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Protein

Sterol regulatory element-binding protein 1

Gene

Srebf1

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 fatty acid and to a lesser degree the cholesterol synthesis pathway. 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'). Isoform SREBP-1A is much more active than isoform SREBP-1C in stimulating transcription from SRE-1-containing promoters.5 Publications

GO - Molecular functioni

  • chromatin binding Source: MGI
  • DNA binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: MGI
  • sterol response element binding Source: HGNC
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: Ensembl
  • transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: MGI
  • transcription factor activity, sequence-specific DNA binding Source: HGNC
  • transcription regulatory region DNA binding Source: MGI

GO - Biological processi

  • aging Source: Ensembl
  • cellular response to fatty acid Source: Ensembl
  • cellular response to starvation Source: HGNC
  • cholesterol metabolic process Source: UniProtKB-KW
  • circadian rhythm Source: UniProtKB
  • fat cell differentiation Source: MGI
  • insulin receptor signaling pathway Source: MGI
  • lipid biosynthetic process Source: UniProtKB
  • lung development Source: Ensembl
  • mRNA transcription from RNA polymerase II promoter Source: MGI
  • negative regulation of insulin secretion Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of cholesterol biosynthetic process Source: MGI
  • positive regulation of fatty acid biosynthetic process Source: BHF-UCL
  • positive regulation of histone deacetylation Source: MGI
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of triglyceride biosynthetic process Source: UniProtKB
  • regulation of fatty acid metabolic process Source: MGI
  • regulation of heart rate by chemical signal Source: MGI
  • regulation of insulin secretion Source: MGI
  • regulation of mitophagy Source: MGI
  • regulation of protein stability Source: MGI
  • regulation of protein targeting to mitochondrion Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB
  • response to cAMP Source: Ensembl
  • response to drug Source: Ensembl
  • response to food Source: Ensembl
  • response to glucagon Source: Ensembl
  • response to glucose Source: MGI
  • response to progesterone Source: Ensembl
  • response to retinoic acid Source: Ensembl
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-1368092. Rora activates gene expression.
R-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 1
Short name:
SREBP-1
Alternative name(s):
Sterol regulatory element-binding transcription factor 1
Cleaved into the following chain:
Gene namesi
Name:Srebf1
Synonyms:Srebp1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:107606. Srebf1.

Subcellular locationi

Processed sterol regulatory element-binding protein 1 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 477CytoplasmicSequence analysisAdd BLAST477
Transmembranei478 – 498HelicalSequence analysisAdd BLAST21
Topological domaini499 – 536LumenalSequence analysisAdd BLAST38
Transmembranei537 – 557HelicalSequence analysisAdd BLAST21
Topological domaini558 – 1134CytoplasmicSequence analysisAdd BLAST577

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • ER to Golgi transport vesicle membrane Source: UniProtKB-SubCell
  • Golgi membrane Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: BHF-UCL
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Mice show high embryonic lethality around day 11 dpc. Surviving mice show a 2-3-fold increase in processed Srebpf2 protein in liver nuclei, 3-fold increase in cholesterol synthesis and 50% increase in cholesterol content of the liver. Mice lacking isoform SREBP-1C show a lack of up-regulation of several lipogenic enzymes in response to high insulin or LXR activation. Mice overexpressing processed isoform SREBP-1A in adipocytes show enlarged white and brown adipocytes, increased rate of fatty acid synthesis and secretion leading to a fatty liver. Mice overexpressing processed isoform SREBP-1C in adipocytes show inhibition of adipocyte differentiation leading to a syndrome similar to human lipodystrophy with loss of peripheral white adipose tissue, diabetes and fatty liver.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi331S → A: Weakly affects phosphorylation by SIK1. 1 Publication1
Mutagenesisi332S → A: Weakly affects phosphorylation by SIK1. 1 Publication1
Mutagenesisi354S → A: Does not affect AMPK-mediated phosphorylation. 1 Publication1
Mutagenesisi389S → A: Abolishes AMPK-mediated phosphorylation. 1 Publication1
Mutagenesisi395S → A: Strongly impairs affects phosphorylation by SIK1. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3616359.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274481 – 1134Sterol regulatory element-binding protein 1Add BLAST1134
ChainiPRO_00003140301 – 480Processed sterol regulatory element-binding protein 1Add BLAST480

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei96PhosphoserineBy similarity1
Modified residuei115PhosphoserineBy similarity1
Modified residuei331Phosphoserine; by SIK11 Publication1
Modified residuei332Phosphoserine; by SIK11 Publication1
Modified residuei389Phosphoserine; by AMPK1 Publication1
Modified residuei395Phosphoserine; by SIK11 Publication1
Modified residuei448PhosphoserineCombined sources1
Modified residuei1047PhosphoserineBy 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.
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-389 by SIK1 represses activity possibly by inhibiting DNA-binding.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei451 – 452Cleavage; by caspase-3 and caspase-7By similarity2
Sitei480 – 481Cleavage; by S2PBy similarity2
Sitei519 – 520Cleavage; by S1PBy similarity2

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9WTN3.
PRIDEiQ9WTN3.

PTM databases

iPTMnetiQ9WTN3.
PhosphoSitePlusiQ9WTN3.

Expressioni

Tissue specificityi

Isoform SREBP-1C predominates in liver, adrenal gland, brain and adipose tissue, whereas isoform SREBP-1A predominates in spleen. Isoform SREBP-1A and isoform SREBP-1C are found in kidney, thymus, testis, muscle, jejunum, and ileum.

Inductioni

Isoform SREBP-1C is expressed in a circadian manner in the liver with a peak at ZT16.1 Publication

Gene expression databases

BgeeiENSMUSG00000020538.
ExpressionAtlasiQ9WTN3. baseline and differential.
GenevisibleiQ9WTN3. 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. Interacts with LMNA. Interacts with CEBPA, the interaction produces a transcriptional synergy (PubMed:17290224).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Sirt1Q923E42EBI-5273743,EBI-1802585
Sumo1P631662EBI-5273743,EBI-80152

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi203495. 6 interactors.
IntActiQ9WTN3. 3 interactors.
STRINGi10090.ENSMUSP00000020846.

Structurei

3D structure databases

ProteinModelPortaliQ9WTN3.
SMRiQ9WTN3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini317 – 367bHLHPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 60Transcriptional activation (acidic)Add BLAST60
Regioni227 – 487Interaction with LMNA1 PublicationAdd BLAST261
Regioni367 – 388Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi61 – 175Pro/Ser-richAdd BLAST115
Compositional biasi420 – 453Gly/Pro/Ser-richAdd BLAST34

Sequence similaritiesi

Belongs to the SREBP family.Curated
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.
InParanoidiQ9WTN3.
KOiK07197.
OMAiGKYTGGH.
OrthoDBiEOG091G01RE.
PhylomeDBiQ9WTN3.
TreeFamiTF313894.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[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 (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform SREBP-1A (identifier: Q9WTN3-1) [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
MDELAFGEAA LEQTLAEMCE LDTAVLNDIE DMLQLINNQD SDFPGLFDAP
60 70 80 90 100
YAGGETGDTG PSSPGANSPE SFSSASLASS LEAFLGGPKV TPAPLSPPPS
110 120 130 140 150
APAALKMYPS VSPFSPGPGI KEEPVPLTIL QPAAPQPSPG TLLPPSFPAP
160 170 180 190 200
PVQLSPAPVL GYSSLPSGFS GTLPGNTQQP PSSLPLAPAP GVLPTPALHT
210 220 230 240 250
QVQSLASQQP LPASAAPRTN TVTSQVQQVP VVLQPHFIKA DSLLLTAVKT
260 270 280 290 300
DAGATVKTAG ISTLAPGTAV QAGPLQTLVS GGTILATVPL VVDTDKLPIH
310 320 330 340 350
RLAAGSKALG SAQSRGEKRT AHNAIEKRYR SSINDKIVEL KDLVVGTEAK
360 370 380 390 400
LNKSAVLRKA IDYIRFLQHS NQKLKQENLT LRSAHKSKSL KDLVSACGSG
410 420 430 440 450
GGTDVSMEGM KPEVVETLTP PPSDAGSPSQ SSPLSFGSRA SSSGGSDSEP
460 470 480 490 500
DSPAFEDSQV KAQRLPSHSR GMLDRSRLAL CVLAFLCLTC NPLASLFGWG
510 520 530 540 550
ILTPSDATGT HRSSGRSMLE AESRDGSNWT QWLLPPLVWL ANGLLVLACL
560 570 580 590 600
ALLFVYGEPV TRPHSGPAVH FWRHRKQADL DLARGDFPQA AQQLWLALQA
610 620 630 640 650
LGRPLPTSNL DLACSLLWNL IRHLLQRLWV GRWLAGQAGG LLRDRGLRKD
660 670 680 690 700
ARASARDAAV VYHKLHQLHA MGKYTGGHLA ASNLALSALN LAECAGDAIS
710 720 730 740 750
MATLAEIYVA AALRVKTSLP RALHFLTRFF LSSARQACLA QSGSVPLAMQ
760 770 780 790 800
WLCHPVGHRF FVDGDWAVHG APPESLYSVA GNPVDPLAQV TRLFREHLLE
810 820 830 840 850
RALNCIAQPS PGAADGDREF SDALGYLQLL NSCSDAAGAP ACSFSVSSSM
860 870 880 890 900
AATTGPDPVA KWWASLTAVV IHWLRRDEEA AERLYPLVEH IPQVLQDTER
910 920 930 940 950
PLPRAALYSF KAARALLDHR KVESSPASLA ICEKASGYLR DSLASTPTGS
960 970 980 990 1000
SIDKAMQLLL CDLLLVARTS LWQRQQSPAS VQVAHGTSNG PQASALELRG
1010 1020 1030 1040 1050
FQHDLSSLRR LAQSFRPAMR RVFLHEATAR LMAGASPART HQLLDRSLRR
1060 1070 1080 1090 1100
RAGSSGKGGT TAELEPRPTW REHTEALLLA SCYLPPAFLS APGQRMSMLA
1110 1120 1130
EAARTVEKLG DHRLLLDCQQ MLLRLGGGTT VTSS
Length:1,134
Mass (Da):120,537
Last modified:July 24, 2007 - v4
Checksum:i3D7422406E07A376
GO
Isoform SREBP-1A-W42 (identifier: Q9WTN3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     90-131: Missing.

Show »
Length:1,092
Mass (Da):116,275
Checksum:i7AD020CB6E87C2E6
GO
Isoform SREBP-1C (identifier: Q9WTN3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MDELAFGEAALEQTLAEMCELDTAVLNDI → MDCTF

Show »
Length:1,110
Mass (Da):117,996
Checksum:iFC912A03CE5C785E
GO
Isoform SREBP-1C-W42 (identifier: Q9WTN3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MDELAFGEAALEQTLAEMCELDTAVLNDI → MDCTF
     90-131: Missing.

Show »
Length:1,068
Mass (Da):113,734
Checksum:i9229327B581AAAD2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti272 – 276Missing in BAE32576 (PubMed:16141072).Curated5
Sequence conflicti272 – 276Missing in AAK54762 (Ref. 6) Curated5
Sequence conflicti795R → P in BAE29268 (PubMed:16141072).Curated1
Sequence conflicti1003H → N in AAH06051 (PubMed:15489334).Curated1
Sequence conflicti1061T → A in AAH06051 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0021511 – 29MDELA…VLNDI → MDCTF in isoform SREBP-1C and isoform SREBP-1C-W42. 2 PublicationsAdd BLAST29
Alternative sequenceiVSP_00215290 – 131Missing in isoform SREBP-1A-W42 and isoform SREBP-1C-W42. 1 PublicationAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK052628 mRNA. Translation: BAC35068.1.
AK150052 mRNA. Translation: BAE29268.1.
AK154424 mRNA. Translation: BAE32576.1.
AK169607 mRNA. Translation: BAE41256.1.
AL669954 Genomic DNA. Translation: CAI25757.1.
AL669954 Genomic DNA. Translation: CAI25758.1.
BC006051 mRNA. Translation: AAH06051.1.
BC056922 mRNA. Translation: AAH56922.1.
AB017337 mRNA. Translation: BAA74795.1.
AF374266 mRNA. Translation: AAK54762.1.
CCDSiCCDS24785.1. [Q9WTN3-1]
PIRiPD0035.
RefSeqiNP_001300908.1. NM_001313979.1.
NP_035610.1. NM_011480.4. [Q9WTN3-1]
XP_006532778.1. XM_006532715.2. [Q9WTN3-3]
UniGeneiMm.278701.

Genome annotation databases

EnsembliENSMUST00000020846; ENSMUSP00000020846; ENSMUSG00000020538. [Q9WTN3-1]
GeneIDi20787.
KEGGimmu:20787.
UCSCiuc007jfn.1. mouse. [Q9WTN3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK052628 mRNA. Translation: BAC35068.1.
AK150052 mRNA. Translation: BAE29268.1.
AK154424 mRNA. Translation: BAE32576.1.
AK169607 mRNA. Translation: BAE41256.1.
AL669954 Genomic DNA. Translation: CAI25757.1.
AL669954 Genomic DNA. Translation: CAI25758.1.
BC006051 mRNA. Translation: AAH06051.1.
BC056922 mRNA. Translation: AAH56922.1.
AB017337 mRNA. Translation: BAA74795.1.
AF374266 mRNA. Translation: AAK54762.1.
CCDSiCCDS24785.1. [Q9WTN3-1]
PIRiPD0035.
RefSeqiNP_001300908.1. NM_001313979.1.
NP_035610.1. NM_011480.4. [Q9WTN3-1]
XP_006532778.1. XM_006532715.2. [Q9WTN3-3]
UniGeneiMm.278701.

3D structure databases

ProteinModelPortaliQ9WTN3.
SMRiQ9WTN3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203495. 6 interactors.
IntActiQ9WTN3. 3 interactors.
STRINGi10090.ENSMUSP00000020846.

Chemistry databases

ChEMBLiCHEMBL3616359.

PTM databases

iPTMnetiQ9WTN3.
PhosphoSitePlusiQ9WTN3.

Proteomic databases

PaxDbiQ9WTN3.
PRIDEiQ9WTN3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020846; ENSMUSP00000020846; ENSMUSG00000020538. [Q9WTN3-1]
GeneIDi20787.
KEGGimmu:20787.
UCSCiuc007jfn.1. mouse. [Q9WTN3-1]

Organism-specific databases

CTDi6720.
MGIiMGI:107606. Srebf1.

Phylogenomic databases

eggNOGiKOG2588. Eukaryota.
ENOG410XSVP. LUCA.
GeneTreeiENSGT00390000017651.
HOGENOMiHOG000007091.
HOVERGENiHBG061592.
InParanoidiQ9WTN3.
KOiK07197.
OMAiGKYTGGH.
OrthoDBiEOG091G01RE.
PhylomeDBiQ9WTN3.
TreeFamiTF313894.

Enzyme and pathway databases

ReactomeiR-MMU-1368092. Rora activates gene expression.
R-MMU-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-MMU-2426168. Activation of gene expression by SREBF (SREBP).

Miscellaneous databases

ChiTaRSiSrebf1. mouse.
PROiQ9WTN3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020538.
ExpressionAtlasiQ9WTN3. baseline and differential.
GenevisibleiQ9WTN3. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[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 nameiSRBP1_MOUSE
AccessioniPrimary (citable) accession number: Q9WTN3
Secondary accession number(s): Q3U458
, Q3UDJ3, Q5SRX5, Q8C733, Q99JK7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 24, 2007
Last modified: November 30, 2016
This is version 157 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.