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Serum response factor (c-fos serum response element-binding transcription factor)

PDB rendering based on 1hbx.
Available structures
1hbx, 1k6o, 1srs
Symbols SRF; MCM1
External IDs OMIM600589 MGI106658 HomoloGene31135 GeneCards: SRF Gene
RNA expression pattern
PBB GE SRF 202401 s at tn.png
PBB GE SRF 202400 s at tn.png
More reference expression data
Species Human Mouse
Entrez 6722 20807
Ensembl ENSG00000112658 ENSMUSG00000015605
UniProt P11831 Q9JM73
RefSeq (mRNA) NM_003131 NM_020493
RefSeq (protein) NP_003122 NP_065239
Location (UCSC) Chr 6:
43.25 - 43.26 Mb
Chr 17:
46.01 - 46.02 Mb
PubMed search [1] [2]

Serum response factor (c-fos serum response element-binding transcription factor), also known as SRF, is a transcription factor.[1]

It is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors.[2] This protein binds to the serum response element (SRE) in the promoter region of target genes. This protein regulates the activity of many immediate-early genes, for example c-fos, and thereby participates in cell cycle regulation, apoptosis, cell growth, and cell differentiation. This gene is the downstream target of many pathways; for example, the mitogen-activated protein kinase pathway (MAPK) that acts through the ternary complex factors (TCFs).[3][4]

SRF is considered very important during the development of the embryo, as it has been linked to the formation of mesoderm.[5][6] In the fully developed mammal, SRF is crucial for the growth of skeletal muscle.[7] Interaction of SRF with other proteins, such as steroid hormone receptors, may contribute to regulation of muscle growth by steroids.[8]

Lack of skin SRF is associated with psoriasis and other skin diseases.[9]


Serum response factor has been shown to interact with NFYA,[10] Src,[11] CREB binding protein,[12] GTF2I,[13][14] ATF6,[15] Nuclear receptor co-repressor 2,[16] CEBPB,[17][18] GATA4,[19][20] Myogenin,[21][22] GTF2F1,[23][24] TEAD1,[25] ELK4,[26][15] Promyelocytic leukemia protein[12] and ASCC3.[27]


  1. ^ Norman C, Runswick M, Pollock R, Treisman R (December 1988). "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. doi:10.1016/0092-8674(88)90244-9. PMID 3203386.  
  2. ^ Shore P, Sharrocks AD (April 1995). "The MADS-box family of transcription factors". Eur. J. Biochem. 229 (1): 1–13. doi:10.1111/j.1432-1033.1995.0001l.x. PMID 7744019.  
  3. ^ Dalton S, Marais R, Wynne J, Treisman R (June 1993). "Isolation and characterization of SRF accessory proteins". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 340 (1293): 325–32. doi:10.1098/rstb.1993.0074. PMID 8103935.  
  4. ^ "SRF serum response factor". Entrez Gene. National Center for Biotechnology Information, National Institutes of Health.  
  5. ^ Sepulveda JL, Vlahopoulos S, Iyer D, Belaguli N, Schwartz RJ (July 2002). "Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity". J. Biol. Chem. 277 (28): 25775–82. doi:10.1074/jbc.M203122200. PMID 11983708.  
  6. ^ Barron MR, Belaguli NS, Zhang SX, Trinh M, Iyer D, Merlo X, Lough JW, Parmacek MS, Bruneau BG, Schwartz RJ (March 2005). "Serum response factor, an enriched cardiac mesoderm obligatory factor, is a downstream gene target for Tbx genes". J. Biol. Chem. 280 (12): 11816–28. doi:10.1074/jbc.M412408200. PMID 15591049.  
  7. ^ Li S, Czubryt MP, McAnally J, Bassel-Duby R, Richardson JA, Wiebel FF, Nordheim A, Olson EN (January 2005). "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. doi:10.1073/pnas.0409103102. PMID 15647354.  
  8. ^ Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ (March 2005). "Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene". J. Biol. Chem. 280 (9): 7786–92. doi:10.1074/jbc.M413992200. PMID 15623502.  
  9. ^ Koegel H, von Tobel L, Schäfer M, Alberti S, Kremmer E, Mauch C, Hohl D, Wang XJ, Beer HD, Bloch W, Nordheim A, Werner S (April 2009). "Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice". J. Clin. Invest. 119 (4): 899–910. doi:10.1172/JCI37771. PMID 19307725.  
  10. ^ Yamada, K; Osawa H, Granner D K (Oct. 1999). "Identification of proteins that interact with NF-YA". FEBS Lett. (NETHERLANDS) 460 (1): 41–5. ISSN 0014-5793. PMID 10571058.  
  11. ^ Kim, H J; Kim J H, Lee J W (Oct. 1998). "Steroid receptor coactivator-1 interacts with serum response factor and coactivates serum response element-mediated transactivations". J. Biol. Chem. (UNITED STATES) 273 (44): 28564–7. ISSN 0021-9258. PMID 9786846.  
  12. ^ a b Matsuzaki, Kazuhito; Minami Takeshi, Tojo Masahide, Honda Yoshiomi, Saitoh Noriko, Nagahiro Shinji, Saya Hideyuki, Nakao Mitsuyoshi (Mar. 2003). "PML-nuclear bodies are involved in cellular serum response". Genes Cells (England) 8 (3): 275–86. ISSN 1356-9597. PMID 12622724.  
  13. ^ Grueneberg, D A; Henry R W, Brauer A, Novina C D, Cheriyath V, Roy A L, Gilman M (Oct. 1997). "A multifunctional DNA-binding protein that promotes the formation of serum response factor/homeodomain complexes: identity to TFII-I". Genes Dev. (UNITED STATES) 11 (19): 2482–93. ISSN 0890-9369. PMID 9334314.  
  14. ^ Kim, D W; Cheriyath V, Roy A L, Cochran B H (Jun. 1998). "TFII-I enhances activation of the c-fos promoter through interactions with upstream elements". Mol. Cell. Biol. (UNITED STATES) 18 (6): 3310–20. ISSN 0270-7306. PMID 9584171.  
  15. ^ a b Zhu, C; Johansen F E, Prywes R (Sep. 1997). "Interaction of ATF6 and serum response factor". Mol. Cell. Biol. (UNITED STATES) 17 (9): 4957–66. ISSN 0270-7306. PMID 9271374.  
  16. ^ Lee, S K; Kim J H, Lee Y C, Cheong J, Lee J W (Apr. 2000). "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. (UNITED STATES) 275 (17): 12470–4. ISSN 0021-9258. PMID 10777532.  
  17. ^ Hanlon, M; Sealy L (May. 1999). "Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta". J. Biol. Chem. (UNITED STATES) 274 (20): 14224–8. ISSN 0021-9258. PMID 10318842.  
  18. ^ Sealy, L; Malone D, Pawlak M (Mar. 1997). "Regulation of the cfos serum response element by C/EBPbeta". Mol. Cell. Biol. (UNITED STATES) 17 (3): 1744–55. ISSN 0270-7306. PMID 9032301.  
  19. ^ Belaguli, N S; Sepulveda J L, Nigam V, Charron F, Nemer M, Schwartz R J (Oct. 2000). "Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators". Mol. Cell. Biol. (UNITED STATES) 20 (20): 7550–8. ISSN 0270-7306. PMID 11003651.  
  20. ^ Morin, S; Paradis P, Aries A, Nemer M (Feb. 2001). "Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor". Mol. Cell. Biol. (United States) 21 (4): 1036–44. doi:10.1128/MCB.21.4.1036-1044.2001. ISSN 0270-7306. PMID 11158291.  
  21. ^ Groisman, R; Masutani H, Leibovitch M P, Robin P, Soudant I, Trouche D, Harel-Bellan A (Mar. 1996). "Physical interaction between the mitogen-responsive serum response factor and myogenic basic-helix-loop-helix proteins". J. Biol. Chem. (UNITED STATES) 271 (9): 5258–64. ISSN 0021-9258. PMID 8617811.  
  22. ^ Biesiada, E; Hamamori Y, Kedes L, Sartorelli V (Apr. 1999). "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. (UNITED STATES) 19 (4): 2577–84. ISSN 0270-7306. PMID 10082523.  
  23. ^ Joliot, V; Demma M, Prywes R (Feb. 1995). "Interaction with RAP74 subunit of TFIIF is required for transcriptional activation by serum response factor". Nature (ENGLAND) 373 (6515): 632–5. doi:10.1038/373632a0. ISSN 0028-0836. PMID 7854423.  
  24. ^ Zhu, H; Joliot V, Prywes R (Feb. 1994). "Role of transcription factor TFIIF in serum response factor-activated transcription". J. Biol. Chem. (UNITED STATES) 269 (5): 3489–97. ISSN 0021-9258. PMID 8106390.  
  25. ^ Gupta, M; Kogut P, Davis F J, Belaguli N S, Schwartz R J, Gupta M P (Mar. 2001). "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. (United States) 276 (13): 10413–22. doi:10.1074/jbc.M008625200. ISSN 0021-9258. PMID 11136726.  
  26. ^ Hassler, M; Richmond T J (Jun. 2001). "The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex". EMBO J. (England) 20 (12): 3018–28. doi:10.1093/emboj/20.12.3018. ISSN 0261-4189. PMID 11406578.  
  27. ^ Jung, Dong-Ju; Sung Hee-Sook, Goo Young-Wha, Lee Hyun Mi, Park Ok Ku, Jung Sung-Yun, Lim Janghoo, Kim Han-Jong, Lee Soo-Kyung, Kim Tae Sung, Lee Jae Woon, Lee Young Chul (Jul. 2002). "Novel transcription coactivator complex containing activating signal cointegrator 1". Mol. Cell. Biol. (United States) 22 (14): 5203–11. ISSN 0270-7306. PMID 12077347.  

External links

This article incorporates text from the United States National Library of Medicine ([3]), which is in the public domain.



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