Serine/arginine-rich splicing factor 1

Details

Name
Serine/arginine-rich splicing factor 1
Synonyms
  • Alternative-splicing factor 1
  • ASF
  • ASF-1
  • pre-mRNA-splicing factor SF2, P33 subunit
  • SF2
  • SF2P33
  • SFRS1
  • Splicing factor, arginine/serine-rich 1
Gene Name
SRSF1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051314|Serine/arginine-rich splicing factor 1
MSGGGVIRGPAGNNDCRIYVGNLPPDIRTKDIEDVFYKYGAIRDIDLKNRRGGPPFAFVE
FEDPRDAEDAVYGRDGYDYDGYRLRVEFPRSGRGTGRGGGGGGGGGAPRGRYGPPSRRSE
NRVVVSGLPPSGSWQDLKDHMREAGDVCYADVYRDGTGVVEFVRKEDMTYAVRKLDNTKF
RSHEGETAYIRVKVDGPRSPSYGRSRSRSRSRSRSRSRSNSRSRSYSPRRSRGSPRYSPR
HSRSRSRT
Number of residues
248
Molecular Weight
27744.335
Theoretical pI
Not Available
GO Classification
Functions
DNA topoisomerase binding / mRNA binding / protein kinase B binding / RNA binding / RS domain binding
Processes
alternative mRNA splicing, via spliceosome / cardiac muscle contraction / in utero embryonic development / liver regeneration / mRNA 3'-end processing / mRNA 5'-splice site recognition / mRNA export from nucleus / mRNA processing / mRNA splice site selection / mRNA splicing, via spliceosome / oligodendrocyte differentiation / positive regulation of RNA splicing / RNA export from nucleus / termination of RNA polymerase II transcription
Components
catalytic step 2 spliceosome / cytoplasm / extracellular exosome / nuclear speck / nucleoplasm / nucleus
General Function
Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway.
Specific Function
Dna topoisomerase binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051315|Serine/arginine-rich splicing factor 1 (SRSF1)
ATGTCGGGAGGTGGTGTGATTCGTGGCCCCGCAGGGAACAACGATTGCCGCATCTACGTG
GGTAACTTACCTCCAGACATCCGAACCAAGGACATTGAGGACGTGTTCTACAAATACGGC
GCTATCCGCGACATCGACCTCAAGAATCGCCGCGGGGGACCGCCCTTCGCCTTCGTTGAG
TTCGAGGACCCGCGAGACGCGGAAGACGCGGTGTATGGTCGCGACGGCTATGATTACGAT
GGGTACCGTCTGCGGGTGGAGTTTCCTCGAAGCGGCCGTGGAACAGGCCGAGGCGGCGGC
GGGGGTGGAGGTGGCGGAGCTCCCCGAGGTCGCTATGGCCCCCCATCCAGGCGGTCTGAA
AACAGAGTGGTTGTCTCTGGACTGCCTCCAAGTGGAAGTTGGCAGGATTTAAAGGATCAC
ATGCGTGAAGCAGGTGATGTATGTTATGCTGATGTTTACCGAGATGGCACTGGTGTCGTG
GAGTTTGTACGGAAAGAAGATATGACCTATGCAGTTCGAAAACTGGATAACACTAAGTTT
AGATCTCATGAGGGAGAAACTGCCTACATCCGGGTTAAAGTTGATGGGCCCAGAAGTCCA
AGTTATGGAAGATCTCGATCTCGAAGCCGTAGTCGTAGCAGAAGCCGTAGCAGAAGCAAC
AGCAGGAGTCGCAGTTACTCCCCAAGGAGAAGCAGAGGATCACCACGCTATTCTCCCCGT
CATAGCAGATCTCGCTCTCGTACATAA
Chromosome Location
17
Locus
17q22
External Identifiers
ResourceLink
UniProtKB IDQ07955
UniProtKB Entry NameSRSF1_HUMAN
HGNC IDHGNC:10780
General References
  1. Ge H, Zuo P, Manley JL: Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators. Cell. 1991 Jul 26;66(2):373-82. [Article]
  2. Krainer AR, Mayeda A, Kozak D, Binns G: Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators. Cell. 1991 Jul 26;66(2):383-94. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Zahler AM, Lane WS, Stolk JA, Roth MB: SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev. 1992 May;6(5):837-47. [Article]
  6. Mayeda A, Zahler AM, Krainer AR, Roth MB: Two members of a conserved family of nuclear phosphoproteins are involved in pre-mRNA splicing. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1301-4. [Article]
  7. Wu JY, Maniatis T: Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell. 1993 Dec 17;75(6):1061-70. [Article]
  8. Zuo P, Manley JL: Functional domains of the human splicing factor ASF/SF2. EMBO J. 1993 Dec;12(12):4727-37. [Article]
  9. Kohtz JD, Jamison SF, Will CL, Zuo P, Luhrmann R, Garcia-Blanco MA, Manley JL: Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA precursors. Nature. 1994 Mar 10;368(6467):119-24. [Article]
  10. Zuo P, Manley JL: The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5' splice sites. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3363-7. [Article]
  11. Tacke R, Manley JL: The human splicing factors ASF/SF2 and SC35 possess distinct, functionally significant RNA binding specificities. EMBO J. 1995 Jul 17;14(14):3540-51. [Article]
  12. Tronchere H, Wang J, Fu XD: A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA. Nature. 1997 Jul 24;388(6640):397-400. [Article]
  13. Caceres JF, Screaton GR, Krainer AR: A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes Dev. 1998 Jan 1;12(1):55-66. [Article]
  14. Ge H, Si Y, Wolffe AP: A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2. Mol Cell. 1998 Dec;2(6):751-9. [Article]
  15. Nayler O, Stratling W, Bourquin JP, Stagljar I, Lindemann L, Jasper H, Hartmann AM, Fackelmayer FO, Ullrich A, Stamm S: SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic Acids Res. 1998 Aug 1;26(15):3542-9. [Article]
  16. Barnard DC, Patton JG: Identification and characterization of a novel serine-arginine-rich splicing regulatory protein. Mol Cell Biol. 2000 May;20(9):3049-57. [Article]
  17. Cazalla D, Zhu J, Manche L, Huber E, Krainer AR, Caceres JF: Nuclear export and retention signals in the RS domain of SR proteins. Mol Cell Biol. 2002 Oct;22(19):6871-82. [Article]
  18. Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ: Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA. 2002 Apr;8(4):426-39. [Article]
  19. Huang Y, Gattoni R, Stevenin J, Steitz JA: SR splicing factors serve as adapter proteins for TAP-dependent mRNA export. Mol Cell. 2003 Mar;11(3):837-43. [Article]
  20. Aubol BE, Chakrabarti S, Ngo J, Shaffer J, Nolen B, Fu XD, Ghosh G, Adams JA: Processive phosphorylation of alternative splicing factor/splicing factor 2. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12601-6. Epub 2003 Oct 10. [Article]
  21. Cazalla D, Newton K, Caceres JF: A novel SR-related protein is required for the second step of Pre-mRNA splicing. Mol Cell Biol. 2005 Apr;25(8):2969-80. [Article]
  22. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  23. Loyer P, Trembley JH, Grenet JA, Busson A, Corlu A, Zhao W, Kocak M, Kidd VJ, Lahti JM: Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection. J Biol Chem. 2008 Mar 21;283(12):7721-32. doi: 10.1074/jbc.M708188200. Epub 2008 Jan 23. [Article]
  24. Ma CT, Velazquez-Dones A, Hagopian JC, Ghosh G, Fu XD, Adams JA: Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1. J Mol Biol. 2008 Feb 8;376(1):55-68. Epub 2007 Aug 21. [Article]
  25. Hagopian JC, Ma CT, Meade BR, Albuquerque CP, Ngo JC, Ghosh G, Jennings PA, Fu XD, Adams JA: Adaptable molecular interactions guide phosphorylation of the SR protein ASF/SF2 by SRPK1. J Mol Biol. 2008 Oct 17;382(4):894-909. doi: 10.1016/j.jmb.2008.07.055. Epub 2008 Jul 26. [Article]
  26. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  27. Huynh N, Ma CT, Giang N, Hagopian J, Ngo J, Adams J, Ghosh G: Allosteric interactions direct binding and phosphorylation of ASF/SF2 by SRPK1. Biochemistry. 2009 Dec 8;48(48):11432-40. doi: 10.1021/bi901107q. [Article]
  28. Ma CT, Hagopian JC, Ghosh G, Fu XD, Adams JA: Regiospecific phosphorylation control of the SR protein ASF/SF2 by SRPK1. J Mol Biol. 2009 Jul 24;390(4):618-34. doi: 10.1016/j.jmb.2009.05.060. Epub 2009 May 27. [Article]
  29. Ray D, Kazan H, Chan ET, Pena Castillo L, Chaudhry S, Talukder S, Blencowe BJ, Morris Q, Hughes TR: Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins. Nat Biotechnol. 2009 Jul;27(7):667-70. doi: 10.1038/nbt.1550. Epub 2009 Jun 28. [Article]
  30. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  31. Sinha R, Allemand E, Zhang Z, Karni R, Myers MP, Krainer AR: Arginine methylation controls the subcellular localization and functions of the oncoprotein splicing factor SF2/ASF. Mol Cell Biol. 2010 Jun;30(11):2762-74. doi: 10.1128/MCB.01270-09. Epub 2010 Mar 22. [Article]
  32. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  33. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  34. Kim YD, Lee JY, Oh KM, Araki M, Araki K, Yamamura K, Jun CD: NSrp70 is a novel nuclear speckle-related protein that modulates alternative pre-mRNA splicing in vivo. Nucleic Acids Res. 2011 May;39(10):4300-14. doi: 10.1093/nar/gkq1267. Epub 2011 Feb 3. [Article]
  35. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  36. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  37. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  38. Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, Yang V, Aguiar M, Kornhauser J, Jia X, Ren J, Beausoleil SA, Silva JC, Vemulapalli V, Bedford MT, Comb MJ: Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics. 2014 Jan;13(1):372-87. doi: 10.1074/mcp.O113.027870. Epub 2013 Oct 15. [Article]
  39. Xiao Z, Chang JG, Hendriks IA, Sigurethsson JO, Olsen JV, Vertegaal AC: System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability. Mol Cell Proteomics. 2015 May;14(5):1419-34. doi: 10.1074/mcp.O114.044792. Epub 2015 Mar 9. [Article]
  40. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  41. Ngo JC, Giang K, Chakrabarti S, Ma CT, Huynh N, Hagopian JC, Dorrestein PC, Fu XD, Adams JA, Ghosh G: A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1. Mol Cell. 2008 Mar 14;29(5):563-76. doi: 10.1016/j.molcel.2007.12.017. [Article]
  42. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB09130Copperapproved, investigationalunknownDetails