Orientation: Minus strand; 25669 bp; Exon count: 22; intron count: 20

SREBF1 gene has 23 transcripts (Table 1)
Table 1. Transcripts of human SREBF1 gene (Ensembl annotation Release 85).

Name	Transcript ID	bp	Protein	Biotype
SREBF1-201	ENST00000261646.9	4178	1147	Protein coding
SREBF1-202	ENST00000355815.8	4253	1177	Protein coding
SREBF1-203	ENST00000395751.8	4653	216	Nonsense mediated decay
SREBF1-204	ENST00000395756.5	3026	113	Nonsense mediated decay
SREBF1-205	ENST00000395757.5	3696	893	Protein coding
SREBF1-206	ENST00000423161.3	1058	325	Protein coding
SREBF1-207	ENST00000447641.5	644	No protein	Retained intron
SREBF1-208	ENST00000469356.3	1323	No protein	Retained intron
SREBF1-209	ENST00000470247.1	374	No Protein	Retained intron
SREBF1-210	ENST00000471445.5	936	No protein	Retained intron
SREBF1-211	ENST00000476994.1	591	No protein	Retained intron
SREBF1-212	ENST00000478616.1	882	163	Protein coding
SREBF1-213	ENST00000485080.6	1230	110	Nonsense mediated decay
SREBF1-214	ENST00000486311.5	473	157	Protein coding
SREBF1-215	ENST00000487401.1	477	No protein	Retained intron
SREBF1-216	ENST00000490796.1	698	No protein	Retained intron
SREBF1-217	ENST00000577897.1	536	66	Protein coding
SREBF1-218	ENST00000578469.1	588	31	Protein coding
SREBF1-219	ENST00000580540.1	540	No protein	Retained intron
SREBF1-220	ENST00000581707.1	695	No protein	Retained intron
SREBF1-221	ENST00000583080.1	482	No protein	Retained intron
SREBF1-222	ENST00000583732.1	580	No protein	Processed transcript
SREBF1-223	ENST00000584760.1	564	No protein	Retained intron

SREBF1 gene encodes 1147 amino acid sized protein which has 121675 Da molecular mass. SREBF1 is helix-loop-helix transcriptional activator required for lipid homeostasis (Figure 3). Regulates transcription of the LDL receptor gene as well as the fatty acid and cholesterol synthesis pathways. 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).

The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. After cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. Alternative promoter usage and splicing result in multiple transcript variants. 6 isoforms are described. Isoform 1A has been choosen as the canonical sequence (provided by RefSeq, Nov 2017). Quaternary structure of protein 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 (By similarity).
Post-translational modifications: 
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 CASP3 and CASP7 (caspase-3 and caspase-7).
Phosphorylated by AMPK (P
rotein kinase AMP-activated catalytic subunits), leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-402 by SIK1 represses activity possibly by inhibiting DNA-binding.
Ubiquitinatylated at Lys347, Lys379, Lys587, Lys675, Lys934, Lys1070.

Expressed in a wide variety of tissues, most abundant in fat and adrenal gland. In fetal tissues, lung and liver shows highest expression. Isoform SREBF-1C predominates in liver, adrenal gland and ovary, whereas isoform SREBF-1A predominates in hepatoma cell lines. Isoform SREBF-1A and isoform SREBF-1C are found in kidney, brain, white fat, and muscle.

Endoplasmic reticulum membrane, golgi membrane, nuclear envelope, nucleoplasm, nucleus, COPII - coated vesicle membrane.

SREBF1 Transcription factor binds to the sterol regulatory element-1 (SRE1) (5-ATCACCCCAC-3) which is a motif found in the promoter of the low density lipoprotein receptor genes and other genes that involved in sterol biosynthesis. Depletion of cholesterol leads to intra-membrane proteolysis, releasing the active portion of SREBF1 containing the basic DNA-binding region from the endoplasmic reticulum membrane. After translocation to the nucleus and binding to its specific DNA sequences, SREBF1 dimers induce the expression of target genes involved in adipogenesis and membrane biogenesis (Nohturfft and Zhang, 2009).

SREBF1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito and frog (Table 2).
Table 2. Pairwise alignment of SREBF1 gene and protein sequences (in distance from human).

Gene		Identity %&
Species	Symbol	Protein	DNA
H. Sapiens	SREBF1
vs. P.troglodytes	SREBF1	98.7	99.0
vs. M.mulatta	SREBF1	97.5	97.1
vs. C.lupus	SREBF1	87.9	87.2
vs. B.taurus	SREBF1	84.5	85.8
vs. M.musculus	Srebf1	81.2	80.9
vs. R.norvegicus	Srebf1	81.6	82.0
vs.  G.gallus	SREBF1	65.8	69.5
vs. X.tropicalis	srebf1	67.0	65.9
vs D.reriro	srebf1	61.3	62.4
vs D.melanogaster	HLH106	37.5	48.4
vs. A.gambiae	AgaP_AGAP000076	39.2	49.7

304 missense, 36 truncating and 3 inframe and 7 other mutations of SREBF1 was identified in 74247 samples from 240 studies (cBioPortal) (Figure 4).

4 SNPs were registered for SREBF1 (according to SNPedia and Human Gene Mutation Database).