| IED ID | IndEnz0002008946 |
| Enzyme Type ID | protease008946 |
| Protein Name |
Sterol regulatory element-binding protein 1 SREBP-1 Class D basic helix-loop-helix protein 1 bHLHd1 Sterol regulatory element-binding transcription factor 1 Cleaved into: Processed sterol regulatory element-binding protein 1 Transcription factor SREBF1 |
| Gene Name | SREBF1 BHLHD1 SREBP1 |
| 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 | MDEPPFSEAALEQALGEPCDLDAALLTDIEDMLQLINNQDSDFPGLFDPPYAGSGAGGTDPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGPGIKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGSPPGNTQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLLQPHFIKADSLLLTAMKTDGATVKAAGLSPLVSGTTVQTGPLPTLVSGGTILATVPLVVDAEKLPINRLAAGSKAPASAQSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLKDLVSACGSGGNTDVLMEGVKTEVEDTLTPPPSDAGSPFQSSPLSLGSRGSGSGGSGSDSEPDSPVFEDSKAKPEQRPSLHSRGMLDRSRLALCTLVFLCLSCNPLASLLGARGLPSPSDTTSVYHSPGRNVLGTESRDGPGWAQWLLPPVVWLLNGLLVLVSLVLLFVYGEPVTRPHSGPAVYFWRHRKQADLDLARGDFAQAAQQLWLALRALGRPLPTSHLDLACSLLWNLIRHLLQRLWVGRWLAGRAGGLQQDCALRVDASASARDAALVYHKLHQLHTMGKHTGGHLTATNLALSALNLAECAGDAVSVATLAEIYVAAALRVKTSLPRALHFLTRFFLSSARQACLAQSGSVPPAMQWLCHPVGHRFFVDGDWSVLSTPWESLYSLAGNPVDPLAQVTQLFREHLLERALNCVTQPNPSPGSADGDKEFSDALGYLQLLNSCSDAAGAPAYSFSISSSMATTTGVDPVAKWWASLTAVVIHWLRRDEEAAERLCPLVEHLPRVLQESERPLPRAALHSFKAARALLGCAKAESGPASLTICEKASGYLQDSLATTPASSSIDKAVQLFLCDLLLVVRTSLWRQQQPPAPAPAAQGTSSRPQASALELRGFQRDLSSLRRLAQSFRPAMRRVFLHEATARLMAGASPTRTHQLLDRSLRRRAGPGGKGGAVAELEPRPTRREHAEALLLASCYLPPGFLSAPGQRVGMLAEAARTLEKLGDRRLLHDCQQMLMRLGGGTTVTSS |
| Enzyme Length | 1147 |
| Uniprot Accession Number | P36956 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [Sterol regulatory element-binding protein 1]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), 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 and lipid homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:32322062}.; FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:8402897, 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:8402897, PubMed:12177166). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:8402897, PubMed:12177166, PubMed:32322062). {ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8402897}.; FUNCTION: [Isoform SREBP-1A]: Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166, PubMed:32497488). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32497488}.; FUNCTION: [Isoform SREBP-1C]: Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166}.; FUNCTION: [Isoform SREBP-1aDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}.; FUNCTION: [Isoform SREBP-1cDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (5); Chain (2); Compositional bias (5); Domain (1); Erroneous initiation (1); Helix (2); Modified residue (8); Motif (1); Mutagenesis (13); Natural variant (12); Region (5); Sequence caution (1); Site (3); Topological domain (3); Transmembrane (2) |
| Keywords | 3D-structure;Activator;Alternative splicing;Cholesterol metabolism;Cytoplasmic vesicle;DNA-binding;Direct protein sequencing;Disease variant;Endoplasmic reticulum;Golgi apparatus;Ichthyosis;Lipid metabolism;Membrane;Nucleus;Phosphoprotein;Reference proteome;Steroid metabolism;Sterol metabolism;Transcription;Transcription regulation;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | P54253; P42858; Q92793; Q96RN5; P19659; Q92793; Q96RN5; Q96EB6; P02545-1 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Sterol regulatory element-binding protein 1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12202038}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9WTN3}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, COPII-coated vesicle membrane {ECO:0000250|UniProtKB:Q9WTN3}; Multi-pass membrane protein {ECO:0000255}. Note=At high sterol concentrations, the SCAP-SREBP is retained in the endoplasmic reticulum. Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed. {ECO:0000250|UniProtKB:Q9WTN3}.; SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding protein 1]: Nucleus {ECO:0000269|PubMed:11477106, ECO:0000269|PubMed:32322062}.; SUBCELLULAR LOCATION: [Isoform SREBP-1aDelta]: Nucleus {ECO:0000269|PubMed:18267114, ECO:0000269|PubMed:32497488}.; SUBCELLULAR LOCATION: [Isoform SREBP-1cDelta]: Nucleus {ECO:0000269|PubMed:18267114, ECO:0000269|PubMed:32497488}. |
| Modified Residue | MOD_RES 98; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P56720; MOD_RES 117; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:18669648; MOD_RES 337; /note=Phosphoserine; by SIK1; /evidence=ECO:0000250|UniProtKB:Q9WTN3; MOD_RES 338; /note=Phosphoserine; by SIK1; /evidence=ECO:0000250|UniProtKB:Q9WTN3; MOD_RES 396; /note=Phosphoserine; by AMPK; /evidence=ECO:0000250|UniProtKB:Q9WTN3; MOD_RES 402; /note=Phosphoserine; by SIK1; /evidence=ECO:0000250|UniProtKB:Q9WTN3; MOD_RES 457; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9WTN3; MOD_RES 1060; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: [Sterol regulatory element-binding protein 1]: Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:8626610, PubMed:32322062). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:8626610, PubMed:32322062). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:8626610, 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:32322062). {ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8626610}.; PTM: Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression (By similarity). Phosphorylation at Ser-402 by SIK1 represses activity possibly by inhibiting DNA-binding (By similarity). {ECO:0000250|UniProtKB:Q9WTN3}.; PTM: [Processed sterol regulatory element-binding protein 1]: 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 | 1AM9; |
| Mapped Pubmed ID | 10397761; 10400691; 10428864; 10585467; 10644685; 10759542; 10805775; 10915800; 11257259; 11279134; 11283257; 11414710; 11567032; 11872672; 11916923; 11994399; 12032166; 12083769; 12145339; 12193656; 12213084; 12242332; 12436350; 12531699; 12640139; 12657626; 12730330; 12752570; 12764144; 12842885; 12963821; 1377680; 14404284; 14633850; 14645851; 14722127; 14742839; 14744869; 14747281; 14748724; 14988272; 15026365; 15085196; 15102555; 15123650; 15260976; 15277400; 15277525; 15286454; 15317819; 15340088; 15452130; 15550381; 15677507; 15728349; 15769984; 15794649; 15798184; 15809359; 15833942; 15899885; 16005884; 16007182; 16054042; 16055439; 16141315; 16153721; 16158080; 16162944; 16198472; 16249184; 16306078; 16381800; 16387548; 16407292; 16429400; 16480961; 16713569; 16804073; 16825193; 16880739; 16885156; 17011499; 17019602; 17141191; 17160088; 17198935; 17296605; 17331464; 17344645; 17428919; 17428920; 17449569; 17452746; 17655842; 17681345; 17684114; 17925399; 17989724; 18065496; 18068676; 18072016; 18192539; 18195716; 18245227; 18272927; 18304434; 18334917; 18360697; 18403372; 18420801; 18435918; 18441015; 18559965; 18635549; 18654640; 18660489; 18682402; 18692268; 18726356; 18727921; 18752865; 18774944; 18835813; 18854425; 18936756; 18996102; 19008011; 19032865; 19040658; 19041766; 19056350; 19056482; 19062325; 19088433; 19126544; 19242521; 19252981; 19292868; 19303849; 19323650; 19336475; 19360318; 19470430; 19533843; 19578796; 19621387; 1968462; 19720801; 19727213; 19733654; 19811452; 19876004; 19878569; 19913121; 19913854; 19948975; 19966780; 20005944; 20026048; 20031551; 20067991; 20071336; 20130133; 20138239; 20145241; 20167577; 20171215; 20173757; 20235787; 20376806; 20450493; 20466882; 20513236; 20534441; 20554776; 20615871; 20628086; 20648548; 20655124; 20711500; 20719759; 20817729; 20863500; 20868688; 20937905; 20965718; 20980003; 21093473; 21145868; 21146170; 21310851; 21325464; 21454655; 21540177; 21609284; 21619898; 21645898; 21652712; 21664250; 21757781; 21775116; 21826653; 21836065; 21871872; 21993218; 22035958; 22059152; 22064655; 22152380; 22258239; 22311022; 22363740; 22384276; 22425645; 22429355; 22474125; 22511764; 22634312; 22672904; 22678801; 22690709; 22786746; 22939624; 22966071; 22984430; 23050906; 23106379; 23147115; 23184344; 23208501; 23226416; 23239344; 23422505; 23465592; 23515281; 23610160; 23680128; 23818099; 23825667; 23913732; 23985808; 24105476; 24152445; 24481861; 24484994; 24614076; 24704425; 24722912; 24729033; 24776759; 24825092; 24868893; 24912190; 24924687; 24931346; 25028659; 25111690; 25199460; 25270091; 25270430; 25353341; 25524705; 25583993; 25589463; 25619842; 25634759; 25655569; 25733328; 25800871; 25801724; 25855506; 25891779; 25893295; 25904332; 25962847; 26028026; 26141060; 26321664; 26392539; 26512780; 26514267; 26555173; 26759235; 26771965; 26830228; 26855332; 26869449; 26898440; 26935028; 26937945; 26982812; 27179781; 27270405; 27281560; 27320911; 27467133; 27477273; 27572914; 27579997; 27939887; 28027934; 28083517; 28173150; 28218386; 28367099; 28628909; 28665143; 28701079; 28743860; 28920951; 29097707; 29108200; 29128630; 29138263; 29183723; 29269047; 29449559; 29486327; 29514980; 29555473; 29609490; 29653103; 29784665; 29803738; 29950559; 29968360; 29988076; 30004626; 30206735; 30231795; 30258014; 30301150; 30354203; 30389501; 30446222; 30567368; 30638930; 30718857; 30791926; 30902980; 30914315; 30954075; 31073170; 31296258; 31299935; 31316083; 31379107; 31409773; 31490983; 31541353; 31601152; 31610782; 31736227; 31861383; 31875875; 31887541; 31998789; 32144382; 32375051; 32449166; 32460545; 32464305; 32568455; 32579932; 33226729; 33229547; 33278777; 33340617; 33471067; 33499275; 33665967; 33922983; 33939316; 34019961; 34033176; 34052307; 34272396; 34531575; 34546840; 34575972; 34610416; 34635799; 34673919; 7531665; 7557387; 7567999; 7592729; 7685352; 7732023; 7909540; 8020941; 8060328; 8156598; 8619637; 8626466; 8626488; 8647822; 8663599; 8674110; 8754811; 8798690; 8976377; 9054427; 9062340; 9065481; 9099716; 9242699; 9300785; 9488713; 9604010; 9634533; 9659902; 9748295; |
| Motif | MOTIF 27..35; /note=9aaTAD; /evidence=ECO:0000269|PubMed:31375868 |
| Gene Encoded By | |
| Mass | 121,675 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |