血清応答因子

SRF
PDBに登録されている構造 PDB オルソログ検索: RCSB PDBe PDBj PDBのIDコード一覧 1HBX, 1K6O, 1SRS
識別子
記号	SRF, MCM1, serum response factor
外部ID	OMIM: 600589 MGI: 106658 HomoloGene: 31135 GeneCards: SRF
遺伝子の位置 (ヒト) 染色体 6番染色体 (ヒト)[1] バンド データ無し 開始点 43,171,269 bp[1] 終点 43,181,506 bp[1]
遺伝子の位置 (マウス) 染色体 17番染色体 (マウス)[2] バンド データ無し 開始点 46,859,255 bp[2] 終点 46,867,101 bp[2]
RNA発現パターン さらなる参照発現データ
遺伝子オントロジー 分子機能 • protein dimerization activity • DNA-binding transcription factor activity • DNA-binding transcription activator activity, RNA polymerase II-specific • RNA polymerase II general transcription initiation factor activity • primary miRNA binding • 転写因子結合 • RNA polymerase II cis-regulatory region sequence-specific DNA binding • protein homodimerization activity • serum response element binding • クロマチン結合 • 血漿タンパク結合 • DNA結合 • sequence-specific DNA binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • chromatin DNA binding • transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding • cis-regulatory region sequence-specific DNA binding • DNA-binding transcription factor activity, RNA polymerase II-specific • ヒストンデアセチラーゼ結合 • RNA polymerase II-specific DNA-binding transcription factor binding 細胞の構成要素 • 細胞質 • 細胞核 • 核質 生物学的プロセス • dorsal aorta morphogenesis • 気管支軟骨発生 • muscle cell cellular homeostasis • lung smooth muscle development • regulation of water loss via skin • transcription by RNA polymerase II • stress fiber assembly • cell migration involved in sprouting angiogenesis • platelet activation • cardiac myofibril assembly • heart looping • 細胞老化 • face development • regulation of cell adhesion • 長期抑圧 • neuron projection development • morphogenesis of an epithelial sheet • positive regulation of filopodium assembly • primitive streak formation • cellular response to glucose stimulus • negative regulation of cell population proliferation • response to cytokine • regulation of transcription, DNA-templated • heart trabecula formation • actin filament organization • 胸腺発生 • angiogenesis involved in wound healing • 血小板形成 • neuron development • in utero embryonic development • transcription, DNA-templated • positive regulation of transcription, DNA-templated • 心臓発生 • positive regulation of cell differentiation • branching involved in blood vessel morphogenesis • positive regulation of axon extension • positive regulation of smooth muscle contraction • 気管軟骨発生 • 毒性物質への反応 • positive regulation of pri-miRNA transcription by RNA polymerase II • positive regulation of transcription by glucose • regulation of smooth muscle cell differentiation • epithelial structure maintenance • associative learning • skin morphogenesis • positive regulation of DNA-binding transcription factor activity • epithelial cell-cell adhesion • neuron migration • positive regulation of transcription initiation from RNA polymerase II promoter • eyelid development in camera-type eye • 甲状腺発生 • negative regulation of amyloid-beta clearance • negative regulation of cell migration • developmental growth • hematopoietic stem cell differentiation • 原腸形成 • trophectodermal cell differentiation • positive thymic T cell selection • ホルモンへの反応 • cell-matrix adhesion • sarcomere organization • actin cytoskeleton organization • megakaryocyte development • 低酸素症への反応 • lung morphogenesis • mesoderm formation • cardiac vascular smooth muscle cell differentiation • mRNA transcription by RNA polymerase II • 多細胞個体の発生 • tangential migration from the subventricular zone to the olfactory bulb • 長期記憶 • contractile actin filament bundle assembly • bicellular tight junction assembly • leukocyte differentiation • 海馬発生 • positive regulation of transcription by RNA polymerase II • erythrocyte development • negative regulation of pri-miRNA transcription by RNA polymerase II • 前脳発生 • cell-cell adhesion 出典:Amigo / QuickGO
オルソログ
種	ヒト	マウス
Entrez	6722	20807
Ensembl	ENSG00000112658	ENSMUSG00000015605
UniProt	P11831,A0A024RD16	Q9JM73
RefSeq (mRNA)	NM_003131 NM_001292001	NM_020493
RefSeq (タンパク質)	NP_001278930 NP_003122 NP_003122.1	NP_065239
場所 (UCSC)	Chr 6: 43.17 – 43.18 Mb	Chr 6: 46.86 – 46.87 Mb
PubMed検索	[3]	[4]
ウィキデータ
閲覧/編集 ヒト 閲覧/編集 マウス

血清応答因子（けっせいおうとういんし、英: serum response factor、略称: SRF）は、転写因子として機能するタンパク質である[5]。

機能

血清応答因子はMADSボックススーパーファミリーに属する転写因子である[6]。このタンパク質は、標的遺伝子のプロモーター内の血清応答エレメント（serum response element; SRE）に結合する。このタンパク質はc-fosを含む多くの最初期遺伝子の活性を調節しており、それによって細胞周期の調節、アポトーシス、細胞成長、細胞分化に関与している。SRFは多くのシグナル伝達経路の下流の標的となっており、一例としてMAPK経路はTCFファミリー（ternary complex factor）を介してSRFの転写活性を調節する[7][8]。

SRFは胚発生時に重要であり、中胚葉の形成と関連づけられている[9][10]。完全に発達した哺乳類では、SRFは骨格筋の成長に重要である[11]。SRFとステロイドホルモン受容体（英語版）などとの相互作用は、ステロイドによる筋成長の調節に寄与している可能性がある[12]。またELK1などのTCFとミオカルディン（英語版）はSRFをめぐって競合し、それぞれ平滑筋遺伝子の発現を抑制、促進する[13]。

臨床的意義

SRFの欠損は乾癬やその他の皮膚疾患と関連している[14]。

相互作用

SRFは次に挙げる因子と相互作用することが示されている。

• ASCC3（英語版）[15]
• ATF6[16]
• CEBPB（英語版）[17][18]
• CERBBP（英語版）[19]
• ELK4（英語版）[16][20]
• GATA4（英語版）[21][22]
• GTF2F1（英語版）[23][24]
• GTF2I（英語版）[25][26]
• Myogenin（英語版）[27][28]
• NFYA（英語版）[29]
• NCOR2（英語版）[30]
• PML[19]
• Src[31]
• TEAD1（英語版）[32]

出典

1. ^ GRCh38: Ensembl release 89: ENSG00000112658 - Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000015605 - Ensembl, May 2017
3. Human PubMed Reference:
4. Mouse PubMed Reference:
5. “Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element”. Cell 55 (6): 989–1003. (December 1988). doi:10.1016/0092-8674(88)90244-9. PMID 3203386. 
6. “The MADS-box family of transcription factors”. Eur. J. Biochem. 229 (1): 1–13. (April 1995). doi:10.1111/j.1432-1033.1995.0001l.x. PMID 7744019. 
7. “Isolation and characterization of SRF accessory proteins”. Philos. Trans. R. Soc. Lond. B Biol. Sci. 340 (1293): 325–32. (June 1993). Bibcode: 1993RSPTB.340..325D. doi:10.1098/rstb.1993.0074. PMID 8103935. 
8. “SRF serum response factor [Homo sapiens (human) - Gene - NCBI]”. www.ncbi.nlm.nih.gov. 2024年10月5日閲覧。
9. “Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity”. J. Biol. Chem. 277 (28): 25775–82. (July 2002). doi:10.1074/jbc.M203122200. PMID 11983708. 
10. “Serum response factor, an enriched cardiac mesoderm obligatory factor, is a downstream gene target for Tbx genes”. J. Biol. Chem. 280 (12): 11816–28. (March 2005). doi:10.1074/jbc.M412408200. PMID 15591049. 
11. “Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice”. Proc. Natl. Acad. Sci. U.S.A. 102 (4): 1082–7. (January 2005). Bibcode: 2005PNAS..102.1082L. doi:10.1073/pnas.0409103102. PMC 545866. PMID 15647354. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC545866/. 
12. “Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene”. J. Biol. Chem. 280 (9): 7786–92. (March 2005). doi:10.1074/jbc.M413992200. PMID 15623502. 
13. Wang, Zhigao; Wang, Da-Zhi; Hockemeyer, Dirk; McAnally, John; Nordheim, Alfred; Olson, Eric N. (2004-03-11). “Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression”. Nature 428 (6979): 185–189. doi:10.1038/nature02382. ISSN 1476-4687. PMID 15014501. https://pubmed.ncbi.nlm.nih.gov/15014501. 
14. “Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice”. J. Clin. Invest. 119 (4): 899–910. (April 2009). doi:10.1172/JCI37771. PMC 2662566. PMID 19307725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662566/. 
15. “Novel transcription coactivator complex containing activating signal cointegrator 1”. Mol. Cell. Biol. 22 (14): 5203–11. (July 2002). doi:10.1128/mcb.22.14.5203-5211.2002. PMC 139772. PMID 12077347. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139772/. 
16. ^ “Interaction of ATF6 and serum response factor”. Mol. Cell. Biol. 17 (9): 4957–66. (September 1997). doi:10.1128/MCB.17.9.4957. PMC 232347. PMID 9271374. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC232347/. 
17. “Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta”. J. Biol. Chem. 274 (20): 14224–8. (May 1999). doi:10.1074/jbc.274.20.14224. PMID 10318842. 
18. “Regulation of the cfos serum response element by C/EBPbeta”. Mol. Cell. Biol. 17 (3): 1744–55. (March 1997). doi:10.1128/mcb.17.3.1744. PMC 231899. PMID 9032301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC231899/. 
19. ^ “PML-nuclear bodies are involved in cellular serum response”. Genes Cells 8 (3): 275–86. (March 2003). doi:10.1046/j.1365-2443.2003.00632.x. PMID 12622724. 
20. “The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex”. EMBO J. 20 (12): 3018–28. (June 2001). doi:10.1093/emboj/20.12.3018. PMC 150215. PMID 11406578. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC150215/. 
21. “Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators”. Mol. Cell. Biol. 20 (20): 7550–8. (October 2000). doi:10.1128/mcb.20.20.7550-7558.2000. PMC 86307. PMID 11003651. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC86307/. 
22. “Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor”. Mol. Cell. Biol. 21 (4): 1036–44. (February 2001). doi:10.1128/MCB.21.4.1036-1044.2001. PMC 99558. PMID 11158291. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99558/. 
23. “Interaction with RAP74 subunit of TFIIF is required for transcriptional activation by serum response factor”. Nature 373 (6515): 632–5. (February 1995). Bibcode: 1995Natur.373..632J. doi:10.1038/373632a0. PMID 7854423. 
24. “Role of transcription factor TFIIF in serum response factor-activated transcription”. J. Biol. Chem. 269 (5): 3489–97. (February 1994). doi:10.1016/S0021-9258(17)41889-8. PMID 8106390. 
25. “A multifunctional DNA-binding protein that promotes the formation of serum response factor/homeodomain complexes: identity to TFII-I”. Genes Dev. 11 (19): 2482–93. (October 1997). doi:10.1101/gad.11.19.2482. PMC 316568. PMID 9334314. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC316568/. 
26. “TFII-I enhances activation of the c-fos promoter through interactions with upstream elements”. Mol. Cell. Biol. 18 (6): 3310–20. (June 1998). doi:10.1128/mcb.18.6.3310. PMC 108912. PMID 9584171. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC108912/. 
27. “Physical interaction between the mitogen-responsive serum response factor and myogenic basic-helix-loop-helix proteins”. J. Biol. Chem. 271 (9): 5258–64. (March 1996). doi:10.1074/jbc.271.9.5258. PMID 8617811. 
28. “Myogenic basic helix-loop-helix proteins and Sp1 interact as components of a multiprotein transcriptional complex required for activity of the human cardiac alpha-actin promoter”. Mol. Cell. Biol. 19 (4): 2577–84. (April 1999). doi:10.1128/MCB.19.4.2577. PMC 84050. PMID 10082523. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84050/. 
29. “Identification of proteins that interact with NF-YA”. FEBS Lett. 460 (1): 41–5. (October 1999). Bibcode: 1999FEBSL.460...41Y. doi:10.1016/s0014-5793(99)01311-3. PMID 10571058. 
30. “Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor”. J. Biol. Chem. 275 (17): 12470–4. (April 2000). doi:10.1074/jbc.275.17.12470. PMID 10777532. 
31. “Steroid receptor coactivator-1 interacts with serum response factor and coactivates serum response element-mediated transactivations”. J. Biol. Chem. 273 (44): 28564–7. (October 1998). doi:10.1074/jbc.273.44.28564. PMID 9786846. 
32. “Physical interaction between the MADS box of serum response factor and the TEA/ATTS DNA-binding domain of transcription enhancer factor-1”. J. Biol. Chem. 276 (13): 10413–22. (March 2001). doi:10.1074/jbc.M008625200. PMID 11136726. 

関連文献

• “Rho-actin signaling to the MRTF coactivators dominates the immediate transcriptional response to serum in fibroblasts”. Genes & Development 28 (9): 943–58. (May 2014). doi:10.1101/gad.239327.114. PMC 4018493. PMID 24732378. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018493/. 
• “Suppression of the ERK–SRF axis facilitates somatic cell reprogramming”. Experimental & Molecular Medicine 50 (2): e448. (Feb 2018). doi:10.1038/emm.2017.279. PMC 5903827. PMID 29472703. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903827/. 
• “Serum Response Factor (SRF) Drives the Transcriptional Upregulation of the MDM4 Oncogene in HCC”. Cancers 13 (2): 199. (January 2021). doi:10.3390/cancers13020199. PMC 7829828. PMID 33429878. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829828/. 
• “Reprogramming progressive cells display low CAG promoter activity”. Stem Cells 39 (1): 43–54. (January 2021). doi:10.1002/stem.3295. PMC 7821215. PMID 33075202. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821215/. 
• “Cyclase-associated protein 2 (CAP2) controls MRTF-A localization and SRF activity in mouse embryonic fibroblasts”. Scientific Reports 11 (1): 4789. (February 2021). Bibcode: 2021NatSR..11.4789K. doi:10.1038/s41598-021-84213-w. PMC 7910472. PMID 33637797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910472/. 

関連項目

• MKL1（英語版）

外部リンク

• Serum Response Factor - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）
• FactorBook SRF