METL8_HUMAN
ID METL8_HUMAN Reviewed; 291 AA.
AC Q9H825; Q53TM9; Q53TQ0;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:34774131, ECO:0000269|PubMed:35017528};
DE AltName: Full=Methyltransferase-like protein 8 {ECO:0000305};
DE AltName: Full=mRNA N(3)-methylcytidine methyltransferase METTL8 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000305|PubMed:28655767};
DE Flags: Precursor;
GN Name=METTL8 {ECO:0000303|PubMed:28655767, ECO:0000312|HGNC:HGNC:25856};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28655767; DOI=10.1074/jbc.m117.798298;
RA Xu L., Liu X., Sheng N., Oo K.S., Liang J., Chionh Y.H., Xu J., Ye F.,
RA Gao Y.G., Dedon P.C., Fu X.Y.;
RT "Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and
RT mRNA in mice and humans.";
RL J. Biol. Chem. 292:14695-14703(2017).
RN [6]
RP SUMOYLATION AT LYS-80, AND MUTAGENESIS OF LYS-80.
RX PubMed=32199293; DOI=10.1016/j.isci.2020.100968;
RA Zhang L.H., Zhang X.Y., Hu T., Chen X.Y., Li J.J., Raida M., Sun N.,
RA Luo Y., Gao X.;
RT "The SUMOylated METTL8 induces R-loop and tumorigenesis via m3C.";
RL IScience 23:100968-100968(2020).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ILE-4; ILE-9 AND ASP-230.
RX PubMed=34774131; DOI=10.1016/j.molcel.2021.10.018;
RA Schoeller E., Marks J., Marchand V., Bruckmann A., Powell C.A.,
RA Reichold M., Mutti C.D., Dettmer K., Feederle R., Huettelmaier S., Helm M.,
RA Oefner P., Minczuk M., Motorin Y., Hafner M., Meister G.;
RT "Balancing of mitochondrial translation through METTL8-mediated m3C
RT modification of mitochondrial tRNAs.";
RL Mol. Cell 81:4810-4825(2021).
RN [8]
RP FUNCTION, AND CAUTION.
RX PubMed=33313824; DOI=10.1093/nar/gkaa1186;
RA Cui J., Liu Q., Sendinc E., Shi Y., Gregory R.I.;
RT "Nucleotide resolution profiling of m3C RNA modification by HAC-seq.";
RL Nucleic Acids Res. 49:e27-e27(2021).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-230.
RX PubMed=35017528; DOI=10.1038/s41467-021-27905-1;
RA Kleiber N., Lemus-Diaz N., Stiller C., Heinrichs M., Mai M.M., Hackert P.,
RA Richter-Dennerlein R., Hoebartner C., Bohnsack K.E., Bohnsack M.T.;
RT "The RNA methyltransferase METTL8 installs m3C32 in mitochondrial
RT tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial
RT translation.";
RL Nat. Commun. 13:209-209(2022).
CC -!- FUNCTION: Mitochondrial S-adenosyl-L-methionine-dependent
CC methyltransferase that mediates N(3)-methylcytidine modification of
CC residue 32 of the tRNA anticodon loop of mitochondrial tRNA(Ser)(UCN)
CC and tRNA(Thr) (PubMed:34774131, PubMed:35017528). N(3)-methylcytidine
CC methylation modification regulates mitochondrial translation efficiency
CC and is required for activity of the respiratory chain (PubMed:34774131,
CC PubMed:35017528). N(3)-methylcytidine methylation of mitochondrial
CC tRNA(Ser)(UCN) requires the formation of N(6)-
CC dimethylallyladenosine(37) (i6A37) by TRIT1 as prerequisite
CC (PubMed:34774131, PubMed:35017528). May also mediate N(3)-
CC methylcytidine modification of mRNAs (PubMed:28655767). The existence
CC of N(3)-methylcytidine modification on mRNAs is however unclear, and
CC additional evidences are required to confirm the role of the N(3)-
CC methylcytidine-specific mRNA methyltransferase activity of METTL8 in
CC vivo (PubMed:34774131, PubMed:33313824). {ECO:0000269|PubMed:28655767,
CC ECO:0000269|PubMed:33313824, ECO:0000269|PubMed:34774131,
CC ECO:0000269|PubMed:35017528}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(32) in tRNA(Ser) + S-adenosyl-L-methionine = H(+) +
CC N(3)-methylcytidine(32) in tRNA(Ser) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:50956, Rhea:RHEA-COMP:12849, Rhea:RHEA-COMP:12851,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74894, ChEBI:CHEBI:82748;
CC Evidence={ECO:0000269|PubMed:34774131, ECO:0000269|PubMed:35017528};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50957;
CC Evidence={ECO:0000269|PubMed:34774131, ECO:0000269|PubMed:35017528};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(32) in tRNA(Thr) + S-adenosyl-L-methionine = H(+) +
CC N(3)-methylcytidine(32) in tRNA(Thr) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:50960, Rhea:RHEA-COMP:12850, Rhea:RHEA-COMP:12852,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74894, ChEBI:CHEBI:82748;
CC Evidence={ECO:0000269|PubMed:34774131, ECO:0000269|PubMed:35017528};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50961;
CC Evidence={ECO:0000269|PubMed:34774131, ECO:0000269|PubMed:35017528};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cytidine in mRNA + S-adenosyl-L-methionine = an N(3)-
CC methylcytidine in mRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60916, Rhea:RHEA-COMP:15145, Rhea:RHEA-COMP:15713,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74894, ChEBI:CHEBI:82748;
CC Evidence={ECO:0000305|PubMed:28655767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60917;
CC Evidence={ECO:0000305|PubMed:28655767};
CC -!- SUBUNIT: Interacts with EP300. {ECO:0000250|UniProtKB:A2AUU0}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:34774131,
CC ECO:0000269|PubMed:35017528}. Note=Mitochondrial protein: the
CC cytoplasmic or nuclear localization observed by some groups is either
CC the result of an incorrect localization caused by N-terminal tagging
CC that interferes with mitochondrial targeting, or splice isoforms that
CC lack the N-terminal mitochondrial transit sequence.
CC {ECO:0000269|PubMed:34774131}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H825-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H825-2; Sequence=VSP_029514;
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METL family.
CC {ECO:0000305}.
CC -!- CAUTION: The existence of N(3)-methylcytidine on mRNA is unclear
CC (PubMed:34774131, PubMed:33313824). A report was unable to detect N(3)-
CC methylcytidine formation in mammalian mRNAs using a nucleotide-
CC resolution sequencing approach (PubMed:33313824). According to another
CC publication, METTL8 has no activity on mRNAs and specifically
CC methylates mitochondrial tRNAs (PubMed:34774131).
CC {ECO:0000269|PubMed:33313824, ECO:0000269|PubMed:34774131}.
CC -!- CAUTION: A publication reported some nucleolar localization
CC (PubMed:32199293). However, the protein used in this publication used a
CC N-terminal tag, which possibly interferes with the mitochondrial
CC targeting (PubMed:34774131). {ECO:0000269|PubMed:32199293,
CC ECO:0000269|PubMed:34774131}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH25250.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAX93077.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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; AK024046; BAB14797.1; -; mRNA.
DR EMBL; AC008065; AAX93077.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC007739; AAX93284.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11215.1; -; Genomic_DNA.
DR EMBL; BC025250; AAH25250.1; ALT_INIT; mRNA.
DR CCDS; CCDS82531.1; -. [Q9H825-2]
DR CCDS; CCDS82532.1; -. [Q9H825-1]
DR RefSeq; NP_001308083.1; NM_001321154.1.
DR RefSeq; NP_001308084.1; NM_001321155.1.
DR RefSeq; NP_001308085.1; NM_001321156.1.
DR RefSeq; NP_001308086.1; NM_001321157.1.
DR RefSeq; NP_001308088.1; NM_001321159.1.
DR RefSeq; NP_001308089.1; NM_001321160.1. [Q9H825-1]
DR RefSeq; NP_001308091.1; NM_001321162.1. [Q9H825-2]
DR AlphaFoldDB; Q9H825; -.
DR SMR; Q9H825; -.
DR STRING; 9606.ENSP00000480056; -.
DR iPTMnet; Q9H825; -.
DR PhosphoSitePlus; Q9H825; -.
DR BioMuta; METTL8; -.
DR DMDM; 160410001; -.
DR EPD; Q9H825; -.
DR jPOST; Q9H825; -.
DR MassIVE; Q9H825; -.
DR MaxQB; Q9H825; -.
DR PaxDb; Q9H825; -.
DR PeptideAtlas; Q9H825; -.
DR PRIDE; Q9H825; -.
DR ProteomicsDB; 81171; -. [Q9H825-1]
DR ProteomicsDB; 81172; -. [Q9H825-2]
DR DNASU; 79828; -.
DR Ensembl; ENST00000392604.6; ENSP00000376382.2; ENSG00000123600.21. [Q9H825-1]
DR Ensembl; ENST00000447486.5; ENSP00000409025.1; ENSG00000123600.21. [Q9H825-2]
DR GeneID; 79828; -.
DR KEGG; hsa:79828; -.
DR UCSC; uc002ugs.5; human. [Q9H825-1]
DR CTD; 79828; -.
DR DisGeNET; 79828; -.
DR GeneCards; METTL8; -.
DR HGNC; HGNC:25856; METTL8.
DR MalaCards; METTL8; -.
DR MIM; 609525; gene.
DR neXtProt; NX_Q9H825; -.
DR OpenTargets; ENSG00000123600; -.
DR VEuPathDB; HostDB:ENSG00000123600; -.
DR eggNOG; KOG2361; Eukaryota.
DR GeneTree; ENSGT00940000159683; -.
DR HOGENOM; CLU_029724_0_0_1; -.
DR InParanoid; Q9H825; -.
DR OrthoDB; 987359at2759; -.
DR PhylomeDB; Q9H825; -.
DR PathwayCommons; Q9H825; -.
DR BioGRID-ORCS; 79828; 5 hits in 244 CRISPR screens.
DR ChiTaRS; METTL8; human.
DR GenomeRNAi; 79828; -.
DR Pharos; Q9H825; Tdark.
DR PRO; PR:Q9H825; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H825; protein.
DR Bgee; ENSG00000123600; Expressed in buccal mucosa cell and 187 other tissues.
DR ExpressionAtlas; Q9H825; baseline and differential.
DR Genevisible; Q9H825; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008174; F:mRNA methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0052735; F:tRNA (cytosine-3-)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; IMP:UniProtKB.
DR GO; GO:0070131; P:positive regulation of mitochondrial translation; IDA:UniProtKB.
DR GO; GO:0106217; P:tRNA C3-cytosine methylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR026113; MeTrfase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR22809; PTHR22809; 1.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Isopeptide bond; Methyltransferase; Mitochondrion;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Transit peptide;
KW tRNA processing; Ubl conjugation.
FT TRANSIT 1..21
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 22..291
FT /note="tRNA N(3)-methylcytidine methyltransferase METTL8,
FT mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000311291"
FT REGION 141..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 93
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 204
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 230
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 256
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT CROSSLNK 80
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:32199293"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029514"
FT MUTAGEN 4
FT /note="I->Q: Partial relocalization to the cytoplasm; when
FT associated with Q-9."
FT /evidence="ECO:0000269|PubMed:34774131"
FT MUTAGEN 9
FT /note="I->Q: Partial relocalization to the cytoplasm; when
FT associated with Q-4."
FT /evidence="ECO:0000269|PubMed:34774131"
FT MUTAGEN 80
FT /note="K->R: Abolished SUMOylation."
FT /evidence="ECO:0000269|PubMed:32199293"
FT MUTAGEN 230
FT /note="D->A: Abolished N(3)-methylcytidine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:34774131,
FT ECO:0000269|PubMed:35017528"
SQ SEQUENCE 291 AA; 33387 MW; 0F239034FC81A9AF CRC64;
MNMIWRNSIS CLRLGKVPHR YQSGYHPVAP LGSRILTDPA KVFEHNMWDH MQWSKEEEAA
ARKKVKENSA VRVLLEEQVK YEREASKYWD TFYKIHKNKF FKDRNWLLRE FPEILPVDQK
PEEKARESSW DHVKTSATNR FSRMHCPTVP DEKNHYEKSS GSSEGQSKTE SDFSNLDSEK
HKKGPMETGL FPGSNATFRI LEVGCGAGNS VFPILNTLEN SPESFLYCCD FASGAVELVK
SHSSYRATQC FAFVHDVCDD GLPYPFPDGI LDVILLVFVL SSIHPDRTLF I
