SRA1

Steroid receptor RNA activator 1 also known as steroid receptor RNA activator protein (SRAP) is a protein that in humans is encoded by the SRA1 gene.[4][5] The mRNA transcribed from the SRA1 gene is a component of the ribonucleoprotein complex containing NCOA1. This functional RNA also encodes a protein.[6]

SRA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MGX, 4NBO
Identifiers
Aliases	SRA1, SRA, SRAP, STRAA1, pp7684, steroid receptor RNA activator 1
External IDs	OMIM: 603819 MGI: 1344414 HomoloGene: 11906 GeneCards: SRA1
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q31.3 Start 140,537,340 bp[1] End 140,558,252 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001105 transcription coactivator activity • GO:0001948 protein binding • ligand-dependent nuclear receptor transcription coactivator activity • steroid receptor RNA activator RNA binding • DNA binding Cellular component • microtubule cytoskeleton • intercellular bridge • cell membrane • cell nucleus • nucleoplasm • cytosol • cytoplasm • ribonucleoprotein • transcription regulator complex • cell leading edge Biological process • regulation of apoptotic process • cell differentiation • positive regulation of receptor activity • cellular proliferation • regulation of transcription, DNA-templated • transcription, DNA-templated • apoptotic process • regulation of transcription from RNA polymerase II promoter • negative regulation of myoblast differentiation • cellular response to estrogen stimulus • positive regulation of nucleic acid-templated transcription Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10011	24068
Ensembl	ENSG00000213523	ENSMUSG00000006050
UniProt	Q9HD15	Q80VJ2
RefSeq (mRNA)	NM_001035235 NM_001253764	NM_001164406 NM_025291
RefSeq (protein)	NP_001030312 NP_001240693	NP_001157878 NP_079567
Location (UCSC)	Chr 5: 140.54 – 140.56 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is involved in transcriptional coactivation by steroid receptor. There is currently data suggesting this gene encodes both a non-coding RNA that functions as part of a ribonucleoprotein complex and a protein coding mRNA. Increased expression of both the transcript and the protein is associated with cancer.[5]

Interactions

SRA1 has been shown to interact with:

• Estrogen receptor alpha,[7]
• DDX17,[7]
• Nuclear receptor coactivator 2,[7] and
• SPEN.[8]

The SRAP has been shown to interact with its SRA RNA counterpart indirectly with the functional sub-structure STR7 of SRA RNA.[9] Originally proposed to be RRM containing, SRAP has been demonstrated to have a helix bundle at its C-terminal end while N-terminal to this domain appears unstructured.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000213523 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, O'Malley BW (April 1999). "A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex". Cell. 97 (1): 17–27. doi:10.1016/S0092-8674(00)80711-4. PMID 10199399.
5. "Entrez Gene: SRA1 steroid receptor RNA activator 1".
6. Chooniedass-Kothari S, Emberley E, Hamedani MK, Troup S, Wang X, Czosnek A, Hube F, Mutawe M, Watson PH, Leygue E (May 2004). "The steroid receptor RNA activator is the first functional RNA encoding a protein". FEBS Letters. 566 (1–3): 43–7. doi:10.1016/j.febslet.2004.03.104. PMID 15147866.
7. Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (March 2001). "A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA". The EMBO Journal. 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. PMC 145523. PMID 11250900.
8. Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM (May 2001). "Sharp, an inducible cofactor that integrates nuclear receptor repression and activation". Genes & Development. 15 (9): 1140–51. doi:10.1101/gad.871201. PMC 312688. PMID 11331609.
9. Hubé F, Velasco G, Rollin J, Furling D, Francastel C (January 2011). "Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation". Nucleic Acids Research. 39 (2): 513–25. doi:10.1093/nar/gkq833. PMC 3025577. PMID 20855289.
10. Bilinovich SM, Davis CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC (April 2014). "The C-terminal domain of SRA1p has a fold more similar to PRP18 than to an RRM and does not directly bind to the SRA1 RNA STR7 region". Journal of Molecular Biology. 426 (8): 1753–65. doi:10.1016/j.jmb.2014.01.007. PMID 24486611.

Further reading

• Ulveling D, Francastel C, Hubé F (April 2011). "When one is better than two: RNA with dual functions" (PDF). Biochimie. 93 (4): 633–44. doi:10.1016/j.biochi.2010.11.004. PMID 21111023.
• Hubé F, Velasco G, Rollin J, Furling D, Francastel C (January 2011). "Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation". Nucleic Acids Research. 39 (2): 513–25. doi:10.1093/nar/gkq833. PMC 3025577. PMID 20855289.
• Cooper C, Guo J, Yan Y, Chooniedass-Kothari S, Hube F, Hamedani MK, Murphy LC, Myal Y, Leygue E (July 2009). "Increasing the relative expression of endogenous non-coding Steroid Receptor RNA Activator (SRA) in human breast cancer cells using modified oligonucleotides". Nucleic Acids Research. 37 (13): 4518–31. doi:10.1093/nar/gkp441. PMC 2715257. PMID 19483093.
• Hube F, Guo J, Chooniedass-Kothari S, Cooper C, Hamedani MK, Dibrov AA, Blanchard AA, Wang X, Deng G, Myal Y, Leygue E (July 2006). "Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines". DNA and Cell Biology. 25 (7): 418–28. doi:10.1089/dna.2006.25.418. hdl:1807.1/831. PMID 16848684.
• Leygue E, Dotzlaw H, Watson PH, Murphy LC (September 1999). "Expression of the steroid receptor RNA activator in human breast tumors". Cancer Research. 59 (17): 4190–3. PMID 10485452.
• Murphy LC, Simon SL, Parkes A, Leygue E, Dotzlaw H, Snell L, Troup S, Adeyinka A, Watson PH (November 2000). "Altered expression of estrogen receptor coregulators during human breast tumorigenesis". Cancer Research. 60 (22): 6266–71. PMID 11103781.
• Cavarretta IT, Mukopadhyay R, Lonard DM, Cowsert LM, Bennett CF, O'Malley BW, Smith CL (February 2002). "Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation". Molecular Endocrinology. 16 (2): 253–70. doi:10.1210/me.16.2.253. PMID 11818499.
• Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK (July 2002). "A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1". The Journal of Biological Chemistry. 277 (29): 26098–102. doi:10.1074/jbc.M204013200. PMID 12118039.
• Ueda T, Mawji NR, Bruchovsky N, Sadar MD (October 2002). "Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells". The Journal of Biological Chemistry. 277 (41): 38087–94. doi:10.1074/jbc.M203313200. PMID 12163482.
• Lanz RB, Razani B, Goldberg AD, O'Malley BW (December 2002). "Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)". Proceedings of the National Academy of Sciences of the United States of America. 99 (25): 16081–6. doi:10.1073/pnas.192571399. PMC 138568. PMID 12444263.
• Emberley E, Huang GJ, Hamedani MK, Czosnek A, Ali D, Grolla A, Lu B, Watson PH, Murphy LC, Leygue E (February 2003). "Identification of new human coding steroid receptor RNA activator isoforms". Biochemical and Biophysical Research Communications. 301 (2): 509–15. doi:10.1016/S0006-291X(02)03070-X. PMID 12565891.
• Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR (August 2003). "Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor". Journal of Molecular Biology. 331 (4): 815–28. doi:10.1016/S0022-2836(03)00795-2. PMID 12909012.
• Deblois G, Giguère V (June 2003). "Ligand-independent coactivation of ERalpha AF-1 by steroid receptor RNA activator (SRA) via MAPK activation". The Journal of Steroid Biochemistry and Molecular Biology. 85 (2–5): 123–31. doi:10.1016/S0960-0760(03)00225-5. PMID 12943696. S2CID 34194523.
• Lanz RB, Chua SS, Barron N, Söder BM, DeMayo F, O'Malley BW (October 2003). "Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo". Molecular and Cellular Biology. 23 (20): 7163–76. doi:10.1128/MCB.23.20.7163-7176.2003. PMC 230309. PMID 14517287.
• Fleming FJ, Hill AD, McDermott EW, O'Higgins NJ, Young LS (January 2004). "Differential recruitment of coregulator proteins steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors to the estrogen receptor-estrogen response element by beta-estradiol and 4-hydroxytamoxifen in human breast cancer". The Journal of Clinical Endocrinology and Metabolism. 89 (1): 375–83. doi:10.1210/jc.2003-031048. PMID 14715875.
• Xu B, Koenig RJ (August 2004). "An RNA-binding domain in the thyroid hormone receptor enhances transcriptional activation". The Journal of Biological Chemistry. 279 (32): 33051–6. doi:10.1074/jbc.M404930200. PMID 15180993.
• Zhao X, Patton JR, Davis SL, Florence B, Ames SJ, Spanjaard RA (August 2004). "Regulation of nuclear receptor activity by a pseudouridine synthase through posttranscriptional modification of steroid receptor RNA activator". Molecular Cell. 15 (4): 549–58. doi:10.1016/j.molcel.2004.06.044. PMID 15327771.
• Coleman KM, Lam V, Jaber BM, Lanz RB, Smith CL (October 2004). "SRA coactivation of estrogen receptor-alpha is phosphorylation-independent, and enhances 4-hydroxytamoxifen agonist activity". Biochemical and Biophysical Research Communications. 323 (1): 332–8. doi:10.1016/j.bbrc.2004.08.090. PMID 15351741.

External links

• SRA1 human gene location in the UCSC Genome Browser.
• SRA1 human gene details in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q9HD15 (Human Steroid receptor RNA activator 1) at the PDBe-KB.
• Overview of all the structural information available in the PDB for UniProt: Q80VJ2 (Mouse Steroid receptor RNA activator 1) at the PDBe-KB.