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FLASH GENE
Symbol SREBF2 contributors: mct/ - updated : 30-12-2015
HGNC name sterol regulatory element binding transcription factor 2
HGNC id 11290
Location 22q13.2      Physical location : 42.229.105 - 42.302.373
Synonym name class D basic helix-loop-helix protein 2
Synonym symbol(s) SREBP2, bHLHd2
DNA
TYPE functioning gene
STRUCTURE 74.23 kb     19 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor
motif
text structure SRE-1, NF-Y binding elements
MAPPING cloned Y linked N status confirmed
Map cen - D22S276 - D22S1157 - SREBF2 - D22S1178 - D22S1041 - qter
Physical map
RANGAP1 22q13.1 Ran GTPase activating protein 1 RoXaN 22q13.2 ubiquitous tetratricopeptide containing protein RoXaN TEF 22q13.1 thyrotrophic embryonic factor TOB2 22q13.2 transducer of ERBB2, 2 PHF5A 22q13.3 PHD finger protein 5A ACO2 22q13.1 aconitase 2, mitochondrial RPC8 22q13.2 RNA polymerase III subunit RPC8 PIPPIN 22q13.2-q13.31 RNA-binding protein pippin PMM1 22q13.2 phosphomannomutase 1 D15Wsu75e 22q13.2 DNA segment, Chr 15, Wayne State University 75, expressed G22P1 22q13.1 thyroid autoantigen 70kDa (Ku antigen) NHP2L1 22q13.2-q13.1 NHP2 non-histone chromosome protein 2-like 1 (S. cerevisiae) FLJ23584 22q13.2 hypothetical protein FLJ23584 HMG17L2 22q13.2 high-mobility group (nonhistone chromosomal) protein 17-like 2 MGC40042 22q13.2 hypothetical protein MGC40042 FLJ22349 22q13.2 hypothetical protein FLJ22349 SREBF2 22q13.2 sterol regulatory element binding transcription factor 2 TNFRSF13C 22q13.1-q13.31 tumor necrosis factor receptor superfamily, member 13C C22orf18 22q13.2-q13.31 chromosome 22 open reading frame 18 SEPT3 22q13.2 septin 3 MGC26816 22q13.31 hypothetical protein MGC26816 NAGA 22q13.2 N-acetylgalactosaminidase, alpha- LOC150368 22q13.31 hypothetical protein LOC150368 LOC91689 22q13.31 hypothetical gene supported by AL449243 NDUFA6 22q13.2 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 6, 14kDa LOC246785 22q13.2 PTD004 pseudogene CYP2D8P2 22q11.22-q11.23 cytochrome P450, family 2, subfamily D, polypeptide 8 pseudogene 2 CYP2D8P1 22q13.2-q13.31 cytochrome P450, family 2, subfamily D, polypeptide 8 pseudogene 1 TCF20 22q13.3 transcription factor 20 (AR1) LOC388906 22 hypothetical gene supported by BC039496
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
19 - 4325 123.56 1141 - 1997 9070916
- polyA site 5200 - 1141 pancreas Miserez
- - - - - - Hua (1996)
form encoded by the "a" class exons (exons 18a and 19a) undergoing sterol-regulated cleavage
- - - - - - Hua (1996)
form encoded by the "c" class exons (18c and 19c) is cleaved less efficiently and is not suppressed by sterols
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx   highly
Lymphoid/Immunelymph node   highly
Skin/Tegumentskin   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • NH2 terminal transcription domain
  • a basic helix-loop-helix (bHLH), leucine zipper
  • a middle hydrophobic region with two transmembrane segments (2TM)
  • a site of sterol-regulated cleavage as the Leu522-Ser523 bond in the middle of the 31-AA hydrophilic loop that projects into the lumen of the endoplasmic reticulum and nuclear envelope
  • a C terminal regulatory domain
    • mono polymer dimer
    HOMOLOGY
    Homologene
    FAMILY
  • basic helix loop helix (BHLH) trancription factors family
  • SREBP family
    • CATEGORY regulatory , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • released from ER to Golgi when sterol levels are low
  • attached to the endoplasmic reticulum (ER) and nuclear envelope by a hairpin domain consisting of two transmembrane regions connected by a short lumenal loop of approximately 30 hydrophilic AAs
    • basic FUNCTION
  • controlling cholesterol homeostasis, key protein regulating cholesterol synthesis and uptake
  • transcriptional regulator, moving from the endoplasmic reticulum to the Golgi in the absence of sterols
  • having a function in endothelial cells in addition to its role in cholesterol uptake and biosynthesis
  • playing a role in the loss of sterol feedback regulation in cancer cells
  • a crucial mediator of the effects of SIRT2 on metabolism)
  • SREBF2 directly activates autophagy genes during cell-sterol depletion, conditions known to induce both autophagy and nuclear SREBF2 levels
  • SREBF2, which can be modulated by the impairment of cerebral cholesterol homeostasis, has a direct role on BACE1 expression and may be involved in Alzheimer disease progression
  • master transcriptional regulator of cholesterol synthesis, that diverts acetyl-CoA into cholesterol synthesis and may thus reduce respiration
  • is a basic helix-loop-helix-leucine zipper transcription factor that positively regulates transcription of target genes involved in cholesterol metabolism
  • enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of SREBF2
  • is a key molecule in aggravating proinflammatory responses in endothelial cells and promoting atherosclerosis
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
  • complexing with SCAP, SREBF1 and importin beta (KPNB1) (forms a tight complex with SCAP in the ER membrane)
    • INTERACTION
    DNA binding to sterol regulatory element
    RNA
    small molecule
    protein
  • cleaved by MBTPS1 in the ER luminal loop between the two membrane spanning regions, initiating the two-step proteolytic process by which the N terminal of SREBF is translocated to nucleus
  • KPNB1
  • down-regulating ABCA1 in vascular endothelial cells
  • interacting with HNF4A (potentiates the SREBP functions and stimulates expression of SREBP-responsive genes in enterohepatic cells)
  • RNF139 hinders SREBPF2 processing through interaction with SREBPF2 and SCAP, regulating its own turnover rate by means of its E3 ubiquitin ligase activity
  • SREBF2, a key transcription factor of cholesterol synthesis, interacted with the AACS promoter was increased during neurite outgrowth
  • sterol sensor SCAP is a key regulator of SREBF2, the major transcription factor controlling cholesterol synthesis
  • SIRT6 is a critical factor for SREBF2 gene regulation
  • multimeric ER proteins ERLIN1 and ERLIN2 are additional SREBF1, SREBF2 regulators
  • SREBPF2 negatively regulates the FXR-mediated transcriptional activation of the FGF19 gene in human intestinal cells
  • FOXO4 interacts with SREBF2 and EPAS1 to modulate CYP51A1 promoter activity
  • SREBF1, SREBF2 actively prevents premature recycling of SCAP-SREBF until initiation of SREBF cleavage
  • HMGCR is a target gene of SREBF2, and luteolin modulates HMGCR transcription by decreasing the expression and nuclear translocation of SREBF2
    • cell & other
    REGULATION
    Other regulated by thyroid hormone
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in hypercholesterolemia
    Susceptibility
  • to vascular dementia
  • to osteoarthritis (OA)
    • Variant & Polymorphism SNP
  • SNP increasing the risk of vascular dementia
  • association of SREBF2 with OA pathogenesis
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheroma 
    targeting SREBF2-inflammasome pathways can be a therapeutic strategy for attenuating atherosclerosis
    ANIMAL & CELL MODELS