AC T01556
XX
ID T01556
XX
DT 14.09.1995 (created); ewi.
DT 16.04.2015 (updated); asv.
CO Copyright (C), QIAGEN.
XX
FA SREBP-1a
XX
SY Sterol Regulatory Element Binding Protein 1a.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G003956 SREBF1; HGNC: SREBF1.
XX
CL C0012; bHLH-ZIP; 1.2.6.3.1.1.
XX
SZ 1147 AA; 121.6 kDa (cDNA) (calc.), 125 kDa (SDS) [5]
XX
SQ MDEPPFSEAALEQALGEPCDLDAALLTDIEDMLQLINNQDSDFPGLFDPPYAGSGAGGTD
SQ PASPDTSSPGSLSPPPATLSSSLEAFLSGPQAAPSPLSPPQPAPTPLKMYPSMPAFSPGP
SQ GIKEESVPLSILQTPTPQPLPGALLPQSFPAPAPPQFSSTPVLGYPSPPGGFSTGSPPGN
SQ TQQPLPGLPLASPPGVPPVSLHTQVQSVVPQQLLTVTAAPTAAPVTTTVTSQIQQVPVLL
SQ QPHFIKADSLLLTAMKTDGATVKAAGLSPLVSGTTVQTGPLPTLVSGGTILATVPLVVDA
SQ EKLPINRLAAGSKAPASAQSRGEKRTAHNAIEKRYRSSINDKIIELKDLVVGTEAKLNKS
SQ AVLRKAIDYIRFLQHSNQKLKQENLSLRTAVHKSKSLKDLVSACGSGGNTDVLMEGVKTE
SQ VEDTLTPPPSDAGSPFQSSPLSLGSRGSGSGGSGSDSEPDSPVFEDSKAKPEQRPSLHSR
SQ GMLDRSRLALCTLVFLCLSCNPLASLLGARGLPSPSDTTSVYHSPGRNVLGTESRDGPGW
SQ AQWLLPPVVWLLNGLLVLVSLVLLFVYGEPVTRPHSGPAVYFWRHRKQADLDLARGDFAQ
SQ AAQQLWLALRALGRPLPTSHLDLACSLLWNLIRHLLQRLWVGRWLAGRAGGLQQDCALRV
SQ DASASARDAALVYHKLHQLHTMGKHTGGHLTATNLALSALNLAECAGDAVSVATLAEIYV
SQ AAALRVKTSLPRALHFLTRFFLSSARQACLAQSGSVPPAMQWLCHPVGHRFFVDGDWSVL
SQ STPWESLYSLAGNPVDPLAQVTQLFREHLLERALNCVTQPNPSPGSADGDKEFSDALGYL
SQ QLLNSCSDAAGAPAYSFSISSSMATTTGVDPVAKWWASLTAVVIHWLRRDEEAAERLCPL
SQ VEHLPRVLQESERPLPRAALHSFKAARALLGCAKAESGPASLTICEKASGYLQDSLATTP
SQ ASSSIDKAVQLFLCDLLLVVRTSLWRQQQPPAPAPAAQGASSRPQASALELRGFQRDLSS
SQ LRRLAQSFRPAMRRVFLHEATARLMAGASPTRTHQLLDRSLRRRAGPGGKGGAVAELEPR
SQ PTRREHAEALLLASCYLPPGFLSAPGQRVGMLAEAARTLEKLGDRRLLHDCQQMLMRLGG
SQ GTTVTSS
XX
SC Swiss-Prot#P36956-1
XX
FT 1 29 
replaced by 1-5 in SREBP-1c [4].
FT 322 374 
PS50888; HLH.
FT 324 374 
PF00010; Helix-loop-helix DNA-binding domain.
FT 329 379 
SM00353; finulus.
FT 460 461 
SCA cleavage site [6].
FT 835 1142 
PF00478; IMP dehydrogenase / GMP reductase domain.
FT 1035 1147 
replaced by 1035-1071 in SREBP-1b and by 1011-1047 in SREBP-1c [4].
XX
SF The isoforms SREBP-1a and SREBP-1c differ only at their extreme N termini, more see SREBP-1c [15];
SF one of the three splice variants, for others see SREBP-1b T01557 and SREBP-1c T01558;
SF bHLH domain exhibits 44% identity with TFE3 [2];
SF in cell extracts, N-terminal proteolytically processed proteins of 59-68 kDa are found to bind to sterol regulatory elements [1] [5];
SF cleaved by the cysteine protease SCA (SREBP cleavage activity) between positions 468 and 469 [6];
SF the mature factor then translocates to the nucleus [5];
XX
CP adult: high in liver, adrenal gland, lower in muscle, kidney, placenta, very low in lung, nearly undetectable in pancreas, brain, heart; fetal: highest levels in liver, lung, lower in kidney, very low in heart, brain [2].
XX
FF suppressed vascular endothelial growth factor (VEGF) promoter activities through the direct interaction with the four proximal tandem SP1 sites [13];
FF protein-protein interaction of SREBP-1a and sp1 in the absence of DNA [14];
FF Sp1 and SREBP-1a added together leads to a synergistic activation of LDLR promoter [16];
FF androgen treatment caused an increase in expression [12];
FF Yin Yang 1 protein (YY1) inhibits the SREBP-mediated activation of the low density lipoprotein receptor (LDLR) in a sensitive and dose-dependent manner. [14];
FF activate transcription by interacting with the C/H1 domain of CBP coactivator [15];
FF Chromatin, TAFs and a new coactivator, which includes CBP, are all required to mediate full synergistic activation by Dp1 and SREBP-1a [16];
FF transcriptional activator, acting through sterol regulatory elements (SRE) [4];
FF sterols may reduce or enhance trans-activation, depending on the amount of SREBP-1 (or cofactors) present [4];
FF SREBP-1 precursors are attached to the nuclear envelope and to the ER [5];
XX
IN T05287 HNF-4alpha; mouse, Mus musculus.
IN T21984 p300; human, Homo sapiens.
IN T23091 p300; Mammalia.
IN T10428 YY1; mouse, Mus musculus.
XX
MX M00220 V$SREBP1_01.
MX M00221 V$SREBP1_02.
MX M01173 V$SREBP1_Q5.
MX M00749 V$SREBP1_Q6.
MX M04632 V$SREBP1_Q6_01.
MX M00776 V$SREBP_Q3.
MX M01168 V$SREBP_Q6.
XX
BS R24183.
BS R22195.
BS R31889.
BS R31890.
BS R31891.
BS R18536.
BS R19294.
BS R26039.
BS R31211.
BS R28157.
BS R04416.
BS R22190.
BS R31366.
BS R31016.
BS R41841.
BS R41842.
BS R21206.
BS R31245.
BS R20296.
BS R20297.
BS R28174.
BS R13175.
BS R13177.
BS R28173.
BS R37141.
BS R37142.
BS R21130.
BS R21060.
BS R21061.
BS R21062.
BS R21063.
BS R21064.
BS R21065.
BS R21066.
BS R21067.
BS R31911.
BS R22767.
BS R31897.
BS R28421.
BS R28422.
BS R28423.
BS R19465.
BS R19307.
BS R29996.
BS R18554.
BS R28444.
BS R04430.
BS R04432.
BS R19305.
BS R19438.
BS R31640.
BS R19452.
BS R25109.
BS R30415.
BS R31238.
BS R04919.
BS R04920.
XX
DR TRANSPATH: MO000025761.
DR TRANSCOMPEL: C00206.
DR TRANSCOMPEL: C00207.
DR TRANSCOMPEL: C00208.
DR TRANSCOMPEL: C00209.
DR TRANSCOMPEL: C00211.
DR EMBL: S66167;
DR EMBL: S66168;
DR EMBL: U00968;
DR UniProtKB: P36956-1;
XX
RN [1]; RE0003430.
RX PUBMED: 8314806.
RA Wang X., Briggs M. R., Hua X., Yokoyama C., Goldstein J. L., Brown M. S.
RT Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter (2. Purification and characterization)
RL J. Biol. Chem. 268:14497-14504 (1993).
RN [2]; RE0003432.
RX PUBMED: 2298751.
RA Smith J. R., Osborne T. F., Goldstein J. L., Brown M. S.
RT Identification of nucleotides responsible for enhancer activity of sterol regulatory element in low density lipoprotein receptor genes
RL J. Biol. Chem. 265:2306-2310 (1990).
RN [3]; RE0003433.
RX PUBMED: 1967820.
RA Goldstein J. L., Brown M. S.
RT Regulation of the mevalonate pathway
RL Nature 343:425-430 (1990).
RN [4]; RE0003434.
RX PUBMED: 8402897.
RA Yokoyama C., Wang X., Briggs M. R., Admon A., Wu J., Hua X., Goldstein J., Brown M. S.
RT SREBP-1, a basic helix-loop-helix leucine zipper protein that controls transcription of the low density lipoprotein receptor gene
RL Cell 75:187-197 (1993).
RN [5]; RE0003435.
RX PUBMED: 8156598.
RA Wang X., Sato R. R., Brown M. S., Hua X., Goldstein J. L.
RT SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
RL Cell 77:53-62 (1994).
RN [6]; RE0005535.
RX PUBMED: 7629113.
RA Wang X., Pai J., Wiedenfeld E. A., Medina J. C., Slaughter C. A., Goldstein J. L., Brown M. S.
RT Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembran domains
RL J. Biol. Chem. 270:18044-18050 (1995).
RN [7]; RE0029395.
RX PUBMED: 10627507.
RA Kotzka J., Muller-Wieland D., Roth G., Kremer L., Munck M., Schurmann S., Knebel B., Krone W.
RT Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade.
RL J. Lipid Res. 41:99-108 (2000).
RN [8]; RE0043449.
RX PUBMED: 12640139.
RA Giandomenico V., Simonsson M., Gronroos E., Ericsson J.
RT Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors
RL Mol. Cell. Biol. 23:2587-99 (2003).
RN [9]; RE0046020.
RX PUBMED: 12145339.
RA Halder S. K., Fink M., Waterman M. R., Rozman D.
RT A cAMP-responsive element binding site is essential for sterol regulation of the human lanosterol 14alpha-demethylase gene (CYP51)
RL Mol. Endocrinol. 16:1853-63 (2002).
RN [10]; RE0051013.
RX PUBMED: 10915800.
RA Roth G., Kotzka J., Kremer L., Lehr S., Lohaus C., Meyer H. E., Krone W., Muller-Wieland D.
RT MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro.
RL J. Biol. Chem. 275:33302-33307 (2000).
RN [11]; RE0066824.
RX PUBMED: 20450493.
RA Ishimoto K., Tachibana K., Hanano I., Yamasaki D., Nakamura H., Kawai M., Urano Y., Tanaka T., Hamakubo T., Sakai J., Kodama T., Doi T.
RT Sterol regulatory element-binding protein 2 and nuclear factor Y controls human farnesyl diphosphate synthase expression and affects cell proliferation in hepatoblastoma cells.
RL Biochem. J. 429:347-357 (2010).
RN [12]; RE0028949.
RX PUBMED: 11579213.
RA Heemers H., Maes B., Foufelle F., Heyns W., Verhoeven G., Swinnen J. V.
RT Androgens stimulate lipogenic gene expression in prostate cancer cells by activation of the sterol regulatory element-binding protein cleavage activating protein/sterol regulatory element-binding protein pathway.
RL Mol. Endocrinol. 15:1817-28 (2001).
RN [13]; RE0047696.
RX PUBMED: 16480961.
RA Motoyama K., Fukumoto S., Koyama H., Emoto M., Shimano H., Maemura K., Nishizawa Y.
RT SREBP inhibits VEGF expression in human smooth muscle cells.
RL Biochem. Biophys. Res. Commun. 342:354-360 (2006).
RN [14]; RE0047713.
RX PUBMED: 10224053.
RA Bennett M. K., Ngo T. T., Athanikar J. N., Rosenfeld J. M., Osborne T. F.
RT Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein.
RL J. Biol. Chem. 274:13025-13032 (1999).
RN [15]; RE0047938.
RX PUBMED: 15340088.
RA Toth J. I., Datta S., Athanikar J. N., Freedman L. P., Osborne T. F.
RT Selective coactivator interactions in gene activation by SREBP-1a and -1c.
RL Mol. Cell. Biol. 24:8288-8300 (2004).
RN [16]; RE0047975.
RX PUBMED: 9765204.
RA Naar A. M., Beaurang P. A., Robinson K. M., Oliner J. D., Avizonis D., Scheek S., Zwicker J., Kadonaga J. T., Tjian R.
RT Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro.
RL Genes Dev. 12:3020-3031 (1998).
XX
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