This gene encodes a member of the a ubiquitously expressed transcription factor that controls cholesterol homeostasis by regulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain and binds the sterol regulatory element 1 motif. Alternate splicing results in multiple transcript variants. [provided b... See more...

Aliases for SREBF2 Gene

Aliases for SREBF2 Gene

  • Sterol Regulatory Element Binding Transcription Factor 2 2 3 5
  • Sterol Regulatory Element-Binding Protein 2 3 4
  • Class D Basic Helix-Loop-Helix Protein 2 3 4
  • SREBP-2 3 4
  • SREBP2 3 4
  • BHLHd2 3 4
  • Sterol Regulatory Element-Binding Transcription Factor 2 4
  • BHLHD2 4

External Ids for SREBF2 Gene

Previous GeneCards Identifiers for SREBF2 Gene

  • GC22P038843
  • GC22P040473
  • GC22P040474
  • GC22P040475
  • GC22P040553
  • GC22P042230
  • GC22P025194
  • GC22P042231
  • GC22P042244
  • GC22P042261
  • GC22P042273
  • GC22P042287

Summaries for SREBF2 Gene

Entrez Gene Summary for SREBF2 Gene

  • This gene encodes a member of the a ubiquitously expressed transcription factor that controls cholesterol homeostasis by regulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain and binds the sterol regulatory element 1 motif. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneCards Summary for SREBF2 Gene

SREBF2 (Sterol Regulatory Element Binding Transcription Factor 2) is a Protein Coding gene. Diseases associated with SREBF2 include Atherosclerosis Susceptibility and Avascular Necrosis. Among its related pathways are Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) and Chks in Checkpoint Regulation. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein dimerization activity. An important paralog of this gene is SREBF1.

UniProtKB/Swiss-Prot Summary for SREBF2 Gene

  • Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.

Gene Wiki entry for SREBF2 Gene

Additional gene information for SREBF2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SREBF2 Gene

Genomics for SREBF2 Gene

GeneHancer (GH) Regulatory Elements for SREBF2 Gene

Promoters and enhancers for SREBF2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SREBF2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SREBF2

Top Transcription factor binding sites by QIAGEN in the SREBF2 gene promoter:
  • ATF6
  • C/EBPalpha
  • CREB
  • deltaCREB
  • GR
  • GR-alpha
  • LCR-F1
  • STAT5A

Genomic Locations for SREBF2 Gene

Genomic Locations for SREBF2 Gene
chr22:41,833,079-41,907,308
(GRCh38/hg38)
Size:
74,230 bases
Orientation:
Plus strand
chr22:42,229,106-42,303,312
(GRCh37/hg19)
Size:
74,207 bases
Orientation:
Plus strand

Genomic View for SREBF2 Gene

Genes around SREBF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SREBF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SREBF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SREBF2 Gene

Proteins for SREBF2 Gene

  • Protein details for SREBF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12772-SRBP2_HUMAN
    Recommended name:
    Sterol regulatory element-binding protein 2
    Protein Accession:
    Q12772
    Secondary Accessions:
    • Q05BD5
    • Q6GTH7
    • Q86V36
    • Q9UH04

    Protein attributes for SREBF2 Gene

    Size:
    1141 amino acids
    Molecular mass:
    123688 Da
    Quaternary structure:
    • Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA. Component of SCAP/SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts (via C-terminal domain) with RNF139.
    SequenceCaution:
    • Sequence=AAH51799.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SREBF2 Gene

    Alternative splice isoforms for SREBF2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SREBF2 Gene

Post-translational modifications for SREBF2 Gene

  • At low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER. In the Golgi complex SREBPs are cleaved sequentially by site-1 and site-2 protease. 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 and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7.
  • Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.
  • Ubiquitination at Lys363, Lys386, Lys660, Lys768, Lys782, Lys805, Lys907, Lys918, Lys934, Lys989, and Lys1067
  • Modification sites at PhosphoSitePlus

Other Protein References for SREBF2 Gene

No data available for DME Specific Peptides for SREBF2 Gene

Domains & Families for SREBF2 Gene

Gene Families for SREBF2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Transcription factors

Protein Domains for SREBF2 Gene

Blocks:
  • Basic helix-loop-helix dimerization domain bHLH
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SREBF2 Gene

GenScript: Design optimal peptide antigens:
  • Sterol regulatory element binding transcription factor 2 (B1AHQ5_HUMAN)
  • SREBF2 protein (Q05BD5_HUMAN)
  • Sterol regulatory element-binding transcription factor 2 (SRBP2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q12772

UniProtKB/Swiss-Prot:

SRBP2_HUMAN :
  • Belongs to the SREBP family.
Family:
  • Belongs to the SREBP family.
genes like me logo Genes that share domains with SREBF2: view

Function for SREBF2 Gene

Molecular function for SREBF2 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.
GENATLAS Biochemistry:
sterol regulatory element binding protein 2,controlling cholesterol homeostasis

Phenotypes From GWAS Catalog for SREBF2 Gene

Gene Ontology (GO) - Molecular Function for SREBF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000247 NOT C-8 sterol isomerase activity IDA 12941800
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 15358760
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IDA 15358760
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with SREBF2: view
genes like me logo Genes that share phenotypes with SREBF2: view

Animal Model Products

CRISPR Products

Targeted motifs for SREBF2 Gene
HOMER Transcription Factor Regulatory Elements motif SREBF2
  • Consensus sequence: CGGTCACGCCAC Submotif: canonical Cell Type: HepG2 GEO ID: GSE31477

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SREBF2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models and Transcription Factor Targets for SREBF2 Gene

Localization for SREBF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SREBF2 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicle, COPII-coated vesicle membrane; Multi-pass membrane protein. Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols.
[Processed sterol regulatory element-binding protein 2]: Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SREBF2 gene
Compartment Confidence
nucleus 5
endoplasmic reticulum 5
golgi apparatus 5
cytosol 4
extracellular 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
endosome 2
lysosome 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
  • Nucleoplasm (3)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SREBF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IDA,IBA 12202038
GO:0005654 nucleoplasm IDA,TAS --
GO:0005737 cytoplasm IDA,IEA 12941800
genes like me logo Genes that share ontologies with SREBF2: view

Pathways & Interactions for SREBF2 Gene

genes like me logo Genes that share pathways with SREBF2: view

SIGNOR curated interactions for SREBF2 Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for SREBF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 15358760
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006629 lipid metabolic process TAS 7903453
GO:0008202 steroid metabolic process IEA --
GO:0008203 cholesterol metabolic process IEA --
genes like me logo Genes that share ontologies with SREBF2: view

Drugs & Compounds for SREBF2 Gene

(16) Drugs for SREBF2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(10) Additional Compounds for SREBF2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SREBF2: view

Transcripts for SREBF2 Gene

mRNA/cDNA for SREBF2 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SREBF2

Alternative Splicing Database (ASD) splice patterns (SP) for SREBF2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12a · 12b · 12c ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b · 18c ^
SP1:
SP2: - - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8: - - - -
SP9:
SP10: -
SP11: -
SP12:
SP13:
SP14:

ExUns: 19a · 19b ^ 20a · 20b ^ 21 ^ 22a · 22b ^ 23 ^ 24 ^ 25 ^ 26 ^ 27a · 27b
SP1: -
SP2:
SP3: - - - -
SP4: - - - -
SP5:
SP6:
SP7:
SP8:
SP9: - - -
SP10:
SP11:
SP12: -
SP13:
SP14:

Relevant External Links for SREBF2 Gene

GeneLoc Exon Structure for
SREBF2

Expression for SREBF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SREBF2 Gene

Protein differential expression in normal tissues from HIPED for SREBF2 Gene

This gene is overexpressed in Platelet (29.9), Fetal testis (19.3), Tonsil (9.5), and Testis (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SREBF2 Gene



Protein tissue co-expression partners for SREBF2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SREBF2

SOURCE GeneReport for Unigene cluster for SREBF2 Gene:

Hs.443258

mRNA Expression by UniProt/SwissProt for SREBF2 Gene:

Q12772-SRBP2_HUMAN
Tissue specificity: Ubiquitously expressed in adult and fetal tissues.

Evidence on tissue expression from TISSUES for SREBF2 Gene

  • Skin(4.7)
  • Nervous system(4.6)
  • Intestine(3.4)
  • Liver(3.4)
  • Blood(2.9)
  • Eye(2.4)
  • Kidney(2.3)
  • Muscle(2.2)
  • Pancreas(2.2)
  • Heart(2)
  • Lung(2)
genes like me logo Genes that share expression patterns with SREBF2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SREBF2 Gene

Orthologs for SREBF2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SREBF2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SREBF2 31 30
  • 98.98 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SREBF2 31 30
  • 89.18 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SREBF2 31 30
  • 87.51 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Srebf2 30
  • 87.5 (n)
mouse
(Mus musculus)
Mammalia Srebf2 17 31 30
  • 87.35 (n)
oppossum
(Monodelphis domestica)
Mammalia SREBF2 31
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SREBF2 31
  • 78 (a)
OneToOne
chicken
(Gallus gallus)
Aves SREBF2 31 30
  • 76.93 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SREBF2 31
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia srebf2 30
  • 66.85 (n)
Str.15699 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.12927 30
zebrafish
(Danio rerio)
Actinopterygii srebf2 31 30
  • 60.75 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta HLH106 31 32
  • 27 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sbp-1 31
  • 20 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9273 31
  • 33 (a)
OneToMany
Species where no ortholog for SREBF2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SREBF2 Gene

ENSEMBL:
Gene Tree for SREBF2 (if available)
TreeFam:
Gene Tree for SREBF2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SREBF2: view image

Paralogs for SREBF2 Gene

Paralogs for SREBF2 Gene

(3) SIMAP similar genes for SREBF2 Gene using alignment to 4 proteins:

  • SRBP2_HUMAN
  • G3V0I8_HUMAN
  • H0Y7E5_HUMAN
  • Q05BD5_HUMAN
genes like me logo Genes that share paralogs with SREBF2: view

Variants for SREBF2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SREBF2 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
711089 Benign: not provided 41,893,295(+) C/G INTRON_VARIANT
727429 Likely Benign: not provided 41,905,430(+) C/A INTRON_VARIANT
748903 Likely Benign: not provided 41,898,716(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
774750 Benign: not provided 41,875,359(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
777727 Benign: not provided 41,868,771(+) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for SREBF2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SREBF2 Gene

Variant ID Type Subtype PubMed ID
esv3558184 CNV deletion 23714750
esv3893484 CNV loss 25118596
nsv1057208 CNV gain 25217958
nsv191436 CNV insertion 16902084
nsv508736 CNV insertion 20534489
nsv955162 CNV deletion 24416366

Variation tolerance for SREBF2 Gene

Residual Variation Intolerance Score: 20% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.04; 92.12% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SREBF2 Gene

Human Gene Mutation Database (HGMD)
SREBF2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SREBF2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SREBF2 Gene

Disorders for SREBF2 Gene

MalaCards: The human disease database

(16) MalaCards diseases for SREBF2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
atherosclerosis susceptibility
  • aths
avascular necrosis
  • avn
familial hypercholesterolemia
  • fh
fatty liver disease
  • steatosis of liver
familial hyperlipidemia
  • familial hyperlipoproteinemia
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for SREBF2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SREBF2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SREBF2 Gene

Publications for SREBF2 Gene

  1. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. (PMID: 7903453) Hua X … Wang X (Proceedings of the National Academy of Sciences of the United States of America 1993) 2 3 4 23 54
  2. Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population. (PMID: 19740467) Liu X … Gu D (Atherosclerosis 2010) 3 23 41 54
  3. The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage. (PMID: 19706601) Irisawa M … Sato R (The Journal of biological chemistry 2009) 3 4 23 54
  4. Polymorphism of the sterol regulatory element-binding protein-2 gene and its association with serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. (PMID: 19263511) Yaju D … Dezhai Y (The American journal of the medical sciences 2009) 3 23 41 54
  5. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death. (PMID: 19116028) Fan YM … Lehtimäki T (Thrombosis journal 2008) 3 23 41 54

Products for SREBF2 Gene

  • Signalway ELISA kits for SREBF2
  • Signalway Proteins for SREBF2

Sources for SREBF2 Gene