SREBF1 (sterol regulatory element binding transcription factor 1)

Gene

• Entrez ID: 6720
• Gene name: Sterol regulatory element binding transcription factor 1
• Gene symbol: SREBF1
• Synonyms: HMD, IFAP2, SREBP1, bHLHd1
• Chromosome: 17
• Chromosome location: 17p11.2
• Summary: This gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a motif that is found in the promoter of the low density lipoprotein receptor gene and other genes involved in sterol biosynthesis. The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively. [provided by RefSeq, Nov 2017]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018325	hsa-miR-335-5p	Microarray	18185580
MIRT037474	hsa-miR-744-5p	CLASH	23622248
MIRT038739	hsa-miR-93-3p	CLASH	23622248
MIRT041670	hsa-miR-484	CLASH	23622248
MIRT043859	hsa-miR-378a-3p	CLASH	23622248
MIRT045315	hsa-miR-185-5p	CLASH	23622248
MIRT045315	hsa-miR-185-5p	Luciferase reporter assay, qRT-PCR, Western blot	23951060
MIRT047574	hsa-miR-10a-5p	CLASH	23622248
MIRT050226	hsa-miR-25-3p	CLASH	23622248
MIRT051418	hsa-let-7e-5p	CLASH	23622248
MIRT054225	hsa-miR-128-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23990020
MIRT054666	hsa-miR-33a-5p	qRT-PCR, Western blot	24300912
MIRT438066	hsa-miR-342-3p	Luciferase reporter assay, qRT-PCR, Western blot	23951060
MIRT439117	hsa-miR-10b-5p	3'LIFE	25074381
MIRT439142	hsa-let-7c-5p	3'LIFE	25074381
MIRT487324	hsa-miR-4474-3p	PAR-CLIP	23592263
MIRT487324	hsa-miR-4474-3p	PAR-CLIP	20371350
MIRT487325	hsa-miR-7108-5p	PAR-CLIP	23592263
MIRT487325	hsa-miR-7108-5p	PAR-CLIP	20371350
MIRT487326	hsa-miR-663b	PAR-CLIP	23592263
MIRT487326	hsa-miR-663b	PAR-CLIP	20371350
MIRT487327	hsa-miR-4725-3p	PAR-CLIP	23592263
MIRT487327	hsa-miR-4725-3p	PAR-CLIP	20371350
MIRT487328	hsa-miR-6780b-5p	PAR-CLIP	23592263
MIRT487328	hsa-miR-6780b-5p	PAR-CLIP	20371350
MIRT487329	hsa-miR-4271	PAR-CLIP	23592263
MIRT487329	hsa-miR-4271	PAR-CLIP	20371350
MIRT487330	hsa-miR-6883-5p	PAR-CLIP	23592263
MIRT487330	hsa-miR-6883-5p	PAR-CLIP	20371350
MIRT487331	hsa-miR-6785-5p	PAR-CLIP	23592263
MIRT487331	hsa-miR-6785-5p	PAR-CLIP	20371350
MIRT487332	hsa-miR-4728-5p	PAR-CLIP	23592263
MIRT487332	hsa-miR-4728-5p	PAR-CLIP	20371350
MIRT487333	hsa-miR-149-3p	PAR-CLIP	23592263
MIRT487333	hsa-miR-149-3p	PAR-CLIP	20371350
MIRT487334	hsa-miR-4743-5p	PAR-CLIP	23592263
MIRT487334	hsa-miR-4743-5p	PAR-CLIP	20371350
MIRT487335	hsa-miR-671-5p	PAR-CLIP	23592263
MIRT487335	hsa-miR-671-5p	PAR-CLIP	20371350
MIRT487336	hsa-miR-6794-5p	PAR-CLIP	23592263
MIRT487336	hsa-miR-6794-5p	PAR-CLIP	20371350
MIRT487337	hsa-miR-4716-3p	PAR-CLIP	23592263
MIRT487337	hsa-miR-4716-3p	PAR-CLIP	20371350
MIRT487338	hsa-miR-6783-5p	PAR-CLIP	23592263
MIRT487338	hsa-miR-6783-5p	PAR-CLIP	20371350
MIRT527531	hsa-miR-4668-5p	PAR-CLIP	22012620
MIRT527532	hsa-miR-95-5p	PAR-CLIP	22012620
MIRT721591	hsa-miR-6749-3p	HITS-CLIP	19536157
MIRT721592	hsa-miR-3156-3p	HITS-CLIP	19536157
MIRT721593	hsa-miR-4290	HITS-CLIP	19536157
MIRT721594	hsa-miR-532-3p	HITS-CLIP	19536157
MIRT721595	hsa-miR-4286	HITS-CLIP	19536157
MIRT721596	hsa-miR-4301	HITS-CLIP	19536157
MIRT721597	hsa-miR-483-3p	HITS-CLIP	19536157
MIRT721598	hsa-miR-7-2-3p	HITS-CLIP	19536157
MIRT721599	hsa-miR-7-1-3p	HITS-CLIP	19536157
MIRT721600	hsa-miR-5688	HITS-CLIP	19536157
MIRT721601	hsa-miR-495-3p	HITS-CLIP	19536157
MIRT740706	hsa-miR-3177-3p	PAR-CLIP	26701625
MIRT741411	hsa-miR-342-5p	PAR-CLIP	26701625
MIRT745859	hsa-miR-4524a-3p	PAR-CLIP	26701625
MIRT745894	hsa-miR-4524b-3p	PAR-CLIP	26701625
MIRT746718	hsa-miR-4663	PAR-CLIP	26701625
MIRT746746	hsa-miR-4664-5p	PAR-CLIP	26701625
MIRT748976	hsa-miR-4796-3p	PAR-CLIP	26701625
MIRT750255	hsa-miR-520g-3p	PAR-CLIP	26701625
MIRT750265	hsa-miR-520h	PAR-CLIP	26701625
MIRT751669	hsa-miR-6069	PAR-CLIP	26701625
MIRT755717	hsa-miR-6782-5p	PAR-CLIP	26701625
MIRT759329	hsa-miR-7160-5p	PAR-CLIP	26701625
MIRT760144	hsa-miR-8077	PAR-CLIP	26701625

Transcription factors

Transcription factor	Regulation	Reference
SP1	Activation	20179320
SP1	Unknown	15462672

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000139	Component	Golgi membrane	TAS
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	23610160
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0003062	Process	Regulation of heart rate by chemical signal	IEA
GO:0003677	Function	DNA binding	ISS
GO:0003682	Function	Chromatin binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	16407292
GO:0004879	Function	Nuclear receptor activity	IDA	23610160
GO:0005515	Function	Protein binding	IPI	14701856, 16713569, 21993218, 23610160, 32814053
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	15358760
GO:0005635	Component	Nuclear envelope	TAS	8156598
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	ISS
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005829	Component	Cytosol	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006629	Process	Lipid metabolic process	TAS	8156598
GO:0007568	Process	Aging	IEA
GO:0007623	Process	Circadian rhythm	TAS
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0008286	Process	Insulin receptor signaling pathway	IEA
GO:0008610	Process	Lipid biosynthetic process	ISS
GO:0009267	Process	Cellular response to starvation	ISS	16407292
GO:0009749	Process	Response to glucose	IEA
GO:0010867	Process	Positive regulation of triglyceride biosynthetic process	ISS
GO:0010876	Process	Lipid localization	IEA
GO:0010883	Process	Regulation of lipid storage	IEA
GO:0012507	Component	ER to Golgi transport vesicle membrane	IEA
GO:0016021	Component	Integral component of membrane	IEA
GO:0019217	Process	Regulation of fatty acid metabolic process	IEA
GO:0019901	Function	Protein kinase binding	IEA
GO:0030324	Process	Lung development	IEA
GO:0030522	Process	Intracellular receptor signaling pathway	IEA
GO:0031065	Process	Positive regulation of histone deacetylation	IEA
GO:0031647	Process	Regulation of protein stability	IMP	24912190
GO:0032094	Process	Response to food	IEA
GO:0032526	Process	Response to retinoic acid	IEA
GO:0032570	Process	Response to progesterone	IEA
GO:0032810	Function	Sterol response element binding	IDA	16407292
GO:0032933	Process	SREBP signaling pathway	IDA	27614840
GO:0032933	Process	SREBP signaling pathway	IMP	27614840
GO:0032991	Component	Protein-containing complex	IEA
GO:0033762	Process	Response to glucagon	IEA
GO:0042493	Process	Response to drug	IEA
GO:0042789	Process	MRNA transcription by RNA polymerase II	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045444	Process	Fat cell differentiation	IEA
GO:0045471	Process	Response to ethanol	IEA
GO:0045540	Process	Regulation of cholesterol biosynthetic process	TAS
GO:0045542	Process	Positive regulation of cholesterol biosynthetic process	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	26437365
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IGI	23610160
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	TAS	23610160
GO:0046676	Process	Negative regulation of insulin secretion	IEA
GO:0046983	Function	Protein dimerization activity	IEA
GO:0051591	Process	Response to cAMP	IEA
GO:0071398	Process	Cellular response to fatty acid	IEA
GO:1903146	Process	Regulation of autophagy of mitochondrion	IMP	24912190
GO:1903214	Process	Regulation of protein targeting to mitochondrion	IMP	24912190
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 184756
• HGNC: 11289
• e!Ensembl: ENSG00000072310

Protein

• UniProt ID: P36956
• Protein name: Sterol regulatory element-binding protein 1 (SREBP-1) (Class D basic helix-loop-helix protein 1) (bHLHd1) (Sterol regulatory element-binding transcription factor 1) [Cleaved into: Processed sterol regulatory element-binding protein 1 (Transcription factor SREBF1)]
• Protein function: [Sterol regulatory element-binding protein 1]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). 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 and lipid homeostasis (By similarity). ; [Processed sterol regulatory element-binding protein 1]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:8402897, PubMed:12177166, PubMed:32322062). 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') (PubMed:8402897, PubMed:12177166). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:8402897, PubMed:12177166, PubMed:32322062). ; [Isoform SREBP-1A]: Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity). ; [Isoform SREBP-1C]: Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity). ; [Isoform SREBP-1aDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. ; [Isoform SREBP-1cDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.
• PDB: 1AM9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00010	HLH	324 → 374	Helix-loop-helix DNA-binding domain	Domain

• Sequence:

  MDEPPFSEAALEQALGEPCDLDAALLTDIEDMLQLINNQDSDFPGLFDPPYAGSGAGGTD
  PASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGP
  GIKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGSPPGN
  TQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLL
  QPHFIKADSLLLTAMKTDGATVKAAGLSPLVSGTTVQTGPLPTLVSGGTILATVPLVVDA
  EKLPINRLAAGSKAPASAQSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKS
  AVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLKDLVSACGSGGNTDVLMEGVKTE
  VEDTLTPPPSDAGSPFQSSPLSLGSRGSGSGGSGSDSEPDSPVFEDSKAKPEQRPSLHSR
  GMLDRSRLALCTLVFLCLSCNPLASLLGARGLPSPSDTTSVYHSPGRNVLGTESRDGPGW
  AQWLLPPVVWLLNGLLVLVSLVLLFVYGEPVTRPHSGPAVYFWRHRKQADLDLARGDFAQ
  AAQQLWLALRALGRPLPTSHLDLACSLLWNLIRHLLQRLWVGRWLAGRAGGLQQDCALRV
  DASASARDAALVYHKLHQLHTMGKHTGGHLTATNLALSALNLAECAGDAVSVATLAEIYV
  AAALRVKTSLPRALHFLTRFFLSSARQACLAQSGSVPPAMQWLCHPVGHRFFVDGDWSVL
  STPWESLYSLAGNPVDPLAQVTQLFREHLLERALNCVTQPNPSPGSADGDKEFSDALGYL
  QLLNSCSDAAGAPAYSFSISSSMATTTGVDPVAKWWASLTAVVIHWLRRDEEAAERLCPL
  VEHLPRVLQESERPLPRAALHSFKAARALLGCAKAESGPASLTICEKASGYLQDSLATTP
  ASSSIDKAVQLFLCDLLLVVRTSLWRQQQPPAPAPAAQGTSSRPQASALELRGFQRDLSS
  LRRLAQSFRPAMRRVFLHEATARLMAGASPTRTHQLLDRSLRRRAGPGGKGGAVAELEPR
  PTRREHAEALLLASCYLPPGFLSAPGQRVGMLAEAARTLEKLGDRRLLHDCQQMLMRLGG
  GTTVTSS

• Sequence length: 1147