MET16_MOUSE
ID MET16_MOUSE Reviewed; 553 AA.
AC Q9CQG2; Q3UMA9; Q9D062;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=RNA N6-adenosine-methyltransferase METTL16 {ECO:0000305};
DE AltName: Full=Methyltransferase 10 domain-containing protein;
DE AltName: Full=Methyltransferase-like protein 16;
DE AltName: Full=N6-adenosine-methyltransferase METTL16 {ECO:0000250|UniProtKB:Q86W50};
DE EC=2.1.1.348 {ECO:0000305|PubMed:29262316};
DE AltName: Full=U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase {ECO:0000250|UniProtKB:Q86W50};
DE EC=2.1.1.346 {ECO:0000250|UniProtKB:Q86W50};
GN Name=Mettl16 {ECO:0000312|MGI:MGI:1914743};
GN Synonyms=Mett10d {ECO:0000312|MGI:MGI:1914743};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Amnion, Embryo, and Mammary gland;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425; SER-429 AND THR-463, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, 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 [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29262316; DOI=10.1016/j.celrep.2017.11.092;
RA Shima H., Matsumoto M., Ishigami Y., Ebina M., Muto A., Sato Y.,
RA Kumagai S., Ochiai K., Suzuki T., Igarashi K.;
RT "S-Adenosylmethionine synthesis is regulated by selective N6-adenosine
RT methylation and mRNA degradation involving METTL16 and YTHDC1.";
RL Cell Rep. 21:3354-3363(2017).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30197299; DOI=10.1016/j.molcel.2018.08.004;
RA Mendel M., Chen K.M., Homolka D., Gos P., Pandey R.R., McCarthy A.A.,
RA Pillai R.S.;
RT "Methylation of structured RNA by the m6A writer METTL16 is essential for
RT mouse embryonic development.";
RL Mol. Cell 71:986-1000(2018).
CC -!- FUNCTION: RNA N6-methyltransferase that methylates adenosine residues
CC at the N(6) position of a subset of RNAs and is involved in S-adenosyl-
CC L-methionine homeostasis by regulating expression of MAT2A transcripts
CC (PubMed:29262316, PubMed:30197299). Able to N6-methylate a subset of
CC mRNAs and U6 small nuclear RNAs (U6 snRNAs) (By similarity). In
CC contrast to the METTL3-METTL14 heterodimer, only able to methylate a
CC limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence
CC and a specific RNA structure (By similarity). Plays a key role in S-
CC adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A
CC mRNAs, altering splicing of MAT2A transcripts: in presence of S-
CC adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and
CC specifically N6-methylates the first hairpin of MAT2A mRNA, preventing
CC recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting
CC splicing and protein production of S-adenosylmethionine synthase (By
CC similarity). In S-adenosyl-L-methionine-limiting conditions, binds the
CC 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl
CC donor, preventing N6-methylation and promoting expression of MAT2A
CC (PubMed:29262316). In addition to mRNAs, also able to mediate N6-
CC methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-
CC methylates adenine in position 43 of U6 snRNAs (By similarity). Also
CC able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA
CC (By similarity). Specifically binds the 3'-end of the MALAT1 long non-
CC coding RNA (By similarity) (PubMed:29262316, PubMed:30197299).
CC {ECO:0000250|UniProtKB:Q86W50, ECO:0000269|PubMed:29262316,
CC ECO:0000269|PubMed:30197299}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine in U6 snRNA + S-adenosyl-L-methionine = H(+) + N(6)-
CC methyladenosine in U6 snRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:52808, Rhea:RHEA-COMP:13573, Rhea:RHEA-COMP:13574,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74449; EC=2.1.1.346;
CC Evidence={ECO:0000250|UniProtKB:Q86W50};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an adenosine in mRNA + S-adenosyl-L-methionine = an N(6)-
CC methyladenosine in mRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:55584, Rhea:RHEA-COMP:12414, Rhea:RHEA-COMP:12417,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74449; EC=2.1.1.348;
CC Evidence={ECO:0000305|PubMed:29262316};
CC -!- ACTIVITY REGULATION: Methyltransferase activity is autoinhibited by the
CC K-loop region that blocks S-adenosyl-L-methionine-binding. Upon
CC activation, K-loop changes conformation, allowing S-adenosyl-L-
CC methionine-binding and subsequent methyltransferase activity. mRNA N6-
CC adenosine-methyltransferase activity is inhibited by zinc.
CC {ECO:0000250|UniProtKB:Q86W50}.
CC -!- SUBUNIT: Interacts with MEPCE. Interacts with LARP7.
CC {ECO:0000250|UniProtKB:Q86W50}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86W50}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q86W50}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CQG2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CQG2-2; Sequence=VSP_029342;
CC -!- DOMAIN: The VCR (vertebrate conserved) regions bind the first hairpin
CC of MAT2A mRNAs. The VCR regions interact with the internal stem-loop
CC within U6 snRNAs, inducing the conformational rearrangement of the A43-
CC containing region of U6 snRNA, thereby modifying the RNA structure to
CC become suitable for productive catalysis by the methyltransferase
CC region. {ECO:0000250|UniProtKB:Q86W50}.
CC -!- DOMAIN: The K-loop region occludes the S-adenosyl-L-methionine-binding
CC pocket. Upon activation, conformation of the K-loop changes, allowing
CC S-adenosyl-L-methionine-binding. {ECO:0000250|UniProtKB:Q86W50}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality: embryos develop until
CC blastocyst stage but development is stopped around the time of
CC implantation (PubMed:30197299). Defects are caused by dysregulation of
CC MAT2A mRNAs (PubMed:30197299). {ECO:0000269|PubMed:30197299}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL16/RlmF
CC family. {ECO:0000305}.
CC -!- CAUTION: According to a report, N6-methylation of MAT2A affects MAT2A
CC mRNA stability instead of preventing splicing (PubMed:29262316).
CC However, it was later shown that N6-methylation of MAT2A transcripts
CC prevents recognition of their 3'-splice site by U2AF1/U2AF35, thereby
CC inhibiting splicing and protein production (By similarity).
CC {ECO:0000250|UniProtKB:Q86W50, ECO:0000269|PubMed:29262316}.
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DR EMBL; AK145022; BAE26189.1; -; mRNA.
DR EMBL; AK011780; BAB27835.1; -; mRNA.
DR EMBL; AK012739; BAB28440.1; -; mRNA.
DR EMBL; AK145662; BAE26574.1; -; mRNA.
DR EMBL; AK168798; BAE40630.1; -; mRNA.
DR EMBL; AL604066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL607024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049897; AAH49897.1; -; mRNA.
DR EMBL; BC054724; AAH54724.1; -; mRNA.
DR CCDS; CCDS25036.1; -. [Q9CQG2-1]
DR RefSeq; NP_080473.1; NM_026197.3. [Q9CQG2-1]
DR RefSeq; XP_006534061.1; XM_006533998.3. [Q9CQG2-1]
DR RefSeq; XP_006534062.1; XM_006533999.2. [Q9CQG2-1]
DR AlphaFoldDB; Q9CQG2; -.
DR SMR; Q9CQG2; -.
DR BioGRID; 212228; 2.
DR STRING; 10090.ENSMUSP00000114682; -.
DR iPTMnet; Q9CQG2; -.
DR PhosphoSitePlus; Q9CQG2; -.
DR EPD; Q9CQG2; -.
DR jPOST; Q9CQG2; -.
DR MaxQB; Q9CQG2; -.
DR PaxDb; Q9CQG2; -.
DR PeptideAtlas; Q9CQG2; -.
DR PRIDE; Q9CQG2; -.
DR ProteomicsDB; 295858; -. [Q9CQG2-1]
DR ProteomicsDB; 295859; -. [Q9CQG2-2]
DR Antibodypedia; 5377; 266 antibodies from 25 providers.
DR DNASU; 67493; -.
DR Ensembl; ENSMUST00000141755; ENSMUSP00000114682; ENSMUSG00000010554. [Q9CQG2-1]
DR GeneID; 67493; -.
DR KEGG; mmu:67493; -.
DR UCSC; uc007kch.1; mouse. [Q9CQG2-1]
DR UCSC; uc011xza.1; mouse. [Q9CQG2-2]
DR CTD; 79066; -.
DR MGI; MGI:1914743; Mettl16.
DR VEuPathDB; HostDB:ENSMUSG00000010554; -.
DR eggNOG; KOG2912; Eukaryota.
DR GeneTree; ENSGT00390000016694; -.
DR HOGENOM; CLU_027534_0_0_1; -.
DR InParanoid; Q9CQG2; -.
DR OrthoDB; 1358504at2759; -.
DR PhylomeDB; Q9CQG2; -.
DR TreeFam; TF313132; -.
DR BRENDA; 2.1.1.346; 3474.
DR BioGRID-ORCS; 67493; 27 hits in 73 CRISPR screens.
DR ChiTaRS; Mettl16; mouse.
DR PRO; PR:Q9CQG2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9CQG2; protein.
DR Bgee; ENSMUSG00000010554; Expressed in manus and 235 other tissues.
DR ExpressionAtlas; Q9CQG2; baseline and differential.
DR Genevisible; Q9CQG2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0052907; F:23S rRNA (adenine(1618)-N(6))-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0001734; F:mRNA (N6-adenosine)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
DR GO; GO:0120048; F:U6 snRNA (adenine-(43)-N(6))-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0030629; F:U6 snRNA 3'-end binding; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; IMP:UniProtKB.
DR GO; GO:1905869; P:negative regulation of 3'-UTR-mediated mRNA stabilization; ISO:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0001510; P:RNA methylation; IDA:UniProtKB.
DR GO; GO:0070475; P:rRNA base methylation; IBA:GO_Central.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0120049; P:snRNA (adenine-N6)-methylation; ISS:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR017182; METTL16/PsiM.
DR InterPro; IPR010286; METTL16/RlmF.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13393; PTHR13393; 1.
DR Pfam; PF05971; Methyltransf_10; 1.
DR PIRSF; PIRSF037350; Mtase_ZK1128_prd; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Methyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..553
FT /note="RNA N6-adenosine-methyltransferase METTL16"
FT /id="PRO_0000310768"
FT REGION 17..20
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 163..167
FT /note="K-loop"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 199..211
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 250..254
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 277..283
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 289..400
FT /note="VCR 1"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 457..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..553
FT /note="VCR 2"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 82
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 110
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 133
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 164
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 184
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 463
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 267..296
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029342"
FT CONFLICT 498
FT /note="R -> H (in Ref. 1; BAE26189)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="R -> G (in Ref. 1; BAB27835)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 62341 MW; 9087B88833F3B783 CRC64;
MALSKSMHAR NRYKDKPPDF AYLASKYPDF KQHIQINLNG RVSLNFKDPE AVRALTCTLL
REDFGLSIDI PLERLIPTVP LRLNYIHWVE DLIGHQDSDK TTLRRGIDIG TGASCIYPLL
GATLNGWYFL ATEVDDMCFN YAKKNVEQNN LSDLIKVVKV PQKTLLMDAL KEESEIVYDF
CMCNPPFFAN QLEAKGVNSR NSRRPPPSSV NTGGITEIMA EGGELEFVKR IIHDSLQLKK
RLRWYSCMLG KKCSLAPLKE ELRIQGVPKV TFTEFCQGRT MRWALAWSFY DDVTVPSPPS
KRRKLEKPRK PITFVVLESV MKELSLKASS LGSETAEGIV VVTTWIEKIL TDLKVQHKRI
PCGREEVSLF LTAIENSWIH LRRKRRERVR QLREVPRAPE DVILALEERK STPKELSSGQ
DVAHSPQESA LCGLDVPGGE AAADGGHCLS QKLLCQEETP EATEDERDEE RGGMEAMESC
KGSSNGAQDG EASEKGDRLD GAAGRYLFKC LVNIKKEAGD AVVEMHWVEG QNRDLMNQLC
TYVRNQILRL VAS
