RTCB_PYRHO
ID RTCB_PYRHO Reviewed; 871 AA.
AC O59245;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=tRNA-splicing ligase RtcB {ECO:0000305};
DE EC=6.5.1.8 {ECO:0000269|PubMed:22320833, ECO:0000269|PubMed:22949672};
DE AltName: Full=3'-phosphate/5'-hydroxy nucleic acid ligase {ECO:0000305};
DE AltName: Full=tRNA ligase RtcB {ECO:0000303|PubMed:24435797};
DE Contains:
DE RecName: Full=Pho hyp2 intein;
DE EC=3.1.-.-;
GN Name=rtcB; OrderedLocusNames=PH1602;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=22320833; DOI=10.1021/bi201921a;
RA Desai K.K., Raines R.T.;
RT "tRNA ligase catalyzes the GTP-dependent ligation of RNA with 3'-phosphate
RT and 5'-hydroxyl termini.";
RL Biochemistry 51:1333-1335(2012).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, ACTIVITY REGULATION, AND MUTAGENESIS
RP OF ASP-65; ASP-95; ASN-592; HIS-593; PHE-594; GLU-596; HIS-794 AND LYS-870.
RX PubMed=24435797; DOI=10.1093/nar/gkt1375;
RA Desai K.K., Cheng C.L., Bingman C.A., Phillips G.N. Jr., Raines R.T.;
RT "A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor
RT specificity and accelerates RNA ligation.";
RL Nucleic Acids Res. 42:3931-3942(2014).
RN [4] {ECO:0007744|PDB:1UC2}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-97 AND 488-871, AND SUBUNIT.
RX PubMed=16485279; DOI=10.1002/prot.20912;
RA Okada C., Maegawa Y., Yao M., Tanaka I.;
RT "Crystal structure of an RtcB homolog protein (PH1602-extein protein) from
RT Pyrococcus horikoshii reveals a novel fold.";
RL Proteins 63:1119-1122(2006).
RN [5] {ECO:0007744|PDB:4DWQ, ECO:0007744|PDB:4DWR}
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH MANGANESE AND GMP,
RP COFACTOR, ACTIVE SITE, FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM,
RP AND MUTAGENESIS OF ASP-65; ASP-95; HIS-593; HIS-719; HIS-794; ARG-798 AND
RP ARG-802.
RX PubMed=22949672; DOI=10.1073/pnas.1213795109;
RA Englert M., Xia S., Okada C., Nakamura A., Tanavde V., Yao M., Eom S.H.,
RA Konigsberg W.H., Soll D., Wang J.;
RT "Structural and mechanistic insights into guanylylation of RNA-splicing
RT ligase RtcB joining RNA between 3'-terminal phosphate and 5'-OH.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:15235-15240(2012).
RN [6] {ECO:0007744|PDB:4ISJ, ECO:0007744|PDB:4ISZ, ECO:0007744|PDB:4IT0}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MANGANESE AND GMP,
RP COFACTOR, ACTIVE SITE, AND REACTION MECHANISM.
RX PubMed=23560983; DOI=10.1021/bi4002375;
RA Desai K.K., Bingman C.A., Phillips G.N. Jr., Raines R.T.;
RT "Structures of the noncanonical RNA ligase RtcB reveal the mechanism of
RT histidine guanylylation.";
RL Biochemistry 52:2518-2525(2013).
CC -!- FUNCTION: Essential for tRNA splicing and maturation (Probable). Acts
CC by directly joining spliced tRNA halves to mature-sized tRNAs
CC (PubMed:22320833, PubMed:22949672). Joins RNA with 2',3'-cyclic-
CC phosphate or 3'-phosphate ends to RNA with 5'-hydroxy ends
CC (PubMed:22320833, PubMed:22949672). {ECO:0000269|PubMed:22320833,
CC ECO:0000269|PubMed:22949672, ECO:0000305|PubMed:22320833}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'-end 3'-phospho-ribonucleotide-RNA + a 5'-end dephospho-
CC ribonucleoside-RNA + GTP = a ribonucleotidyl-ribonucleotide-RNA +
CC diphosphate + GMP; Xref=Rhea:RHEA:68076, Rhea:RHEA-COMP:10463,
CC Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17355, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58115, ChEBI:CHEBI:83062,
CC ChEBI:CHEBI:138284, ChEBI:CHEBI:173118; EC=6.5.1.8;
CC Evidence={ECO:0000269|PubMed:22320833, ECO:0000269|PubMed:22949672};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'-end 2',3'-cyclophospho-ribonucleotide-RNA + a 5'-end
CC dephospho-ribonucleoside-RNA + GTP + H2O = a ribonucleotidyl-
CC ribonucleotide-RNA + diphosphate + GMP + H(+); Xref=Rhea:RHEA:68080,
CC Rhea:RHEA-COMP:10464, Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17355,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58115, ChEBI:CHEBI:83064,
CC ChEBI:CHEBI:138284, ChEBI:CHEBI:173118; EC=6.5.1.8;
CC Evidence={ECO:0000269|PubMed:22320833};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:22320833, ECO:0000269|PubMed:22949672,
CC ECO:0000269|PubMed:23560983};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:22949672,
CC ECO:0000269|PubMed:23560983};
CC -!- ACTIVITY REGULATION: Activated by archease, which accelerates both the
CC RNA 3'-P guanylylation and ligation steps (PubMed:24435797). Archease
CC also expands the NTP specificity of RtcB, enabling the efficient use of
CC dGTP, ATP or ITP (PubMed:24435797). {ECO:0000269|PubMed:24435797}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16485279,
CC ECO:0000269|PubMed:22949672}.
CC -!- PTM: This protein undergoes a protein self splicing that involves a
CC post-translational excision of the intervening region (intein) followed
CC by peptide ligation. {ECO:0000305}.
CC -!- MISCELLANEOUS: Ligation proceeds through 3 nucleotidyl transfer steps,
CC with 2',3'-cyclic phosphate termini being hydrolyzed to 3'-P termini in
CC a step that precedes 3'-P activation with GMP. In the first nucleotidyl
CC transfer step, RtcB reacts with GTP to form a covalent RtcB-histidine-
CC GMP intermediate with release of PPi; in the second step, the GMP
CC moiety is transferred to the RNA 3'-P; in the third step, the 5'-OH
CC from the opposite RNA strand attacks the activated 3'-P to form a
CC 3',5'-phosphodiester bond and release GMP.
CC {ECO:0000305|PubMed:22949672, ECO:0000305|PubMed:23560983}.
CC -!- SIMILARITY: Belongs to the RtcB family. {ECO:0000305}.
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DR EMBL; BA000001; BAA30714.1; -; Genomic_DNA.
DR PIR; B71039; B71039.
DR PDB; 1UC2; X-ray; 2.15 A; A/B=1-97, A/B=488-871.
DR PDB; 4DWQ; X-ray; 2.25 A; A/B=1-97, A/B=488-871.
DR PDB; 4DWR; X-ray; 1.48 A; A/B=1-97, A/B=488-871.
DR PDB; 4ISJ; X-ray; 2.34 A; A/B=1-97, A/B=488-871.
DR PDB; 4ISZ; X-ray; 2.30 A; A/B=1-97, A/B=488-871.
DR PDB; 4IT0; X-ray; 2.40 A; A/B=1-97, A/B=488-871.
DR PDB; 7LFQ; X-ray; 2.70 A; A=406-871.
DR PDBsum; 1UC2; -.
DR PDBsum; 4DWQ; -.
DR PDBsum; 4DWR; -.
DR PDBsum; 4ISJ; -.
DR PDBsum; 4ISZ; -.
DR PDBsum; 4IT0; -.
DR PDBsum; 7LFQ; -.
DR AlphaFoldDB; O59245; -.
DR SMR; O59245; -.
DR STRING; 70601.3258031; -.
DR EnsemblBacteria; BAA30714; BAA30714; BAA30714.
DR KEGG; pho:PH1602; -.
DR eggNOG; arCOG03158; Archaea.
DR eggNOG; arCOG04246; Archaea.
DR OMA; VHNCGVR; -.
DR BRENDA; 6.5.1.8; 5244.
DR EvolutionaryTrace; O59245; -.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0019002; F:GMP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0003972; F:RNA ligase (ATP) activity; IDA:UniProtKB.
DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR GO; GO:0006314; P:intron homing; IEA:UniProtKB-KW.
DR GO; GO:0000394; P:RNA splicing, via endonucleolytic cleavage and ligation; IDA:UniProtKB.
DR GO; GO:0008033; P:tRNA processing; IEA:UniProtKB-KW.
DR Gene3D; 3.10.28.10; -; 1.
DR Gene3D; 3.90.1860.10; -; 2.
DR InterPro; IPR003586; Hint_dom_C.
DR InterPro; IPR003587; Hint_dom_N.
DR InterPro; IPR036844; Hint_dom_sf.
DR InterPro; IPR027434; Homing_endonucl.
DR InterPro; IPR006142; INTEIN.
DR InterPro; IPR030934; Intein_C.
DR InterPro; IPR004042; Intein_endonuc.
DR InterPro; IPR006141; Intein_N.
DR InterPro; IPR004860; LAGLIDADG_2.
DR InterPro; IPR001233; RtcB.
DR InterPro; IPR036025; RtcB-like_sf.
DR PANTHER; PTHR11118; PTHR11118; 1.
DR Pfam; PF14528; LAGLIDADG_3; 1.
DR Pfam; PF01139; RtcB; 1.
DR PRINTS; PR00379; INTEIN.
DR SMART; SM00305; HintC; 1.
DR SMART; SM00306; HintN; 1.
DR SUPFAM; SSF103365; SSF103365; 2.
DR SUPFAM; SSF51294; SSF51294; 1.
DR SUPFAM; SSF55608; SSF55608; 1.
DR TIGRFAMs; TIGR01443; intein_Cterm; 1.
DR TIGRFAMs; TIGR01445; intein_Nterm; 1.
DR PROSITE; PS50818; INTEIN_C_TER; 1.
DR PROSITE; PS50819; INTEIN_ENDONUCLEASE; 1.
DR PROSITE; PS50817; INTEIN_N_TER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; DNA-binding; Endonuclease;
KW GTP-binding; Hydrolase; Intron homing; Ligase; Manganese; Metal-binding;
KW Nuclease; Nucleotide-binding; Protein splicing; tRNA processing.
FT CHAIN 1..97
FT /note="tRNA-splicing ligase RtcB, 1st part"
FT /id="PRO_0000232535"
FT CHAIN 98..487
FT /note="Pho hyp2 intein"
FT /id="PRO_0000232536"
FT CHAIN 488..871
FT /note="tRNA-splicing ligase RtcB, 2nd part"
FT /id="PRO_0000232537"
FT DOMAIN 248..374
FT /note="DOD-type homing endonuclease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00273"
FT ACT_SITE 794
FT /note="GMP-histidine intermediate"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 95
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 488
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 488
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 592..596
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 593
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 624
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 719..720
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 719
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 768..771
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 775
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 794..797
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT BINDING 870
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:23560983"
FT MUTAGEN 65
FT /note="D->A: Abolishes formation of guanylylated RtcB
FT intermediate."
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:24435797"
FT MUTAGEN 95
FT /note="D->A: Abolishes tRNA ligation activity."
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:24435797"
FT MUTAGEN 592
FT /note="N->A: Abolishes tRNA ligation activity in vitro."
FT /evidence="ECO:0000269|PubMed:24435797"
FT MUTAGEN 593
FT /note="H->A: Abolishes tRNA ligation activity."
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:24435797"
FT MUTAGEN 594
FT /note="F->A: Abolishes tRNA ligation activity in vitro. Can
FT be rescued in presence of archease (PH1536)."
FT /evidence="ECO:0000269|PubMed:24435797"
FT MUTAGEN 596
FT /note="E->A: Abolishes tRNA ligation activity in vitro. Can
FT be rescued in presence of archease (PH1536)."
FT /evidence="ECO:0000269|PubMed:24435797"
FT MUTAGEN 719
FT /note="H->A: Only produces few amount of guanylylated RtcB
FT intermediate."
FT /evidence="ECO:0000269|PubMed:22949672"
FT MUTAGEN 794
FT /note="H->A: Loss of function. Abolishes formation of
FT guanylylated RtcB intermediate."
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:24435797"
FT MUTAGEN 794
FT /note="H->K: Loss of function. Still able to form some
FT guanylylated RtcB intermediate but is unable to carry out
FT subsequent transfer of GMP."
FT /evidence="ECO:0000269|PubMed:22949672,
FT ECO:0000269|PubMed:24435797"
FT MUTAGEN 798
FT /note="R->A: Impaired formation of guanylylated RtcB
FT intermediate."
FT /evidence="ECO:0000269|PubMed:22949672"
FT MUTAGEN 802
FT /note="R->A: Impaired formation of guanylylated RtcB
FT intermediate."
FT /evidence="ECO:0000269|PubMed:22949672"
FT MUTAGEN 870
FT /note="K->A: Abolishes tRNA ligation activity in vitro. Can
FT be rescued in presence of archease (PH1536)."
FT /evidence="ECO:0000269|PubMed:24435797"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 422..429
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:1UC2"
FT HELIX 434..437
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 439..442
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 452..459
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 462..464
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 466..473
FT /evidence="ECO:0007829|PDB:4DWR"
FT TURN 474..476
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 489..493
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 499..502
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 503..505
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 506..516
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 531..533
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 535..540
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 542..547
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 553..558
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 560..563
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 575..581
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 582..584
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 594..604
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 606..611
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 618..625
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 628..645
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 646..648
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 656..658
FT /evidence="ECO:0007829|PDB:4DWQ"
FT HELIX 666..701
FT /evidence="ECO:0007829|PDB:4DWR"
FT TURN 705..709
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 713..729
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 732..745
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 756..758
FT /evidence="ECO:0007829|PDB:4DWR"
FT TURN 759..761
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 764..767
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 775..779
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 782..787
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 788..793
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 798..800
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 802..806
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 811..820
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 824..826
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 831..835
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 838..840
FT /evidence="ECO:0007829|PDB:4DWR"
FT HELIX 844..853
FT /evidence="ECO:0007829|PDB:4DWR"
FT STRAND 856..869
FT /evidence="ECO:0007829|PDB:4DWR"
SQ SEQUENCE 871 AA; 98125 MW; 989723B0089288F4 CRC64;
MVVPLKRIDK IRWEIPKFDK RMRVPGRVYA DEVLLEKMKN DRTLEQATNV AMLPGIYKYS
IVMPDGHQGY GFPIGGVAAF DVKEGVISPG GIGYDINCLA PGTRVLTEHG YWLKIEEMPE
KFKLQRLRVY NIEEGHNDFS KVVFVAEREV GSEEKAIRIV TESGKVIEGS EDHPVLTPEG
YVYLRNVKEG DYILVYPFEG VPYEEKKGVI LDESAFEGED PQVVKFLRER NLIPLQWKDP
KVGILARILG FALANGYISE NDNLTFHGKE EVLREVRKDL EELGIEAIVA EEDKLKVTSR
EFAFLLEKLG MAHDSIPEWI IEGPLWIKRN FLAGLFGANG SIVEFKGDVP LPITLTHSRE
LLNDVSRILE GFKVRAKIKM GKNGSYQLVI EDEDSIRNFL GRINYEYDPE KKARGLIAYA
YLKFKELMKG NLMTFEEFAR DRGYEGGFVA EKVIEVKSVK PEYDKFYDIG VYHSAHNFIA
NGIVVHNCGV RLIRTNLTEK EVRPRIKQLV DTLFKNVPSG VGSQGRIKLH WTQIDDVLVD
GAKWAVDNGY GWERDLERLE EGGRMEGADP EAVSQRAKQR GAPQLGSLGS GNHFLEVQVV
DKIFDPEVAK AYGLFEGQVV VMVHTGSRGL GHQVASDYLR IMERAIRKYR IPWPDRELVS
VPFQSEEGQR YFSAMKAAAN FAWANRQMIT HWVRESFQEV FKQDPEGDLG MDIVYDVAHN
IGKVEEHEVD GKRVKVIVHR KGATRAFPPG HEAVPRLYRD VGQPVLIPGS MGTASYILAG
TEGAMKETFG STCHGAGRVL SRKAATRQYR GDRIRQELLN RGIYVRAASM RVVAEEAPGA
YKNVDNVVKV VSEAGIAKLV ARMRPIGVAK G
