SRSF protein kinase 2

NameSRSF protein kinase 2
Synonyms
  • 2.7.11.1
  • Serine/arginine-rich protein-specific kinase 2
  • SFRS protein kinase 2
  • SR-protein-specific kinase 2
Gene NameSRPK2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037279|SRSF protein kinase 2
MSVNSEKSSSSERPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDP
ADYCKGGYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTE
TALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS
NYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQ
KAGAPPPSGSAVSTAPQQKPIGKISKNKKKKLKKKQKRQAELLEKRLQEIEELEREAERK
IIEENITSAAPSNDQDGEYCPEVKLKTTGLEEAAEAETAKDNGEAEDQEEKEDAEKENIE
KDEDDVDQELANIDPTWIESPKTNGHIENGPFSLEQQLDDEDDDEEDCPNPEEYNLDEPN
AESDYTYSSSYEQFNGELPNGRHKIPESQFPEFSTSLFSGSLEPVACGSVLSEGSPLTEQ
EESSPSHDRSRTVSASSTGDLPKAKTRAADLLVNPLDPRNADKIRVKIADLGNACWVHKH
FTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGEDYSRDEDHIA
HIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFT
DFLIPMLEMVPEKRASAGECLRHPWLNS
Number of residues688
Molecular Weight77525.955
Theoretical pI4.65
GO Classification
Functions
  • ATP binding
  • protein serine/threonine kinase activity
  • 14-3-3 protein binding
  • magnesium ion binding
  • poly(A) RNA binding
Processes
  • positive regulation of neuron apoptotic process
  • negative regulation of viral genome replication
  • positive regulation of viral genome replication
  • RNA splicing
  • spliceosomal complex assembly
  • regulation of mRNA splicing, via spliceosome
  • nuclear speck organization
  • cell differentiation
  • innate immune response
  • protein phosphorylation
  • positive regulation of cell proliferation
  • intracellular signal transduction
  • angiogenesis
  • positive regulation of gene expression
  • positive regulation of cell cycle
Components
  • cytoplasm
  • nucleus
  • nucleolus
  • nucleoplasm
General FunctionProtein serine/threonine kinase activity
Specific FunctionSerine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression. This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression. Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation. Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28. Can mediate hepatitis B virus (HBV) core protein phosphorylation. Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1857944
UniProtKB IDP78362
UniProtKB Entry NameSRPK2_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019557|SRSF protein kinase 2 (SRPK2)
ATGTCAGTTAACTCTGAGAAGTCGTCCTCTTCAGAAAGGCCGGAGCCTCAACAGAAAGCT
CCTTTAGTTCCTCCTCCTCCACCGCCACCACCACCACCACCGCCACCTTTGCCAGACCCC
ACACCCCCGGAGCCAGAGGAGGAGATCCTGGGATCAGATGATGAGGAGCAAGAGGACCCT
GCGGACTACTGCAAAGGTGGATATCATCCAGTGAAAATTGGAGACCTCTTCAATGGCCGG
TATCATGTTATTAGAAAGCTTGGATGGGGGCACTTCTCTACTGTCTGGCTGTGCTGGGAT
ATGCAGGGGAAAAGATTTGTTGCAATGAAAGTTGTAAAAAGTGCCCAGCATTATACGGAG
ACAGCCTTGGATGAAATAAAATTGCTCAAATGTGTTCGAGAAAGTGATCCCAGTGACCCA
AACAAAGACATGGTGGTCCAGCTCATTGACGACTTCAAGATTTCAGGCATGAATGGGATA
CATGTCTGCATGGTCTTCGAAGTACTTGGCCACCATCTCCTCAAGTGGATCATCAAATCC
AACTATCAAGGCCTCCCAGTACGTTGTGTGAAGAGTATCATTCGACAGGTCCTTCAAGGG
TTAGATTACTTACACAGTAAGTGCAAGATCATTCATACTGACATAAAGCCGGAAAATATC
TTGATGTGTGTGGATGATGCATATGTGAGAAGAATGGCAGCTGAGGCCACTGAGTGGCAG
AAAGCAGGTGCTCCTCCTCCTTCAGGGTCTGCAGTGAGTACGGCTCCACAGCAGAAACCT
ATAGGAAAAATATCTAAAAACAAAAAGAAAAAACTGAAAAAGAAACAGAAGAGGCAGGCT
GAGTTATTGGAGAAGCGCCTGCAGGAGATAGAAGAATTGGAGCGAGAAGCTGAAAGGAAA
ATAATAGAAGAAAACATCACCTCAGCTGCACCTTCCAATGACCAGGATGGCGAATACTGC
CCAGAGGTGAAACTAAAAACAACAGGATTAGAGGAGGCGGCTGAGGCAGAGACTGCAAAG
GACAATGGTGAAGCTGAGGACCAGGAAGAGAAAGAAGATGCTGAGAAAGAAAACATTGAA
AAAGATGAAGATGATGTAGATCAGGAACTTGCGAACATAGACCCTACGTGGATAGAATCA
CCTAAAACCAATGGCCATATTGAGAATGGCCCATTCTCACTGGAGCAGCAACTGGACGAT
GAAGATGATGATGAAGAAGACTGCCCAAATCCTGAGGAATATAATCTTGATGAGCCAAAT
GCAGAAAGTGATTACACATATAGCAGCTCCTATGAACAATTCAATGGTGAATTGCCAAAT
GGACGACATAAAATTCCCGAGTCACAGTTCCCAGAGTTTTCCACCTCGTTGTTCTCTGGA
TCCTTAGAACCTGTGGCCTGCGGCTCTGTGCTTTCTGAGGGATCACCACTTACTGAGCAA
GAGGAGAGCAGTCCATCCCATGACAGAAGCAGAACGGTTTCAGCCTCCAGTACTGGGGAT
TTGCCAAAAGCAAAAACCCGGGCAGCTGACTTGTTGGTGAATCCCCTGGATCCGCGGAAT
GCAGATAAAATTAGAGTAAAAATTGCTGACCTGGGAAATGCTTGTTGGGTGCATAAACAC
TTCACGGAAGACATCCAGACGCGTCAGTACCGCTCCATAGAGGTTTTAATAGGAGCGGGG
TACAGCACCCCTGCGGACATCTGGAGCACGGCGTGTATGGCATTTGAGCTGGCAACGGGA
GATTATTTGTTTGAACCACATTCTGGGGAAGACTATTCCAGAGACGAAGACCACATAGCC
CACATCATAGAGCTGCTAGGCAGTATTCCAAGGCACTTTGCTCTATCTGGAAAATATTCT
CGGGAATTCTTCAATCGCAGAGGAGAACTGCGACACATCACCAAGCTGAAGCCCTGGAGC
CTCTTTGATGTACTTGTGGAAAAGTATGGCTGGCCCCATGAAGATGCTGCACAGTTTACA
GATTTCCTGATCCCGATGTTAGAAATGGTTCCAGAAAAACGAGCCTCAGCTGGCGAATGC
CTTCGGCATCCTTGGTTGAATTCTTAG
GenBank Gene IDU88666
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:11306
Chromosome Location7
Locus7q22-q31.1
References
  1. Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD: SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. J Cell Biol. 1998 Feb 23;140(4):737-50. 9472028
  2. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. 12853948
  3. 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. 15489334
  4. Daub H, Blencke S, Habenberger P, Kurtenbach A, Dennenmoser J, Wissing J, Ullrich A, Cotten M: Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein. J Virol. 2002 Aug;76(16):8124-37. 12134018
  5. Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC: Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. Anal Chem. 2004 May 15;76(10):2763-72. 15144186
  6. Zheng Y, Fu XD, Ou JH: Suppression of hepatitis B virus replication by SRPK1 and SRPK2 via a pathway independent of the phosphorylation of the viral core protein. Virology. 2005 Nov 10;342(1):150-8. Epub 2005 Aug 24. 16122776
  7. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. 16964243
  8. Jang SW, Yang SJ, Ehlen A, Dong S, Khoury H, Chen J, Persson JL, Ye K: Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1. Cancer Res. 2008 Jun 15;68(12):4559-70. doi: 10.1158/0008-5472.CAN-08-0021. 18559500
  9. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  10. Mathew R, Hartmuth K, Mohlmann S, Urlaub H, Ficner R, Luhrmann R: Phosphorylation of human PRP28 by SRPK2 is required for integration of the U4/U6-U5 tri-snRNP into the spliceosome. Nat Struct Mol Biol. 2008 May;15(5):435-43. doi: 10.1038/nsmb.1415. Epub 2008 Apr 20. 18425142
  11. 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. 18669648
  12. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  13. Jang SW, Liu X, Fu H, Rees H, Yepes M, Levey A, Ye K: Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons. J Biol Chem. 2009 Sep 4;284(36):24512-25. doi: 10.1074/jbc.M109.026237. Epub 2009 Jul 10. 19592491
  14. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  15. 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. 20068231
  16. 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. 21269460
  17. Edmond V, Moysan E, Khochbin S, Matthias P, Brambilla C, Brambilla E, Gazzeri S, Eymin B: Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. EMBO J. 2011 Feb 2;30(3):510-23. doi: 10.1038/emboj.2010.333. Epub 2010 Dec 14. 21157427
  18. Giannakouros T, Nikolakaki E, Mylonis I, Georgatsou E: Serine-arginine protein kinases: a small protein kinase family with a large cellular presence. FEBS J. 2011 Feb;278(4):570-86. doi: 10.1111/j.1742-4658.2010.07987.x. Epub 2011 Jan 12. 21205200
  19. Hong Y, Jang SW, Ye K: The N-terminal fragment from caspase-cleaved serine/arginine protein-specific kinase2 (SRPK2) translocates into the nucleus and promotes apoptosis. J Biol Chem. 2011 Jan 7;286(1):777-86. doi: 10.1074/jbc.M110.193441. Epub 2010 Nov 5. 21056976
  20. 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. 21406692
  21. 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. 24275569
  22. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846