L_SFTS
ID L_SFTS Reviewed; 2084 AA.
AC I0DF35; A0A125SZQ2; F1BV96;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48 {ECO:0000269|PubMed:32313945};
DE AltName: Full=Large structural protein;
DE AltName: Full=Replicase;
DE AltName: Full=Transcriptase;
DE Includes:
DE RecName: Full=cap-snatching endonuclease;
DE EC=3.1.-.- {ECO:0000269|PubMed:31914382, ECO:0000269|PubMed:32313945};
OS Dabie bandavirus (Severe fever with thrombocytopenia virus) (Huaiyangshan
OS banyangvirus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Bandavirus; Dabie bandavirus.
OX NCBI_TaxID=1003835;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate AH12/China/2010;
RX PubMed=21410387; DOI=10.1056/nejmoa1010095;
RA Yu X.J., Liang M.F., Zhang S.Y., Liu Y., Li J.D., Sun Y.L., Zhang L.,
RA Zhang Q.F., Popov V.L., Li C., Qu J., Li Q., Zhang Y.P., Hai R., Wu W.,
RA Wang Q., Zhan F.X., Wang X.J., Kan B., Wang S.W., Wan K.L., Jing H.Q.,
RA Lu J.X., Yin W.W., Zhou H., Guan X.H., Liu J.F., Bi Z.Q., Liu G.H., Ren J.,
RA Wang H., Zhao Z., Song J.D., He J.R., Wan T., Zhang J.S., Fu X.P.,
RA Sun L.N., Dong X.P., Feng Z.J., Yang W.Z., Hong T., Zhang Y., Walker D.H.,
RA Wang Y., Li D.X.;
RT "Fever with thrombocytopenia associated with a novel bunyavirus in China.";
RL N. Engl. J. Med. 364:1523-1532(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=WCH/97/HN/China/2011;
RA Liu W., Zhuang L.;
RT "Novel Bunyavirus Infection in China: Preliminary Clinical Characteristics
RT and Treatment Effects.";
RL Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=SPL057A {ECO:0000312|EMBL:BAU51056.1};
RX PubMed=25762790; DOI=10.1093/infdis/jiv144;
RA Yoshikawa T., Shimojima M., Fukushi S., Tani H., Fukuma A., Taniguchi S.,
RA Singh H., Suda Y., Shirabe K., Toda S., Shimazu Y., Nomachi T., Gokuden M.,
RA Morimitsu T., Ando K., Yoshikawa A., Kan M., Uramoto M., Osako H., Kida K.,
RA Takimoto H., Kitamoto H., Terasoma F., Honda A., Maeda K., Takahashi T.,
RA Yamagishi T., Oishi K., Morikawa S., Saijo M.;
RT "Phylogenetic and Geographic Relationships of Severe Fever With
RT Thrombocytopenia Syndrome Virus in China, South Korea, and Japan.";
RL J. Infect. Dis. 212:889-898(2015).
RN [4]
RP REVIEW.
RX PubMed=28418734; DOI=10.1080/1040841x.2017.1307805;
RA Amroun A., Priet S., de Lamballerie X., Querat G.;
RT "Bunyaviridae RdRps: structure, motifs, and RNA synthesis machinery.";
RL Crit. Rev. Microbiol. 43:753-778(2017).
RN [5]
RP SUBCELLULAR LOCATION.
RC STRAIN=YG1;
RX PubMed=29467349; DOI=10.2220/biomedres.39.27;
RA Lundu T., Tsuda Y., Ito R., Shimizu K., Kobayashi S., Yoshii K.,
RA Yoshimatsu K., Arikawa J., Kariwa H.;
RT "Targeting of severe fever with thrombocytopenia syndrome virus structural
RT proteins to the ERGIC (endoplasmic reticulum Golgi intermediate
RT compartment) and Golgi complex.";
RL Biomed. Res. 39:27-38(2018).
RN [6]
RP REVIEW.
RX PubMed=31948728; DOI=10.1016/j.tim.2019.12.006;
RA Olschewski S., Cusack S., Rosenthal M.;
RT "The Cap-Snatching Mechanism of Bunyaviruses.";
RL Trends Microbiol. 28:293-303(2020).
RN [7] {ECO:0007829|PDB:6XYA, ECO:0007829|PDB:6Y6K}
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1695-1810 IN COMPLEX WITH
RP MAGNESIUM, DOMAIN, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-112 AND ASP-1126,
RP AND FUNCTION.
RC STRAIN=Isolate AH12/China/2010;
RX PubMed=32313945; DOI=10.1093/nar/gkaa253;
RA Vogel D., Thorkelsson S.R., Quemin E.R.J., Meier K., Kouba T., Gogrefe N.,
RA Busch C., Reindl S., Gunther S., Cusack S., Grunewald K., Rosenthal M.;
RT "Structural and functional characterization of the severe fever with
RT thrombocytopenia syndrome virus L protein.";
RL Nucleic Acids Res. 48:5749-5765(2020).
RN [8] {ECO:0007744|PDB:6L42}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), AND DOMAIN.
RC STRAIN=WCH/97/HN/China/2011;
RX PubMed=32341479; DOI=10.1038/s41564-020-0712-2;
RA Wang P., Liu L., Liu A., Yan L., He Y., Shen S., Hu M., Guo Y., Liu H.,
RA Liu C., Lu Y., Wang P., Deng F., Rao Z., Lou Z.;
RT "Structure of severe fever with thrombocytopenia syndrome virus L protein
RT elucidates the mechanisms of viral transcription initiation.";
RL Nat. Microbiol. 5:864-871(2020).
RN [9] {ECO:0007744|PDB:6NTV}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-226, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, FUNCTION, COFACTOR, AND MUTAGENESIS OF HIS-80; ASP-92;
RP ASP-112 AND GLU-126.
RX PubMed=31914382; DOI=10.1016/j.celrep.2019.12.020;
RA Wang W., Shin W.J., Zhang B., Choi Y., Yoo J.S., Zimmerman M.I.,
RA Frederick T.E., Bowman G.R., Gross M.L., Leung D.W., Jung J.U.,
RA Amarasinghe G.K.;
RT "The Cap-Snatching SFTSV Endonuclease Domain Is an Antiviral Target.";
RL Cell Rep. 30:153-163.e5(2020).
RN [10] {ECO:0007744|PDB:7ALP}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS).
RX PubMed=33927385; DOI=10.1038/s41564-021-00901-3;
RA Cusack S., Rosenthal M.;
RT "Errors in the deposited SFTSV L protein structure.";
RL Nat. Microbiol. 6:549-550(2021).
RN [11]
RP STRUCTURE REVISION.
RX PubMed=33883698; DOI=10.1038/s41564-021-00906-y;
RA Wang P., Liu L., Liu A., Yan L., He Y., Shen S., Hu M., Guo Y., Liu H.,
RA Liu C., Lu Y., Wang P., Deng F., Rao Z., Lou Z.;
RT "Author Correction: Structure of severe fever with thrombocytopenia
RT syndrome virus L protein elucidates the mechanisms of viral transcription
RT initiation.";
RL Nat. Microbiol. 6:697-698(2021).
CC -!- FUNCTION: RNA-dependent RNA polymerase, which is responsible for the
CC replication and transcription of the viral RNA genome using antigenomic
CC RNA as an intermediate (By similarity). During transcription,
CC synthesizes subgenomic RNAs and assures their capping by a cap-
CC snatching mechanism, which involves the endonuclease activity cleaving
CC the host capped pre-mRNAs (PubMed:31914382). These short capped RNAs
CC are then used as primers for viral transcription. The 3'-end of
CC subgenomic mRNAs molecules are not polyadenylated. During replication,
CC the polymerase binds the 5' and 3' vRNA extremities at distinct sites
CC (PubMed:32313945). In turn, significant conformational changes occur in
CC the polymerase and in vRNA to initiate active RNA synthesis (By
CC similarity). As a consequence of the use of the same enzyme for both
CC transcription and replication, these mechanisms need to be well
CC coordinated (By similarity). {ECO:0000250|UniProtKB:A5HC98,
CC ECO:0000250|UniProtKB:P27316, ECO:0000269|PubMed:31914382,
CC ECO:0000269|PubMed:32313945}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539,
CC ECO:0000269|PubMed:32313945};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site
CC (PubMed:31914382). The divalent metal ions are crucial for catalytic
CC activity (PubMed:31948728). {ECO:0000269|PubMed:31914382,
CC ECO:0000269|PubMed:31948728};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P27316};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P27316};
CC Note=For polymerase activity. Initiation activity is stronger in the
CC presence of Mn(2+) than in the presence of Mg(2+).
CC {ECO:0000250|UniProtKB:P27316};
CC -!- ACTIVITY REGULATION: Inhibited by Baloxavir acid (BXA).
CC {ECO:0000269|PubMed:31914382}.
CC -!- SUBUNIT: Homomultimer (By similarity). Interacts with the glycoprotein
CC N; this interaction allows efficient polymerase packaging into virus
CC particles (By similarity). Interacts with nucleoprotein N (By
CC similarity). {ECO:0000250|UniProtKB:P27316}.
CC -!- SUBCELLULAR LOCATION: Host Golgi apparatus
CC {ECO:0000269|PubMed:29467349}. Host endoplasmic reticulum
CC {ECO:0000269|PubMed:29467349}. Host endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000269|PubMed:29467349}. Virion
CC {ECO:0000250|UniProtKB:P20470}.
CC -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN)
CC (PubMed:32313945, PubMed:32341479). The central region contains the
CC RdRp activity (PubMed:32313945, PubMed:32341479). The C-terminus
CC contains the cap-binding region (PubMed:32313945, PubMed:32341479).
CC {ECO:0000269|PubMed:32313945, ECO:0000269|PubMed:32341479}.
CC -!- MISCELLANEOUS: Classified as His(+) endonuclease since it has a
CC histidine upstream of the active site that coordinates the first
CC cation. {ECO:0000303|PubMed:31948728}.
CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC {ECO:0000305}.
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DR EMBL; JQ341188; AFH88226.1; -; Genomic_RNA.
DR EMBL; HQ116417; ADX31993.1; -; Viral_cRNA.
DR EMBL; AB983500; BAU51056.1; -; Viral_cRNA.
DR PDB; 6L42; EM; 3.40 A; A=1-2084.
DR PDB; 6NTV; X-ray; 2.40 A; A/B/C=1-226.
DR PDB; 6XYA; X-ray; 1.35 A; B=1695-1810.
DR PDB; 6Y6K; EM; 3.78 A; A=1-2084.
DR PDB; 7ALP; EM; 3.40 A; U=1-2084.
DR PDBsum; 6L42; -.
DR PDBsum; 6NTV; -.
DR PDBsum; 6XYA; -.
DR PDBsum; 6Y6K; -.
DR PDBsum; 7ALP; -.
DR SASBDB; I0DF35; -.
DR SMR; I0DF35; -.
DR Proteomes; UP000148607; Genome.
DR Proteomes; UP000168380; Genome.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-EC.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR InterPro; IPR022531; DUF3770.
DR InterPro; IPR029124; L_protein_N.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR007322; RNA_pol_bunyavir.
DR Pfam; PF04196; Bunya_RdRp; 1.
DR Pfam; PF12603; DUF3770; 1.
DR Pfam; PF15518; L_protein_N; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host endoplasmic reticulum; Host Golgi apparatus; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Reference proteome; Transferase;
KW Virion.
FT CHAIN 1..2084
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000456059"
FT DOMAIN 969..1172
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 20..221
FT /note="Endonuclease"
FT /evidence="ECO:0000269|PubMed:32313945,
FT ECO:0000269|PubMed:32341479"
FT REGION 1695..1810
FT /note="Cap-binding"
FT /evidence="ECO:0000269|PubMed:32313945,
FT ECO:0000269|PubMed:32341479"
FT ACT_SITE 145
FT /note="For endonuclease activity"
FT /evidence="ECO:0000303|PubMed:31914382"
FT BINDING 80
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 112
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 112
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 126
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 1127
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000269|PubMed:32313945,
FT ECO:0000269|PubMed:32341479"
FT SITE 1703
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT SITE 1707
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT SITE 1719
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT SITE 1772
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT VARIANT 128
FT /note="T -> S (in strain: SPL057A and Isolate AH12/China/
FT 2010)"
FT /evidence="ECO:0000269|PubMed:21410387,
FT ECO:0000269|PubMed:25762790"
FT VARIANT 251
FT /note="E -> K (in strain: SPL057A and Isolate AH12/China/
FT 2010)"
FT /evidence="ECO:0000269|PubMed:21410387,
FT ECO:0000269|PubMed:25762790"
FT VARIANT 284
FT /note="S -> N (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 317
FT /note="A -> S (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 343
FT /note="S -> T (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 444..449
FT /note="KESHDA -> RESHET (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 448..449
FT /note="DA -> ET (in strain: Isolate AH12/China/2010)"
FT /evidence="ECO:0000269|PubMed:21410387"
FT VARIANT 470
FT /note="A -> T (in strain: Isolate AH12/China/2010)"
FT /evidence="ECO:0000269|PubMed:21410387"
FT VARIANT 479
FT /note="V -> I (in strain: Isolate AH12/China/2010)"
FT /evidence="ECO:0000269|PubMed:21410387"
FT VARIANT 570
FT /note="I -> V (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 586
FT /note="E -> D (in strain: SPL057A and Isolate AH12/China/
FT 2010)"
FT /evidence="ECO:0000269|PubMed:21410387,
FT ECO:0000269|PubMed:25762790"
FT VARIANT 1061
FT /note="E -> D (in strain: Isolate AH12/China/2010)"
FT /evidence="ECO:0000269|PubMed:21410387"
FT VARIANT 1157
FT /note="K -> R (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 1208
FT /note="T -> S (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 1433
FT /note="T -> A (in strain: SPL057A)"
FT /evidence="ECO:0000269|PubMed:25762790"
FT VARIANT 1711
FT /note="I -> V (in strain: Isolate AH12/China/2010)"
FT /evidence="ECO:0000269|PubMed:21410387"
FT MUTAGEN 80
FT /note="H->A: Drastically decreased endonuclease activity."
FT /evidence="ECO:0000269|PubMed:31914382"
FT MUTAGEN 92
FT /note="D->A: Drastically decreased endonuclease activity."
FT /evidence="ECO:0000269|PubMed:31914382"
FT MUTAGEN 112
FT /note="D->A: Complete loss of endonclease activity."
FT /evidence="ECO:0000269|PubMed:31914382,
FT ECO:0000305|PubMed:32313945"
FT MUTAGEN 126
FT /note="E->A: Drastically decreased endonuclease activity."
FT /evidence="ECO:0000269|PubMed:31914382"
FT MUTAGEN 1126
FT /note="D->A: Complete loss of polymerase activity."
FT /evidence="ECO:0000305|PubMed:32313945"
SQ SEQUENCE 2084 AA; 235406 MW; 5605E4EFFED76AFA CRC64;
MNLEVLCGRI NVENGLSLGE PGLYDQIYDR PGLPDLDVTV DATGVTVDIG AVPDSASQLG
SSINAGLITI QLSEAYKINH DFTFSGLSKT TDRRLSEVFP ITHDGSDGMT PDVIHTRLDG
TIVVVEFTTT RSHNIGGLEA AYRTKIEKYR DPISRRVDIM ENPRVFFGVI VVSSGGVLSN
MPLTQDEAEE LMYRFCIANE IYTKARSMDA DIELQKSEEE LEAISRALSF FSLFEPNIER
VEGTFPNSEI EMLEQFLSTP ADVDFITKTL KAKEVEAYAD LCDSHYLKPE KTIQERLEIN
RCEAIDKTQD LLAGLHARSN KQTSLNRGTV KLPPWLPKPS SESIDIKTDS GFGSLMDHGA
YGELWAKCLL DVSLGNVEGV VSDPAKELDI AISDDPEKDT PKEAKITYRR FKPALSSSAR
QEFSLQGVEG KKWKRMAANQ KKEKESHDAL SPFLDVEDIG DFLTFNNLLA DSRYGDESVQ
RAVSILLEKA SAMQDTELTH ALNDSFKRNL SSNVVQWSLW VSCLAQELAS ALKQHCRAGE
FIIKKLKFWP IYVIIKPTKS SSHIFYSLGI RKADVTRRLT GRVFSETIDA GEWELTEFKS
LKTCKLTNLV NLPCTMLNSI AFWREKLGVA PWLVRKPCSE LREQVGLTFL ISLEDKSKTE
EIITLTRYTQ MEGFVSPPML PKPQKMLGKL DGPLRTKLQV YLLRKHLDCM VRIASQPFSL
IPREGRVEWG GTFHAISGRS TNLENMVNSW YIGYYKNKEE STELNALGEM YKKIVEMEED
KPSSPEFLGW GDTDSPKKHE FSRSFLRAAC SSLEREIAQR HGRQWKQNLE ERVLREIGTK
NILDLASMKA TSNFSKDWEL YSEVQTKEYH RSKLLEKMAT LIEKGVMWYI DAVGQAWKAV
LDDGCMRICL FKKNQHGGLR EIYVMDANAR LVQFGVETMA RCVCELSPHE TVANPRLKNS
IIENHGLKSA RSLGPGSINI NSSNDAKKWN QGHYTTKLAL VLCWFMPAKF HRFIWAAISM
FRRKKMMVDL RFLAHLSSKS ESRSSDPFRE AMTDAFHGNR EVSWMDKGRT YIKTETGMMQ
GILHFTSSLL HSCVQSFYKS YFVSKLKEGY MGESISGVVD VIEGSDDSAI MISIRPKSDM
DEVRSRFFVA NLLHSVKFLN PLFGIYSSEK STVNTVYCVE YNSEFHFHRH LVRPTLRWIA
ASHQISETEA LASRQEDYSN LLTQCLEGGA SFSLTYLIQC AQLLHHYMLL GLCLHPLFGT
FMGMLISDPD PALGFFLMDN PAFAGGAGFR FNLWRACKTT DLGRKYAYYF NEIQGKTKGD
EDYRALDATS GGTLSHSVMV YWGDRKKYQA LLNRMGLPED WVEQIDENPG VLYRRAANKK
ELLLKLAEKV HSPGVTSSLS KGHVVPRVVA AGVYLLSRHC FRFSSSIHGR GSTQKASLIK
LLMMSSISAM KHGGSLNPNQ ERMLFPQAQE YDRVCTLLEE VEHLTGKFVV RERNIVRSRI
DLFQEPVDLR CKAEDLVSEV WFGLKRTKLG PRLLKEEWDK LRASFAWLST DPSETLRDGP
FLSHVQFRNF IAHVDAKSRS VRLLGAPVKK SGGVTTISQV VRMNFFPGFS LEAEKSLDNQ
ERLESISILK HVLFMVLNGP YTEEYKLEMI IEAFSTLVIP QPSEVIRKSR TMTLCLLSNY
LSSRGGSILD QIERAQSGTL GGFSKPQKTF IRPGGGVGYK GKGVWTGVME DTHVQILIDG
DGTSNWLEEI RLSSDARLYD VIESIRRLCD DLGINNRVAS AYRGHCMVRL SGFKIKPASR
TDGCPVRIME RGFRIRELQN PDEVKMRVRG DILNLSVTIQ EGRVMNILSY RPRDTDISES
AAAYLWSNRD LFSFGKKEPS CSWICLKTLD NWAWSHASVL LANDRKTQGI DNRAMGNIFR
DCLEGSLRKQ GLMRSKLTEM VEKNVVPLTT QELVDILEED IDFSDVIAVE LSEGSLDIES
IFDGAPILWS AEVEEFGEGV VAVSYSSKYY HLTLMDQAAI TMCAIMGKEG CRGLLTEKRC
MAAIREQVRP FLIFLQIPED SISWVSDQFC DSRGLDEEST IMWG
