THCAS_CANSA
ID THCAS_CANSA Reviewed; 545 AA.
AC Q8GTB6; Q33DQ4; Q5NTX8;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Tetrahydrocannabinolic acid synthase {ECO:0000303|Ref.4};
DE Short=THCA synthase {ECO:0000303|Ref.4};
DE EC=1.21.3.7 {ECO:0000269|PubMed:15190053, ECO:0000269|PubMed:17669365, ECO:0000269|Ref.4};
DE AltName: Full=Delta(1)-tetrahydrocannabinolic acid synthase {ECO:0000303|PubMed:15190053};
DE Flags: Precursor;
GN Name=THCAS {ECO:0000303|Ref.4};
OS Cannabis sativa (Hemp) (Marijuana).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Rosales; Cannabaceae; Cannabis.
OX NCBI_TaxID=3483;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 29-52; 330-339; 426-437 AND
RP 441-455, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP GLYCOSYLATION, AND MUTAGENESIS OF HIS-92; ARG-108; ARG-110; HIS-114 AND
RP HIS-208.
RX PubMed=15190053; DOI=10.1074/jbc.m403693200;
RA Sirikantaramas S., Morimoto S., Shoyama Y., Ishikawa Y., Wada Y.,
RA Shoyama Y., Taura F.;
RT "The gene controlling marijuana psychoactivity: molecular cloning and
RT heterologous expression of Delta1-tetrahydrocannabinolic acid synthase from
RT Cannabis sativa L.";
RL J. Biol. Chem. 279:39767-39774(2004).
RN [2]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16024552; DOI=10.1093/pcp/pci166;
RA Sirikantaramas S., Taura F., Tanaka Y., Ishikawa Y., Morimoto S.,
RA Shoyama Y.;
RT "Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana
RT psychoactivity, is secreted into the storage cavity of the glandular
RT trichomes.";
RL Plant Cell Physiol. 46:1578-1582(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND VARIANT LEU-63.
RC STRAIN=001, 010, 013, 020, 053, 054, and 069;
RX PubMed=16143478; DOI=10.1016/j.forsciint.2005.07.005;
RA Kojoma M., Seki H., Yoshida S., Muranaka T.;
RT "DNA polymorphisms in the tetrahydrocannabinolic acid (THCA) synthase gene
RT in 'drug-type' and 'fiber-type' Cannabis sativa L.";
RL Forensic Sci. Int. 159:132-140(2006).
RN [4]
RP PROTEIN SEQUENCE OF 29-44, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, AND ACTIVITY
RP REGULATION.
RA Taura F., Morimoto S., Shoyama Y.;
RT "First direct evidence for the mechanism of delta(1)-tetra
RT hydrocannabinolic acid biosynthesis.";
RL J. Am. Chem. Soc. 117:9766-9767(1995).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND GLYCOSYLATION.
RX PubMed=17669365; DOI=10.1016/j.bbrc.2007.07.079;
RA Taura F., Dono E., Sirikantaramas S., Yoshimura K., Shoyama Y.,
RA Morimoto S.;
RT "Production of Delta(1)-tetrahydrocannabinolic acid by the biosynthetic
RT enzyme secreted from transgenic Pichia pastoris.";
RL Biochem. Biophys. Res. Commun. 361:675-680(2007).
RN [6]
RP REVIEW.
RX PubMed=17712812; DOI=10.1002/cbdv.200790145;
RA Taura F., Sirikantaramas S., Shoyama Y., Shoyama Y., Morimoto S.;
RT "Phytocannabinoids in Cannabis sativa: recent studies on biosynthetic
RT enzymes.";
RL Chem. Biodivers. 4:1649-1663(2007).
RN [7]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 28-545 IN COMPLEX WITH FAD,
RP MUTAGENESIS OF HIS-114; HIS-292; TYR-417; GLU-442 AND TYR-484,
RP GLYCOSYLATION AT ASN-65; ASN-89; ASN-168; ASN-329; ASN-467 AND ASN-499, AND
RP DISULFIDE BOND.
RX PubMed=22766313; DOI=10.1016/j.jmb.2012.06.030;
RA Shoyama Y., Tamada T., Kurihara K., Takeuchi A., Taura F., Arai S.,
RA Blaber M., Shoyama Y., Morimoto S., Kuroki R.;
RT "Structure and function of delta(1)-tetrahydrocannabinolic acid (THCA)
RT synthase, the enzyme controlling the psychoactivity of Cannabis sativa.";
RL J. Mol. Biol. 423:96-105(2012).
CC -!- FUNCTION: Oxidoreductase involved in the biosynthesis of cannabinoids-
CC related terpenophenolic natural products, which have pharmacological
CC activity (PubMed:15190053, PubMed:17669365, Ref.4). Catalyzes the
CC oxidative cyclization of the monoterpene moiety in cannabigerolic acid
CC (CBGA), producing delta(9)-tetrahydrocannabinolate (THCA), the major
CC cannabioid in drug-type Cannabis plants (PubMed:15190053,
CC PubMed:17669365, Ref.4). Can also use cannabinerolic acid as substrate,
CC but not cannabigerol or cannabinerol (PubMed:15190053, PubMed:17669365,
CC Ref.4). {ECO:0000269|PubMed:15190053, ECO:0000269|PubMed:17669365,
CC ECO:0000269|Ref.4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cannabigerolate + O2 = Delta(9)-tetrahydrocannabinolate +
CC H2O2; Xref=Rhea:RHEA:34135, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:66962, ChEBI:CHEBI:66963; EC=1.21.3.7;
CC Evidence={ECO:0000269|PubMed:15190053, ECO:0000269|PubMed:17669365,
CC ECO:0000269|Ref.4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34136;
CC Evidence={ECO:0000269|PubMed:15190053, ECO:0000269|PubMed:17669365,
CC ECO:0000269|Ref.4};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:22766313};
CC Note=Binds 1 FAD per subunit in a bicovalent manner.
CC {ECO:0000269|PubMed:22766313};
CC -!- ACTIVITY REGULATION: Inhibited by Hg(2+). {ECO:0000269|Ref.4}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=134 uM for cannabigerolic acid {ECO:0000269|PubMed:15190053,
CC ECO:0000269|Ref.4};
CC KM=254 uM for cannabinerolic acid {ECO:0000269|PubMed:15190053,
CC ECO:0000269|Ref.4};
CC Vmax=2.68 nmol/sec/mg enzyme with cannabigerolic acid as substrate
CC {ECO:0000269|PubMed:15190053, ECO:0000269|Ref.4};
CC Vmax=0.37 nmol/sec/mg enzyme with cannabinerolic acid as substrate
CC {ECO:0000269|PubMed:15190053, ECO:0000269|Ref.4};
CC Note=kcat is 0.30 sec(-1) for cannabigerolate.;
CC pH dependence:
CC Optimum pH is 5.5-6.0. {ECO:0000269|PubMed:15190053,
CC ECO:0000269|Ref.4};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000303|PubMed:30468448}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:22766313, ECO:0000269|Ref.4}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16024552}. Secreted,
CC extracellular space, apoplast {ECO:0000269|PubMed:16024552}.
CC Note=Sorted from the secretory cells into the storage cavity of
CC glandular trichomes. {ECO:0000269|PubMed:16024552}.
CC -!- TISSUE SPECIFICITY: Expressed in the secretory cells of glandular
CC trichomes. {ECO:0000269|PubMed:16024552}.
CC -!- PTM: Glycosylated when produced in a heterologous system. The
CC deglycosylated THCA synthase has more catalytic activity than the
CC glycosylated form. {ECO:0000269|PubMed:15190053,
CC ECO:0000269|PubMed:17669365}.
CC -!- PTM: The FAD cofactor is bound via a bicovalent 6-S-cysteinyl, 8alpha-
CC N1-histidyl FAD linkage. {ECO:0000269|PubMed:22766313}.
CC -!- POLYMORPHISM: Several isoforms of the active tetrahydrocannabinolic
CC acid synthase found in the 'drug-type' cannabis plants exist due to
CC polymorphism. {ECO:0000269|PubMed:16143478}.
CC -!- MISCELLANEOUS: THCA synthase might contribute to the self-defense of
CC Cannabis plants by producing both THCA and hydrogen peroxide, but since
CC these reaction products are toxic to the plant itself, THCA synthase
CC must be secreted from secretory cells into the storage cavity to avoid
CC cellular damage.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; AB057805; BAC41356.1; -; mRNA.
DR EMBL; AB212829; BAE48241.1; -; Genomic_DNA.
DR EMBL; AB212832; BAE48244.1; -; Genomic_DNA.
DR EMBL; AB212834; BAE48246.1; -; Genomic_DNA.
DR EMBL; AB212835; BAE48247.1; -; Genomic_DNA.
DR EMBL; AB212837; BAE48249.1; -; Genomic_DNA.
DR EMBL; AB212838; BAE48250.1; -; Genomic_DNA.
DR EMBL; AB183698; BAD82947.1; -; Genomic_DNA.
DR EMBL; AB183699; BAD82948.1; -; Genomic_DNA.
DR EMBL; AB183700; BAD82949.1; -; Genomic_DNA.
DR EMBL; AB183701; BAD82950.1; -; Genomic_DNA.
DR EMBL; AB183702; BAD82951.1; -; Genomic_DNA.
DR EMBL; AB183703; BAD82952.1; -; Genomic_DNA.
DR EMBL; AB183704; BAD82953.1; -; Genomic_DNA.
DR EMBL; AB183705; BAD82954.1; -; Genomic_DNA.
DR PDB; 3VTE; X-ray; 2.75 A; A=28-545.
DR PDBsum; 3VTE; -.
DR AlphaFoldDB; Q8GTB6; -.
DR SMR; Q8GTB6; -.
DR KEGG; ag:BAC41356; -.
DR BioCyc; MetaCyc:MON-12033; -.
DR BRENDA; 1.21.3.7; 1159.
DR UniPathway; UPA00213; -.
DR GO; GO:0048046; C:apoplast; IEA:UniProtKB-SubCell.
DR GO; GO:0102778; F:delta9-tetrahydrocannabinolate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:1901696; P:cannabinoid biosynthetic process; TAS:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoplast; Direct protein sequencing; Disulfide bond; FAD;
KW Flavoprotein; Glycoprotein; Oxidoreductase; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:15190053, ECO:0000269|Ref.4"
FT CHAIN 29..545
FT /note="Tetrahydrocannabinolic acid synthase"
FT /id="PRO_0000421142"
FT DOMAIN 77..251
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 484
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:22766313"
FT BINDING 109..115
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 120
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 176
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 180..184
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 190
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 236
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 241
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT BINDING 292
FT /ligand="cannabigerolate"
FT /ligand_id="ChEBI:CHEBI:66962"
FT /evidence="ECO:0000305|PubMed:22766313"
FT BINDING 417
FT /ligand="cannabigerolate"
FT /ligand_id="ChEBI:CHEBI:66962"
FT /evidence="ECO:0000305|PubMed:22766313"
FT BINDING 442
FT /ligand="cannabigerolate"
FT /ligand_id="ChEBI:CHEBI:66962"
FT /evidence="ECO:0000250|UniProtKB:G2QG48"
FT BINDING 481..483
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:22766313, ECO:0007744|PDB:3VTE"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:22766313, ECO:0007744|PDB:3VTE"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:22766313, ECO:0007744|PDB:3VTE"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:22766313, ECO:0007744|PDB:3VTE"
FT CARBOHYD 467
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:22766313, ECO:0007744|PDB:3VTE"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:22766313, ECO:0007744|PDB:3VTE"
FT DISULFID 37..99
FT /evidence="ECO:0000269|PubMed:22766313,
FT ECO:0007744|PDB:3VTE"
FT CROSSLNK 114..176
FT /note="6-(S-cysteinyl)-8alpha-(pros-histidyl)-FAD (His-
FT Cys)"
FT /evidence="ECO:0000269|PubMed:22766313"
FT VARIANT 63
FT /note="I -> L (in strain: 001)"
FT /evidence="ECO:0000269|PubMed:16143478"
FT MUTAGEN 92
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:15190053"
FT MUTAGEN 108
FT /note="R->A: Strongly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:15190053"
FT MUTAGEN 110
FT /note="R->A: Strongly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:15190053"
FT MUTAGEN 114
FT /note="H->A: Loss of FAD binding and loss of catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:15190053,
FT ECO:0000269|PubMed:22766313"
FT MUTAGEN 208
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:15190053"
FT MUTAGEN 292
FT /note="H->A: Strongly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:22766313"
FT MUTAGEN 417
FT /note="Y->F: Reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:22766313"
FT MUTAGEN 442
FT /note="E->Q: Slightly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:22766313"
FT MUTAGEN 484
FT /note="Y->F: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22766313"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 60..66
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 90..103
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:3VTE"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 124..131
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:3VTE"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 204..210
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 240..247
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 255..262
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 266..279
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 287..297
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 308..319
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 321..331
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 347..353
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 367..371
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 379..390
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 394..402
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 403..406
FT /evidence="ECO:0007829|PDB:3VTE"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 412..418
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:3VTE"
FT STRAND 441..449
FT /evidence="ECO:0007829|PDB:3VTE"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 455..468
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 487..489
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 500..510
FT /evidence="ECO:0007829|PDB:3VTE"
FT HELIX 515..525
FT /evidence="ECO:0007829|PDB:3VTE"
SQ SEQUENCE 545 AA; 61927 MW; 6C24D805208E7421 CRC64;
MNCSAFSFWF VCKIIFFFLS FHIQISIANP RENFLKCFSK HIPNNVANPK LVYTQHDQLY
MSILNSTIQN LRFISDTTPK PLVIVTPSNN SHIQATILCS KKVGLQIRTR SGGHDAEGMS
YISQVPFVVV DLRNMHSIKI DVHSQTAWVE AGATLGEVYY WINEKNENLS FPGGYCPTVG
VGGHFSGGGY GALMRNYGLA ADNIIDAHLV NVDGKVLDRK SMGEDLFWAI RGGGGENFGI
IAAWKIKLVA VPSKSTIFSV KKNMEIHGLV KLFNKWQNIA YKYDKDLVLM THFITKNITD
NHGKNKTTVH GYFSSIFHGG VDSLVDLMNK SFPELGIKKT DCKEFSWIDT TIFYSGVVNF
NTANFKKEIL LDRSAGKKTA FSIKLDYVKK PIPETAMVKI LEKLYEEDVG AGMYVLYPYG
GIMEEISESA IPFPHRAGIM YELWYTASWE KQEDNEKHIN WVRSVYNFTT PYVSQNPRLA
YLNYRDLDLG KTNHASPNNY TQARIWGEKY FGKNFNRLVK VKTKVDPNNF FRNEQSIPPL
PPHHH
