Sterol regulatory element-binding protein 2

NameSterol regulatory element-binding protein 2
SynonymsBHLHD2 Class D basic helix-loop-helix protein 2 SREBP-2 SREBP2 Sterol regulatory element-binding transcription factor 2
Gene NameSREBF2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037297|Sterol regulatory element-binding protein 2
MDDSGELGGLETMETLTELGDELTLGDIDEMLQFVSNQVGEFPDLFSEQLCSSFPGSGGS
GSSSGSSGSSSSSSNGRGSSSGAVDPSVQRSFTQVTLPSFSPSAASPQAPTLQVKVSPTS
VPTTPRATPILQPRPQPQPQPQTQLQQQTVMITPTFSTTPQTRIIQQPLIYQNAATSFQV
LQPQVQSLVTSSQVQPVTIQQQVQTVQAQRVLTQTANGTLQTLAPATVQTVAAPQVQQVP
VLVQPQIIKTDSLVLTTLKTDGSPVMAAVQNPALTALTTPIQTAALQVPTLVGSSGTILT
TMPVMMGQEKVPIKQVPGGVKQLEPPKEGERRTTHNIIEKRYRSSINDKIIELKDLVMGT
DAKMHKSGVLRKAIDYIKYLQQVNHKLRQENMVLKLANQKNKLLKGIDLGSLVDNEVDLK
IEDFNQNVLLMSPPASDSGSQAGFSPYSIDSEPGSPLLDDAKVKDEPDSPPVALGMVDRS
RILLCVLTFLCLSFNPLTSLLQWGGAHDSDQHPHSGSGRSVLSFESGSGGWFDWMMPTLL
LWLVNGVIVLSVFVKLLVHGEPVIRPHSRSSVTFWRHRKQADLDLARGDFAAAAGNLQTC
LAVLGRALPTSRLDLACSLSWNVIRYSLQKLRLVRWLLKKVFQCRRATPATEAGFEDEAK
TSARDAALAYHRLHQLHITGKLPAGSACSDVHMALCAVNLAECAEEKIPPSTLVEIHLTA
AMGLKTRCGGKLGFLASYFLSRAQSLCGPEHSAVPDSLRWLCHPLGQKFFMERSWSVKSA
AKESLYCAQRNPADPIAQVHQAFCKNLLERAIESLVKPQAKKKAGDQEEESCEFSSALEY
LKLLHSFVDSVGVMSPPLSRSSVLKSALGPDIICRWWTSAITVAISWLQGDDAAVRSHFT
KVERIPKALEVTESPLVKAIFHACRAMHASLPGKADGQQSSFCHCERASGHLWSSLNVSG
ATSDPALNHVVQLLTCDLLLSLRTALWQKQASASQAVGETYHASGAELAGFQRDLGSLRR
LAHSFRPAYRKVFLHEATVRLMAGASPTRTHQLLEHSLRRRTTQSTKHGEVDAWPGQRER
ATAILLACRHLPLSFLSSPGQRAVLLAEAARTLEKVGDRRSCNDCQQMIVKLGGGTAIAA
S
Number of residues1141
Molecular Weight123686.44
Theoretical pINone
GO Classification
Functions
    protein C-terminus binding
RNA polymerase II core promoter proximal region sequence-specific DNA binding
transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding
E-box binding
Processes
    positive regulation of transcription from RNA polymerase II promoter
lipid metabolic process
regulation of mitophagy
negative regulation of transcription from RNA polymerase II promoter
cholesterol metabolic process
cellular response to laminar fluid shear stress
response to low-density lipoprotein particle
regulation of cholesterol homeostasis
positive regulation of protein targeting to mitochondrion
positive regulation of cholesterol storage
small molecule metabolic process
transcription, DNA-templated
regulation of lipid transport by negative regulation of transcription from RNA polymerase II promoter
negative regulation of cholesterol efflux
cellular response to starvation
Components
    ER to Golgi transport vesicle membrane
cytoplasm
Golgi membrane
nucleus
endoplasmic reticulum
endoplasmic reticulum membrane
SREBP-SCAP-Insig complex
cytosol
nucleoplasm
General FunctionTranscriptional repressor activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific FunctionTranscriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.
Transmembrane Regions480-500 534-554
GenBank Protein ID
UniProtKB IDQ12772
UniProtKB Entry NameSRBP2_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0019819|Sterol regulatory element-binding protein 2 (SREBF2)
ATGGACGACAGCGGCGAGCTGGGTGGTCTGGAGACCATGGAGACCCTCACGGAGCTGGGC
GACGAGCTGACCCTGGGAGACATCGACGAGATGCTGCAATTTGTCAGTAATCAAGTGGGA
GAGTTCCCTGACTTGTTTTCAGAACAGCTGTGTAGCTCCTTTCCTGGCAGTGGTGGTAGT
GGTAGCAGCAGCGGCAGCAGTGGCAGCAGCAGCAGCAGCAGCAATGGCAGGGGCAGCAGC
AGCGGAGCTGTGGACCCTTCAGTGCAACGGTCATTCACCCAGGTCACATTACCTTCCTTC
TCTCCCTCGGCGGCCTCCCCACAGGCTCCAACTCTGCAAGTCAAGGTTTCTCCCACCTCA
GTTCCCACCACACCCAGGGCAACTCCTATTCTTCAGCCCCGCCCCCAGCCCCAGCCTCAA
CCTCAAACTCAGCTGCAACAACAGACGGTAATGATCACGCCAACATTCAGCACCACTCCG
CAGACGAGGATCATCCAGCAGCCTTTGATATACCAGAATGCAGCTACTAGCTTTCAAGTC
CTTCAGCCTCAAGTCCAAAGCCTGGTGACATCCTCCCAGGTACAGCCGGTCACCATTCAG
CAGCAGGTGCAGACAGTACAGGCCCAGCGGGTGCTGACACAAACGGCCAATGGCACGCTG
CAGACCCTTGCCCCGGCTACGGTGCAGACAGTTGCTGCGCCACAGGTGCAGCAGGTCCCG
GTCCTGGTCCAGCCTCAGATCATCAAGACAGATTCCCTTGTTTTGACCACACTGAAGACA
GATGGCAGCCCTGTTATGGCTGCGGTCCAGAACCCGGCCCTCACCGCCCTCACCACCCCT
ATCCAGACGGCTGCCCTTCAAGTACCAACCCTGGTGGGCAGCAGTGGGACCATTCTGACC
ACAATGCCTGTAATGATGGGGCAAGAGAAAGTGCCCATTAAGCAGGTACCTGGGGGAGTC
AAGCAGCTTGAGCCCCCCAAAGAAGGAGAAAGGCGGACAACCCATAATATCATTGAGAAA
CGATATCGCTCCTCCATCAATGACAAAATCATCGAATTGAAAGACCTGGTCATGGGGACA
GACGCCAAGATGCACAAGTCTGGCGTTCTGAGGAAGGCCATTGATTACATCAAATACTTG
CAGCAGGTCAATCATAAACTGCGCCAGGAGAACATGGTGCTGAAGCTGGCAAATCAAAAG
AACAAGCTTCTAAAGGGCATCGACCTAGGCAGTCTGGTGGACAATGAGGTGGACCTGAAG
ATCGAGGACTTTAATCAGAATGTCCTTCTGATGTCCCCCCCAGCCTCTGACTCAGGGTCC
CAGGCTGGCTTCTCTCCCTACTCCATTGACTCTGAGCCAGGAAGCCCTCTATTGGATGAT
GCAAAGGTCAAAGATGAGCCAGACTCTCCTCCTGTGGCGCTGGGCATGGTAGACCGCTCA
CGGATTCTTCTGTGTGTCCTCACCTTCCTGTGCCTCTCCTTTAACCCCCTGACTTCCCTG
CTGCAGTGGGGAGGGGCCCACGACTCTGACCAGCACCCACACTCAGGCTCTGGCCGCAGT
GTCCTGTCATTCGAGTCAGGTTCTGGGGGCTGGTTTGACTGGATGATGCCTACTCTTCTC
TTATGGCTGGTAAATGGTGTGATTGTCCTGAGCGTCTTTGTGAAGCTGCTGGTTCATGGG
GAGCCAGTGATCCGGCCACACTCGCGCTCCTCGGTCACCTTCTGGAGGCACCGGAAACAG
GCAGATCTGGATCTCGCCAGAGGAGATTTTGCAGCTGCTGCCGGCAACCTACAAACCTGC
CTGGCAGTTTTGGGCCGGGCACTGCCCACCTCCCGCCTGGACCTGGCCTGCAGCCTCTCC
TGGAACGTGATCCGCTACAGCCTGCAGAAGCTACGCCTGGTGCGCTGGCTGCTCAAGAAA
GTCTTCCAGTGCCGGCGGGCCACGCCAGCCACTGAGGCAGGCTTTGAAGACGAAGCTAAG
ACCAGCGCCCGGGATGCGGCTCTGGCCTATCACCGGCTGCACCAGCTGCACATCACAGGG
AAGCTTCCTGCAGGATCCGCCTGTTCCGATGTACACATGGCGTTGTGTGCCGTGAACCTG
GCTGAATGTGCAGAGGAGAAGATCCCACCGAGCACACTGGTTGAGATCCATCTGACTGCT
GCCATGGGGCTCAAGACCCGGTGTGGAGGCAAGCTGGGCTTCCTGGCCAGCTACTTCCTC
AGCCGAGCCCAGAGCCTGTGTGGCCCCGAGCACAGTGCTGTTCCTGACTCCCTGCGCTGG
CTCTGCCACCCCCTGGGCCAGAAGTTTTTCATGGAGCGGAGCTGGTCTGTGAAGTCAGCT
GCCAAGGAGAGTCTATACTGTGCCCAGAGGAACCCAGCTGACCCCATTGCGCAGGTCCAC
CAGGCCTTCTGCAAGAACCTGCTGGAGCGAGCTATAGAGTCCTTGGTGAAACCTCAGGCC
AAGAAGAAGGCTGGAGACCAGGAAGAAGAGAGCTGTGAATTCTCCAGTGCTCTGGAGTAC
TTGAAATTACTTCATTCTTTTGTGGACTCTGTGGGGGTTATGAGCCCCCCACTCTCCAGG
AGCTCCGTGCTCAAGTCCGCCCTGGGTCCAGACATCATCTGTCGGTGGTGGACGTCTGCA
ATCACTGTGGCCATCAGCTGGCTCCAGGGAGACGATGCAGCTGTGCGCTCTCATTTTACC
AAAGTGGAACGCATCCCCAAGGCCCTGGAAGTGACAGAGAGCCCCCTGGTGAAGGCCATC
TTCCATGCCTGCAGAGCCATGCATGCCTCACTCCCTGGGAAAGCAGATGGGCAGCAGAGT
TCCTTCTGCCATTGCGAGAGGGCCAGTGGCCACCTATGGAGCAGCCTCAACGTCAGTGGG
GCCACCTCTGACCCTGCCCTCAACCACGTGGTCCAGCTGCTCACCTGTGACCTGCTACTG
TCGCTACGGACAGCGCTCTGGCAAAAACAGGCCAGTGCCAGCCAGGCTGTGGGGGAGACC
TACCACGCGTCAGGCGCTGAACTGGCGGGCTTCCAACGGGACCTGGGCAGCCTGCGCAGG
CTGGCACACAGCTTCCGCCCAGCATACCGCAAGGTGTTCCTGCATGAAGCCACCGTGCGC
CTGATGGCAGGAGCCAGCCCCACCCGCACCCACCAGCTGCTGGAACACAGCCTGCGGCGG
CGCACCACGCAGAGCACCAAGCACGGAGAGGTGGATGCCTGGCCCGGCCAGCGAGAGCGG
GCCACCGCCATCCTGCTGGCCTGCCGCCACCTGCCCCTCTCCTTCCTCTCCTCCCCGGGC
CAGCGGGCAGTGCTGCTGGCCGAAGCTGCCCGCACCCTGGAGAAGGTGGGCGACCGGCGC
TCCTGCAACGACTGCCAGCAGATGATTGTTAAGCTGGGTGGTGGCACTGCCATTGCCGCC
TCCTGA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:11290
Chromosome Location22
LocusNone
References
  1. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30.[15461802 ]
  2. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95.[10591208 ]
  3. Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS: SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 1993 Oct 8;75(1):187-97.[8402897 ]
  4. Hua X, Sakai J, Brown MS, Goldstein JL: Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane. J Biol Chem. 1996 Apr 26;271(17):10379-84.[8626610 ]
  5. Pai JT, Brown MS, Goldstein JL: Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5437-42.[8643593 ]
  6. Duncan EA, Dave UP, Sakai J, Goldstein JL, Brown MS: Second-site cleavage in sterol regulatory element-binding protein occurs at transmembrane junction as determined by cysteine panning. J Biol Chem. 1998 Jul 10;273(28):17801-9.[9651382 ]
  7. Ye J, Dave UP, Grishin NV, Goldstein JL, Brown MS: Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5123-8.[10805775 ]
  8. Irisawa M, Inoue J, Ozawa N, Mori K, Sato R: The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage. J Biol Chem. 2009 Oct 16;284(42):28995-9004. doi: 10.1074/jbc.M109.041376. Epub 2009 Aug 25.[19706601 ]
  9. Lee SJ, Sekimoto T, Yamashita E, Nagoshi E, Nakagawa A, Imamoto N, Yoshimura M, Sakai H, Chong KT, Tsukihara T, Yoneda Y: The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor. Science. 2003 Nov 28;302(5650):1571-5.[14645851 ]
  10. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7.[16959974 ]
  11. Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X: SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11603-7.[7903453 ]
  12. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7.[15489334 ]

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