VE2_HPV16
ID VE2_HPV16 Reviewed; 365 AA.
AC P03120; Q71BI4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Regulatory protein E2 {ECO:0000255|HAMAP-Rule:MF_04001};
GN Name=E2 {ECO:0000255|HAMAP-Rule:MF_04001};
OS Human papillomavirus type 16.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=333760;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2990099; DOI=10.1016/0042-6822(85)90214-4;
RA Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W.G.;
RT "Human papillomavirus type 16 DNA sequence.";
RL Virology 145:181-185(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate European German 131;
RA Terai M., Fu L., Ma Z., Burk R.D.;
RT "Cloning and sequencing of non-European human papillomavirus (HPV) variant
RT complete genomes from cervicovaginal cells by an overlapping PCR method.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=3033289; DOI=10.1128/jvi.61.5.1630-1638.1987;
RA Phelps W.C., Howley P.M.;
RT "Transcriptional trans-activation by the human papillomavirus type 16 E2
RT gene product.";
RL J. Virol. 61:1630-1638(1987).
RN [4]
RP FUNCTION.
RX PubMed=1326651; DOI=10.1128/jvi.66.10.5949-5958.1992;
RA Del Vecchio A.M., Romanczuk H., Howley P.M., Baker C.C.;
RT "Transient replication of human papillomavirus DNAs.";
RL J. Virol. 66:5949-5958(1992).
RN [5]
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, AND DIMERIZATION.
RX PubMed=7645246; DOI=10.1006/viro.1995.1424;
RA Sanders C.M., Stern P.L., Maitland N.J.;
RT "Characterization of human papillomavirus type 16 E2 protein and subdomains
RT expressed in insect cells.";
RL Virology 211:418-433(1995).
RN [6]
RP FUNCTION, AND INTERACTION WITH L2.
RX PubMed=15681049; DOI=10.1016/j.virusres.2004.07.004;
RA Okoye A., Cordano P., Taylor E.R., Morgan I.M., Everett R., Campo M.S.;
RT "Human papillomavirus 16 L2 inhibits the transcriptional activation
RT function, but not the DNA replication function, of HPV-16 E2.";
RL Virus Res. 108:1-14(2005).
RN [7]
RP INTERACTION WITH E7.
RX PubMed=16439535; DOI=10.1128/jvi.80.4.1787-1797.2006;
RA Gammoh N., Grm H.S., Massimi P., Banks L.;
RT "Regulation of human papillomavirus type 16 E7 activity through direct
RT protein interaction with the E2 transcriptional activator.";
RL J. Virol. 80:1787-1797(2006).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST BRD4.
RX PubMed=16611886; DOI=10.1128/jvi.80.9.4276-4285.2006;
RA Schweiger M.R., You J., Howley P.M.;
RT "Bromodomain protein 4 mediates the papillomavirus E2 transcriptional
RT activation function.";
RL J. Virol. 80:4276-4285(2006).
RN [9]
RP INTERACTION WITH HOST TAF1.
RX PubMed=18580066; DOI=10.1159/000141706;
RA Centeno F., Ramirez-Salazar E., Garcia-Villa E., Gariglio P., Garrido E.;
RT "TAF1 interacts with and modulates human papillomavirus 16 E2-dependent
RT transcriptional regulation.";
RL Intervirology 51:137-143(2008).
RN [10]
RP SUMOYLATION, MUTAGENESIS OF LYS-292, AND SUBCELLULAR LOCATION.
RX PubMed=18619639; DOI=10.1016/j.virol.2008.06.008;
RA Wu Y.C., Roark A.A., Bian X.L., Wilson V.G.;
RT "Modification of papillomavirus E2 proteins by the small ubiquitin-like
RT modifier family members (SUMOs).";
RL Virology 378:329-338(2008).
RN [11]
RP PHOSPHORYLATION.
RX PubMed=19781729; DOI=10.1016/j.virol.2009.08.046;
RA Johansson C., Graham S.V., Dornan E.S., Morgan I.M.;
RT "The human papillomavirus 16 E2 protein is stabilised in S phase.";
RL Virology 394:194-199(2009).
RN [12]
RP INTERACTION WITH HOST TOPBP1.
RX PubMed=22973044; DOI=10.1128/jvi.01002-12;
RA Donaldson M.M., Mackintosh L.J., Bodily J.M., Dornan E.S., Laimins L.A.,
RA Morgan I.M.;
RT "An interaction between human papillomavirus 16 E2 and TopBP1 is required
RT for optimum viral DNA replication and episomal genome establishment.";
RL J. Virol. 86:12806-12815(2012).
RN [13]
RP PHOSPHORYLATION AT SER-243, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25340539; DOI=10.1371/journal.pone.0110882;
RA Chang S.W., Liu W.C., Liao K.Y., Tsao Y.P., Hsu P.H., Chen S.L.;
RT "Phosphorylation of HPV-16 E2 at serine 243 enables binding to Brd4 and
RT mitotic chromosomes.";
RL PLoS ONE 9:E110882-E110882(2014).
RN [14]
RP INTERACTION WITH PROTEIN L1, AND SUBCELLULAR LOCATION.
RX PubMed=25911730; DOI=10.1099/vir.0.000162;
RA Siddiqa A., Leon K.C., James C.D., Bhatti M.F., Roberts S., Parish J.L.;
RT "The human papillomavirus type 16 L1 protein directly interacts with E2 and
RT enhances E2-dependent replication and transcription activation.";
RL J. Gen. Virol. 96:2274-2285(2015).
RN [15]
RP FUNCTION.
RX PubMed=26365679; DOI=10.1016/j.virusres.2015.09.008;
RA Gauson E.J., Wang X., Dornan E.S., Herzyk P., Bristol M., Morgan I.M.;
RT "Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate
RT host genome expression and cellular movement.";
RL Virus Res. 211:1-8(2015).
RN [16]
RP ROLE AS ANTIGEN IN HEAD AND NECK SQUAMOUS CELL CARCINOMA.
RX PubMed=33208941; DOI=10.1038/s41586-020-2931-3;
RA Wieland A., Patel M.R., Cardenas M.A., Eberhardt C.S., Hudson W.H.,
RA Obeng R.C., Griffith C.C., Wang X., Chen Z.G., Kissick H.T., Saba N.F.,
RA Ahmed R.;
RT "Defining HPV-specific B cell responses in patients with head and neck
RT cancer.";
RL Nature 597:274-278(2021).
RN [17]
RP ROLE AS ANTIGEN IN HEAD AND NECK SQUAMOUS CELL CARCINOMA.
RX PubMed=34471285; DOI=10.1038/s41586-021-03862-z;
RA Eberhardt C.S., Kissick H.T., Patel M.R., Cardenas M.A., Prokhnevska N.,
RA Obeng R.C., Nasti T.H., Griffith C.C., Im S.J., Wang X., Shin D.M.,
RA Carrington M., Chen Z.G., Sidney J., Sette A., Saba N.F., Wieland A.,
RA Ahmed R.;
RT "Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck
RT cancer.";
RL Nature 597:279-284(2021).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-201, AND TRANSACTIVATION DOMAIN.
RX PubMed=10089541; DOI=10.1107/s0907444998010889;
RA Burns J.E., Moroz O.V., Antson A.A., Sanders C.M., Wilson K.S.,
RA Maitland N.J.;
RT "Expression, crystallization and preliminary X-ray analysis of the E2
RT transactivation domain from papillomavirus type 16.";
RL Acta Crystallogr. D 54:1471-1474(1998).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 285-365, DIMERIZATION, AND
RP DNA-BINDING DOMAIN.
RX PubMed=9878365; DOI=10.1006/jmbi.1998.2260;
RA Hegde R.S., Androphy E.J.;
RT "Crystal structure of the E2 DNA-binding domain from human papillomavirus
RT type 16: implications for its DNA binding-site selection mechanism.";
RL J. Mol. Biol. 284:1479-1489(1998).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-201.
RX PubMed=10693813; DOI=10.1038/35001638;
RA Antson A.A., Burns J.E., Moroz O.V., Scott D.J., Sanders C.M.,
RA Bronstein I.B., Dodson G.G., Wilson K.S., Maitland N.J.;
RT "Structure of the intact transactivation domain of the human papillomavirus
RT E2 protein.";
RL Nature 403:805-809(2000).
RN [21]
RP STRUCTURE BY NMR OF 286-365.
RX PubMed=15702528; DOI=10.1023/b:jnmr.0000048942.96866.76;
RA Nadra A.D., Eliseo T., Mok Y.K., Almeida C.L., Bycroft M., Paci M.,
RA de Prat-Gay G., Cicero D.O.;
RT "Solution structure of the HPV-16 E2 DNA binding domain, a transcriptional
RT regulator with a dimeric beta-barrel fold.";
RL J. Biomol. NMR 30:211-214(2004).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 1-201, AND INTERACTION WITH HOST
RP BRD4.
RX PubMed=17189190; DOI=10.1016/j.molcel.2006.11.002;
RA Abbate E.A., Voitenleitner C., Botchan M.R.;
RT "Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a
RT peptide that ablates HPV chromosomal association.";
RL Mol. Cell 24:877-889(2006).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 285-365.
RX PubMed=17915949; DOI=10.1021/bi701104q;
RA Dellarole M., Sanchez I.E., Freire E., de Prat-Gay G.;
RT "Increased stability and DNA site discrimination of 'single chain' variants
RT of the dimeric beta-barrel DNA binding domain of the human papillomavirus
RT E2 transcriptional regulator.";
RL Biochemistry 46:12441-12450(2007).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 283-365.
RX PubMed=21482558; DOI=10.1096/fj.10-176461;
RA Bose K., Meinke G., Bohm A., Baleja J.D.;
RT "Design and characterization of an enhanced repressor of human
RT papillomavirus E2 protein.";
RL FASEB J. 25:2354-2361(2011).
CC -!- FUNCTION: Plays a role in the initiation of viral DNA replication. A
CC dimer of E2 interacts with a dimer of E1 in order to improve
CC specificity of E1 DNA binding activity. Once the complex recognizes and
CC binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also
CC regulates viral transcription through binding to the E2RE response
CC element (5'-ACCNNNNNNGGT-3') present in multiple copies in the
CC regulatory regions of the viral genome. Activates or represses
CC transcription depending on E2RE's position with regards to proximal
CC promoter elements including the TATA-box. Repression occurs by
CC sterically hindering the assembly of the transcription initiation
CC complex. {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:1326651,
CC ECO:0000269|PubMed:15681049, ECO:0000269|PubMed:16611886,
CC ECO:0000269|PubMed:25340539, ECO:0000269|PubMed:26365679,
CC ECO:0000269|PubMed:3033289}.
CC -!- SUBUNIT: Binds DNA as homodimer. Interacts with protein E1; this
CC interaction greatly increases E1 DNA-binding activity. Interacts with
CC protein L1; this interaction enhances E2-dependent replication and
CC transcription activation. Interacts with protein L2; this interaction
CC inhibits E2 transcriptional activity but not DNA replication function
CC E2. Interacts with protein E7; this interaction inhibits E7 oncogenic
CC activity. Interacts with host TAF1; this interaction modulates E2-
CC dependent transcriptional regulation. Interacts with host BRD4; this
CC interaction mediates E2 transcriptional activation function.
CC Additionally, the interaction with host BRD4 on mitotic chromosomes
CC mediates tethering of the viral genome. Interacts with host TOPBP1;
CC this interaction is required for optimal viral DNA replication.
CC {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:15681049,
CC ECO:0000269|PubMed:16439535, ECO:0000269|PubMed:16611886,
CC ECO:0000269|PubMed:17189190, ECO:0000269|PubMed:18580066,
CC ECO:0000269|PubMed:22973044, ECO:0000269|PubMed:25911730,
CC ECO:0000269|PubMed:7645246, ECO:0000269|PubMed:9878365}.
CC -!- INTERACTION:
CC P03120; P03114: E1; NbExp=3; IntAct=EBI-1779322, EBI-7387308;
CC P03120; O60885: BRD4; Xeno; NbExp=4; IntAct=EBI-1779322, EBI-723869;
CC P03120; O60885-1: BRD4; Xeno; NbExp=2; IntAct=EBI-1779322, EBI-9345088;
CC P03120; Q9H0C5: BTBD1; Xeno; NbExp=3; IntAct=EBI-1779322, EBI-935503;
CC P03120; P17676: CEBPB; Xeno; NbExp=2; IntAct=EBI-1779322, EBI-969696;
CC P03120; P79101: CPSF3; Xeno; NbExp=2; IntAct=EBI-1779322, EBI-7894416;
CC P03120; O19137: CPSF4; Xeno; NbExp=3; IntAct=EBI-1779322, EBI-7894441;
CC P03120; P31274: HOXC9; Xeno; NbExp=3; IntAct=EBI-1779322, EBI-1779423;
CC P03120; P22736: NR4A1; Xeno; NbExp=3; IntAct=EBI-1779322, EBI-721550;
CC P03120; P03132: Rep68; Xeno; NbExp=2; IntAct=EBI-1779322, EBI-7387242;
CC P03120; Q92547: TOPBP1; Xeno; NbExp=2; IntAct=EBI-1779322, EBI-308302;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04001,
CC ECO:0000269|PubMed:18619639, ECO:0000269|PubMed:25340539,
CC ECO:0000269|PubMed:25911730, ECO:0000269|PubMed:7645246}.
CC -!- PTM: Phosphorylated. Phosphorylation at Ser-243 mediates binding to
CC host Brd4 and is required for host chromosome binding.
CC {ECO:0000255|HAMAP-Rule:MF_04001, ECO:0000269|PubMed:25340539,
CC ECO:0000269|PubMed:7645246}.
CC -!- PTM: Sumoylation plays a regulatory role in E2 transcriptional
CC activity. {ECO:0000255|HAMAP-Rule:MF_04001,
CC ECO:0000269|PubMed:18619639}.
CC -!- MISCELLANEOUS: HPV16, in comparison to HPV types 6 and 11, is more
CC often associated with malignant genital cancers in humans.
CC -!- MISCELLANEOUS: Part of the antigens expressed and presented within HPV-
CC positive head and neck tumors. {ECO:0000269|PubMed:33208941,
CC ECO:0000269|PubMed:34471285}.
CC -!- SIMILARITY: Belongs to the papillomaviridae E2 protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04001}.
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DR EMBL; K02718; AAA46941.1; -; Genomic_DNA.
DR EMBL; AF536179; AAQ10715.1; -; Genomic_DNA.
DR PIR; A03669; W2WLHS.
DR RefSeq; NP_041328.1; NC_001526.4.
DR PDB; 1BY9; X-ray; 2.20 A; A=285-365.
DR PDB; 1DTO; X-ray; 1.90 A; A=1-201.
DR PDB; 1R8P; NMR; -; A/B=286-365.
DR PDB; 1ZZF; NMR; -; A/B=286-365.
DR PDB; 2NNU; X-ray; 1.59 A; A=1-201.
DR PDB; 2Q79; X-ray; 1.80 A; A=285-365.
DR PDB; 3MI7; X-ray; 2.20 A; X=283-365.
DR PDBsum; 1BY9; -.
DR PDBsum; 1DTO; -.
DR PDBsum; 1R8P; -.
DR PDBsum; 1ZZF; -.
DR PDBsum; 2NNU; -.
DR PDBsum; 2Q79; -.
DR PDBsum; 3MI7; -.
DR BMRB; P03120; -.
DR SASBDB; P03120; -.
DR SMR; P03120; -.
DR BioGRID; 4263559; 4.
DR DIP; DIP-44574N; -.
DR IntAct; P03120; 64.
DR MINT; P03120; -.
DR BindingDB; P03120; -.
DR ChEMBL; CHEMBL4656; -.
DR DrugCentral; P03120; -.
DR iPTMnet; P03120; -.
DR PRIDE; P03120; -.
DR DNASU; 1489080; -.
DR GeneID; 1489080; -.
DR KEGG; vg:1489080; -.
DR EvolutionaryTrace; P03120; -.
DR PRO; PR:P03120; -.
DR Proteomes; UP000009251; Genome.
DR Proteomes; UP000106302; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044163; C:host cytoskeleton; IDA:CACAO.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0006275; P:regulation of DNA replication; IEA:UniProtKB-UniRule.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR GO; GO:0039693; P:viral DNA genome replication; IEA:UniProtKB-UniRule.
DR Gene3D; 1.10.287.30; -; 1.
DR Gene3D; 2.170.200.10; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR HAMAP; MF_04001; PPV_E2; 1.
DR InterPro; IPR035975; E2/EBNA1_C_sf.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR000427; Papillomavirus_E2_C.
DR InterPro; IPR001866; Papillomavirus_E2_N.
DR InterPro; IPR033668; Reg_prot_E2.
DR InterPro; IPR036050; Regulatory_protein_E2_N.
DR InterPro; IPR042503; Regulatory_protein_E2_N_1.
DR InterPro; IPR042504; Regulatory_protein_E2_N_2.
DR Pfam; PF00511; PPV_E2_C; 1.
DR Pfam; PF00508; PPV_E2_N; 1.
DR SUPFAM; SSF51332; SSF51332; 1.
DR SUPFAM; SSF54957; SSF54957; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA replication; DNA-binding; Early protein;
KW Host nucleus; Isopeptide bond; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..365
FT /note="Regulatory protein E2"
FT /id="PRO_0000133195"
FT REGION 1..200
FT /note="Transactivation domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001,
FT ECO:0000269|PubMed:10089541"
FT REGION 285..365
FT /note="DNA-binding domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001,
FT ECO:0000269|PubMed:9878365"
FT MOD_RES 243
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:25340539"
FT CROSSLNK 292
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04001,
FT ECO:0000269|PubMed:18619639"
FT MUTAGEN 292
FT /note="K->R: Complete loss of sumoylation."
FT /evidence="ECO:0000269|PubMed:18619639"
FT CONFLICT 77
FT /note="L -> P (in Ref. 2; AAQ10715)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="I -> T (in Ref. 2; AAQ10715)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="P -> S (in Ref. 2; AAQ10715)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="T -> K (in Ref. 2; AAQ10715)"
FT /evidence="ECO:0000305"
FT HELIX 1..21
FT /evidence="ECO:0007829|PDB:2NNU"
FT HELIX 26..48
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:2NNU"
FT HELIX 62..83
FT /evidence="ECO:0007829|PDB:2NNU"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:2NNU"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:2NNU"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 110..121
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 127..141
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:2NNU"
FT HELIX 171..178
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 184..190
FT /evidence="ECO:0007829|PDB:2NNU"
FT STRAND 286..293
FT /evidence="ECO:0007829|PDB:2Q79"
FT HELIX 295..305
FT /evidence="ECO:0007829|PDB:2Q79"
FT HELIX 306..311
FT /evidence="ECO:0007829|PDB:2Q79"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:2Q79"
FT STRAND 331..336
FT /evidence="ECO:0007829|PDB:2Q79"
FT HELIX 340..349
FT /evidence="ECO:0007829|PDB:2Q79"
FT STRAND 356..363
FT /evidence="ECO:0007829|PDB:2Q79"
SQ SEQUENCE 365 AA; 41825 MW; 27581F82B246E112 CRC64;
METLCQRLNV CQDKILTHYE NDSTDLRDHI DYWKHMRLEC AIYYKAREMG FKHINHQVVP
TLAVSKNKAL QAIELQLTLE TIYNSQYSNE KWTLQDVSLE VYLTAPTGCI KKHGYTVEVQ
FDGDICNTMH YTNWTHIYIC EEASVTVVEG QVDYYGLYYV HEGIRTYFVQ FKDDAEKYSK
NKVWEVHAGG QVILCPTSVF SSNEVSSPEI IRQHLANHPA ATHTKAVALG TEETQTTIQR
PRSEPDTGNP CHTTKLLHRD SVDSAPILTA FNSSHKGRIN CNSNTTPIVH LKGDANTLKC
LRYRFKKHCT LYTAVSSTWH WTGHNVKHKS AIVTLTYDSE WQRDQFLSQV KIPKTITVST
GFMSI
