SREBF2
entrez
6721
canonical
uniprot
Q12772
canonical
ensembl
ENSG00000198911
resolver
ensp
ENSP00000354476
resolver
ensp
ENSP00000543372
resolver
ensp
ENSP00000740700
resolver
ensp
ENSP00000782114
resolver
genesymbol
SREBF2
resolver
genesymbol_syn
BHLHD2
resolver
genesymbol_syn
SREBP2
resolver
hgnc
HGNC:11290
resolver
uniprot
Q05BD5
resolver
uniprot
Q6GTH7
resolver
uniprot
Q86V36
resolver
uniprot
Q9UH04
resolver
uniprot_entry
SRBP2_HUMAN
resolver
uniprot_sec
Q05BD5
resolver
uniprot_sec
Q6GTH7
resolver
uniprot_sec
Q86V36
resolver
uniprot_sec
Q9UH04
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:Q3U1N2}.
uniprot
proteins
amino_acid_sequence
MDDSGELGGLETMETLTELGDELTLGDIDEMLQFVSNQVGEFPDLFSEQLCSSFPGSGGSGSSSGSSGSSSSSSNGRGSSSGAVDPSVQRSFTQVTLPSFSPSAASPQAPTLQVKVSPTSVPTTPRATPILQPRPQPQPQPQTQLQQQTVMITPTFSTTPQTRIIQQPLIYQNAATSFQVLQPQVQSLVTSSQVQPVTIQQQVQTVQAQRVLTQTANGTLQTLAPATVQTVAAPQVQQVPVLVQPQIIKTDSLVLTTLKTDGSPVMAAVQNPALTALTTPIQTAALQVPTLVGSSGTILTTMPVMMGQEKVPIKQVPGGVKQLEPPKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNKLLKGIDLGSLVDNEVDLKIEDFNQNVLLMSPPASDSGSQAGFSPYSIDSEPGSPLLDDAKVKDEPDSPPVALGMVDRSRILLCVLTFLCLSFNPLTSLLQWGGAHDSDQHPHSGSGRSVLSFESGSGGWFDWMMPTLLLWLVNGVIVLSVFVKLLVHGEPVIRPHSRSSVTFWRHRKQADLDLARGDFAAAAGNLQTCLAVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKKVFQCRRATPATEAGFEDEAKTSARDAALAYHRLHQLHITGKLPAGSACSDVHMALCAVNLAECAEEKIPPSTLVEIHLTAAMGLKTRCGGKLGFLASYFLSRAQSLCGPEHSAVPDSLRWLCHPLGQKFFMERSWSVKSAAKESLYCAQRNPADPIAQVHQAFCKNLLERAIESLVKPQAKKKAGDQEEESCEFSSALEYLKLLHSFVDSVGVMSPPLSRSSVLKSALGPDIICRWWTSAITVAISWLQGDDAAVRSHFTKVERIPKALEVTESPLVKAIFHACRAMHASLPGKADGQQSSFCHCERASGHLWSSLNVSGATSDPALNHVVQLLTCDLLLSLRTALWQKQASASQAVGETYHASGAELAGFQRDLGSLRRLAHSFRPAYRKVFLHEATVRLMAGASPTRTHQLLEHSLRRRTTQSTKHGEVDAWPGQRERATAILLACRHLPLSFLSSPGQRAVLLAEAARTLEKVGDRRSCNDCQQMIVKLGGGTAIAAS
uniprot
proteins
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:12177166, PubMed:7903453). 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}.
uniprot
proteins
mass_dalton
123688
uniprot
proteins
mutagenesis
MUTAGEN 342; /note="Y->R: Abolished transactivation activity."; /evidence="ECO:0000269|PubMed:12177166"; MUTAGEN 478..481; /note="DRSR->AAAA: Loss of cleavage by S2P."; /evidence="ECO:0000269|PubMed:8626610, ECO:0000269|PubMed:9651382"; MUTAGEN 478..481; /note="DRSR->AS: Loss of cleavage by S2P."; /evidence="ECO:0000269|PubMed:8626610, ECO:0000269|PubMed:9651382"; MUTAGEN 478; /note="D->A: No effect on proteolytic processing in response to low sterol."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 479..481; /note="RSR->AAA: Loss of cleavage by S2P."; /evidence="ECO:0000269|PubMed:9651382"; MUTAGEN 479; /note="R->A: No effect on cleavage by S2P."; /evidence="ECO:0000269|PubMed:9651382"; MUTAGEN 481; /note="R->A: No effect on cleavage by S2P."; /evidence="ECO:0000269|PubMed:9651382"; MUTAGEN 484..485; /note="LC->FF: No effect on cleavage by S2P."; /evidence="ECO:0000269|PubMed:9651382"; MUTAGEN 484; /note="L->A: No effect on cleavage by S2P."; /evidence="ECO:0000269|PubMed:9651382"; MUTAGEN 485; /note="C->A: No effect on cleavage by S2P."; /evidence="ECO:0000269|PubMed:9651382"; MUTAGEN 490..491; /note="LC->NP: Restores cleavage by S2P; when associated with F-495 and L-496. No effect on site of cleavage by S2P."; /evidence="ECO:0000269|PubMed:10805775"; MUTAGEN 495..496; /note="NP->FL: Loss of cleavage by S2P."; /evidence="ECO:0000269|PubMed:10805775"; MUTAGEN 495; /note="N->F: Reduced cleavage by S2P."; /evidence="ECO:0000269|PubMed:10805775"; MUTAGEN 496; /note="P->L: Reduced cleavage by S2P."; /evidence="ECO:0000269|PubMed:10805775"; MUTAGEN 519; /note="R->A: Loss of proteolytic processing in response to low sterol."; /evidence="ECO:0000269|PubMed:8626610"; MUTAGEN 519; /note="R->K: No effect on proteolytic processing in response to low sterol."; /evidence="ECO:0000269|PubMed:8626610
uniprot
proteins
post_translational_modification
PTM: [Sterol regulatory element-binding protein 2]: Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:10805775, PubMed:32322062, PubMed:8626610, PubMed:9651382). 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:10805775, PubMed:9651382). 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: [Sterol regulatory element-binding protein 2]: SCAP-free SREBF2 is ubiquitinated by the BCR(ARMC5) complex, leading to its degradation. {ECO:0000269|PubMed:35862218}.; 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}.
uniprot
proteins
protein_family
SREBP family
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
10805775
uniprot
proteins
pubmed
11477106
uniprot
proteins
pubmed
12177166
uniprot
proteins
pubmed
12202038
uniprot
proteins
pubmed
14645851
uniprot
proteins
pubmed
15461802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
19706601
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
26311497
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28849786
uniprot
proteins
pubmed
32322062
uniprot
proteins
pubmed
35120642
uniprot
proteins
pubmed
35862218
uniprot
proteins
pubmed
7903453
uniprot
proteins
pubmed
8402897
uniprot
proteins
pubmed
8626610
uniprot
proteins
pubmed
8643593
uniprot
proteins
pubmed
9651382
uniprot
proteins
sequence_length
1141
uniprot
proteins
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:0000269|PubMed:26311497, ECO:0000269|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:26311497, 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}.
uniprot
proteins
transmembrane_region
TRANSMEM 480..500; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 534..554; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins