SREBF1
entrez
6720
canonical
uniprot
P36956
canonical
ensembl
ENSG00000072310
resolver
ensp
ENSP00000261646
resolver
ensp
ENSP00000348069
resolver
ensp
ENSP00000379106
resolver
ensp
ENSP00000562530
resolver
ensp
ENSP00000562534
resolver
ensp
ENSP00000562536
resolver
ensp
ENSP00000588880
resolver
genesymbol
SREBF1
resolver
genesymbol_syn
BHLHD1
resolver
genesymbol_syn
SREBP1
resolver
hgnc
HGNC:11289
resolver
uniprot
B0I4X3
resolver
uniprot
B0I4X4
resolver
uniprot
B3KR77
resolver
uniprot
D3DXC4
resolver
uniprot
Q16062
resolver
uniprot
Q59F52
resolver
uniprot
Q6P4R7
resolver
uniprot
Q6PFW7
resolver
uniprot
Q6PJ36
resolver
uniprot
Q8TAK9
resolver
uniprot_entry
B3KR77_HUMAN
resolver
uniprot_entry
SRBP1_HUMAN
resolver
uniprot_sec
B0I4X3
resolver
uniprot_sec
B0I4X4
resolver
uniprot_sec
D3DXC4
resolver
uniprot_sec
Q16062
resolver
uniprot_sec
Q59F52
resolver
uniprot_sec
Q6P4R7
resolver
uniprot_sec
Q6PFW7
resolver
uniprot_sec
Q6PJ36
resolver
uniprot_sec
Q8TAK9
resolver
activity_regulation
ACTIVITY REGULATION: Activation by cleavage is down-regulated upon activation of SIRT3-dependent PRKAA1/AMPK-alpha signaling cascade which leads to inhibition of ATP-consuming lipogenesis to restore cellular energy balance. {ECO:0000250|UniProtKB:Q9WTN3}.
uniprot
proteins
amino_acid_sequence
MDEPPFSEAALEQALGEPCDLDAALLTDIEDMLQLINNQDSDFPGLFDPPYAGSGAGGTDPASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGPGIKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGSPPGNTQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLLQPHFIKADSLLLTAMKTDGATVKAAGLSPLVSGTTVQTGPLPTLVSGGTILATVPLVVDAEKLPINRLAAGSKAPASAQSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKSAVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLKDLVSACGSGGNTDVLMEGVKTEVEDTLTPPPSDAGSPFQSSPLSLGSRGSGSGGSGSDSEPDSPVFEDSKAKPEQRPSLHSRGMLDRSRLALCTLVFLCLSCNPLASLLGARGLPSPSDTTSVYHSPGRNVLGTESRDGPGWAQWLLPPVVWLLNGLLVLVSLVLLFVYGEPVTRPHSGPAVYFWRHRKQADLDLARGDFAQAAQQLWLALRALGRPLPTSHLDLACSLLWNLIRHLLQRLWVGRWLAGRAGGLQQDCALRVDASASARDAALVYHKLHQLHTMGKHTGGHLTATNLALSALNLAECAGDAVSVATLAEIYVAAALRVKTSLPRALHFLTRFFLSSARQACLAQSGSVPPAMQWLCHPVGHRFFVDGDWSVLSTPWESLYSLAGNPVDPLAQVTQLFREHLLERALNCVTQPNPSPGSADGDKEFSDALGYLQLLNSCSDAAGAPAYSFSISSSMATTTGVDPVAKWWASLTAVVIHWLRRDEEAAERLCPLVEHLPRVLQESERPLPRAALHSFKAARALLGCAKAESGPASLTICEKASGYLQDSLATTPASSSIDKAVQLFLCDLLLVVRTSLWRQQQPPAPAPAAQGTSSRPQASALELRGFQRDLSSLRRLAQSFRPAMRRVFLHEATARLMAGASPTRTHQLLDRSLRRRAGPGGKGGAVAELEPRPTRREHAEALLLASCYLPPGFLSAPGQRVGMLAEAARTLEKLGDRRLLHDCQQMLMRLGGGTTVTSS
uniprot
proteins
disease_involvement
DISEASE: IFAP syndrome 2 (IFAP2) [MIM:619016]: An autosomal dominant form of IFAP syndrome, a disease characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. IFAP2 patients manifest ichthyosis follicularis or follicular hyperkeratosis, hyperkeratotic plaques, sparse to no body hair, and photophobia with punctate corneal epithelial defects, corneal pannus, and complicated cataract. Ultrastructural hair analysis shows trichorrhexis nodosa. {ECO:0000269|PubMed:32497488}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mucoepithelial dysplasia, hereditary (HMD) [MIM:158310]: An autosomal dominant genodermatosis mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo. {ECO:0000269|PubMed:31790666, ECO:0000269|PubMed:32902915}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
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:12177166, PubMed:32322062, PubMed:8402897). 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:12177166, PubMed:8402897). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:12177166, PubMed:32322062, PubMed:8402897). {ECO:0000250|UniProtKB:Q9WTN3, 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}.
uniprot
proteins
mass_dalton
121675
uniprot
proteins
mutagenesis
MUTAGEN 335; /note="Y->R: Abolished transactivation activity."; /evidence="ECO:0000269|PubMed:12177166"; MUTAGEN 455; /note="S->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 456; /note="D->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 457; /note="S->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 460; /note="D->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 466; /note="D->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 481; /note="G->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 482; /note="M->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 483; /note="L->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 484..487; /note="DRSR->AS: Strong reduction of proteolytic processing in response to low sterol."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 484; /note="D->A: Loss of proteolytic processing in response to low sterol."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 485; /note="R->A: No effect on proteolytic processing."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 527; /note="R->A: Loss of proteolytic processing in response to low sterol. Transcriptionally inactive."; /evidence="ECO:0000269|PubMed:32497488, ECO:0000269|PubMed:8626610
uniprot
proteins
post_translational_modification
PTM: [Sterol regulatory element-binding protein 1]: Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:32322062, PubMed:8626610). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:32322062, PubMed:8626610). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:32322062, PubMed:8626610). 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: [Sterol regulatory element-binding protein 1]: SCAP-free SREBF1 is ubiquitinated by the BCR(ARMC5) complex, leading to its degradation. {ECO:0000269|PubMed:35862218}.; 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}.
uniprot
proteins
protein_family
SREBP family
uniprot
proteins
pubmed
11477106
uniprot
proteins
pubmed
12177166
uniprot
proteins
pubmed
12202038
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
18267114
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
26311497
uniprot
proteins
pubmed
28849786
uniprot
proteins
pubmed
31375868
uniprot
proteins
pubmed
31790666
uniprot
proteins
pubmed
32322062
uniprot
proteins
pubmed
32497488
uniprot
proteins
pubmed
32902915
uniprot
proteins
pubmed
35862218
uniprot
proteins
pubmed
7759101
uniprot
proteins
pubmed
8402897
uniprot
proteins
pubmed
8626610
uniprot
proteins
pubmed
9634703
uniprot
proteins
sequence_length
1147
uniprot
proteins
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:0000305|PubMed:26311497}; 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}.
uniprot
proteins
transmembrane_region
TRANSMEM 488..508; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 548..568; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins