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Protein

Sterol regulatory element-binding protein 2

Gene

Srebf2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (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 (By similarity).By similarity

GO - Molecular functioni

  • chromatin binding Source: RGD
  • protein dimerization activity Source: InterPro
  • sequence-specific DNA binding Source: MGI

GO - Biological processi

  • aging Source: RGD
  • cholesterol metabolic process Source: UniProtKB-KW
  • lipid biosynthetic process Source: RGD
  • positive regulation of transcription, DNA-templated Source: RGD
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to drug Source: RGD
  • response to hormone Source: RGD
  • response to lead ion Source: RGD
  • response to lipid Source: RGD
  • spermatogenesis Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding
Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transcription, Transcription regulation

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1307751. Srebf2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 473CytoplasmicSequence analysisAdd BLAST473
Transmembranei474 – 494HelicalSequence analysisAdd BLAST21
Topological domaini495 – 525LumenalSequence analysisAdd BLAST31
Transmembranei526 – 546HelicalSequence analysisAdd BLAST21
Topological domaini547 – 1133CytoplasmicSequence analysisAdd BLAST587

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003170611 – 1133Sterol regulatory element-binding protein 2Add BLAST1133
ChainiPRO_00003170621 – 476Processed sterol regulatory element-binding protein 2By similarityAdd BLAST476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki456Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1090PhosphoserineBy 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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei460 – 461Cleavage; by caspase-3 and caspase-7By similarity2
Sitei476 – 477Cleavage; by S2PBy similarity2
Sitei514 – 515Cleavage; by S1PBy similarity2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ3T1I5.
PRIDEiQ3T1I5.

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. 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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000052893.

Structurei

3D structure databases

ProteinModelPortaliQ3T1I5.
SMRiQ3T1I5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini322 – 372bHLHPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 50Transcriptional activation (acidic)Sequence analysisAdd BLAST50
Regioni229 – 483Interaction with LMNABy similarityAdd BLAST255
Regioni372 – 393Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi98 – 134Pro-richSequence analysisAdd BLAST37
Compositional biasi124 – 238Gln-richSequence analysisAdd BLAST115

Sequence similaritiesi

Belongs to the SREBP family.Sequence analysis

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2588. Eukaryota.
ENOG410XSVP. LUCA.
HOGENOMiHOG000007091.
HOVERGENiHBG061592.
InParanoidiQ3T1I5.
KOiK09107.
PhylomeDBiQ3T1I5.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
IPR003006. Ig/MHC_CS.
PfamiView protein in Pfam
PF00010. HLH. 1 hit.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q3T1I5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDENSELGGL ETMETLTELG DELTLGDIDE MLQFVSNQVG EFSDLFSEQL
60 70 80 90 100
CSSFPGGGGG SGSGGTSNNS SGRGTSGGAA DPAVQRSFSQ VPLSTFSPSS
110 120 130 140 150
TSPQAPALQV KVSPTPPRAT PVLQPRPQPQ PQPPAQLQQQ TVMITPTFST
160 170 180 190 200
APQTRIIQQP LIYQNAATSF QVLQPQVQSL VTSSQVQPVT IQQQVQTVQA
210 220 230 240 250
QRVLTQTANG TLQTLAPATV QTVATPQVQQ VPVLVQPQII KTDSLVLTTL
260 270 280 290 300
KTDGSPVMAA VQNPALTALT APIQTAALQV PTLVGSNGAI LTTMPVMMGQ
310 320 330 340 350
EKVPIKQVPG GVKQLEPPKE GERRTTHNII EKRYRSSIND KIIELKDLVM
360 370 380 390 400
GTDAKMHKSG VLRKAIDYIK YLQQVNHKLR QENMVLKLAN QKNKLLKGID
410 420 430 440 450
LGSLVDSDVD LKIDDFNQNV LLMSPPASDS GSQAGFSPYS IDSEPGSPLL
460 470 480 490 500
DDAKVKDEPD SPPVALGMVD RSRILLCVLT FLGLSFNPLT SLLQWGGAHN
510 520 530 540 550
PDQHPYSGSG RNVLSLESGS GGWFDWMMPT LLLWLLNGVI VLSVFVKLLV
560 570 580 590 600
HGEPVIRPHS RSSVTFWRHR KQADLDLAKG DFAAAAANLQ TCLSVLGRAL
610 620 630 640 650
PTSRLDLACS LSWNVIRYSL QKLRLVRWLL KKVFQRWRAT PATAAGFEDE
660 670 680 690 700
AKSSARDAAL AYHRLHQLHI TGKLPAGSAC SDVHMALCAV NLAECAEEKI
710 720 730 740 750
PPSTLVEIHL TAAMGLKTRC GGKLGFLASY FLNRAQSLCG PEHSAVPDSL
760 770 780 790 800
RWLCHPLGQK FFMERSWSIK SAAKDSLYCA QRNPADPIAQ VHQAFCKHLL
810 820 830 840 850
ERAVEALVKP QAKKKAGDRE EESCEFSSAL EFLKLLHSFV DSVGFVASPF
860 870 880 890 900
SSSSVLRSAL GPDVVCRWWT SAITVAISWL QGDDAAVRSH FTEVERVPKA
910 920 930 940 950
LEVTESPLVK AVFYACRAMH ASLSGKADGQ QNSFCHCERA SGHLWSSLNV
960 970 980 990 1000
SGTTSDPSLN HVVQLLTCDL LLSLRTTLWQ KQASASQLLG ETYHASGTEL
1010 1020 1030 1040 1050
AGFQRDLGSL RRLAHSFRPA YRKVFLHEAT VRLMAGASPT RTHQLLEHSL
1060 1070 1080 1090 1100
RRRTTQNTKH GEVDTWPGQR ERATAILLAC RHLPLSFLSS PGQRAVLLAE
1110 1120 1130
AARTLEKVGD RRSCSDCQQM IVKLGGGTAI AAS
Length:1,133
Mass (Da):122,976
Last modified:October 11, 2005 - v1
Checksum:i148A5DA3165A0236
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC101902 mRNA. Translation: AAI01903.1.
RefSeqiNP_001028866.1. NM_001033694.1.
UniGeneiRn.41063.

Genome annotation databases

GeneIDi300095.
KEGGirno:300095.
UCSCiRGD:1307751. rat.

Similar proteinsi

Entry informationi

Entry nameiSRBP2_RAT
AccessioniPrimary (citable) accession number: Q3T1I5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: October 11, 2005
Last modified: August 30, 2017
This is version 89 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families