CARM1_MOUSE
ID CARM1_MOUSE Reviewed; 608 AA.
AC Q9WVG6; Q3TYB9; Q8K1Y5; Q91W24; Q99KX8;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Histone-arginine methyltransferase CARM1;
DE EC=2.1.1.319 {ECO:0000269|PubMed:11341840, ECO:0000269|PubMed:17882261, ECO:0000269|PubMed:19843527, ECO:0000269|PubMed:19897492, ECO:0000269|PubMed:21138967};
DE AltName: Full=Coactivator-associated arginine methyltransferase 1;
DE AltName: Full=Protein arginine N-methyltransferase 4;
GN Name=Carm1; Synonyms=Prmt4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF 189-VAL--ASP-191,
RP FUNCTION, TISSUE SPECIFICITY, METHYLATION OF HISTONE H3, AND INTERACTION
RP WITH NCOA1; NCOA2 AND NCOA3.
RC TISSUE=Embryo;
RX PubMed=10381882; DOI=10.1126/science.284.5423.2174;
RA Chen D., Ma H., Hong H., Koh S.S., Huang S.-M., Schurter B.T., Aswad D.W.,
RA Stallcup M.R.;
RT "Regulation of transcription by a protein methyltransferase.";
RL Science 284:2174-2177(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 261-608 (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary gland, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-608 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Visual cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION IN METHYLATION OF HISTONE H3, AND CATALYTIC ACTIVITY.
RX PubMed=11341840; DOI=10.1021/bi002631b;
RA Schurter B.T., Koh S.S., Chen D., Bunick G.J., Harp J.M., Hanson B.L.,
RA Henschen-Edman A., Mackay D.R., Stallcup M.R., Aswad D.W.;
RT "Methylation of histone H3 by coactivator-associated arginine
RT methyltransferase 1.";
RL Biochemistry 40:5747-5756(2001).
RN [5]
RP METHYLATION OF HISTONE H3.
RX PubMed=11747826; DOI=10.1016/s0960-9822(01)00600-5;
RA Ma H., Baumann C.T., Li H., Strahl B.D., Rice R., Jelinek M.A., Aswad D.W.,
RA Allis C.D., Hager G.L., Stallcup M.R.;
RT "Hormone-dependent, CARM1-directed, arginine-specific methylation of
RT histone H3 on a steroid-regulated promoter.";
RL Curr. Biol. 11:1981-1985(2001).
RN [6]
RP FUNCTION, METHYLATION OF EP300 AND CREBBP, MUTAGENESIS OF 189-VAL--ASP-191,
RP AND INTERACTION WITH EP300 AND CREBBP.
RX PubMed=11701890; DOI=10.1126/science.1065961;
RA Xu W., Chen H., Du K., Asahara H., Tini M., Emerson B.M., Montminy M.,
RA Evans R.M.;
RT "A transcriptional switch mediated by cofactor methylation.";
RL Science 294:2507-2511(2001).
RN [7]
RP METHYLATION OF HISTONE H3.
RX PubMed=12498683; DOI=10.1016/s0960-9822(02)01387-8;
RA Daujat S., Bauer U.-M., Shah V., Turner B., Berger S., Kouzarides T.;
RT "Crosstalk between CARM1 methylation and CBP acetylation on histone H3.";
RL Curr. Biol. 12:2090-2097(2002).
RN [8]
RP METHYLATION OF HISTONE H3.
RX PubMed=11751582; DOI=10.1093/embo-reports/kvf013;
RA Bauer U.-M., Daujat S., Nielsen S.J., Nightingale K., Kouzarides T.;
RT "Methylation at arginine 17 of histone H3 is linked to gene activation.";
RL EMBO Rep. 3:39-44(2002).
RN [9]
RP METHYLATION OF PABPC1.
RX PubMed=11850402; DOI=10.1093/embo-reports/kvf052;
RA Lee J., Bedford M.T.;
RT "PABP1 identified as an arginine methyltransferase substrate using high-
RT density protein arrays.";
RL EMBO Rep. 3:268-273(2002).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH
RP MEF2C.
RX PubMed=11713257; DOI=10.1074/jbc.m109835200;
RA Chen S.L., Loffler K.A., Chen D., Stallcup M.R., Muscat G.E.;
RT "The coactivator-associated arginine methyltransferase is necessary for
RT muscle differentiation: CARM1 coactivates myocyte enhancer factor-2.";
RL J. Biol. Chem. 277:4324-4333(2002).
RN [11]
RP FUNCTION, MUTAGENESIS OF GLU-267, AND INTERACTION WITH CTNNB1.
RX PubMed=11983685; DOI=10.1074/jbc.m110865200;
RA Koh S.S., Li H., Lee Y.-H., Widelitz R.B., Chuong C.-M., Stallcup M.R.;
RT "Synergistic coactivator function by coactivator-associated arginine
RT methyltransferase (CARM) 1 and beta-catenin with two different classes of
RT DNA-binding transcriptional activators.";
RL J. Biol. Chem. 277:26031-26035(2002).
RN [12]
RP METHYLATION OF ELAVL1.
RX PubMed=12237300; DOI=10.1074/jbc.m206187200;
RA Li H., Park S., Kilburn B., Jelinek M.A., Henschen-Edman A., Aswad D.W.,
RA Stallcup M.R., Laird-Offringa I.A.;
RT "Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing
RT protein, by CARM1. Coactivator-associated arginine methyltransferase.";
RL J. Biol. Chem. 277:44623-44630(2002).
RN [13]
RP CHARACTERIZATION, AND HOMOOLIGOMERIZATION.
RX PubMed=12351636; DOI=10.1074/jbc.m207623200;
RA Teyssier C., Chen D., Stallcup M.R.;
RT "Requirement for multiple domains of the protein arginine methyltransferase
RT CARM1 in its transcriptional coactivator function.";
RL J. Biol. Chem. 277:46066-46072(2002).
RN [14]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH EP300 AND NCOA2, AND MUTAGENESIS
RP OF GLU-267.
RX PubMed=11997499; DOI=10.1128/mcb.22.11.3621-3632.2002;
RA Lee Y.-H., Koh S.S., Zhang X., Cheng X., Stallcup M.R.;
RT "Synergy among nuclear receptor coactivators: selective requirement for
RT protein methyltransferase and acetyltransferase activities.";
RL Mol. Cell. Biol. 22:3621-3632(2002).
RN [15]
RP FUNCTION, DISRUPTION PHENOTYPE, AND METHYLATION OF PABPC1.
RX PubMed=12756295; DOI=10.1073/pnas.1232272100;
RA Yadav N., Lee J., Kim J., Shen J., Hu M.C.-T., Aldaz C.M., Bedford M.T.;
RT "Specific protein methylation defects and gene expression perturbations in
RT coactivator-associated arginine methyltransferase 1-deficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6464-6468(2003).
RN [16]
RP FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=15186775; DOI=10.1016/j.cell.2004.05.009;
RA An W., Kim J., Roeder R.G.;
RT "Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional
RT activation by p53.";
RL Cell 117:735-748(2004).
RN [17]
RP METHYLATION OF HISTONE H3.
RX PubMed=15339660; DOI=10.1016/j.cell.2004.08.020;
RA Cuthbert G.L., Daujat S., Snowden A.W., Erdjument-Bromage H., Hagiwara T.,
RA Yamada M., Schneider R., Gregory P.D., Tempst P., Bannister A.J.,
RA Kouzarides T.;
RT "Histone deimination antagonizes arginine methylation.";
RL Cell 118:545-553(2004).
RN [18]
RP FUNCTION, AND INTERACTION WITH FLII.
RX PubMed=14966289; DOI=10.1128/mcb.24.5.2103-2117.2004;
RA Lee Y.-H., Campbell H.D., Stallcup M.R.;
RT "Developmentally essential protein flightless I is a nuclear receptor
RT coactivator with actin binding activity.";
RL Mol. Cell. Biol. 24:2103-2117(2004).
RN [19]
RP METHYLATION OF HISTONE H3, FUNCTION, AND INTERACTION WITH RELA.
RX PubMed=15616592; DOI=10.1038/sj.emboj.7600500;
RA Covic M., Hassa P.O., Saccani S., Buerki C., Meier N.I., Lombardi C.,
RA Imhof R., Bedford M.T., Natoli G., Hottiger M.O.;
RT "Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-
RT kappaB-dependent gene expression.";
RL EMBO J. 24:85-96(2005).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16508003; DOI=10.1128/mcb.26.6.2273-2285.2006;
RA Fujiwara T., Mori Y., Chu D.L., Koyama Y., Miyata S., Tanaka H., Yachi K.,
RA Kubo T., Yoshikawa H., Tohyama M.;
RT "CARM1 regulates proliferation of PC12 cells by methylating HuD.";
RL Mol. Cell. Biol. 26:2273-2285(2006).
RN [21]
RP FUNCTION, INTERACTION WITH TRIM24, AND IDENTIFICATION IN A COMPLEX WITH
RP TRIM24 AND NCOA2.
RX PubMed=16322096; DOI=10.1210/me.2005-0393;
RA Teyssier C., Ou C.Y., Khetchoumian K., Losson R., Stallcup M.R.;
RT "Transcriptional intermediary factor 1alpha mediates physical interaction
RT and functional synergy between the coactivator-associated arginine
RT methyltransferase 1 and glucocorticoid receptor-interacting protein 1
RT nuclear receptor coactivators.";
RL Mol. Endocrinol. 20:1276-1286(2006).
RN [22]
RP FUNCTION.
RX PubMed=17218272; DOI=10.1016/j.molcel.2006.11.019;
RA Cheng D., Cote J., Shaaban S., Bedford M.T.;
RT "The arginine methyltransferase CARM1 regulates the coupling of
RT transcription and mRNA processing.";
RL Mol. Cell 25:71-83(2007).
RN [23]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18188184; DOI=10.1038/sj.embor.7401151;
RA Yadav N., Cheng D., Richard S., Morel M., Iyer V.R., Aldaz C.M.,
RA Bedford M.T.;
RT "CARM1 promotes adipocyte differentiation by coactivating PPARgamma.";
RL EMBO Rep. 9:193-198(2008).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, INTERACTION WITH EP300 AND NCOA3,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-154; SER-217 AND SER-229, AND
RP PHOSPHORYLATION AT SER-217.
RX PubMed=19843527; DOI=10.1074/jbc.m109.065524;
RA Feng Q., He B., Jung S.Y., Song Y., Qin J., Tsai S.Y., Tsai M.J.,
RA O'Malley B.W.;
RT "Biochemical control of CARM1 enzymatic activity by phosphorylation.";
RL J. Biol. Chem. 284:36167-36174(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, SUBUNIT, AND
RP MUTAGENESIS OF ARG-169 AND TYR-173.
RX PubMed=19897492; DOI=10.1074/jbc.m109.035865;
RA Kim D., Lee J., Cheng D., Li J., Carter C., Richie E., Bedford M.T.;
RT "Enzymatic activity is required for the in vivo functions of CARM1.";
RL J. Biol. Chem. 285:1147-1152(2010).
RN [27]
RP METHYLATION AT ARG-551, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF
RP ARG-551, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21138967; DOI=10.1093/nar/gkq1246;
RA Kuhn P., Chumanov R., Wang Y., Ge Y., Burgess R.R., Xu W.;
RT "Automethylation of CARM1 allows coupling of transcription and mRNA
RT splicing.";
RL Nucleic Acids Res. 39:2717-2726(2011).
RN [28]
RP FUNCTION, INTERACTION WITH SKP2, AND SUBCELLULAR LOCATION.
RX PubMed=30366907; DOI=10.1101/gad.315564.118;
RA Liu Y., Wang T., Ji Y.J., Johnson K., Liu H., Johnson K., Bailey S.,
RA Suk Y., Lu Y.N., Liu M., Wang J.;
RT "A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-
RT induced nutrient stress.";
RL Genes Dev. 32:1380-1397(2018).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 147-490 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH
RP NCOA2/GRIP1, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=17882261; DOI=10.1038/sj.emboj.7601856;
RA Yue W.W., Hassler M., Roe S.M., Thompson-Vale V., Pearl L.H.;
RT "Insights into histone code syntax from structural and biochemical studies
RT of CARM1 methyltransferase.";
RL EMBO J. 26:4402-4412(2007).
CC -!- FUNCTION: Methylates (mono- and asymmetric dimethylation) the guanidino
CC nitrogens of arginyl residues in several proteins involved in DNA
CC packaging, transcription regulation, pre-mRNA splicing, and mRNA
CC stability. Recruited to promoters upon gene activation together with
CC histone acetyltransferases from EP300/P300 and p160 families,
CC methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric
CC dimethylarginine (H3R17me2a), leading to activates transcription via
CC chromatin remodeling. During nuclear hormone receptor activation and
CC TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either
CC one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and
CC NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During
CC myogenic transcriptional activation, acts together with NCOA3/ACTR as a
CC coactivator for MEF2C. During monocyte inflammatory stimulation, acts
CC together with EP300/P300 as a coactivator for NF-kappa-B. Acts as
CC coactivator for PPARG, promotes adipocyte differentiation and the
CC accumulation of brown fat tissue. Plays a role in the regulation of
CC pre-mRNA alternative splicing by methylation of splicing factors. Also
CC seems to be involved in p53/TP53 transcriptional activation. Methylates
CC EP300/P300, both at 'Arg-2142', which may loosen its interaction with
CC NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which
CC impairs its interaction with CREB and inhibits CREB-dependent
CC transcriptional activation. Also methylates arginine residues in RNA-
CC binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-
CC stabilizing properties and the half-life of their target mRNAs. Acts as
CC a transcriptional coactivator of ACACA/acetyl-CoA carboxylase by
CC enriching H3R17 methylation at its promoter, thereby positively
CC regulating fatty acid synthesis (PubMed:30366907).
CC {ECO:0000269|PubMed:10381882, ECO:0000269|PubMed:11341840,
CC ECO:0000269|PubMed:11701890, ECO:0000269|PubMed:11713257,
CC ECO:0000269|PubMed:11983685, ECO:0000269|PubMed:11997499,
CC ECO:0000269|PubMed:12756295, ECO:0000269|PubMed:14966289,
CC ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15616592,
CC ECO:0000269|PubMed:16322096, ECO:0000269|PubMed:17218272,
CC ECO:0000269|PubMed:17882261, ECO:0000269|PubMed:18188184,
CC ECO:0000269|PubMed:19843527, ECO:0000269|PubMed:19897492,
CC ECO:0000269|PubMed:21138967, ECO:0000269|PubMed:30366907}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H(+) +
CC N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:48096, Rhea:RHEA-COMP:10532, Rhea:RHEA-
CC COMP:11991, ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61897; EC=2.1.1.319;
CC Evidence={ECO:0000269|PubMed:11341840, ECO:0000269|PubMed:17882261,
CC ECO:0000269|PubMed:19843527, ECO:0000269|PubMed:19897492,
CC ECO:0000269|PubMed:21138967};
CC -!- ACTIVITY REGULATION: Methylation of H3R17 (H3R17me) by CARM1 is
CC stimulated by preacetylation of H3 'Lys-18' (H3K18ac) H3 'Lys-23'
CC (H3K23ac) by EP300 and blocked by citrullination of H3 'Arg-17'
CC (H3R17ci) by PADI4. {ECO:0000269|PubMed:17882261}.
CC -!- SUBUNIT: Homodimer. Interacts with NR1H4. Interacts with SNRPC (By
CC similarity). Interacts with the C-terminus of NCOA2/GRIP1, NCO3/ACTR
CC and NCOA1/SRC1. Part of a complex consisting of CARM1, EP300/P300 and
CC NCOA2/GRIP1. Interacts with FLII, TP53, myogenic factor MEF2,
CC EP300/P300, TRIM24, CREBBP and CTNNB1. Interacts with RELA. Identified
CC in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with
CC NCOA3/SRC3. Interacts with SKP2 (PubMed:30366907). Interacts (via PH
CC domain-like fold) with C9orf72 (PubMed:30366907). {ECO:0000250,
CC ECO:0000269|PubMed:10381882, ECO:0000269|PubMed:11701890,
CC ECO:0000269|PubMed:11713257, ECO:0000269|PubMed:11983685,
CC ECO:0000269|PubMed:11997499, ECO:0000269|PubMed:14966289,
CC ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15616592,
CC ECO:0000269|PubMed:16322096, ECO:0000269|PubMed:17882261,
CC ECO:0000269|PubMed:19843527, ECO:0000269|PubMed:19897492,
CC ECO:0000269|PubMed:30366907}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11713257,
CC ECO:0000269|PubMed:19843527, ECO:0000269|PubMed:30366907}. Cytoplasm
CC {ECO:0000269|PubMed:11713257, ECO:0000269|PubMed:19843527,
CC ECO:0000269|PubMed:30366907}. Note=Mainly nuclear during the G1, S and
CC G2 phases of the cell cycle (By similarity). Cytoplasmic during
CC mitosis, after breakup of the nuclear membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q86X55}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WVG6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WVG6-2; Sequence=VSP_012508;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Within the brain, present
CC in proliferating cells from lateral ventricular zone and dentate gyrus
CC (at protein level). {ECO:0000269|PubMed:10381882,
CC ECO:0000269|PubMed:16508003}.
CC -!- DEVELOPMENTAL STAGE: At 9 dpc, expression is prominent in the neural
CC tube and somites. {ECO:0000269|PubMed:11713257}.
CC -!- PTM: Phosphorylation at Ser-217 is strongly increased during mitosis,
CC and decreases rapidly to a very low, basal level after entry into the
CC G1 phase of the cell cycle (By similarity). Phosphorylation at Ser-217
CC interferes with S-adenosyl-L-methionine binding and strongly reduces
CC methyltransferase activity. Phosphorylation at Ser-217 may promote
CC cytosolic location. {ECO:0000250, ECO:0000269|PubMed:19843527}.
CC -!- PTM: Auto-methylated on Arg-551. Methylation enhances transcription
CC coactivator activity. Methylation is required for its role in the
CC regulation of pre-mRNA alternative splicing.
CC {ECO:0000269|PubMed:10381882, ECO:0000269|PubMed:11701890,
CC ECO:0000269|PubMed:11747826, ECO:0000269|PubMed:11751582,
CC ECO:0000269|PubMed:11850402, ECO:0000269|PubMed:12237300,
CC ECO:0000269|PubMed:12498683, ECO:0000269|PubMed:12756295,
CC ECO:0000269|PubMed:15339660, ECO:0000269|PubMed:15616592,
CC ECO:0000269|PubMed:21138967}.
CC -!- DISRUPTION PHENOTYPE: Neonatal lethality. The lungs of neonates do not
CC inflate and they do not breathe. The same neonate lethality is observed
CC with mutants that produce CARM1 protein without enzyme activity.
CC Embryos are distinctly smaller at 18.5 dpc. They show reduced lipid
CC accumulation in brown adipose tissue and reduced amounts of brown
CC adipose tissue. Thymocyte differentiation is blocked at an early stage.
CC Mutants display complete loss of protein methylation of the CARM1
CC substrates PABPC1 and EP300/P300. {ECO:0000269|PubMed:12756295,
CC ECO:0000269|PubMed:18188184, ECO:0000269|PubMed:19897492}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Protein arginine N-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01015}.
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DR EMBL; AF117887; AAD41265.2; -; mRNA.
DR EMBL; BC003964; AAH03964.1; -; mRNA.
DR EMBL; BC008263; AAH08263.1; -; mRNA.
DR EMBL; BC036974; AAH36974.1; -; mRNA.
DR EMBL; AK158757; BAE34644.1; -; mRNA.
DR CCDS; CCDS22906.1; -. [Q9WVG6-1]
DR CCDS; CCDS52736.1; -. [Q9WVG6-2]
DR RefSeq; NP_067506.2; NM_021531.6. [Q9WVG6-1]
DR RefSeq; NP_694781.1; NM_153141.1. [Q9WVG6-2]
DR PDB; 2V74; X-ray; 2.70 A; B/D/F/H=147-490.
DR PDB; 2V7E; X-ray; 2.70 A; A/B=147-490.
DR PDB; 5IH3; X-ray; 1.77 A; A/B/C/D=130-487.
DR PDB; 5IS6; X-ray; 2.01 A; A/B/C/D=130-487.
DR PDB; 5IS7; X-ray; 2.29 A; A/B/C/D=130-487.
DR PDB; 5IS8; X-ray; 2.71 A; A/B/C/D=130-507.
DR PDB; 5IS9; X-ray; 2.40 A; A/B/C/D=130-487.
DR PDB; 5ISA; X-ray; 2.40 A; A/B/C/D=130-490.
DR PDB; 5ISB; X-ray; 2.00 A; A/B/C/D=130-487.
DR PDB; 5ISC; X-ray; 2.60 A; A/B/C/D=130-487.
DR PDB; 5ISD; X-ray; 2.60 A; A/B/C/D=130-487.
DR PDB; 5ISE; X-ray; 2.10 A; A/B/C/D=130-487.
DR PDB; 5ISF; X-ray; 2.22 A; A/B/C/D=130-487.
DR PDB; 5ISG; X-ray; 2.42 A; A/B/C/D=130-487.
DR PDB; 5ISH; X-ray; 2.15 A; A/B/C/D=130-487.
DR PDB; 5ISI; X-ray; 2.74 A; A/B/C/D=130-487.
DR PDB; 5K8V; X-ray; 2.25 A; A/B/C/D=130-487.
DR PDB; 5K8W; X-ray; 2.10 A; A/B/C/D=130-487.
DR PDB; 5K8X; X-ray; 1.99 A; A/B/C/D=130-487.
DR PDB; 5LGP; X-ray; 2.04 A; A/B/C/D=130-487.
DR PDB; 5LGQ; X-ray; 2.11 A; A/B/C/D=130-487.
DR PDB; 5LGR; X-ray; 2.00 A; A/B/C/D=130-487.
DR PDB; 5LGS; X-ray; 2.10 A; A/B/C/D=130-487.
DR PDB; 5LKJ; X-ray; 2.60 A; A/B/C/D=130-497.
DR PDB; 5LV2; X-ray; 2.29 A; A/B/C/D/E/F/G/H=130-487.
DR PDB; 5LV3; X-ray; 1.80 A; A/B/C/D=130-487.
DR PDB; 5NTC; X-ray; 2.25 A; A/B/C/D=130-497.
DR PDB; 5TBH; X-ray; 2.34 A; A/B/C/D=130-487.
DR PDB; 5TBI; X-ray; 2.29 A; A/B/C/D=130-487.
DR PDB; 5TBJ; X-ray; 2.32 A; A/B/C/D=130-487.
DR PDB; 7OKP; X-ray; 2.20 A; A/B/C/D=130-497.
DR PDB; 7OS4; X-ray; 2.54 A; A/B/C/D=130-497.
DR PDB; 7PPQ; X-ray; 2.10 A; A/B/C/D=130-487.
DR PDB; 7PPY; X-ray; 2.42 A; A/B/C/D=130-487.
DR PDB; 7PU8; X-ray; 2.19 A; A/B/C/D=130-487.
DR PDB; 7PUC; X-ray; 2.19 A; A/B/C/D=130-487.
DR PDB; 7PUQ; X-ray; 2.09 A; A/B/C/D=130-486.
DR PDB; 7PV6; X-ray; 2.40 A; A/B/C/D=130-497.
DR PDBsum; 2V74; -.
DR PDBsum; 2V7E; -.
DR PDBsum; 5IH3; -.
DR PDBsum; 5IS6; -.
DR PDBsum; 5IS7; -.
DR PDBsum; 5IS8; -.
DR PDBsum; 5IS9; -.
DR PDBsum; 5ISA; -.
DR PDBsum; 5ISB; -.
DR PDBsum; 5ISC; -.
DR PDBsum; 5ISD; -.
DR PDBsum; 5ISE; -.
DR PDBsum; 5ISF; -.
DR PDBsum; 5ISG; -.
DR PDBsum; 5ISH; -.
DR PDBsum; 5ISI; -.
DR PDBsum; 5K8V; -.
DR PDBsum; 5K8W; -.
DR PDBsum; 5K8X; -.
DR PDBsum; 5LGP; -.
DR PDBsum; 5LGQ; -.
DR PDBsum; 5LGR; -.
DR PDBsum; 5LGS; -.
DR PDBsum; 5LKJ; -.
DR PDBsum; 5LV2; -.
DR PDBsum; 5LV3; -.
DR PDBsum; 5NTC; -.
DR PDBsum; 5TBH; -.
DR PDBsum; 5TBI; -.
DR PDBsum; 5TBJ; -.
DR PDBsum; 7OKP; -.
DR PDBsum; 7OS4; -.
DR PDBsum; 7PPQ; -.
DR PDBsum; 7PPY; -.
DR PDBsum; 7PU8; -.
DR PDBsum; 7PUC; -.
DR PDBsum; 7PUQ; -.
DR PDBsum; 7PV6; -.
DR AlphaFoldDB; Q9WVG6; -.
DR SMR; Q9WVG6; -.
DR BioGRID; 208501; 27.
DR DIP; DIP-44593N; -.
DR IntAct; Q9WVG6; 8.
DR MINT; Q9WVG6; -.
DR STRING; 10090.ENSMUSP00000034703; -.
DR BindingDB; Q9WVG6; -.
DR ChEMBL; CHEMBL5538; -.
DR iPTMnet; Q9WVG6; -.
DR PhosphoSitePlus; Q9WVG6; -.
DR EPD; Q9WVG6; -.
DR MaxQB; Q9WVG6; -.
DR PaxDb; Q9WVG6; -.
DR PRIDE; Q9WVG6; -.
DR ProteomicsDB; 279910; -. [Q9WVG6-1]
DR ProteomicsDB; 279911; -. [Q9WVG6-2]
DR Antibodypedia; 25589; 654 antibodies from 40 providers.
DR DNASU; 59035; -.
DR Ensembl; ENSMUST00000034703; ENSMUSP00000034703; ENSMUSG00000032185. [Q9WVG6-1]
DR Ensembl; ENSMUST00000115395; ENSMUSP00000111053; ENSMUSG00000032185. [Q9WVG6-2]
DR GeneID; 59035; -.
DR KEGG; mmu:59035; -.
DR UCSC; uc009olu.2; mouse. [Q9WVG6-1]
DR UCSC; uc009olw.2; mouse. [Q9WVG6-2]
DR CTD; 10498; -.
DR MGI; MGI:1913208; Carm1.
DR VEuPathDB; HostDB:ENSMUSG00000032185; -.
DR eggNOG; KOG1500; Eukaryota.
DR GeneTree; ENSGT00940000160377; -.
DR HOGENOM; CLU_017375_0_1_1; -.
DR InParanoid; Q9WVG6; -.
DR OMA; KWLKPQG; -.
DR OrthoDB; 840669at2759; -.
DR PhylomeDB; Q9WVG6; -.
DR TreeFam; TF323332; -.
DR BRENDA; 2.1.1.319; 3474.
DR Reactome; R-MMU-3214858; RMTs methylate histone arginines.
DR Reactome; R-MMU-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR BioGRID-ORCS; 59035; 14 hits in 81 CRISPR screens.
DR ChiTaRS; Carm1; mouse.
DR EvolutionaryTrace; Q9WVG6; -.
DR PRO; PR:Q9WVG6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9WVG6; protein.
DR Bgee; ENSMUSG00000032185; Expressed in internal carotid artery and 270 other tissues.
DR ExpressionAtlas; Q9WVG6; baseline and differential.
DR Genevisible; Q9WVG6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:MGI.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0035642; F:histone methyltransferase activity (H3-R17 specific); IDA:UniProtKB.
DR GO; GO:0008469; F:histone-arginine N-methyltransferase activity; ISO:MGI.
DR GO; GO:0070577; F:lysine-acetylated histone binding; IDA:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0008276; F:protein methyltransferase activity; IDA:MGI.
DR GO; GO:0016274; F:protein-arginine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0035242; F:protein-arginine omega-N asymmetric methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0060350; P:endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0034969; P:histone arginine methylation; IDA:UniProtKB.
DR GO; GO:0034971; P:histone H3-R17 methylation; IDA:UniProtKB.
DR GO; GO:0034970; P:histone H3-R2 methylation; ISO:MGI.
DR GO; GO:0016571; P:histone methylation; IDA:MGI.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IGI:MGI.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IDA:HGNC-UCL.
DR GO; GO:2000171; P:negative regulation of dendrite development; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0071168; P:protein localization to chromatin; IMP:MGI.
DR GO; GO:0006479; P:protein methylation; IMP:MGI.
DR GO; GO:0003420; P:regulation of growth plate cartilage chondrocyte proliferation; IMP:MGI.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1902415; P:regulation of mRNA binding; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0051591; P:response to cAMP; ISO:MGI.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025799; Arg_MeTrfase.
DR InterPro; IPR020989; Histone-Arg_MeTrfase_N.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR11006; PTHR11006; 1.
DR Pfam; PF11531; CARM1; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51678; SAM_MT_PRMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Cytoplasm;
KW Methylation; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..608
FT /note="Histone-arginine methyltransferase CARM1"
FT /id="PRO_0000212339"
FT DOMAIN 147..454
FT /note="SAM-dependent MTase PRMT-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01015"
FT REGION 28..139
FT /note="Interaction with C9orf72"
FT /evidence="ECO:0000269|PubMed:30366907"
FT REGION 347..380
FT /note="Required for nuclear translocation"
FT /evidence="ECO:0000269|PubMed:30366907"
FT REGION 500..608
FT /note="Transactivation domain"
FT BINDING 160
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 169
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 193
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 215
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 244
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 272
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19843527"
FT MOD_RES 551
FT /note="Dimethylated arginine"
FT /evidence="ECO:0000269|PubMed:21138967"
FT VAR_SEQ 540..562
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012508"
FT MUTAGEN 154
FT /note="Y->A,F,R: Loss of S-adenosyl-L-methionine binding.
FT Loss of protein methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19843527"
FT MUTAGEN 169
FT /note="R->A: Loss of protein methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19897492"
FT MUTAGEN 173
FT /note="Y->A: Reduces protein methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19897492"
FT MUTAGEN 189..191
FT /note="VLD->AAA: Abolishes histone methyltransferase
FT activity and coactivator activity."
FT /evidence="ECO:0000269|PubMed:10381882,
FT ECO:0000269|PubMed:11701890"
FT MUTAGEN 217
FT /note="S->A: Loss of S-adenosyl-L-methionine binding. Loss
FT of protein methyltransferase activity. Localized in the
FT nucleus."
FT /evidence="ECO:0000269|PubMed:19843527"
FT MUTAGEN 217
FT /note="S->C,T: Loss of S-adenosyl-L-methionine binding.
FT Loss of protein methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19843527"
FT MUTAGEN 217
FT /note="S->E: Loss of S-adenosyl-L-methionine binding. Loss
FT of protein methyltransferase activity. Localized in the
FT cytosol."
FT /evidence="ECO:0000269|PubMed:19843527"
FT MUTAGEN 229
FT /note="S->E: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:19843527"
FT MUTAGEN 267
FT /note="E->Q: Abolishes histone methyltransferase activity
FT and reduces coactivator activity."
FT /evidence="ECO:0000269|PubMed:11983685,
FT ECO:0000269|PubMed:11997499"
FT MUTAGEN 551
FT /note="R->K: Abolishes dimethylation. Impairs transcription
FT coactivator activity and regulation of alternative
FT splicing. No effect on methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:21138967"
FT CONFLICT 400
FT /note="I -> L (in Ref. 3; BAE34644)"
FT /evidence="ECO:0000305"
FT HELIX 137..141
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 157..164
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 167..179
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:5K8V"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 219..229
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 269..275
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 280..288
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 290..298
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:2V74"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 328..336
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:5IH3"
FT HELIX 365..368
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 369..378
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 383..397
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 418..429
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 434..444
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 448..457
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:5IH3"
FT STRAND 463..469
FT /evidence="ECO:0007829|PDB:5IH3"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:7OKP"
SQ SEQUENCE 608 AA; 65854 MW; C621F2AA9FBA2DA3 CRC64;
MAAAAATAVG PGAGSAGVAG PGGAGPCATV SVFPGARLLT IGDANGEIQR HAEQQALRLE
VRAGPDAAGI ALYSHEDVCV FKCSVSRETE CSRVGRQSFI ITLGCNSVLI QFATPHDFCS
FYNILKTCRG HTLERSVFSE RTEESSAVQY FQFYGYLSQQ QNMMQDYVRT GTYQRAILQN
HTDFKDKIVL DVGCGSGILS FFAAQAGARK IYAVEASTMA QHAEVLVKSN NLTDRIVVIP
GKVEEVSLPE QVDIIISEPM GYMLFNERML ESYLHAKKYL KPSGNMFPTI GDVHLAPFTD
EQLYMEQFTK ANFWYQPSFH GVDLSALRGA AVDEYFRQPV VDTFDIRILM AKSVKYTVNF
LEAKEGDLHR IEIPFKFHML HSGLVHGLAF WFDVAFIGSI MTVWLSTAPT EPLTHWYQVR
CLFQSPLFAK AGDTLSGTCL LIANKRQSYD ISIVAQVDQT GSKSSNLLDL KNPFFRYTGT
TPSPPPGSHY TSPSENMWNT GSTYNLSSGV AVAGMPTAYD LSSVIAGGSS VGHNNLIPLA
NTGIVNHTHS RMGSIMSTGI VQGSSGAQGG GGSSSAHYAV NNQFTMGGPA ISMASPMSIP
TNTMHYGS
