Protein Srebf1

URN urn:agi-llid:6720
Connectivity 576
Name Srebf1
Description sterol regulatory element-binding transcription factor 1
Notes 2 years after bilio-pancreatic diversion the degree of fat mass loss seems to interfere with regulatory binding protein 1c (SREBP-1c)gene suppression to preserve an adequate amount of fat storage 2 years after bilio-pancreatic diversion the degree of fat mass loss seems to interfere with regulatory binding protein 1c (SREBP-1c)gene suppression to preserve an adequate amount of fat storage. APOA5 gene expression is regulated by the LXR ligand T0901317 in a negative manner through SREBP-1c. EC nuclei showed strong SREBP staining in human atherosclerotic lesions, suggesting a role for SREBP. Endothelial cholesterol depletion & SREBP activation play a role in inflammatory processes in which phospholipid oxidation products accumulate. High levels of SREBP-1 protein is associted with during prostate cancer progression to androgen independence. Phagocytosis triggered the proteolytic activation of SREBP-1a and SREBP-2; upon overexpression of these proteins, phagocytosis-induced transcription and lipid synthesis were blocked; SREBPs are essential regulators of membrane biogenesis. Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. Role of the SREBF-1 gene in genetic predisposition of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. SREBP-1 has a novel role as negative regulator of gluconeogenic genes through a cross-talk with HNF-4alpha interference with PGC-1 recruitment. SREBP-1 has a role in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression. SREBP-1 homodimers and heterodimers localize in the nucleus and activate transcription. SREBP-1 not necessary for hepatic Akt-mediated hypoglycemic effect. Myr-Akt-induced hypertriglyceridemia and hepatic triglyceride accumulation mediated by Akt-induced SREBP-1 expression and mechanism involving fatty acid synthesis independent of SREBP-1. SREBP-1a and the CRE-bound proteins are essential for the SREBP-dependent response. SREBP-1ac mRNA was detectable in all tissues studied, although at lower levels than the major SREBP-1a & -1c isoforms. Transcription of SREBP-1ac mRNA was detectable in all tissues studied, although at lower levels than the major SREBP-1a & -1c isoforms. SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver. SREBP-1c gene is a candidate for human insulin resistance and a variant might influence diabetes risk. SREBP-1c is involved in the effect of insulin on HKII gene transcription. SREBP1a and APOB have roles in total and low-density lipoprotein cholesterol levels in patients with coronary artery disease. Sphinglipids in endocytic compartments serve as a ""molecular trap"" for cholesterol, leading to a reduction in cholesterol at the endoplasmic reticulum, induction of sterol regulatory element-binding protein-1 cleavage, and up-regulation of LDL receptors. Tethered SREBP-1a and -2 homodimers, similar to the monomeric forms, activated target genes more robustly than tethered SREBP-1c homodimers. This gene encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a decamer flanking the low density lipoprotein receptor gene and some genes involved in sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. This review shows how SREBP-1 might play a role in the development of cellular features belonging to lipotoxicity and, possibly, syndrome X. Transfected from humans into transgenic mice, SREBP-1c and endogenous lipogenesis could be involved in beta-cell dysfunction and diabetes. Transgenic SHR overexpressing SREBP-1a is nonobese rat model of fatty liver, disordered glucose and lipid metabolism, and hypertension. Possible model for studying pathogenesis and treatment of metabolic syndrome associated with hepatic steatosis. While the SREBP-1a and -1c isoforms differentially activate transcription, the molecular basis of this difference is unknown. Here we define the differences between these proteins that confer the enhanced activity of SREBP-1a. A strong graded interaction between SREBF-1a -36del/G genotypes and response of plasma apoA-I to treatment with fluvastatin. Activation of SREBP-1 by Akt leads to the induction of key enzymes of the cholesterol and fatty acid biosynthesis pathways, and thus membrane lipid biosynthesis. Effect of SREBP-1a expression on lipid metabolism at the level of the cellular protein network and the protein pattern of mitochondria. Expression altered in obesity and niddm. Expression of SREBP-1 is affected by polyunsaturated fatty acids in human cells. HCG and insulin cause a switch toward expression of the SREBP-1c isoform with consequent effects on fatty acid synthesis in culturred ganulosa cells (SRESBP-1c). May play discrete role in the regulation of the resistin gene expression. Molecular cloning of promoter; studies suggest that PDX-1 and HNF-4 both stimulate SREBP-1c gene expression. NSREBPs are essential for high levels of lipid synthesis in the liver and indicate that Insig's modulate nSREBP levels by binding and retaining SCAP in the ER. Results provide evidence that insulin action on sterol regulatory element binding protein (SREBP)-1c is dysregulated in adipose tissue from type 2 diabetic subjects. The SREBP-1c.BETA2.E47 complex is in a DNA looping structure which is required for efficient recruitment of CREB-binding protein/p300. Transcriptional activities to different target promoters of lipogenic and cholesterogenic genes.

Pathway InsulinR -> ELK-SRF/SREBF signaling
IGF1R -> ELK-SRF/HIF1A/MYC/SREBF signaling
FibronectinR -> AP-1/ELK-SRF/SREBF signaling
sterol regulatory element-binding protein signaling pathway

GO Molecular Function transcription regulator activity
chromatin binding
transcription factor activity
RNA polymerase II transcription factor activity
protein complex binding
DNA binding
sequence-specific DNA binding
sterol response element binding
specific RNA polymerase II transcription factor activity

GO Cellular Component protein complex
membrane
cytoplasm
endoplasmic reticulum membrane
cytoplasmic vesicle
endoplasmic reticulum
Golgi apparatus
Golgi membrane
ER to Golgi transport vesicle membrane
nuclear envelope
nucleus
microsome
integral to membrane

GO Biological Process aging
lung development
regulation of heart rate by chemical signal
regulation of insulin secretion
negative regulation of insulin secretion
cellular response to starvation
regulation of fatty acid metabolic process
regulation of transcription
negative regulation of transcription from RNA polymerase II promoter
positive regulation of triglyceride biosynthetic process
positive regulation of transcription
positive regulation of fatty acid biosynthetic process
positive regulation of gene-specific transcription
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription via sterol regulatory element binding
positive regulation of histone deacetylation
regulation of transcription from RNA polymerase II promoter
transcription
cellular response to insulin stimulus
insulin receptor signaling pathway
response to drug
response to food
response to organic cyclic substance
response to cAMP
response to lipid
response to peptide hormone stimulus
response to fatty acid
response to insulin stimulus
response to glucagon stimulus
response to progesterone stimulus
response to glucose stimulus
response to retinoic acid
positive regulation of cholesterol biosynthetic process
lipid metabolic process
lipid biosynthetic process
steroid metabolic process
cholesterol metabolic process

Ariadne Ontology Ubiquitous bHLH-ZIP factors

Group Ubiquitous bHLH-ZIP factors
transcription regulator activity
aging
lung development
regulation of heart rate by chemical signal
regulation of insulin secretion
negative regulation of insulin secretion
cellular response to starvation
regulation of fatty acid metabolic process
regulation of transcription
negative regulation of transcription from RNA polymerase II promoter
positive regulation of triglyceride biosynthetic process
positive regulation of transcription
positive regulation of fatty acid biosynthetic process
positive regulation of gene-specific transcription
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription via sterol regulatory element binding
positive regulation of histone deacetylation
regulation of transcription from RNA polymerase II promoter
transcription
cellular response to insulin stimulus
insulin receptor signaling pathway
response to drug
response to food
response to organic cyclic substance
response to cAMP
response to lipid
response to peptide hormone stimulus
response to fatty acid
response to insulin stimulus
response to glucagon stimulus
response to progesterone stimulus
response to glucose stimulus
response to retinoic acid
positive regulation of cholesterol biosynthetic process
lipid metabolic process
lipid biosynthetic process
steroid metabolic process
cholesterol metabolic process
chromatin binding
transcription factor activity
RNA polymerase II transcription factor activity
protein complex binding
DNA binding
sequence-specific DNA binding
sterol response element binding
specific RNA polymerase II transcription factor activity
protein complex
membrane
cytoplasm
endoplasmic reticulum membrane
cytoplasmic vesicle
endoplasmic reticulum
Golgi apparatus
Golgi membrane
ER to Golgi transport vesicle membrane
nuclear envelope
nucleus
microsome
integral to membrane

MedScan ID 6720

Hugo ID 11289

Human chromosome position 17p11.2

LocusLink ID 6720
20787
78968
216809
276754

Alias SREBP1
bHLHd1
SREBP-1c
sterol regulatory element-binding protein 1
SREBP-1
OTTHUMP00000065591
OTTHUMP00000065592
OTTHUMP00000065593
class D basic helix-loop-helix protein 1
sterol regulatory element binding protein-1
sterol regulatory element-binding transcription factor 1
ADD1
ADD-1
SREBP1c
SREBP-1a
D630008H06
RP23-456O18.1
OTTMUSP00000005985
OTTMUSP00000005986
OTTMUSP00000005987
sterol regulatory element binding factor 1
adipocyte determination- and differentiation-dependent factor 1
ADD1/SREBP
ADD1/SREBP-1
ADD1/SREBP-1c
LOC124554
LOC276754
Srebf I
SREBF1
SRE-binding factor 1
SRE-binding factor I
SRE-binding protein-1a
SRE-binding protein-1c
SREBP
SREBP I
SREBP-1/ADD1
sterol regulatory element binding factor I
sterol regulatory element binding protein
Sterol regulatory element binding protein I
sterol regulatory element binding transcription factor 1
sterol regulatory element binding transcription factor I
sterol regulatory element-binding protein
sterol response element binding protein
sterol response element binding protein 1
sterol response element binding protein-1
sterol response element-binding protein
sterol response element-binding protein 1
sterol response element-binding protein I
sterol response element-binding protein-1
sterol response element-binding protein-1c
sterol responsive element-binding protein-1c
Srebf1s
SREBP1s
Srebf Is
SREBP Is

Organism Homo sapiens
Mus musculus
Rattus norvegicus

GenBank ID NC_000017
NM_004176
NP_004167
NM_001005291
NP_001005291
NT_010718
NW_001838410
NW_926628
AC_000149
AC_000060
AC122129
CH471196
EAW55688
EAW55689
EAW55690
EAW55691
AB209609
BAD92846
AB373958
BAG06742
AB373959
BAG06743
AK091131
BAG52289
AK095325
BAG53027
AK128320
BAG54659
AK293795
BAG57207
AK294800
BAG57920
AK297113
BAG59620
BC023621
AAH23621
BC026962
AAH26962
BC057388
AAH57388
BC063281
AAH63281
BE208013
BI906407
BQ025047
CR616334
S66167
AAB28522
S66168
AAB28523
U00968
AAC50051
P36956
NC_000077
NM_011480
NP_035610
NT_096135
NW_001030469
AC_000033
AL669954
CAI25756
CAI25757
CAI25758
CH466678
EDL26614
EDL26615
EDL26616
AB017337
BAA74795
AF374266
AAK54762
AK040663
AK052628
BAC35068
AK150052
BAE29268
AK154424
BAE32576
AK158269
BAE34440
AK169607
BAE41256
AK205046
AK209898
AK216773
BC006051
AAH06051
BC056922
AAH56922
Q3TYX1
Q9WTN3
NC_005109
XM_213329
XP_213329
NW_047334
NW_001084656
XM_001075680
XP_001075680
AC_000078
CH473948
EDM04632
EDM04633
AF286469
AAG28733
AF286470
AAG28734
P56720
NG_007101
Q5SRX6
AI132428
AI060765
AA475250
Q6P4R7
AI386259
AI595781
AI786503
Q6PFW7
Q8TAK9
Q6PJ36
AI552487
Q59F52
AI326423
AA498625
BG084558

OMIM ID 184756

Mouse chromosome position 11
11 B2

GO ID 0003702
0032810
0003700
0009267
0008203
0006629
0045944
0006357
0008202
0012507
0005794
0000139
0031410
0005783
0005789
0016021
0016020
0005635
0005634
0003677
0003682
0032403
0043565
0003704
0030528
0008286
0046676
0000122
0045542
0045723
0043193
0031065
0045941
0035104
0010867
0019217
0003062
0050796
0045449
0009749
0006350
0005737
0005792
0043234
0007568
0032869
0008610
0030324
0051591
0042493
0070542
0032094
0033762
0032868
0033993
0014070
0043434
0032570
0032526
0005515
0006355
0005795

Rat chromosome position 10q22

Swiss-Prot Accession P36956
Q9WTN3
Q3TYX1
P56720
Q99PI6
Q99PI7
Q3U458
Q3UDJ3
Q5SRX5
Q8C733
Q99JK7
Q16062
Q59F52
Q6P4R7
Q6PFW7
Q6PJ36
Q8TAK9
D3DXC4
Q5SRX6

PIR ID PD0035
A48845

Unigene ID Hs.592123
Mm.278701
Rn.198857
Rn.221929
Mm.296366
Rn.217688
Rn.801
Rn.95306
Hs.554776
Hs.190284

KEGG ID hsa:6720
mmu:20787
rno:78968

Swiss-Prot ID SRBP1_RAT
SRBP1_MOUSE
SRBP1_HUMAN
D3DXC4_HUMAN

Cell Localization Endoplasmic reticulum membrane
Golgi apparatus membrane
Cytoplasmic vesicle
COPII-coated vesicle membrane
Nucleus

IPI ID IPI00560536
IPI00562316
IPI00223219
IPI00226436
IPI00387320
IPI00750980
IPI00220878
IPI00418428
IPI00419318
IPI00795043
IPI00796121
IPI00796977
IPI00797516
IPI00764709
IPI00369557
IPI00778258

Homologene ID 3079

RGD ID 69423

MGI ID 107606

KEGG pathway Insulin signaling pathway