SREBP-2

SREBF2
Estruturas disponíveis
PDB	Pesquisa Human UniProt: PDBe RCSB
Lista de códigos id do PDB
	1UKL
Identificadores
Nomes alternativos	SREBF2, SREBP-2
IDs externos	OMIM: 600481 HomoloGene: 20966 GeneCards: SREBF2
Ontologia genética
Função molecular	• C-8 sterol isomerase activity; • DNA binding; • protein dimerization activity; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • E-box binding; • protein C-terminus binding; • GO:0001948, GO:0016582 ligação a proteínas plasmáticas; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Componente celular	• citoplasma; • integral component of membrane; • citosol; • SREBP-SCAP-Insig complex; • complexo de Golgi; • endoplasmic reticulum membrane; • membrane; • Golgi membrane; • retículo endoplasmático; • ER to Golgi transport vesicle membrane; • GO:0016023 cytoplasmic vesicle; • núcleo celular; • cariolinfa; • mitocôndria; • intracellular membrane-bounded organelle;
Processo biológico	• steroid metabolic process; • GO:0009373 regulation of transcription, DNA-templated; • positive regulation of protein targeting to mitochondrion; • metabolismo dos lipídios; • positive regulation of cholesterol storage; • cellular response to laminar fluid shear stress; • cellular response to starvation; • cholesterol metabolic process; • GO:1901227 negative regulation of transcription by RNA polymerase II; • transcription, DNA-templated; • regulation of autophagy of mitochondrion; • negative regulation of cholesterol efflux; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • regulation of cholesterol biosynthetic process; • cellular response to low-density lipoprotein particle stimulus;
	Sources:Amigo / QuickGO
Ortólogos
	6721
	n/a
	ENSG00000198911
	n/a
	Q12772
	n/a
	NM_004599
	n/a
	NP_004590
	n/a
	Wikidata
Ver/Editar Humano

Proteína de ligação ao elemento regulador de esterol 2 (SREBP-2) também conhecida como fator de transcrição de ligação ao elemento regulador de esterol 2 (SREBF2) é uma proteína que em humanos é codificada pelo gene SREBF2. A proteína SREBP-2 desempenha um papel vital nos genes relacionados ao colesterol, regula a função dos macrófagos na resposta inflamatória.

Função

Este gene codifica um fator de transcrição expresso onipresente que controla a homeostase do colesterol, estimulando a transcrição de genes regulados por esteróis. A proteína codificada contém um domínio básico de zíper de leucina em hélice em hélice (bHLH-Zip). Vários polimorfismos de nucleotídeo único (SNPs) do SREBF2 foram identificados e alguns deles estão associados ao maior risco de osteoartrite do joelho.

Interações

Demonstrou-se que o SREBF2 interage com a INSIG1 e a proteína de ligação ao CREB.

Referências

↑ «Human PubMed Reference:»
↑ Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X (dezembro de 1993). «SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element». Proceedings of the National Academy of Sciences of the United States of America. 90 (24): 11603–7. Bibcode:1993PNAS...9011603H. PMC 48032. PMID 7903453. doi:10.1073/pnas.90.24.11603
↑ «Unlocking the secrets of faster wound healing». Tech Explorist (em inglês). 30 de agosto de 2019. Consultado em 30 de agosto de 2019
↑ «Entrez Gene: SREBF2 sterol regulatory element binding transcription factor 2» ^{[ligação inativa]}
↑ Qiu XM, Jin CT, Wang W (abril de 2014). «Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population». The Journal of International Medical Research. 42 (2): 320–8. PMID 24496149. doi:10.1177/0300060513507392
↑ Dobrosotskaya IY, Goldstein JL, Brown MS, Rawson RB (setembro de 2003). «Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs». The Journal of Biological Chemistry. 278 (37): 35837–43. PMID 12842885. doi:10.1074/jbc.M306476200
↑ Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (agosto de 2002). «Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER». Cell. 110 (4): 489–500. PMID 12202038. doi:10.1016/S0092-8674(02)00872-3
↑ Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R (novembro de 1996). «SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein». Genes & Development. 10 (22): 2903–11. PMID 8918891. doi:10.1101/gad.10.22.2903

Leitura adicional

Osborne TF (agosto de 2001). «CREating a SCAP-less liver keeps SREBPs pinned in the ER membrane and prevents increased lipid synthesis in response to low cholesterol and high insulin». Genes & Development. 15 (15): 1873–8. PMID 11485982. doi:10.1101/gad.916601
Szolkiewicz M, Chmielewski M, Nogalska A, Stelmanska E, Swierczynski J, Rutkowski B (janeiro de 2007). «The potential role of sterol regulatory element binding protein transcription factors in renal injury». Journal of Renal Nutrition. 17 (1): 62–5. PMID 17198935. doi:10.1053/j.jrn.2006.10.009
Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH (fevereiro de 1995). «Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13». Genomics. 25 (3): 667–73. PMID 7759101. doi:10.1016/0888-7543(95)80009-B
Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS (outubro de 1993). «SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene». Cell. 75 (1): 187–97. PMID 8402897. doi:10.1016/S0092-8674(05)80095-9
Wang X, Zelenski NG, Yang J, Sakai J, Brown MS, Goldstein JL (março de 1996). «Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis». The EMBO Journal. 15 (5): 1012–20. PMC 449996. PMID 8605870. doi:10.1002/j.1460-2075.1996.tb00438.x
Hua X, Sakai J, Brown MS, Goldstein JL (abril de 1996). «Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane». The Journal of Biological Chemistry. 271 (17): 10379–84. PMID 8626610. doi:10.1074/jbc.271.17.10379
Pai JT, Brown MS, Goldstein JL (maio de 1996). «Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins». Proceedings of the National Academy of Sciences of the United States of America. 93 (11): 5437–42. Bibcode:1996PNAS...93.5437P. PMC 39264. PMID 8643593. doi:10.1073/pnas.93.11.5437
Sato R, Inoue J, Kawabe Y, Kodama T, Takano T, Maeda M (outubro de 1996). «Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2». The Journal of Biological Chemistry. 271 (43): 26461–4. PMID 8900111. doi:10.1074/jbc.271.43.26461
Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R (novembro de 1996). «SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein». Genes & Development. 10 (22): 2903–11. PMID 8918891. doi:10.1101/gad.10.22.2903
Miserez AR, Cao G, Probst LC, Hobbs HH (fevereiro de 1997). «Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2)». Genomics. 40 (1): 31–40. PMID 9070916. doi:10.1006/geno.1996.4525
Duncan EA, Brown MS, Goldstein JL, Sakai J (maio de 1997). «Cleavage site for sterol-regulated protease localized to a leu-Ser bond in the lumenal loop of sterol regulatory element-binding protein-2». The Journal of Biological Chemistry. 272 (19): 12778–85. PMID 9139737. doi:10.1074/jbc.272.19.12778
Harris IR, Farrell AM, Holleran WM, Jackson S, Grunfeld C, Elias PM, Feingold KR (fevereiro de 1998). «Parallel regulation of sterol regulatory element binding protein-2 and the enzymes of cholesterol and fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes and murine epidermis». Journal of Lipid Research. 39 (2): 412–22. PMID 9508001
Kan HY, Pissios P, Chambaz J, Zannis VI (fevereiro de 1999). «DNA binding specificity and transactivation properties of SREBP-2 bound to multiple sites on the human apoA-II promoter». Nucleic Acids Research. 27 (4): 1104–17. PMC 148292. PMID 9927745. doi:10.1093/nar/27.4.1104
Seidah NG, Mowla SJ, Hamelin J, Mamarbachi AM, Benjannet S, Touré BB, Basak A, Munzer JS, Marcinkiewicz J, Zhong M, Barale JC, Lazure C, Murphy RA, Chrétien M, Marcinkiewicz M (fevereiro de 1999). «Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization». Proceedings of the National Academy of Sciences of the United States of America. 96 (4): 1321–6. Bibcode:1999PNAS...96.1321S. PMC 15461. PMID 9990022. doi:10.1073/pnas.96.4.1321
Nagoshi E, Imamoto N, Sato R, Yoneda Y (julho de 1999). «Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip». Molecular Biology of the Cell. 10 (7): 2221–33. PMC 25438. PMID 10397761. doi:10.1091/mbc.10.7.2221
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 (dezembro de 1999). «The DNA sequence of human chromosome 22». Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. PMID 10591208. doi:10.1038/990031
DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ (dezembro de 1999). «Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi». Cell. 99 (7): 703–12. PMID 10619424. doi:10.1016/S0092-8674(00)81668-2
Kotzka J, Müller-Wieland D, Roth G, Kremer L, Munck M, Schürmann S, Knebel B, Krone W (janeiro de 2000). «Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade». Journal of Lipid Research. 41 (1): 99–108. PMID 10627507
Yang T, Goldstein JL, Brown MS (setembro de 2000). «Overexpression of membrane domain of SCAP prevents sterols from inhibiting SCAP.SREBP exit from endoplasmic reticulum». The Journal of Biological Chemistry. 275 (38): 29881–6. PMID 10896675. doi:10.1074/jbc.M005439200

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[1] «Human PubMed Reference:»

[pmid7903453-2] Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X (dezembro de 1993). «SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element». Proceedings of the National Academy of Sciences of the United States of America. 90 (24): 11603–7. Bibcode:1993PNAS...9011603H. PMC 48032. PMID 7903453. doi:10.1073/pnas.90.24.11603

[3] «Unlocking the secrets of faster wound healing». Tech Explorist (em inglês). 30 de agosto de 2019. Consultado em 30 de agosto de 2019

[entrez-4] «Entrez Gene: SREBF2 sterol regulatory element binding transcription factor 2» ^{[ligação inativa]}

[pmid_=_24496149-5] Qiu XM, Jin CT, Wang W (abril de 2014). «Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population». The Journal of International Medical Research. 42 (2): 320–8. PMID 24496149. doi:10.1177/0300060513507392

[pmid12842885-6] Dobrosotskaya IY, Goldstein JL, Brown MS, Rawson RB (setembro de 2003). «Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs». The Journal of Biological Chemistry. 278 (37): 35837–43. PMID 12842885. doi:10.1074/jbc.M306476200

[pmid12202038-7] Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (agosto de 2002). «Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER». Cell. 110 (4): 489–500. PMID 12202038. doi:10.1016/S0092-8674(02)00872-3

[pmid8918891-8] Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R (novembro de 1996). «SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein». Genes & Development. 10 (22): 2903–11. PMID 8918891. doi:10.1101/gad.10.22.2903