-1098, AND RP 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 [15] RP INTERACTION WITH PAQR3, AND SUBCELLULAR LOCATION. RX PubMed=26311497; DOI=10.1038/ncomms9100; RA Xu D., Wang Z., Zhang Y., Jiang W., Pan Y., Song B.L., Chen Y.; RT "PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to RT the Golgi apparatus."; RL Nat. Commun. 6:8100-8100(2015). RN [16] 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 [17] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-464, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SCAP, AND PROTEOLYTIC RP CLEAVAGE. RX PubMed=32322062; DOI=10.1038/s41586-020-2183-2; RA Xu D., Wang Z., Xia Y., Shao F., Xia W., Wei Y., Li X., Qian X., Lee J.H., RA Du L., Zheng Y., Lv G., Leu J.S., Wang H., Xing D., Liang T., Hung M.C., RA Lu Z.; RT "The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis."; RL Nature 580:530-535(2020). RN [19] RP REGION. RX PubMed=35120642; DOI=10.1016/j.cels.2022.01.002; RA Staller M.V., Ramirez E., Kotha S.R., Holehouse A.S., Pappu R.V., RA Cohen B.A.; RT "Directed mutational scanning reveals a balance between acidic and RT hydrophobic residues in strong human activation domains."; RL Cell Syst. 13:334-345.e5(2022). RN [20] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 343-403. RX PubMed=14645851; DOI=10.1126/science.1088372; RA Lee S.J., Sekimoto T., Yamashita E., Nagoshi E., Nakagawa A., Imamoto N., RA Yoshimura M., Sakai H., Chong K.T., Tsukihara T., Yoneda Y.; RT "The structure of importin-beta bound to SREBP-2: nuclear import of a RT transcription factor."; RL Science 302:1571-1575(2003). RN [21] RP VARIANTS [LARGE SCALE ANALYSIS] SER-273 AND LYS-347. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: [Sterol regulatory element-binding protein 2]: Precursor of CC the transcription factor form (Processed sterol regulatory element- CC binding protein 2), which is embedded in the endoplasmic reticulum CC membrane (PubMed:32322062). Low sterol concentrations promote CC processing of this form, releasing the transcription factor form that CC translocates into the nucleus and activates transcription of genes CC involved in cholesterol biosynthesis (PubMed:32322062). CC {ECO:0000269|PubMed:32322062}. CC -!- FUNCTION: [Processed sterol regulatory element-binding protein 2]: Key CC transcription factor that regulates expression of genes involved in CC cholesterol biosynthesis (PubMed:12177166, PubMed:32322062). Binds to CC the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual CC sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') CC and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:12177166, PubMed:7903453). CC Regulates transcription of genes related to cholesterol synthesis CC pathway (PubMed:12177166, PubMed:32322062). CC {ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32322062, CC ECO:0000269|PubMed:7903453}. CC -!- ACTIVITY REGULATION: Activation by cleavage is down-regulated upon CC activation of SIRT3-dependent PRKAA1/AMPK-alpha signaling cascade which CC leads to inhibition of ATP-consuming lipogenesis to restore cellular CC energy balance. {ECO:0000250|UniProtKB:Q3U1N2}. CC -!- SUBUNIT: [Sterol regulatory element-binding protein 2]: Forms a tight CC complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum CC membrane and the Golgi apparatus (PubMed:19706601, PubMed:26311497, CC PubMed:32322062). Interacts with PAQR3; the interaction anchors the CC SCAP-SREBP complex to the Golgi apparatus in low cholesterol conditions CC (PubMed:26311497). Interacts (via C-terminal domain) with RNF139 CC (PubMed:19706601). {ECO:0000269|PubMed:19706601, CC ECO:0000269|PubMed:26311497, ECO:0000269|PubMed:32322062}. CC -!- SUBUNIT: [Processed sterol regulatory element-binding protein 2]: CC Homodimer; efficient DNA binding of the soluble transcription factor CC fragment requires dimerization with another bHLH protein (By CC similarity). Interacts with LMNA (By similarity). CC {ECO:0000250|UniProtKB:Q3U1N2}. CC -!- INTERACTION: CC Q12772; Q92793: CREBBP; NbExp=2; IntAct=EBI-465059, EBI-81215; CC Q12772; Q14192: FHL2; NbExp=5; IntAct=EBI-465059, EBI-701903; CC Q12772; P20036: HLA-DPA1; NbExp=3; IntAct=EBI-465059, EBI-2802853; CC Q12772; P41235: HNF4A; NbExp=2; IntAct=EBI-465059, EBI-1049011; CC Q12772; Q96RN5: MED15; NbExp=2; IntAct=EBI-465059, EBI-394506; CC Q12772; Q13952-2: NFYC; NbExp=3; IntAct=EBI-465059, EBI-11956831; CC Q12772; P08047: SP1; NbExp=3; IntAct=EBI-465059, EBI-298336; CC Q12772; P04637: TP53; NbExp=3; IntAct=EBI-465059, EBI-366083; CC -!- SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 2]: CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:12202038}; Multi- CC pass membrane protein {ECO:0000255}. Golgi apparatus membrane CC {ECO:0000269|PubMed:26311497, ECO:0000269|PubMed:28849786}; Multi-pass CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, COPII-coated CC vesicle membrane {ECO:0000303|PubMed:28849786}; Multi-pass membrane CC protein {ECO:0000255}. Note=At high sterol concentrations, the SCAP- CC SREBP is retained in the endoplasmic reticulum (PubMed:32322062). Low CC sterol concentrations promote recruitment into COPII-coated vesicles CC and transport of the SCAP-SREBP to the Golgi, where it is processed CC (PubMed:32322062). {ECO:0000269|PubMed:26311497, CC ECO:0000269|PubMed:32322062}. CC -!- SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding CC protein 2]: Nucleus {ECO:0000269|PubMed:11477106, CC ECO:0000269|PubMed:32322062}. Note=Transported into the nucleus with CC the help of importin-beta. Dimerization of the bHLH domain is a CC prerequisite for importin beta-dependent nuclear import. CC {ECO:0000250|UniProtKB:Q3U1N2}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q12772-1; Sequence=Displayed; CC Name=2; CC IsoId=Q12772-2; Sequence=VSP_054283, VSP_054284, VSP_054285; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in adult and fetal tissues. CC {ECO:0000269|PubMed:7903453}. CC -!- PTM: [Sterol regulatory element-binding protein 2]: Processed in the CC Golgi apparatus, releasing the protein from the membrane CC (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). At CC low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles CC for export from the endoplasmic reticulum (PubMed:10805775, CC PubMed:32322062, PubMed:8626610, PubMed:9651382). In the Golgi, complex CC SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 CC (MBTPS2, S2P) protease (PubMed:10805775, PubMed:32322062, CC PubMed:8626610, PubMed:9651382). The first cleavage by site-1 protease CC occurs within the luminal loop, the second cleavage by site-2 protease CC occurs within the first transmembrane domain, releasing the CC transcription factor from the Golgi membrane (PubMed:10805775, CC PubMed:9651382). Apoptosis triggers cleavage by the cysteine proteases CC caspase-3 and caspase-7. Cleavage and activation is induced by mediated CC cholesterol efflux (PubMed:8643593). {ECO:0000269|PubMed:10805775, CC ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8626610, CC ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9651382}. CC -!- PTM: Phosphorylated by AMPK, leading to suppress protein processing and CC nuclear translocation, and repress target gene expression. CC {ECO:0000250|UniProtKB:Q3U1N2}. CC -!- PTM: [Processed sterol regulatory element-binding protein 2]: CC Ubiquitinated; the nuclear form has a rapid turnover and is rapidly CC ubiquitinated and degraded by the proteasome in the nucleus. CC {ECO:0000269|PubMed:11477106}. CC -!- SIMILARITY: Belongs to the SREBP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH51799.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U02031; AAA50746.1; -; mRNA. DR EMBL; CT841522; CAJ86452.1; -; mRNA. DR EMBL; AL021453; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z99716; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC051385; AAH51385.1; -; mRNA. DR EMBL; BC051799; AAH51799.1; ALT_INIT; mRNA. DR EMBL; BC056158; AAH56158.1; -; mRNA. DR CCDS; CCDS14023.1; -. [Q12772-1] DR PIR; A49397; A54962. DR RefSeq; NP_004590.2; NM_004599.3. [Q12772-1] DR PDB; 1UKL; X-ray; 3.00 A; C/D/E/F=343-403. DR PDBsum; 1UKL; -. DR AlphaFoldDB; Q12772; -. DR SMR; Q12772; -. DR BioGRID; 112599; 326. DR ComplexPortal; CPX-25721; SREBP-SCAP transcription regulator complex, SREBF2 variant. DR CORUM; Q12772; -. DR DIP; DIP-263N; -. DR ELM; Q12772; -. DR IntAct; Q12772; 95. DR MINT; Q12772; -. DR STRING; 9606.ENSP00000354476; -. DR BindingDB; Q12772; -. DR ChEMBL; CHEMBL1795166; -. DR CarbonylDB; Q12772; -. DR GlyCosmos; Q12772; 2 sites, 1 glycan. DR GlyGen; Q12772; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q12772; -. DR PhosphoSitePlus; Q12772; -. DR BioMuta; SREBF2; -. DR DMDM; 116242800; -. DR jPOST; Q12772; -. DR MassIVE; Q12772; -. DR PaxDb; 9606-ENSP00000354476; -. DR PeptideAtlas; Q12772; -. DR ProteomicsDB; 58919; -. [Q12772-1] DR Pumba; Q12772; -. DR Antibodypedia; 13093; 495 antibodies from 38 providers. DR DNASU; 6721; -. DR Ensembl; ENST00000361204.9; ENSP00000354476.4; ENSG00000198911.13. [Q12772-1] DR GeneID; 6721; -. DR KEGG; hsa:6721; -. DR MANE-Select; ENST00000361204.9; ENSP00000354476.4; NM_004599.4; NP_004590.2. DR UCSC; uc003bbi.5; human. [Q12772-1] DR AGR; HGNC:11290; -. DR CTD; 6721; -. DR DisGeNET; 6721; -. DR GeneCards; SREBF2; -. DR HGNC; HGNC:11290; SREBF2. DR HPA; ENSG00000198911; Low tissue specificity. DR MalaCards; SREBF2; -. DR MIM; 600481; gene. DR neXtProt; NX_Q12772; -. DR OpenTargets; ENSG00000198911; -. DR PharmGKB; PA336; -. DR VEuPathDB; HostDB:ENSG00000198911; -. DR eggNOG; KOG2588; Eukaryota. DR GeneTree; ENSGT00940000157339; -. DR HOGENOM; CLU_008042_0_0_1; -. DR InParanoid; Q12772; -. DR OMA; QQAVMIT; -. DR OrthoDB; 2133190at2759; -. DR PhylomeDB; Q12772; -. DR TreeFam; TF313894; -. DR PathwayCommons; Q12772; -. DR Reactome; R-HSA-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF). DR Reactome; R-HSA-191273; Cholesterol biosynthesis. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP). DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination. DR SignaLink; Q12772; -. DR SIGNOR; Q12772; -. DR BioGRID-ORCS; 6721; 51 hits in 1191 CRISPR screens. DR ChiTaRS; SREBF2; human. DR EvolutionaryTrace; Q12772; -. DR GeneWiki; SREBF2; -. DR GenomeRNAi; 6721; -. DR Pharos; Q12772; Tchem. DR PRO; PR:Q12772; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q12772; protein. DR Bgee; ENSG00000198911; Expressed in ganglionic eminence and 209 other cell types or tissues. DR ExpressionAtlas; Q12772; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. 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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032937; C:SREBP-SCAP-Insig complex; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProt. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0070888; F:E-box binding; IDA:BHF-UCL. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; NAS:BHF-UCL. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEP:BHF-UCL. DR GO; GO:0009267; P:cellular response to starvation; IMP:ParkinsonsUK-UCL. DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW. DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc. DR GO; GO:0090370; P:negative regulation of cholesterol efflux; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IDA:UniProt. DR GO; GO:0010886; P:positive regulation of cholesterol storage; IDA:BHF-UCL. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:1901524; P:regulation of mitophagy; HMP:ParkinsonsUK-UCL. DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISS:UniProtKB. DR GO; GO:0032933; P:SREBP signaling pathway; IDA:CACAO. DR CDD; cd18922; bHLHzip_SREBP2; 1. DR FunFam; 4.10.280.10:FF:000016; Sterol regulatory element-binding transcription factor 1; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR IDEAL; IID00242; -. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR PANTHER; PTHR46062; STEROL REGULATORY ELEMENT-BINDING PROTEIN; 1. DR PANTHER; PTHR46062:SF3; STEROL REGULATORY ELEMENT-BINDING PROTEIN 2; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cholesterol metabolism; KW Cytoplasmic vesicle; Direct protein sequencing; DNA-binding; KW Endoplasmic reticulum; Golgi apparatus; Isopeptide bond; Lipid metabolism; KW Membrane; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Steroid metabolism; Sterol metabolism; Transcription; KW Transcription regulation; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT CHAIN 1..1141 FT /note="Sterol regulatory element-binding protein 2" FT /id="PRO_0000127452" FT CHAIN 1..484 FT /note="Processed sterol regulatory element-binding protein FT 2" FT /evidence="ECO:0000305|PubMed:10805775, FT ECO:0000305|PubMed:9651382" FT /id="PRO_0000314033" FT TOPO_DOM 1..479 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 480..500 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 501..533 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 534..554 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 555..1139 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 330..380 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT REGION 1..50 FT /note="Transcriptional activation (acidic)" FT /evidence="ECO:0000269|PubMed:35120642" FT REGION 48..144 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 237..491 FT /note="Interaction with LMNA" FT /evidence="ECO:0000250|UniProtKB:Q3U1N2" FT REGION 380..401 FT /note="Leucine-zipper" FT COMPBIAS 63..82 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 88..97 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 98..110 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 114..126 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 468..469 FT /note="Cleavage; by caspase-3 and caspase-7" FT /evidence="ECO:0000269|PubMed:8643593" FT SITE 484..485 FT /note="Cleavage; by MBTPS2" FT /evidence="ECO:0000269|PubMed:10805775, FT ECO:0000269|PubMed:9651382" FT SITE 522..523 FT /note="Cleavage; by MBTPS1" FT /evidence="ECO:0000269|PubMed:10805775" FT MOD_RES 855 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1098 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 464 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 273..275 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054283" FT VAR_SEQ 589..684 FT /note="DFAAAAGNLQTCLAVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKK FT VFQCRRATPATEAGFEDEAKTSARDAALAYHRLHQLHITGKLPA -> VYGKKSGATHS FT IEEELNIHISRGTRTRTLLSSRRFCSCCRQPTNLPGSFGPGTAHLPPGPGLQPLLERDP FT LQPAEATPGALAAQESLPVPAGHASH (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054284" FT VAR_SEQ 685..1141 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054285" FT VARIANT 273 FT /note="A -> S (in a breast cancer sample; somatic mutation; FT dbSNP:rs2077134829)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036394" FT VARIANT 347 FT /note="N -> K (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036395" FT VARIANT 536 FT /note="M -> L (in dbSNP:rs17002714)" FT /id="VAR_049550" FT VARIANT 595 FT /note="G -> A (in dbSNP:rs2228314)" FT /evidence="ECO:0000269|PubMed:7903453" FT /id="VAR_028440" FT VARIANT 623 FT /note="V -> M (in dbSNP:rs2229440)" FT /id="VAR_028441" FT VARIANT 860 FT /note="R -> S (in dbSNP:rs2228313)" FT /id="VAR_049551" FT MUTAGEN 342 FT /note="Y->R: Abolished transactivation activity." FT /evidence="ECO:0000269|PubMed:12177166" FT MUTAGEN 478..481 FT /note="DRSR->AAAA: Loss of cleavage by S2P." FT /evidence="ECO:0000269|PubMed:8626610, FT ECO:0000269|PubMed:9651382" FT MUTAGEN 478..481 FT /note="DRSR->AS: Loss of cleavage by S2P." FT /evidence="ECO:0000269|PubMed:8626610, FT ECO:0000269|PubMed:9651382" FT MUTAGEN 478 FT /note="D->A: No effect on proteolytic processing in FT response to low sterol." FT /evidence="ECO:0000269|PubMed:8626610" FT MUTAGEN 479..481 FT /note="RSR->AAA: Loss of cleavage by S2P." FT /evidence="ECO:0000269|PubMed:9651382" FT MUTAGEN 479 FT /note="R->A: No effect on cleavage by S2P." FT /evidence="ECO:0000269|PubMed:9651382" FT MUTAGEN 481 FT /note="R->A: No effect on cleavage by S2P." FT /evidence="ECO:0000269|PubMed:9651382" FT MUTAGEN 484..485 FT /note="LC->FF: No effect on cleavage by S2P." FT /evidence="ECO:0000269|PubMed:9651382" FT MUTAGEN 484 FT /note="L->A: No effect on cleavage by S2P." FT /evidence="ECO:0000269|PubMed:9651382" FT MUTAGEN 485 FT /note="C->A: No effect on cleavage by S2P." FT /evidence="ECO:0000269|PubMed:9651382" FT MUTAGEN 490..491 FT /note="LC->NP: Restores cleavage by S2P; when associated FT with F-495 and L-496. No effect on site of cleavage by FT S2P." FT /evidence="ECO:0000269|PubMed:10805775" FT MUTAGEN 495..496 FT /note="NP->FL: Loss of cleavage by S2P." FT /evidence="ECO:0000269|PubMed:10805775" FT MUTAGEN 495 FT /note="N->F: Reduced cleavage by S2P." FT /evidence="ECO:0000269|PubMed:10805775" FT MUTAGEN 496 FT /note="P->L: Reduced cleavage by S2P." FT /evidence="ECO:0000269|PubMed:10805775" FT MUTAGEN 519 FT /note="R->A: Loss of proteolytic processing in response to FT low sterol." FT /evidence="ECO:0000269|PubMed:8626610" FT MUTAGEN 519 FT /note="R->K: No effect on proteolytic processing in FT response to low sterol." FT /evidence="ECO:0000269|PubMed:8626610" FT CONFLICT 961 FT /note="A -> G (in Ref. 1; AAA50746)" FT /evidence="ECO:0000305" FT CONFLICT 1045 FT /note="A -> G (in Ref. 1; AAA50746)" FT /evidence="ECO:0000305" FT HELIX 346..357 FT /evidence="ECO:0007829|PDB:1UKL" FT TURN 366..368 FT /evidence="ECO:0007829|PDB:1UKL" FT HELIX 369..399 FT /evidence="ECO:0007829|PDB:1UKL" SQ SEQUENCE 1141 AA; 123688 MW; 481B1D8E2A2306D2 CRC64; MDDSGELGGL ETMETLTELG DELTLGDIDE MLQFVSNQVG EFPDLFSEQL CSSFPGSGGS GSSSGSSGSS SSSSNGRGSS SGAVDPSVQR SFTQVTLPSF SPSAASPQAP TLQVKVSPTS VPTTPRATPI LQPRPQPQPQ PQTQLQQQTV MITPTFSTTP QTRIIQQPLI YQNAATSFQV LQPQVQSLVT SSQVQPVTIQ QQVQTVQAQR VLTQTANGTL QTLAPATVQT VAAPQVQQVP VLVQPQIIKT DSLVLTTLKT DGSPVMAAVQ NPALTALTTP IQTAALQVPT LVGSSGTILT TMPVMMGQEK VPIKQVPGGV KQLEPPKEGE RRTTHNIIEK RYRSSINDKI IELKDLVMGT DAKMHKSGVL RKAIDYIKYL QQVNHKLRQE NMVLKLANQK NKLLKGIDLG SLVDNEVDLK IEDFNQNVLL MSPPASDSGS QAGFSPYSID SEPGSPLLDD AKVKDEPDSP PVALGMVDRS RILLCVLTFL CLSFNPLTSL LQWGGAHDSD QHPHSGSGRS VLSFESGSGG WFDWMMPTLL LWLVNGVIVL SVFVKLLVHG EPVIRPHSRS SVTFWRHRKQ ADLDLARGDF AAAAGNLQTC LAVLGRALPT SRLDLACSLS WNVIRYSLQK LRLVRWLLKK VFQCRRATPA TEAGFEDEAK TSARDAALAY HRLHQLHITG KLPAGSACSD VHMALCAVNL AECAEEKIPP STLVEIHLTA AMGLKTRCGG KLGFLASYFL SRAQSLCGPE HSAVPDSLRW LCHPLGQKFF MERSWSVKSA AKESLYCAQR NPADPIAQVH QAFCKNLLER AIESLVKPQA KKKAGDQEEE SCEFSSALEY LKLLHSFVDS VGVMSPPLSR SSVLKSALGP DIICRWWTSA ITVAISWLQG DDAAVRSHFT KVERIPKALE VTESPLVKAI FHACRAMHAS LPGKADGQQS SFCHCERASG HLWSSLNVSG ATSDPALNHV VQLLTCDLLL SLRTALWQKQ ASASQAVGET YHASGAELAG FQRDLGSLRR LAHSFRPAYR KVFLHEATVR LMAGASPTRT HQLLEHSLRR RTTQSTKHGE VDAWPGQRER ATAILLACRH LPLSFLSSPG QRAVLLAEAA RTLEKVGDRR SCNDCQQMIV KLGGGTAIAA S //