Q3U1N2 · SRBP2_MOUSE

  • Protein
    Sterol regulatory element-binding protein 2
  • Gene
    Srebf2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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 (By similarity).
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:16100574, PubMed:9616204).

Processed sterol regulatory element-binding protein 2

Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis (PubMed:9616204).
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') (By similarity).
Regulates transcription of genes related to cholesterol synthesis pathway (PubMed:9616204).

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.

Features

Showing features for site.

TypeIDPosition(s)Description
Site457-458Cleavage; by caspase-3 and caspase-7
Site473-474Cleavage; by MBTPS2
Site511-512Cleavage; by MBTPS1

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentdendrite
Cellular ComponentER to Golgi transport vesicle membrane
Cellular ComponentGolgi membrane
Cellular Componentmembrane
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular ComponentSREBP-SCAP-Insig complex
Molecular Functionchromatin binding
Molecular FunctionDNA binding
Molecular FunctionDNA-binding transcription factor activity
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription repressor activity, RNA polymerase II-specific
Molecular FunctionE-box binding
Molecular Functionprotein dimerization activity
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Functionsequence-specific DNA binding
Molecular Functiontranscription cis-regulatory region binding
Biological Processcellular response to low-density lipoprotein particle stimulus
Biological Processcellular response to starvation
Biological Processcholesterol homeostasis
Biological Processcholesterol metabolic process
Biological Processnegative regulation of cholesterol efflux
Biological Processpositive regulation of cholesterol biosynthetic process
Biological Processpositive regulation of cholesterol storage
Biological Processpositive regulation of DNA-templated transcription
Biological Processpositive regulation of miRNA transcription
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of DNA-templated transcription
Biological Processregulation of Notch signaling pathway
Biological Processresponse to hormone
Biological ProcessSREBP signaling pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Sterol regulatory element-binding protein 2
  • Short names
    SREBP-2
  • Alternative names
    • Sterol regulatory element-binding transcription factor 2
  • Cleaved into 1 chains

Gene names

    • Name
      Srebf2
    • Synonyms
      Srebp2

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • Swiss albino
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q3U1N2
  • Secondary accessions
    • Q925C2
    • Q9ESZ4

Proteomes

Organism-specific databases

Subcellular Location

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: At high sterol concentrations, the SCAP-SREBP is retained in the endoplasmic reticulum (By similarity).
Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed (By similarity).

Processed sterol regulatory element-binding protein 2

Nucleus
Note: Transported into the nucleus with the help of importin-beta (PubMed:10397761, PubMed:11283257).
Dimerization of the bHLH domain is a prerequisite for importin beta-dependent nuclear import (PubMed:10397761, PubMed:11283257).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-470Cytoplasmic
Transmembrane471-491Helical
Topological domain492-522Lumenal
Transmembrane523-543Helical
Topological domain544-1130Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Death around embryonic day 7-8.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis369-383In L1.2.3A mutant; reduced affinity for importin-beta.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 52 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, cross-link, modified residue.

TypeIDPosition(s)Description
ChainPRO_00003170601-473Processed sterol regulatory element-binding protein 2
ChainPRO_00003170591-1130Sterol regulatory element-binding protein 2
Cross-link453Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue1087Phosphoserine

Post-translational modification

Sterol regulatory element-binding protein 2

Processed in the Golgi apparatus, releasing the protein from the membrane. At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum. In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases. 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. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. Cleavage and activation is induced by mediated cholesterol efflux.
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.

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.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Sterol regulatory element-binding protein 2

Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane. Interacts (via C-terminal domain) with RNF139.

Processed sterol regulatory element-binding protein 2

Homodimer; efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein (PubMed:11283257).
Interacts with LMNA (PubMed:11929849).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q3U1N2Srf Q9JM733EBI-645275, EBI-493266

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region1-50Transcriptional activation (acidic)
Compositional bias53-106Polar residues
Region53-133Disordered
Compositional bias115-131Pro residues
Region226-480Interaction with LMNA
Domain319-369bHLH
Region369-390Leucine-zipper

Sequence similarities

Belongs to the SREBP family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q3U1N2-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    1,130
  • Mass (Da)
    122,911
  • Last updated
    2008-02-05 v2
  • Checksum
    052E858B0C3945F2
MDESSELGVLETMETLTELGDELTLGDIDEMLQFVSNQVGEFPDLFSEQLCSSFPGGGSNGGSGNNSSGRGNNGGATDPAVQRSFSQVPLSTFSPSAASPQAPALQVKVSPTPPRATPVLQPRPQPQPQPPAQLQQQTVMITPTFSTAPQTRIIQQPLIYQNAATSFQVLQPQVQSLVTSPQVQPVTIQQQVQTVQAQRVLTQTANGTLQTLAPATVQTVAAPQVQQVPVLVQPQIIKTDSLVLTTLKTDGSPVMAAVQNPALTALTAPIQTAALQVPTLVGSNGTILTTMPVMMGQEKVPIKQVPGGVKQLDPPKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGTDAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNKLLKGIDLGSLVDSDVDLKIDDFNQNVLLMSPPASDSGSQAGFSPYSIDSEPGSPLLDDAKVKDEPDSPPVALGMVDRSRILLCVLTFLGLSFNPLTSLLQWGGAHNTDQHPYSGSGRSVLSLESGAGGWFDWMVPTLLLWLVNGVIVLSVFVKLLVHGEPVIRPHSRPSVTFWRHRKQADLDLAKGDFAAAAANLQTCLSVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKKVFQRWRATPATAAGFEDEAKSSARDAALAYHRLHQLHITGKLPAGSACSDVHMALCAVNLAECAEEKILPSTLIEIHLTAAMGLKTRCGGKLGFLASYFLNRAQSLCGPEHSTVPDSLRWLCHPLGQKFFMERSWSIKSAAKESLYCAQRSPADPIAQVHQAFCKNLLERAVESLVKPQAKKKAGDQEEESCEFSSALEYLKLLHSFVDSVGFVTSPFSSSSVLRSALGPDVICRWWTSAVTMAISWLQGDDAAVRSRFTEVERVPKALEVTESPLVKAVFYTCRAMHASLSGKADGQQNSFCHCERASGHLWSSLNVSGTTSDPSLNHVIQLFTCDLLLSLRTALWQKQASASQLLGETYHASGTELAGFQRDLGSLRRLAHSFRPAYRKVFLHEATVRLMAGASPTRTHQLLEHSLRRRPTQNTKHGEVDTWPGQRERATAILLACRHLPLSFLSSPGQRAVLLAEAARTLEKVGDRRSCSDCQQMIVKLGGGTAIAAS

Q3U1N2-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 57-96: Missing
    • 1105-1130: VGDRRSCSDCQQMIVKLGGGTAIAAS → SCEDEGKTDCSELLPAKAFGSFRASRTMGRAP

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A2R8VHQ9A0A2R8VHQ9_MOUSESrebf2247
A0A2R8VH82A0A2R8VH82_MOUSESrebf2193

Features

Showing features for compositional bias, alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Compositional bias53-106Polar residues
Alternative sequenceVSP_05265857-96in isoform 2
Compositional bias115-131Pro residues
Sequence conflict334in Ref. 3; AAK54763
Sequence conflict621in Ref. 3; AAK54763
Sequence conflict698in Ref. 3; AAK54763
Sequence conflict899in Ref. 3; AAK54763
Alternative sequenceVSP_0526591105-1130in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK155857
EMBL· GenBank· DDBJ
BAE33463.1
EMBL· GenBank· DDBJ
mRNA
AC105358
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AF374267
EMBL· GenBank· DDBJ
AAK54763.1
EMBL· GenBank· DDBJ
mRNA
AF289715
EMBL· GenBank· DDBJ
AAG01859.2
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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