| IED ID | IndEnz0002009433 |
| Enzyme Type ID | protease009433 |
| Protein Name |
Sterol regulatory element-binding protein 2 SREBP-2 Class D basic helix-loop-helix protein 2 bHLHd2 Sterol regulatory element-binding transcription factor 2 Cleaved into: Processed sterol regulatory element-binding protein 2 Transcription factor SREBF2 |
| Gene Name | SREBF2 BHLHD2 SREBP2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MDDSGELGGLETMETLTELGDELTLGDIDEMLQFVSNQVGEFPDLFSEQLCSSFPGSGGSGSSSGSSGSSSSSSNGRGSSSGAVDPSVQRSFTQVTLPSFSPSAASPQAPTLQVKVSPTSVPTTPRATPILQPRPQPQPQPQTQLQQQTVMITPTFSTTPQTRIIQQPLIYQNAATSFQVLQPQVQSLVTSSQVQPVTIQQQVQTVQAQRVLTQTANGTLQTLAPATVQTVAAPQVQQVPVLVQPQIIKTDSLVLTTLKTDGSPVMAAVQNPALTALTTPIQTAALQVPTLVGSSGTILTTMPVMMGQEKVPIKQVPGGVKQLEPPKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNKLLKGIDLGSLVDNEVDLKIEDFNQNVLLMSPPASDSGSQAGFSPYSIDSEPGSPLLDDAKVKDEPDSPPVALGMVDRSRILLCVLTFLCLSFNPLTSLLQWGGAHDSDQHPHSGSGRSVLSFESGSGGWFDWMMPTLLLWLVNGVIVLSVFVKLLVHGEPVIRPHSRSSVTFWRHRKQADLDLARGDFAAAAGNLQTCLAVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKKVFQCRRATPATEAGFEDEAKTSARDAALAYHRLHQLHITGKLPAGSACSDVHMALCAVNLAECAEEKIPPSTLVEIHLTAAMGLKTRCGGKLGFLASYFLSRAQSLCGPEHSAVPDSLRWLCHPLGQKFFMERSWSVKSAAKESLYCAQRNPADPIAQVHQAFCKNLLERAIESLVKPQAKKKAGDQEEESCEFSSALEYLKLLHSFVDSVGVMSPPLSRSSVLKSALGPDIICRWWTSAITVAISWLQGDDAAVRSHFTKVERIPKALEVTESPLVKAIFHACRAMHASLPGKADGQQSSFCHCERASGHLWSSLNVSGATSDPALNHVVQLLTCDLLLSLRTALWQKQASASQAVGETYHASGAELAGFQRDLGSLRRLAHSFRPAYRKVFLHEATVRLMAGASPTRTHQLLEHSLRRRTTQSTKHGEVDAWPGQRERATAILLACRHLPLSFLSSPGQRAVLLAEAARTLEKVGDRRSCNDCQQMIVKLGGGTAIAAS |
| Enzyme Length | 1141 |
| Uniprot Accession Number | Q12772 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [Sterol regulatory element-binding protein 2]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis (PubMed:32322062). {ECO:0000269|PubMed:32322062}.; FUNCTION: [Processed sterol regulatory element-binding protein 2]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis (PubMed:12177166, PubMed:32322062). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:7903453, PubMed:12177166). Regulates transcription of genes related to cholesterol synthesis pathway (PubMed:12177166, PubMed:32322062). {ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:7903453}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Chain (2); Compositional bias (1); Cross-link (1); Domain (1); Erroneous initiation (1); Helix (2); Modified residue (2); Mutagenesis (16); Natural variant (6); Region (4); Sequence conflict (2); Site (3); Topological domain (3); Transmembrane (2); Turn (1) |
| Keywords | 3D-structure;Activator;Alternative splicing;Cholesterol metabolism;Cytoplasmic vesicle;DNA-binding;Direct protein sequencing;Endoplasmic reticulum;Golgi apparatus;Isopeptide bond;Lipid metabolism;Membrane;Nucleus;Phosphoprotein;Reference proteome;Steroid metabolism;Sterol metabolism;Transcription;Transcription regulation;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | Q92793; Q14192; P41235; Q96RN5; Q13952-2; P08047; P04637 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 2]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12202038}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000303|PubMed:28849786}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, COPII-coated vesicle membrane {ECO:0000303|PubMed:28849786}; Multi-pass membrane protein {ECO:0000255}. Note=At high sterol concentrations, the SCAP-SREBP is retained in the endoplasmic reticulum (PubMed:32322062). Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed (PubMed:32322062). {ECO:0000269|PubMed:32322062}.; SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding protein 2]: Nucleus {ECO:0000269|PubMed:11477106, ECO:0000269|PubMed:32322062}. Note=Transported into the nucleus with the help of importin-beta. Dimerization of the bHLH domain is a prerequisite for importin beta-dependent nuclear import. {ECO:0000250|UniProtKB:Q3U1N2}. |
| Modified Residue | MOD_RES 855; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 1098; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: [Sterol regulatory element-binding protein 2]: Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:8626610, PubMed:32322062, PubMed:9651382, PubMed:10805775). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:8626610, PubMed:32322062, PubMed:9651382, PubMed:10805775). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:8626610, PubMed:9651382, PubMed:10805775, PubMed:32322062). The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane (PubMed:9651382, PubMed:10805775). Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. Cleavage and activation is induced by mediated cholesterol efflux (PubMed:8643593). {ECO:0000269|PubMed:10805775, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8626610, ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9651382}.; PTM: Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. {ECO:0000250|UniProtKB:Q3U1N2}.; PTM: [Processed sterol regulatory element-binding protein 2]: Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus. {ECO:0000269|PubMed:11477106}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 1UKL; |
| Mapped Pubmed ID | 10397761; 10400691; 10428864; 10644685; 10976766; 11279134; 11283257; 11394999; 11567032; 11872672; 12032166; 12083769; 12145339; 12193656; 12242332; 12801623; 12842885; 12855700; 12963821; 1377680; 14404284; 14500290; 14512514; 14522948; 14765107; 14988395; 15026365; 15085196; 15211801; 15260976; 15277525; 15358760; 15388640; 15452130; 15527767; 15547298; 15550381; 15610069; 15721010; 15728349; 15798184; 15836632; 15899885; 15907797; 16054042; 16082694; 16141315; 16158080; 16169070; 16227610; 16335799; 16466730; 16697011; 16763159; 16799563; 16901265; 17008555; 17011499; 17198935; 17383658; 17428919; 17428920; 17449569; 17500595; 17604677; 17702963; 17921436; 17925399; 18032389; 18072016; 18195716; 18272927; 18321953; 18403372; 18559965; 18579430; 18654640; 18660489; 18726356; 18936756; 18954446; 18959802; 19041766; 19056482; 19088433; 19116028; 19143832; 19155782; 19231010; 19263511; 19323650; 19460711; 19497963; 19582494; 1968462; 19740467; 19906111; 19913121; 19948975; 20031551; 20111910; 20138239; 20144195; 20149798; 20167577; 20213556; 20379614; 20450493; 20460578; 20466882; 20566875; 20628086; 20711500; 20732877; 20734064; 20936779; 20937905; 20965718; 20980003; 21044070; 21454655; 21613400; 21757058; 21944868; 21988832; 22153697; 22182810; 22265415; 22429355; 22573382; 22573671; 22662110; 23044239; 23050906; 23102786; 23158139; 23239344; 23454642; 23825667; 23838163; 24321096; 24353279; 24382701; 24478315; 24496149; 24868893; 24908080; 24992162; 25005769; 25028659; 25188917; 25201120; 25488447; 25733328; 25914460; 25933205; 25998247; 26028026; 26302339; 26321664; 26512780; 26514267; 26535009; 26728456; 26855332; 26883200; 26984409; 27703009; 27771555; 27778136; 27841945; 28173150; 28249167; 28367087; 28696297; 28901487; 28920951; 29336468; 29449559; 29466876; 29503034; 29601949; 29678744; 29712938; 29748249; 30195495; 30366764; 30394316; 30579780; 30718857; 31417158; 31432128; 31455613; 31490983; 31664866; 31744820; 31827541; 31875875; 32028704; 32054686; 32883951; 33106423; 33605122; 34021134; 34347016; 7531665; 7557387; 7685352; 8020941; 8138712; 8156598; 8619637; 8626466; 8626488; 8647822; 8663599; 8674110; 8754811; 8798690; 8976377; 9065481; 9242699; 9482253; 9488713; 9604010; 9634533; 9634703; 9659902; 9705348; 9748295; |
| Motif | |
| Gene Encoded By | |
| Mass | 123,688 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |