NameHistone-arginine methyltransferase CARM1
Synonyms
  • 2.1.1.319
  • Coactivator-associated arginine methyltransferase 1
  • PRMT4
  • Protein arginine N-methyltransferase 4
Gene NameCARM1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009311|Histone-arginine methyltransferase CARM1
MAAAAAAVGPGAGGAGSAVPGGAGPCATVSVFPGARLLTIGDANGEIQRHAEQQALRLEV
RAGPDSAGIALYSHEDVCVFKCSVSRETECSRVGKQSFIITLGCNSVLIQFATPNDFCSF
YNILKTCRGHTLERSVFSERTEESSAVQYFQFYGYLSQQQNMMQDYVRTGTYQRAILQNH
TDFKDKIVLDVGCGSGILSFFAAQAGARKIYAVEASTMAQHAEVLVKSNNLTDRIVVIPG
KVEEVSLPEQVDIIISEPMGYMLFNERMLESYLHAKKYLKPSGNMFPTIGDVHLAPFTDE
QLYMEQFTKANFWYQPSFHGVDLSALRGAAVDEYFRQPVVDTFDIRILMAKSVKYTVNFL
EAKEGDLHRIEIPFKFHMLHSGLVHGLAFWFDVAFIGSIMTVWLSTAPTEPLTHWYQVRC
LFQSPLFAKAGDTLSGTCLLIANKRQSYDISIVAQVDQTGSKSSNLLDLKNPFFRYTGTT
PSPPPGSHYTSPSENMWNTGSTYNLSSGMAVAGMPTAYDLSSVIASGSSVGHNNLIPLAN
TGIVNHTHSRMGSIMSTGIVQGSSGAQGSGGGSTSAHYAVNSQFTMGGPAISMASPMSIP
TNTMHYGS
Number of residues608
Molecular Weight65853.185
Theoretical pINot Available
GO Classification
Functions
  • histone methyltransferase activity (H3-R17 specific)
  • lysine-acetylated histone binding
  • ligand-dependent nuclear receptor transcription coactivator activity
  • transcription regulatory region DNA binding
  • protein methyltransferase activity
  • transcription coactivator activity
  • beta-catenin binding
  • histone-arginine N-methyltransferase activity
  • protein-arginine N-methyltransferase activity
  • protein-arginine omega-N asymmetric methyltransferase activity
  • histone methyltransferase activity
Processes
  • histone methylation
  • positive regulation of fat cell differentiation
  • transcription, DNA-templated
  • aging
  • viral process
  • endochondral bone morphogenesis
  • histone H3-R17 methylation
  • histone H3-R2 methylation
  • intracellular estrogen receptor signaling pathway
  • negative regulation of protein binding
  • negative regulation of dendrite development
  • chromatin organization
  • regulation of intracellular estrogen receptor signaling pathway
  • regulation of growth plate cartilage chondrocyte proliferation
  • small molecule metabolic process
  • regulation of mRNA binding
  • regulation of transcription, DNA-templated
  • response to cAMP
  • peptidyl-arginine methylation, to asymmetrical-dimethyl arginine
  • positive regulation of cell proliferation
  • cellular lipid metabolic process
Components
  • RNA polymerase II transcription factor complex
  • cytoplasm
  • nucleus
  • cytosol
  • nucleoplasm
General FunctionTranscription regulatory region dna binding
Specific FunctionMethylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ86X55
UniProtKB Entry NameCARM1_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0013733|Histone-arginine methyltransferase CARM1 (CARM1)
ATGGCAGCGGCGGCGGCGGCGGTGGGGCCGGGCGCGGGCGGCGCGGGGTCGGCGGTCCCG
GGCGGCGCGGGGCCCTGCGCTACCGTGTCGGTGTTCCCCGGCGCCCGCCTCCTCACCATC
GGCGACGCGAACGGCGAGATCCAGCGGCACGCGGAGCAGCAGGCGCTGCGCCTCGAGGTG
CGCGCCGGCCCGGACTCGGCGGGCATCGCCCTCTACAGCCATGAAGATGTGTGTGTCTTT
AAGTGCTCAGTGTCCCGAGAGACAGAGTGCAGCCGTGTGGGCAAGCAGTCCTTCATCATC
ACCCTGGGCTGCAACAGCGTCCTCATCCAGTTCGCCACACCCAACGATTTCTGTTCCTTC
TACAACATCCTGAAAACCTGCCGGGGCCACACCCTGGAGCGGTCTGTGTTCAGCGAGCGG
ACGGAGGAGTCTTCTGCCGTGCAGTACTTCCAGTTTTATGGCTACCTGTCCCAGCAGCAG
AACATGATGCAGGACTACGTGCGGACAGGCACCTACCAGCGCGCCATCCTGCAAAACCAC
ACCGACTTCAAGGACAAGATCGTTCTTGATGTTGGCTGTGGCTCTGGGATCCTGTCGTTT
TTTGCCGCCCAAGCTGGAGCACGGAAAATCTACGCGGTGGAGGCCAGCACCATGGCCCAG
CACGCTGAGGTCTTGGTGAAGAGTAACAACCTGACGGACCGCATCGTGGTCATCCCGGGC
AAGGTGGAGGAGGTGTCACTCCCCGAGCAGGTGGACATCATCATCTCGGAGCCCATGGGC
TACATGCTCTTCAACGAGCGCATGCTGGAGAGCTACCTCCACGCCAAGAAGTACCTGAAG
CCCAGCGGAAACATGTTTCCTACCATTGGTGACGTCCACCTTGCACCCTTCACGGATGAA
CAGCTCTACATGGAGCAGTTCACCAAGGCCAACTTCTGGTACCAGCCATCTTTCCATGGA
GTGGACCTGTCGGCCCTCCGAGGTGCCGCGGTGGATGAGTATTTCCGGCAGCCTGTGGTG
GACACATTTGACATCCGGATCCTGATGGCCAAGTCTGTCAAGTACACGGTGAACTTCTTA
GAAGCCAAAGAAGGAGATTTGCACAGGATAGAAATCCCATTCAAATTCCACATGCTGCAT
TCAGGGCTGGTCCACGGCCTGGCTTTCTGGTTTGACGTTGCTTTCATCGGCTCCATAATG
ACCGTGTGGCTGTCCACAGCCCCGACAGAGCCCCTGACCCACTGGTACCAGGTGCGGTGC
CTGTTCCAGTCACCACTGTTCGCCAAGGCAGGGGACACGCTCTCAGGGACATGTCTGCTT
ATTGCCAACAAAAGACAGAGCTACGACATCAGTATTGTGGCCCAGGTGGACCAGACCGGC
TCCAAGTCCAGTAACCTCCTGGATCTGAAAAACCCCTTCTTTAGATACACGGGCACAACG
CCCTCACCCCCACCCGGCTCCCACTACACATCTCCCTCGGAAAACATGTGGAACACGGGC
AGCACCTACAACCTCAGCAGCGGGATGGCCGTGGCAGGGATGCCGACCGCCTATGACTTG
AGCAGTGTTATTGCCAGTGGCTCCAGCGTGGGCCACAACAACCTGATTCCTTTAGCCAAC
ACGGGGATTGTCAATCACACCCACTCCCGGATGGGCTCCATAATGAGCACGGGGATTGTC
CAAGGGTCCTCCGGCGCCCAGGGCAGTGGTGGTGGCAGCACGAGTGCCCACTATGCAGTC
AACAGCCAGTTCACCATGGGCGGCCCCGCCATCTCCATGGCGTCGCCCATGTCCATCCCG
ACCAACACCATGCACTACGGGAGCTAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:23393
Chromosome Location19
LocusNot Available
References
  1. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  2. 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
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. 17974005
  4. Li H, Park S, Kilburn B, Jelinek MA, Henschen-Edman A, Aswad DW, Stallcup MR, Laird-Offringa IA: Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase. J Biol Chem. 2002 Nov 22;277(47):44623-30. Epub 2002 Sep 16. 12237300
  5. Hong H, Kao C, Jeng MH, Eble JN, Koch MO, Gardner TA, Zhang S, Li L, Pan CX, Hu Z, MacLennan GT, Cheng L: Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status. Cancer. 2004 Jul 1;101(1):83-9. 15221992
  6. Ananthanarayanan M, Li S, Balasubramaniyan N, Suchy FJ, Walsh MJ: Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1. J Biol Chem. 2004 Dec 24;279(52):54348-57. Epub 2004 Oct 6. 15471871
  7. Lee YH, Coonrod SA, Kraus WL, Jelinek MA, Stallcup MR: Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3611-6. Epub 2005 Feb 24. 15731352
  8. Jeong SJ, Lu H, Cho WK, Park HU, Pise-Masison C, Brady JN: Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax. J Virol. 2006 Oct;80(20):10036-44. 17005681
  9. Miao F, Li S, Chavez V, Lanting L, Natarajan R: Coactivator-associated arginine methyltransferase-1 enhances nuclear factor-kappaB-mediated gene transcription through methylation of histone H3 at arginine 17. Mol Endocrinol. 2006 Jul;20(7):1562-73. Epub 2006 Feb 23. 16497732
  10. 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
  11. Lakowski TM, Frankel A: Kinetic analysis of human protein arginine N-methyltransferase 2: formation of monomethyl- and asymmetric dimethyl-arginine residues on histone H4. Biochem J. 2009 Jun 26;421(2):253-61. doi: 10.1042/BJ20090268. 19405910
  12. Feng Q, He B, Jung SY, Song Y, Qin J, Tsai SY, Tsai MJ, O'Malley BW: Biochemical control of CARM1 enzymatic activity by phosphorylation. J Biol Chem. 2009 Dec 25;284(52):36167-74. doi: 10.1074/jbc.M109.065524. Epub 2009 Oct 20. 19843527
  13. 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
  14. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. 22223895
  15. Sack JS, Thieffine S, Bandiera T, Fasolini M, Duke GJ, Jayaraman L, Kish KF, Klei HE, Purandare AV, Rosettani P, Troiani S, Xie D, Bertrand JA: Structural basis for CARM1 inhibition by indole and pyrazole inhibitors. Biochem J. 2011 Jun 1;436(2):331-9. doi: 10.1042/BJ20102161. 21410432