CARM1_RAT
ID CARM1_RAT Reviewed; 651 AA.
AC Q4AE70; Q4AE68; Q4AE69; Q4AE71;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Histone-arginine methyltransferase CARM1;
DE EC=2.1.1.319 {ECO:0000250|UniProtKB:Q9WVG6};
DE AltName: Full=Coactivator-associated arginine methyltransferase 1;
DE AltName: Full=Protein arginine N-methyltransferase 4;
GN Name=Carm1; Synonyms=Prmt4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION OF ISOFORM 3,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INTERACTION WITH SNRPC.
RC TISSUE=Fetal brain;
RX PubMed=15944154; DOI=10.1074/jbc.m502173200;
RA Ohkura N., Takahashi M., Yaguchi H., Nagamura Y., Tsukada T.;
RT "Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-
RT mRNA splicing in an isoform-specific manner.";
RL J. Biol. Chem. 280:28927-28935(2005).
RN [2]
RP METHYLATION OF ELAV4, AND SUBCELLULAR LOCATION.
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 [3]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 28-507 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=17882262; DOI=10.1038/sj.emboj.7601855;
RA Troffer-Charlier N., Cura V., Hassenboehler P., Moras D., Cavarelli J.;
RT "Functional insights from structures of coactivator-associated arginine
RT methyltransferase 1 domains.";
RL EMBO J. 26:4391-4401(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 (By similarity).
CC {ECO:0000250|UniProtKB:Q9WVG6, ECO:0000269|PubMed:15944154}.
CC -!- FUNCTION: Isoform 3 specifically affects pre-mRNA splicing. This
CC activity is independent from methyltransferase activity.
CC {ECO:0000269|PubMed:15944154}.
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:0000250|UniProtKB:Q9WVG6};
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:0000250}.
CC -!- SUBUNIT: Homodimer (Probable). Interacts with NR1H4. Interacts with the
CC C-terminus of NCOA2/GRIP1, NCO3/ACTR and NCOA1/SRC1. Part of a complex
CC consisting of CARM1, EP300/P300 and NCOA2/GRIP1. Interacts with FLII,
CC TP53, myogenic factor MEF2, EP300/P300, TRIM24, CREBBP and CTNNB1.
CC Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1.
CC Interacts with NCOA3/SRC3. Interacts with RELA (By similarity).
CC Interacts with SNRPC. Interacts with SKP2 (By similarity). Interacts
CC (via PH domain-like fold) with C9orf72 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9WVG6, ECO:0000269|PubMed:15944154,
CC ECO:0000269|PubMed:17882262, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16508003}. Cytoplasm
CC {ECO:0000269|PubMed:16508003}. 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=4;
CC Comment=Named isoforms=2.;
CC Name=1; Synonyms=CARM1-v2;
CC IsoId=Q4AE70-1; Sequence=Displayed;
CC Name=2; Synonyms=CARM1-v1;
CC IsoId=Q4AE70-2; Sequence=VSP_020384;
CC Name=3; Synonyms=CARM1-v3;
CC IsoId=Q4AE70-3; Sequence=VSP_020382, VSP_020385;
CC Name=4; Synonyms=CARM1-v4;
CC IsoId=Q4AE70-4; Sequence=VSP_020383;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed at low levels in brain,
CC liver and testis. Isoform 2 is highly expressed in brain, liver,
CC skeletal muscle and testis. Isoform 3 is highly expressed in spleen,
CC liver and kidney. Isoform 4 is expressed in spleen, liver and kidney.
CC {ECO:0000269|PubMed:15944154}.
CC -!- DEVELOPMENTAL STAGE: Isoforms 2 and 3 are expressed in fetal brain.
CC {ECO:0000269|PubMed:15944154}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-217 interferes with S-adenosyl-L-methionine
CC binding and strongly reduces methyltransferase activity.
CC Phosphorylation at Ser-217 is strongly increased during mitosis, and
CC decreases rapidly to a very low, basal level after entry into the G1
CC phase of the cell cycle. Phosphorylation at Ser-217 may promote
CC location in the cytosol (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Protein arginine N-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01015}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB201114; BAE16333.1; -; mRNA.
DR EMBL; AB201115; BAE16334.1; -; mRNA.
DR EMBL; AB201116; BAE16335.1; -; mRNA.
DR EMBL; AB201117; BAE16336.1; -; mRNA.
DR RefSeq; NP_001025212.1; NM_001030041.3. [Q4AE70-2]
DR RefSeq; NP_001029260.1; NM_001034088.2. [Q4AE70-4]
DR PDB; 2OQB; X-ray; 1.69 A; A/B=28-140.
DR PDB; 3B3F; X-ray; 2.20 A; A/B/C/D=140-480.
DR PDB; 3B3G; X-ray; 2.40 A; A/B=140-480.
DR PDB; 3B3J; X-ray; 2.55 A; A=28-507.
DR PDBsum; 2OQB; -.
DR PDBsum; 3B3F; -.
DR PDBsum; 3B3G; -.
DR PDBsum; 3B3J; -.
DR AlphaFoldDB; Q4AE70; -.
DR SMR; Q4AE70; -.
DR IntAct; Q4AE70; 1.
DR STRING; 10116.ENSRNOP00000042739; -.
DR CarbonylDB; Q4AE70; -.
DR PhosphoSitePlus; Q4AE70; -.
DR jPOST; Q4AE70; -.
DR PRIDE; Q4AE70; -.
DR Ensembl; ENSRNOT00000041577; ENSRNOP00000049428; ENSRNOG00000031129. [Q4AE70-1]
DR Ensembl; ENSRNOT00000048245; ENSRNOP00000042739; ENSRNOG00000031129. [Q4AE70-2]
DR GeneID; 363026; -.
DR KEGG; rno:363026; -.
DR UCSC; RGD:1305879; rat. [Q4AE70-1]
DR CTD; 10498; -.
DR RGD; 1305879; Carm1.
DR GeneTree; ENSGT00940000160377; -.
DR HOGENOM; CLU_017375_0_1_1; -.
DR InParanoid; Q4AE70; -.
DR OMA; KWLKPQG; -.
DR OrthoDB; 840669at2759; -.
DR PhylomeDB; Q4AE70; -.
DR TreeFam; TF323332; -.
DR Reactome; R-RNO-3214858; RMTs methylate histone arginines.
DR Reactome; R-RNO-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR EvolutionaryTrace; Q4AE70; -.
DR PRO; PR:Q4AE70; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000031129; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q4AE70; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0042054; F:histone methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0035642; F:histone methyltransferase activity (H3-R17 specific); ISS:UniProtKB.
DR GO; GO:0008469; F:histone-arginine N-methyltransferase activity; ISO:RGD.
DR GO; GO:0070577; F:lysine-acetylated histone binding; ISS:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0008276; F:protein methyltransferase activity; ISO:RGD.
DR GO; GO:0016274; F:protein-arginine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0035242; F:protein-arginine omega-N asymmetric methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0060350; P:endochondral bone morphogenesis; ISO:RGD.
DR GO; GO:0034969; P:histone arginine methylation; ISS:UniProtKB.
DR GO; GO:0034971; P:histone H3-R17 methylation; ISS:UniProtKB.
DR GO; GO:0034970; P:histone H3-R2 methylation; ISO:RGD.
DR GO; GO:0016571; P:histone methylation; ISO:RGD.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; ISO:RGD.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:2000171; P:negative regulation of dendrite development; IMP:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:RGD.
DR GO; GO:0006479; P:protein methylation; ISO:RGD.
DR GO; GO:0003420; P:regulation of growth plate cartilage chondrocyte proliferation; ISO:RGD.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1902415; P:regulation of mRNA binding; IMP:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; IDA:RGD.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
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; mRNA processing; mRNA splicing; Nucleus;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..651
FT /note="Histone-arginine methyltransferase CARM1"
FT /id="PRO_0000249250"
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:0000250|UniProtKB:Q9WVG6"
FT REGION 347..380
FT /note="Required for nuclear translocation"
FT /evidence="ECO:0000250|UniProtKB:Q9WVG6"
FT REGION 500..651
FT /note="Transactivation domain"
FT /evidence="ECO:0000250"
FT REGION 581..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 600..617
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0000250|UniProtKB:Q86X55"
FT MOD_RES 551
FT /note="Dimethylated arginine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVG6"
FT VAR_SEQ 540..643
FT /note="ANTGIVNHTHSRMGSIMSTGIVQGNRVAGPWAGDLPPGLRTRSSYQWGPGRL
FT RGHAGSSVPMTCPTGSSGAQGGGGSSSAHYAVNNQFTMGGPAISMASPMSIP -> GEC
FT PLGSMACQGRTGICQWPAKPVLGSLPPLSLS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15944154"
FT /id="VSP_020382"
FT VAR_SEQ 540..605
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15944154"
FT /id="VSP_020383"
FT VAR_SEQ 564..606
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15944154"
FT /id="VSP_020384"
FT VAR_SEQ 644..651
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15944154"
FT /id="VSP_020385"
FT STRAND 31..42
FT /evidence="ECO:0007829|PDB:2OQB"
FT STRAND 49..63
FT /evidence="ECO:0007829|PDB:2OQB"
FT STRAND 65..73
FT /evidence="ECO:0007829|PDB:2OQB"
FT STRAND 79..86
FT /evidence="ECO:0007829|PDB:2OQB"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2OQB"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:2OQB"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:2OQB"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:2OQB"
FT HELIX 115..128
FT /evidence="ECO:0007829|PDB:2OQB"
FT HELIX 143..154
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 157..165
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 167..179
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:3B3F"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:3B3G"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 219..229
FT /evidence="ECO:0007829|PDB:3B3F"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:3B3F"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 261..264
FT /evidence="ECO:0007829|PDB:3B3J"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 269..275
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 280..288
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 290..298
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 328..336
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:3B3F"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:3B3F"
FT HELIX 365..368
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 369..378
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 383..397
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:3B3J"
FT STRAND 418..429
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 434..444
FT /evidence="ECO:0007829|PDB:3B3F"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 448..457
FT /evidence="ECO:0007829|PDB:3B3F"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 463..469
FT /evidence="ECO:0007829|PDB:3B3F"
FT STRAND 474..477
FT /evidence="ECO:0007829|PDB:3B3J"
SQ SEQUENCE 651 AA; 70341 MW; 2C71ED2D8E1BE12F 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 VQGNRVAGPW AGDLPPGLRT RSSYQWGPGR LRGHAGSSVP
MTCPTGSSGA QGGGGSSSAH YAVNNQFTMG GPAISMASPM SIPTNTMHYG S
