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Protein

Sterol regulatory element-binding protein 2

Gene

Srebf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-MMU-2426168. Activation of gene expression by SREBF (SREBP).

Names & Taxonomyi

Protein namesi
Recommended name:
Sterol regulatory element-binding protein 2
Short name:
SREBP-2
Alternative name(s):
Sterol regulatory element-binding transcription factor 2
Cleaved into the following chain:
Gene namesi
Name:Srebf2Imported
Synonyms:Srebp2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:107585. Srebf2.

Subcellular locationi

  • Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
  • Golgi apparatus membrane By similarity; Multi-pass membrane protein By similarity
  • Cytoplasmic vesicleCOPII-coated vesicle membrane By similarity; Multi-pass membrane protein By similarity

  • Note: Moves from the endoplasmic reticulum to the Golgi in the absence of sterols.By similarity
Processed sterol regulatory element-binding protein 2 :
  • Nucleus PROSITE-ProRule annotationBy similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 470CytoplasmicSequence analysisAdd BLAST470
Transmembranei471 – 491HelicalSequence analysisAdd BLAST21
Topological domaini492 – 522LumenalSequence analysisAdd BLAST31
Transmembranei523 – 543HelicalSequence analysisAdd BLAST21
Topological domaini544 – 1130CytoplasmicSequence analysisAdd BLAST587

GO - Cellular componenti

  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • ER to Golgi transport vesicle membrane Source: UniProtKB-SubCell
  • Golgi membrane Source: UniProtKB-SubCell
  • membrane Source: BHF-UCL
  • nucleoplasm Source: Reactome
  • nucleus Source: BHF-UCL
  • SREBP-SCAP-Insig complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Death around embryonic day 7-8.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003170591 – 1130Sterol regulatory element-binding protein 2Add BLAST1130
ChainiPRO_00003170601 – 473Processed sterol regulatory element-binding protein 2By similarityAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1087PhosphoserineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei457 – 458Cleavage; by caspase-3 and caspase-7By similarity2
Sitei473 – 474Cleavage; by S2PBy similarity2
Sitei511 – 512Cleavage; by S1PBy similarity2

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ3U1N2.
PaxDbiQ3U1N2.
PeptideAtlasiQ3U1N2.
PRIDEiQ3U1N2.

PTM databases

iPTMnetiQ3U1N2.
PhosphoSitePlusiQ3U1N2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000022463.
CleanExiMM_SREBF2.
GenevisibleiQ3U1N2. MM.

Interactioni

Subunit structurei

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 (By similarity). 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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SrfQ9JM733EBI-645275,EBI-493266

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203496. 3 interactors.
IntActiQ3U1N2. 1 interactor.
MINTiMINT-1739369.
STRINGi10090.ENSMUSP00000023100.

Structurei

3D structure databases

ProteinModelPortaliQ3U1N2.
SMRiQ3U1N2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini319 – 369bHLHPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 50Transcriptional activation (acidic)Sequence analysisAdd BLAST50
Regioni226 – 480Interaction with LMNABy similarityAdd BLAST255
Regioni369 – 390Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi95 – 131Pro-richSequence analysisAdd BLAST37
Compositional biasi114 – 233Gln-richSequence analysisAdd BLAST120
Compositional biasi121 – 235Gln-richSequence analysisAdd BLAST115

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2588. Eukaryota.
ENOG410XSVP. LUCA.
GeneTreeiENSGT00390000017651.
HOGENOMiHOG000007091.
HOVERGENiHBG061592.
InParanoidiQ3U1N2.
KOiK09107.
OMAiQEEESCE.
OrthoDBiEOG091G01RE.
PhylomeDBiQ3U1N2.
TreeFamiTF313894.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003006. Ig/MHC_CS.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q3U1N2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDESSELGVL ETMETLTELG DELTLGDIDE MLQFVSNQVG EFPDLFSEQL
60 70 80 90 100
CSSFPGGGSN GGSGNNSSGR GNNGGATDPA VQRSFSQVPL STFSPSAASP
110 120 130 140 150
QAPALQVKVS PTPPRATPVL QPRPQPQPQP PAQLQQQTVM ITPTFSTAPQ
160 170 180 190 200
TRIIQQPLIY QNAATSFQVL QPQVQSLVTS PQVQPVTIQQ QVQTVQAQRV
210 220 230 240 250
LTQTANGTLQ TLAPATVQTV AAPQVQQVPV LVQPQIIKTD SLVLTTLKTD
260 270 280 290 300
GSPVMAAVQN PALTALTAPI QTAALQVPTL VGSNGTILTT MPVMMGQEKV
310 320 330 340 350
PIKQVPGGVK QLDPPKEGER RTTHNIIEKR YRSSINDKII ELKDLVMGTD
360 370 380 390 400
AKMHKSGVLR KAIDYIKYLQ QVNHKLRQEN MVLKLANQKN KLLKGIDLGS
410 420 430 440 450
LVDSDVDLKI DDFNQNVLLM SPPASDSGSQ AGFSPYSIDS EPGSPLLDDA
460 470 480 490 500
KVKDEPDSPP VALGMVDRSR ILLCVLTFLG LSFNPLTSLL QWGGAHNTDQ
510 520 530 540 550
HPYSGSGRSV LSLESGAGGW FDWMVPTLLL WLVNGVIVLS VFVKLLVHGE
560 570 580 590 600
PVIRPHSRPS VTFWRHRKQA DLDLAKGDFA AAAANLQTCL SVLGRALPTS
610 620 630 640 650
RLDLACSLSW NVIRYSLQKL RLVRWLLKKV FQRWRATPAT AAGFEDEAKS
660 670 680 690 700
SARDAALAYH RLHQLHITGK LPAGSACSDV HMALCAVNLA ECAEEKILPS
710 720 730 740 750
TLIEIHLTAA MGLKTRCGGK LGFLASYFLN RAQSLCGPEH STVPDSLRWL
760 770 780 790 800
CHPLGQKFFM ERSWSIKSAA KESLYCAQRS PADPIAQVHQ AFCKNLLERA
810 820 830 840 850
VESLVKPQAK KKAGDQEEES CEFSSALEYL KLLHSFVDSV GFVTSPFSSS
860 870 880 890 900
SVLRSALGPD VICRWWTSAV TMAISWLQGD DAAVRSRFTE VERVPKALEV
910 920 930 940 950
TESPLVKAVF YTCRAMHASL SGKADGQQNS FCHCERASGH LWSSLNVSGT
960 970 980 990 1000
TSDPSLNHVI QLFTCDLLLS LRTALWQKQA SASQLLGETY HASGTELAGF
1010 1020 1030 1040 1050
QRDLGSLRRL AHSFRPAYRK VFLHEATVRL MAGASPTRTH QLLEHSLRRR
1060 1070 1080 1090 1100
PTQNTKHGEV DTWPGQRERA TAILLACRHL PLSFLSSPGQ RAVLLAEAAR
1110 1120 1130
TLEKVGDRRS CSDCQQMIVK LGGGTAIAAS
Length:1,130
Mass (Da):122,911
Last modified:February 5, 2008 - v2
Checksum:i052E858B0C3945F2
GO
Isoform 21 Publication (identifier: Q3U1N2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     57-96: Missing.
     1105-1130: VGDRRSCSDCQQMIVKLGGGTAIAAS → SCEDEGKTDCSELLPAKAFGSFRASRTMGRAP

Note: No experimental confirmation available.Curated
Show »
Length:1,096
Mass (Da):119,913
Checksum:iBCAF1B3BC6845F5B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti334S → F in AAK54763 (PubMed:11929849).Curated1
Sequence conflicti621R → H in AAK54763 (PubMed:11929849).Curated1
Sequence conflicti698L → P in AAK54763 (PubMed:11929849).Curated1
Sequence conflicti899E → K in AAK54763 (PubMed:11929849).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05265857 – 96Missing in isoform 2. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_0526591105 – 1130VGDRR…AIAAS → SCEDEGKTDCSELLPAKAFG SFRASRTMGRAP in isoform 2. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK155857 mRNA. Translation: BAE33463.1.
AC105358 Genomic DNA. No translation available.
AF374267 mRNA. Translation: AAK54763.1.
AF289715 mRNA. Translation: AAG01859.2.
CCDSiCCDS27683.1. [Q3U1N2-1]
RefSeqiNP_150087.1. NM_033218.1. [Q3U1N2-1]
UniGeneiMm.38016.
Mm.9002.

Genome annotation databases

EnsembliENSMUST00000023100; ENSMUSP00000023100; ENSMUSG00000022463. [Q3U1N2-1]
GeneIDi20788.
KEGGimmu:20788.
UCSCiuc007wyi.1. mouse. [Q3U1N2-1]
uc011zwr.1. mouse. [Q3U1N2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK155857 mRNA. Translation: BAE33463.1.
AC105358 Genomic DNA. No translation available.
AF374267 mRNA. Translation: AAK54763.1.
AF289715 mRNA. Translation: AAG01859.2.
CCDSiCCDS27683.1. [Q3U1N2-1]
RefSeqiNP_150087.1. NM_033218.1. [Q3U1N2-1]
UniGeneiMm.38016.
Mm.9002.

3D structure databases

ProteinModelPortaliQ3U1N2.
SMRiQ3U1N2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203496. 3 interactors.
IntActiQ3U1N2. 1 interactor.
MINTiMINT-1739369.
STRINGi10090.ENSMUSP00000023100.

PTM databases

iPTMnetiQ3U1N2.
PhosphoSitePlusiQ3U1N2.

Proteomic databases

MaxQBiQ3U1N2.
PaxDbiQ3U1N2.
PeptideAtlasiQ3U1N2.
PRIDEiQ3U1N2.

Protocols and materials databases

DNASUi20788.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023100; ENSMUSP00000023100; ENSMUSG00000022463. [Q3U1N2-1]
GeneIDi20788.
KEGGimmu:20788.
UCSCiuc007wyi.1. mouse. [Q3U1N2-1]
uc011zwr.1. mouse. [Q3U1N2-2]

Organism-specific databases

CTDi6721.
MGIiMGI:107585. Srebf2.

Phylogenomic databases

eggNOGiKOG2588. Eukaryota.
ENOG410XSVP. LUCA.
GeneTreeiENSGT00390000017651.
HOGENOMiHOG000007091.
HOVERGENiHBG061592.
InParanoidiQ3U1N2.
KOiK09107.
OMAiQEEESCE.
OrthoDBiEOG091G01RE.
PhylomeDBiQ3U1N2.
TreeFamiTF313894.

Enzyme and pathway databases

ReactomeiR-MMU-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-MMU-2426168. Activation of gene expression by SREBF (SREBP).

Miscellaneous databases

ChiTaRSiSrebf2. mouse.
PROiQ3U1N2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022463.
CleanExiMM_SREBF2.
GenevisibleiQ3U1N2. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003006. Ig/MHC_CS.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSRBP2_MOUSE
AccessioniPrimary (citable) accession number: Q3U1N2
Secondary accession number(s): Q925C2, Q9ESZ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: November 2, 2016
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Mice overexpressing processed Srebf2 show preferential activation of cholesterol over fatty acid synthesis in liver and adipose tissue.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.