Serum response factor

Serum response factor (c-fos serum response element-binding transcription factor)
PDB rendering based on 1hbx.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1HBX​, 1K6O​, 1SRS​
Identifiers
Symbols	SRF ; MCM1
External IDs	OMIM: 600589 MGI: 106658 HomoloGene: 31135 GeneCards: SRF Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcription factor activity, RNA polymerase II core promoter sequence-specific • transcription factor activity, RNA polymerase II transcription factor binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • transcription factor activity, sequence-specific DNA binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • protein binding • transcription factor binding • serum response element binding • chromatin DNA binding • protein homodimerization activity • histone deacetylase binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • cytoplasm Biological process • patterning of blood vessels • response to hypoxia • mesoderm formation • neuron migration • trophectodermal cell differentiation • heart looping • morphogenesis of an epithelial sheet • cell migration involved in sprouting angiogenesis • positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation • transcription from RNA polymerase II promoter • cell-matrix adhesion • small GTPase mediated signal transduction • heart development • long-term memory • negative regulation of cell proliferation • associative learning • response to toxic substance • response to hormone • epithelial structure maintenance • positive regulation of transcription via serum response element binding • hippocampus development • tangential migration from the subventricular zone to the olfactory bulb • contractile actin filament bundle assembly • regulation of cell adhesion • platelet activation • platelet formation • negative regulation of cell migration • neuron projection development • regulation of water loss via skin • response to cytokine • megakaryocyte development • dorsal aorta morphogenesis • mRNA transcription from RNA polymerase II promoter • stress fiber assembly • skin morphogenesis • positive thymic T cell selection • sarcomere organization • positive regulation of cell differentiation • positive regulation of axon extension • positive regulation of transcription from RNA polymerase II promoter • positive regulation of smooth muscle contraction • positive regulation of transcription by glucose • muscle cell cellular homeostasis • developmental growth • neuron development • erythrocyte development • positive regulation of sequence-specific DNA binding transcription factor activity • regulation of smooth muscle cell differentiation • positive regulation of filopodium assembly • cardiac myofibril assembly • angiogenesis involved in wound healing • hematopoietic stem cell differentiation • positive regulation of transcription initiation from RNA polymerase II promoter • long term synaptic depression • heart trabecula formation • lung morphogenesis • bronchus cartilage development • trachea cartilage development • cardiac vascular smooth muscle cell differentiation • eyelid development in camera-type eye • lung smooth muscle development • bicellular tight junction assembly • cellular response to glucose stimulus • primitive streak formation • epithelial cell-cell adhesion • cellular senescence • negative regulation of beta-amyloid clearance Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6722	20807
Ensembl	ENSG00000112658	ENSMUSG00000015605
UniProt	P11831	Q9JM73
RefSeq (mRNA)	NM_001292001	NM_020493
RefSeq (protein)	NP_001278930	NP_065239
Location (UCSC)	Chr 6: 43.17 – 43.18 Mb	Chr 17: 46.55 – 46.56 Mb
PubMed search

Serum response factor, also known as SRF, is a transcription factor.^[1]

Function

Serum response factor 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 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] Interaction of SRF with other proteins such as myocardin or Elk-1 may enhance or suppress expression of genes important for growth of vascular smooth muscle.

Clinical significance

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

Interactions

Serum response factor has been shown to interact with:

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

References

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. PMC 545866. 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. PMC 2662566. PMID 19307725.
10. Jung DJ, Sung HS, Goo YW, Lee HM, Park OK, Jung SY, Lim J, Kim HJ, Lee SK, Kim TS, Lee JW, Lee YC (July 2002). "Novel transcription coactivator complex containing activating signal cointegrator 1". Mol. Cell. Biol. 22 (14): 5203–11. doi:10.1128/mcb.22.14.5203-5211.2002. PMC 139772. PMID 12077347.
11. Zhu C, Johansen FE, Prywes R (September 1997). "Interaction of ATF6 and serum response factor". Mol. Cell. Biol. 17 (9): 4957–66. PMC 232347. PMID 9271374.
12. Hanlon M, Sealy L (May 1999). "Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta". J. Biol. Chem. 274 (20): 14224–8. doi:10.1074/jbc.274.20.14224. PMID 10318842.
13. Sealy L, Malone D, Pawlak M (March 1997). "Regulation of the cfos serum response element by C/EBPbeta". Mol. Cell. Biol. 17 (3): 1744–55. doi:10.1128/mcb.17.3.1744. PMC 231899. PMID 9032301.
14. Matsuzaki K, Minami T, Tojo M, Honda Y, Saitoh N, Nagahiro S, Saya H, Nakao M (March 2003). "PML-nuclear bodies are involved in cellular serum response". Genes Cells 8 (3): 275–86. doi:10.1046/j.1365-2443.2003.00632.x. PMID 12622724.
15. Hassler M, Richmond TJ (June 2001). "The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex". EMBO J. 20 (12): 3018–28. doi:10.1093/emboj/20.12.3018. PMC 150215. PMID 11406578.
16. Belaguli NS, Sepulveda JL, Nigam V, Charron F, Nemer M, Schwartz RJ (October 2000). "Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators". Mol. Cell. Biol. 20 (20): 7550–8. doi:10.1128/mcb.20.20.7550-7558.2000. PMC 86307. PMID 11003651.
17. Morin S, Paradis P, Aries A, Nemer M (February 2001). "Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor". Mol. Cell. Biol. 21 (4): 1036–44. doi:10.1128/MCB.21.4.1036-1044.2001. PMC 99558. PMID 11158291.
18. Joliot V, Demma M, Prywes R (February 1995). "Interaction with RAP74 subunit of TFIIF is required for transcriptional activation by serum response factor". Nature 373 (6515): 632–5. doi:10.1038/373632a0. PMID 7854423.
19. Zhu H, Joliot V, Prywes R (February 1994). "Role of transcription factor TFIIF in serum response factor-activated transcription". J. Biol. Chem. 269 (5): 3489–97. PMID 8106390.
20. Grueneberg DA, Henry RW, Brauer A, Novina CD, Cheriyath V, Roy AL, Gilman M (October 1997). "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. doi:10.1101/gad.11.19.2482. PMC 316568. PMID 9334314.
21. Kim DW, Cheriyath V, Roy AL, Cochran BH (June 1998). "TFII-I enhances activation of the c-fos promoter through interactions with upstream elements". Mol. Cell. Biol. 18 (6): 3310–20. doi:10.1128/mcb.18.6.3310. PMC 108912. PMID 9584171.
22. Groisman R, Masutani H, Leibovitch MP, Robin P, Soudant I, Trouche D, Harel-Bellan A (March 1996). "Physical interaction between the mitogen-responsive serum response factor and myogenic basic-helix-loop-helix proteins". J. Biol. Chem. 271 (9): 5258–64. doi:10.1074/jbc.271.9.5258. PMID 8617811.
23. Biesiada E, Hamamori Y, Kedes L, Sartorelli V (April 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. 19 (4): 2577–84. PMC 84050. PMID 10082523.
24. Yamada K, Osawa H, Granner DK (October 1999). "Identification of proteins that interact with NF-YA". FEBS Lett. 460 (1): 41–5. doi:10.1016/s0014-5793(99)01311-3. PMID 10571058.
25. Lee SK, Kim JH, Lee YC, Cheong J, Lee JW (April 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. 275 (17): 12470–4. doi:10.1074/jbc.275.17.12470. PMID 10777532.
26. Kim HJ, Kim JH, Lee JW (October 1998). "Steroid receptor coactivator-1 interacts with serum response factor and coactivates serum response element-mediated transactivations". J. Biol. Chem. 273 (44): 28564–7. doi:10.1074/jbc.273.44.28564. PMID 9786846.
27. Gupta M, Kogut P, Davis FJ, Belaguli NS, Schwartz RJ, Gupta MP (March 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. 276 (13): 10413–22. doi:10.1074/jbc.M008625200. PMID 11136726.

External links

• Serum Response Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook SRF

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