ID POLG_NVN68 Reviewed; 1789 AA. AC Q83883; DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JAN-2024, entry version 136. DE RecName: Full=Genome polyprotein; DE Contains: DE RecName: Full=Protein p48; DE Contains: DE RecName: Full=NTPase; DE EC=3.6.1.15; DE AltName: Full=p41; DE Contains: DE RecName: Full=Protein p22; DE Contains: DE RecName: Full=Viral genome-linked protein; DE AltName: Full=VPG; DE Contains: DE RecName: Full=3C-like protease; DE Short=3CLpro; DE EC=3.4.22.66; DE AltName: Full=Calicivirin; DE Contains: DE RecName: Full=RNA-directed RNA polymerase; DE Short=RdRp; DE EC=2.7.7.48; GN ORFNames=ORF1; OS Norovirus (strain Human/NoV/United States/Norwalk/1968/GI) OS (Hu/NV/NV/1968/US). OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; OC Picornavirales; Caliciviridae; Norovirus; Norwalk virus. OX NCBI_TaxID=524364; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 3-1789. RX PubMed=8391187; DOI=10.1006/viro.1993.1345; RA Jiang X., Wang M., Wang K., Estes M.K.; RT "Sequence and genomic organization of Norwalk virus."; RL Virology 195:51-61(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-3. RX PubMed=8883366; DOI=10.1007/bf00284649; RA Hardy M.E., Estes M.K.; RT "Completion of the Norwalk virus genome sequence."; RL Virus Genes 12:287-290(1996). RN [3] RP FUNCTION OF VPG. RX PubMed=569187; DOI=10.1099/0022-1317-41-2-443; RA Burroughs J.N., Brown F.; RT "Presence of a covalently linked protein on calicivirus RNA."; RL J. Gen. Virol. 41:443-446(1978). RN [4] RP FUNCTION OF NTPASE. RX PubMed=11160659; DOI=10.1128/jvi.75.4.1611-1619.2001; RA Pfister T., Wimmer E.; RT "Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent RT nucleoside triphosphatase."; RL J. Virol. 75:1611-1619(2001). RN [5] RP MUTAGENESIS OF ASP-394; PHE-395; GLN-398; GLY-399; GLU-1154; ASP-1167 AND RP GLU-1281. RX PubMed=12367748; DOI=10.1016/s0168-1702(02)00114-4; RA Hardy M.E., Crone T.J., Brower J.E., Ettayebi K.; RT "Substrate specificity of the Norwalk virus 3C-like proteinase."; RL Virus Res. 89:29-39(2002). RN [6] RP INTERACTION WITH HUMAN VAPA. RX PubMed=14557663; DOI=10.1128/jvi.77.21.11790-11797.2003; RA Ettayebi K., Hardy M.E.; RT "Norwalk virus nonstructural protein p48 forms a complex with the SNARE RT regulator VAP-A and prevents cell surface expression of vesicular RT stomatitis virus G protein."; RL J. Virol. 77:11790-11797(2003). RN [7] RP PROTEOLYTIC PROCESSING OF POLYPROTEIN. RX PubMed=17554035; DOI=10.1099/vir.0.82797-0; RA Scheffler U., Rudolph W., Gebhardt J., Rohayem J.; RT "Differential cleavage of the norovirus polyprotein precursor by two active RT forms of the viral protease."; RL J. Gen. Virol. 88:2013-2018(2007). RN [8] RP REVIEW. RX PubMed=16168575; DOI=10.1016/j.femsle.2005.08.031; RA Hardy M.E.; RT "Norovirus protein structure and function."; RL FEMS Microbiol. Lett. 253:1-8(2005). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1100-1281. RX PubMed=16641296; DOI=10.1128/jvi.80.10.5050-5058.2006; RA Zeitler C.E., Estes M.K., Venkataram Prasad B.V.; RT "X-ray crystallographic structure of the Norwalk virus protease at 1.5-A RT resolution."; RL J. Virol. 80:5050-5058(2006). CC -!- FUNCTION: Protein p48 may play a role in viral replication by CC interacting with host VAPA, a vesicle-associated membrane protein that CC plays a role in SNARE-mediated vesicle fusion. This interaction may CC target replication complex to intracellular membranes. CC -!- FUNCTION: NTPase presumably plays a role in replication. Despite having CC similarities with helicases, does not seem to display any helicase CC activity. CC -!- FUNCTION: Protein P22 may play a role in targeting replication complex CC to intracellular membranes. CC -!- FUNCTION: Viral genome-linked protein is covalently linked to the 5'- CC end of the positive-strand, negative-strand genomic RNAs and subgenomic CC RNA. Acts as a genome-linked replication primer. May recruit ribosome CC to viral RNA thereby promoting viral proteins translation. CC -!- FUNCTION: 3C-like protease processes the polyprotein: 3CLpro-RdRp is CC first released by autocleavage, then all other proteins are cleaved. CC May cleave host polyadenylate-binding protein thereby inhibiting CC cellular translation (By similarity). {ECO:0000250}. CC -!- FUNCTION: RNA-directed RNA polymerase replicates genomic and CC antigenomic RNA by recognizing replications specific signals. CC Transcribes also a subgenomic mRNA by initiating RNA synthesis CC internally on antigenomic RNA. This sgRNA codes for structural CC proteins. Catalyzes the covalent attachment VPg with viral RNAs (By CC similarity). {ECO:0000255|PROSITE-ProRule:PRU00539}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; CC -!- CATALYTIC ACTIVITY: CC Reaction=Endopeptidase with a preference for cleavage when the P1 CC position is occupied by Glu-|-Xaa and the P1' position is occupied by CC Gly-|-Yaa.; EC=3.4.22.66; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00870}; 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 -!- SUBUNIT: [Protein p48]: Interacts with human VAPA. CC {ECO:0000269|PubMed:14557663}. CC -!- SUBCELLULAR LOCATION: [Protein p48]: Host membrane {ECO:0000305}; CC Single-pass membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [NTPase]: Host membrane {ECO:0000305}; Single- CC pass membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Protein p22]: Host membrane {ECO:0000305}; CC Single-pass membrane protein {ECO:0000305}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. 3CLpro CC is first autocatalytically cleaved, then processes the whole CC polyprotein. {ECO:0000255|PROSITE-ProRule:PRU00870, CC ECO:0000269|PubMed:17554035}. CC -!- PTM: VPg is uridylylated by the polymerase and is covalently attached CC to the 5'-end of the polyadenylated genomic and subgenomic RNAs. This CC uridylylated form acts as a nucleotide-peptide primer for the CC polymerase (By similarity). {ECO:0000250}. 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; M87661; AAB50465.1; -; Genomic_RNA. DR PIR; A53260; A53260. DR PIR; C37471; C37471. DR PIR; C53260; C53260. DR PIR; D37471; D37471. DR PIR; E37471; E37471. DR RefSeq; NP_056820.1; NC_001959.2. DR PDB; 2FYQ; X-ray; 1.50 A; A=1101-1281. DR PDB; 2FYR; X-ray; 2.20 A; A=1101-1281. DR PDB; 2LNC; NMR; -; A=1101-1281. DR PDB; 3UR6; X-ray; 1.50 A; A/B=1101-1281. DR PDB; 3UR9; X-ray; 1.65 A; A/B=1101-1281. DR PDB; 4IMQ; X-ray; 1.50 A; A=1101-1281. DR PDB; 4IMZ; X-ray; 1.70 A; A=1101-1281. DR PDB; 4IN1; X-ray; 2.05 A; A=1101-1281. DR PDB; 4IN2; X-ray; 2.40 A; A/B=1100-1281. DR PDB; 4INH; X-ray; 1.70 A; A/B/C/D/E/F/G/H=1101-1281. DR PDB; 4XBB; X-ray; 1.85 A; A=1101-1281. DR PDB; 4XBC; X-ray; 1.60 A; A=1101-1281. DR PDB; 4XBD; X-ray; 1.45 A; A/B=1101-1281. DR PDB; 5DG6; X-ray; 2.35 A; A/B=1101-1281. DR PDB; 5DGJ; X-ray; 1.00 A; A=1101-1281. DR PDB; 5E0G; X-ray; 1.20 A; A=1101-1281. DR PDB; 5E0H; X-ray; 1.95 A; A/B=1101-1281. DR PDB; 5E0J; X-ray; 1.20 A; A=1101-1281. DR PDB; 5T6D; X-ray; 2.10 A; A/B=1101-1281. DR PDB; 5T6F; X-ray; 1.90 A; A/B=1101-1281. DR PDB; 5T6G; X-ray; 2.45 A; A/B=1101-1281. DR PDB; 5TG1; X-ray; 1.40 A; A=1101-1281. DR PDB; 5TG2; X-ray; 1.75 A; A=1101-1281. DR PDB; 5WEJ; X-ray; 1.95 A; A/B=1101-1281. DR PDB; 6BIB; X-ray; 1.95 A; A/B=1101-1281. DR PDB; 6BIC; X-ray; 2.25 A; A/B=1101-1281. DR PDB; 6BID; X-ray; 1.15 A; A=1101-1281. DR PDB; 6W5H; X-ray; 1.85 A; A/B/C/D=1101-1281. DR PDB; 6W5J; X-ray; 1.85 A; A/B=1101-1281. DR PDB; 6W5K; X-ray; 1.95 A; A/B/C/D=1101-1281. DR PDB; 6W5L; X-ray; 2.10 A; A/B/C/D=1101-1281. DR PDBsum; 2FYQ; -. DR PDBsum; 2FYR; -. DR PDBsum; 2LNC; -. DR PDBsum; 3UR6; -. DR PDBsum; 3UR9; -. DR PDBsum; 4IMQ; -. DR PDBsum; 4IMZ; -. DR PDBsum; 4IN1; -. DR PDBsum; 4IN2; -. DR PDBsum; 4INH; -. DR PDBsum; 4XBB; -. DR PDBsum; 4XBC; -. DR PDBsum; 4XBD; -. DR PDBsum; 5DG6; -. DR PDBsum; 5DGJ; -. DR PDBsum; 5E0G; -. DR PDBsum; 5E0H; -. DR PDBsum; 5E0J; -. DR PDBsum; 5T6D; -. DR PDBsum; 5T6F; -. DR PDBsum; 5T6G; -. DR PDBsum; 5TG1; -. DR PDBsum; 5TG2; -. DR PDBsum; 5WEJ; -. DR PDBsum; 6BIB; -. DR PDBsum; 6BIC; -. DR PDBsum; 6BID; -. DR PDBsum; 6W5H; -. DR PDBsum; 6W5J; -. DR PDBsum; 6W5K; -. DR PDBsum; 6W5L; -. DR BMRB; Q83883; -. DR SMR; Q83883; -. DR IntAct; Q83883; 1. DR BindingDB; Q83883; -. DR MEROPS; C37.001; -. DR GeneID; 1491970; -. DR KEGG; vg:1491970; -. DR BRENDA; 3.4.22.66; 8731. DR EvolutionaryTrace; Q83883; -. DR Proteomes; UP000000826; Segment. DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0003723; F:RNA binding; IEA:InterPro. DR GO; GO:0003724; F:RNA helicase activity; IEA:InterPro. DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro. DR Gene3D; 1.20.960.20; -; 1. DR Gene3D; 3.30.70.270; -; 2. DR Gene3D; 6.10.20.70; -; 1. DR Gene3D; 6.10.250.3230; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR043502; DNA/RNA_pol_sf. DR InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir. DR InterPro; IPR014759; Helicase_SF3_ssRNA_vir. DR InterPro; IPR001665; Norovirus_pept_C37. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase. DR InterPro; IPR001205; RNA-dir_pol_C. DR InterPro; IPR007094; RNA-dir_pol_PSvirus. DR InterPro; IPR013614; Viral_PP_Calicivir_N. DR Pfam; PF08405; Calici_PP_N; 1. DR Pfam; PF05416; Peptidase_C37; 1. DR Pfam; PF00680; RdRP_1; 1. DR Pfam; PF00910; RNA_helicase; 1. DR PRINTS; PR00917; SRSVCYSPTASE. DR SUPFAM; SSF56672; DNA/RNA polymerases; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS51537; NV_3CL_PRO; 1. DR PROSITE; PS50507; RDRP_SSRNA_POS; 1. DR PROSITE; PS51218; SF3_HELICASE_2; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Covalent protein-RNA linkage; Host membrane; KW Host-virus interaction; Hydrolase; Membrane; Nucleotide-binding; KW Nucleotidyltransferase; Phosphoprotein; Protease; Reference proteome; KW RNA-directed RNA polymerase; Thiol protease; Transferase; Transmembrane; KW Transmembrane helix; Viral RNA replication. FT CHAIN 1..1789 FT /note="Genome polyprotein" FT /id="PRO_0000341617" FT CHAIN 1..398 FT /note="Protein p48" FT /id="PRO_0000341618" FT CHAIN 399..761 FT /note="NTPase" FT /id="PRO_0000341619" FT CHAIN 762..962 FT /note="Protein p22" FT /id="PRO_0000341620" FT CHAIN 963..1100 FT /note="Viral genome-linked protein" FT /id="PRO_0000341621" FT CHAIN 1101..1281 FT /note="3C-like protease" FT /id="PRO_0000341622" FT CHAIN 1282..1789 FT /note="RNA-directed RNA polymerase" FT /id="PRO_0000341623" FT TRANSMEM 359..379 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 402..422 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 870..890 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 532..697 FT /note="SF3 helicase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551" FT DOMAIN 1101..1281 FT /note="Peptidase C37" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00870" FT DOMAIN 1516..1637 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 958..981 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 10..25 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1130 FT /note="For 3CLpro activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00870" FT ACT_SITE 1154 FT /note="For 3CLpro activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00870" FT ACT_SITE 1239 FT /note="For 3CLpro activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00870" FT BINDING 560..567 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551" FT SITE 398..399 FT /note="Cleavage; by 3CLpro" FT SITE 761..762 FT /note="Cleavage; by 3CLpro" FT SITE 962..963 FT /note="Cleavage; by 3CLpro" FT SITE 1100..1101 FT /note="Cleavage; by 3CLpro" FT SITE 1281..1282 FT /note="Cleavage; by 3CLpro" FT MOD_RES 992 FT /note="O-(5'-phospho-RNA)-tyrosine" FT /evidence="ECO:0000250" FT MUTAGEN 394 FT /note="D->A,E,N: No effect on p48-p41 cleavage." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 395 FT /note="F->G: Complete loss of p48-p41 cleavage." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 395 FT /note="F->I,Y: No effect on p48-p41 cleavage." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 398 FT /note="Q->E,N: No effect on p48-p41 cleavage." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 398 FT /note="Q->G: Complete loss of p48-p41 cleavage." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 399 FT /note="G->A: No effect on p48-p41 cleavage." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 1154 FT /note="E->G: Complete loss of 3CLpro activity." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 1167 FT /note="D->G: No effect on 3CLpro activity." FT /evidence="ECO:0000269|PubMed:12367748" FT MUTAGEN 1281 FT /note="E->Q: No effect on 3CLpro activity." FT /evidence="ECO:0000269|PubMed:12367748" FT HELIX 1103..1106 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1109..1112 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1115..1128 FT /evidence="ECO:0007829|PDB:5DGJ" FT HELIX 1129..1131 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1137..1139 FT /evidence="ECO:0007829|PDB:5DGJ" FT HELIX 1144..1146 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1147..1152 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1155..1162 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1182..1188 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1190..1192 FT /evidence="ECO:0007829|PDB:2LNC" FT STRAND 1194..1209 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1212..1221 FT /evidence="ECO:0007829|PDB:5DGJ" FT HELIX 1223..1225 FT /evidence="ECO:0007829|PDB:5DGJ" FT HELIX 1226..1229 FT /evidence="ECO:0007829|PDB:5TG1" FT TURN 1232..1234 FT /evidence="ECO:0007829|PDB:5E0J" FT HELIX 1236..1238 FT /evidence="ECO:0007829|PDB:6BID" FT STRAND 1242..1247 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1250..1260 FT /evidence="ECO:0007829|PDB:5DGJ" FT TURN 1262..1265 FT /evidence="ECO:0007829|PDB:5E0J" FT STRAND 1266..1270 FT /evidence="ECO:0007829|PDB:5DGJ" FT STRAND 1275..1278 FT /evidence="ECO:0007829|PDB:4IN2" SQ SEQUENCE 1789 AA; 198694 MW; 6C84EF9EE62809B9 CRC64; MMMASKDVVP TAASSENANN NSSIKSRLLA RLKGSGGATS PPNSIKITNQ DMALGLIGQV PAPKATSVDV PKQQRDRPPR TVAEVQQNLR WTERPQDQNV KTWDELDHTT KQQILDEHAE WFDAGGLGPS TLPTSHERYT HENDEGHQVK WSAREGVDLG ISGLTTVSGP EWNMCPLPPV DQRSTTPATE PTIGDMIEFY EGHIYHYAIY IGQGKTVGVH SPQAAFSITR ITIQPISAWW RVCYVPQPKQ RLTYDQLKEL ENEPWPYAAV TNNCFEFCCQ VMCLEDTWLQ RKLISSGRFY HPTQDWSRDT PEFQQDSKLE MVRDAVLAAI NGLVSRPFKD LLGKLKPLNV LNLLSNCDWT FMGVVEMVVL LLELFGIFWN PPDVSNFIAS LLPDFHLQGP EDLARDLVPI VLGGIGLAIG FTRDKVSKMM KNAVDGLRAA TQLGQYGLEI FSLLKKYFFG GDQTEKTLKD IESAVIDMEV LSSTSVTQLV RDKQSARAYM AILDNEEEKA RKLSVRNADP HVVSSTNALI SRISMARAAL AKAQAEMTSR MRPVVIMMCG PPGIGKTKAA EHLAKRLANE IRPGGKVGLV PREAVDHWDG YHGEEVMLWD DYGMTKIQED CNKLQAIADS APLTLNCDRI ENKGMQFVSD AIVITTNAPG PAPVDFVNLG PVCRRVDFLV YCTAPEVEHT RKVSPGDTTA LKDCFKPDFS HLKMELAPQG GFDNQGNTPF GKGVMKPTTI NRLLIQAVAL TMERQDEFQL QGPTYDFDTD RVAAFTRMAR ANGLGLISMA SLGKKLRSVT TIEGLKNALS GYKISKCSIQ WQSRVYIIES DGASVQIKED KQALTPLQQT INTASLAITR LKAARAVAYA SCFQSAITTI LQMAGSALVI NRAVKRMFGT RTAAMALEGP GKEHNCRVHK AKEAGKGPIG HDDMVERFGL CETEEEESED QIQMVPSDAV PEGKNKGKTK KGRGRKNNYN AFSRRGLSDE EYEEYKKIRE EKNGNYSIQE YLEDRQRYEE ELAEVQAGGD GGIGETEMEI RHRVFYKSKS KKHQQEQRRQ LGLVTGSDIR KRKPIDWTPP KNEWADDDRE VDYNEKINFE APPTLWSRVT KFGSGWGFWV SPTVFITTTH VVPTGVKEFF GEPLSSIAIH QAGEFTQFRF SKKMRPDLTG MVLEEGCPEG TVCSVLIKRD SGELLPLAVR MGAIASMRIQ GRLVHGQSGM LLTGANAKGM DLGTIPGDCG APYVHKRGND WVVCGVHAAA TKSGNTVVCA VQAGEGETAL EGGDKGHYAG HEIVRYGSGP ALSTKTKFWR SSPEPLPPGV YEPAYLGGKD PRVQNGPSLQ QVLRDQLKPF ADPRGRMPEP GLLEAAVETV TSMLEQTMDT PSPWSYADAC QSLDKTTSSG YPHHKRKNDD WNGTTFVGEL GEQAAHANNM YENAKHMKPI YTAALKDELV KPEKIYQKVK KRLLWGADLG TVVRAARAFG PFCDAIKSHV IKLPIKVGMN TIEDGPLIYA EHAKYKNHFD ADYTAWDSTQ NRQIMTESFS IMSRLTASPE LAEVVAQDLL APSEMDVGDY VIRVKEGLPS GFPCTSQVNS INHWIITLCA LSEATGLSPD VVQSMSYFSF YGDDEIVSTD IDFDPARLTQ ILKEYGLKPT RPDKTEGPIQ VRKNVDGLVF LRRTISRDAA GFQGRLDRAS IERQIFWTRG PNHSDPSETL VPHTQRKIQL ISLLGEASLH GEKFYRKISS KVIHEIKTGG LEMYVPGWQA MFRWMRFHDL GLWTGDRDLL PEFVNDDGV //