ID   LTP_EBVB9               Reviewed;        3149 AA.
AC   P03186; Q777G4;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 113.
DE   RecName: Full=Large tegument protein deneddylase {ECO:0000255|HAMAP-Rule:MF_04044};
DE            EC=3.4.19.12 {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:20190741, ECO:0000269|PubMed:24586164, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34543352};
DE            EC=3.4.22.- {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:20190741};
GN   ORFNames=BPLF1;
OS   Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Lymphocryptovirus;
OC   Lymphocryptovirus humangamma4; Epstein-Barr virus (strain GD1).
OX   NCBI_TaxID=10377;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=6087149; DOI=10.1038/310207a0;
RA   Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J.,
RA   Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C.,
RA   Tuffnell P.S., Barrell B.G.;
RT   "DNA sequence and expression of the B95-8 Epstein-Barr virus genome.";
RL   Nature 310:207-211(1984).
RN   [2]
RP   GENOME REANNOTATION.
RX   PubMed=12771413; DOI=10.1099/vir.0.19054-0;
RA   de Jesus O., Smith P.R., Spender L.C., Elgueta Karstegl C., Niller H.H.,
RA   Huang D., Farrell P.J.;
RT   "Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter
RT   for the BART (CST, BARF0) RNAs of EBV.";
RL   Virology 84:1443-1450(2003).
RN   [3]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15534216; DOI=10.1073/pnas.0407320101;
RA   Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E.,
RA   Illanes D., Sarracino D., Kieff E.;
RT   "Proteins of purified Epstein-Barr virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004).
RN   [4]
RP   FUNCTION.
RX   PubMed=19244336; DOI=10.1128/jvi.02195-08;
RA   Whitehurst C.B., Ning S., Bentz G.L., Dufour F., Gershburg E.,
RA   Shackelford J., Langelier Y., Pagano J.S.;
RT   "The EBV deubiquitinating enzyme, BPLF1, reduces EBV ribonucleotide
RT   reductase activity.";
RL   J. Virol. 83:4345-4353(2009).
RN   [5]
RP   FUNCTION, AND MUTAGENESIS OF CYS-61.
RX   PubMed=20190741; DOI=10.1038/ncb2035;
RA   Gastaldello S., Hildebrand S., Faridani O., Callegari S., Palmkvist M.,
RA   Di Guglielmo C., Masucci M.G.;
RT   "A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication
RT   by regulating the activity of cullin-RING ligases.";
RL   Nat. Cell Biol. 12:351-361(2010).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH HOST CUL1 AND CUL4A.
RX   PubMed=22474075; DOI=10.1093/jmcb/mjs012;
RA   Gastaldello S., Callegari S., Coppotelli G., Hildebrand S., Song M.,
RA   Masucci M.G.;
RT   "Herpes virus deneddylases interrupt the cullin-RING ligase neddylation
RT   cycle by inhibiting the binding of CAND1.";
RL   J. Mol. Cell Biol. 4:242-251(2012).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-61, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=24586164; DOI=10.1371/journal.ppat.1003960;
RA   van Gent M., Braem S.G., de Jong A., Delagic N., Peeters J.G., Boer I.G.,
RA   Moynagh P.N., Kremmer E., Wiertz E.J., Ovaa H., Griffin B.D., Ressing M.E.;
RT   "Epstein-Barr virus large tegument protein BPLF1 contributes to innate
RT   immune evasion through interference with toll-like receptor signaling.";
RL   PLoS Pathog. 10:e1003960-e1003960(2014).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-61, AND INTERACTION WITH
RP   HOST TRIM25 AND YWHAZ.
RX   PubMed=29357390; DOI=10.1371/journal.ppat.1006852;
RA   Gupta S., Ylae-Anttila P., Callegari S., Tsai M.H., Delecluse H.J.,
RA   Masucci M.G.;
RT   "Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25
RT   autoubiquitination and functional inactivation of the RIG-I signalosome.";
RL   PLoS Pathog. 14:e1006852-e1006852(2018).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-61, AND INTERACTION WITH
RP   HOST TRIM25 AND YWHAZ.
RX   PubMed=31710640; DOI=10.1371/journal.ppat.1008146;
RA   Gupta S., Ylae-Anttila P., Sandalova T., Sun R., Achour A., Masucci M.G.;
RT   "14-3-3 scaffold proteins mediate the inactivation of trim25 and inhibition
RT   of the type I interferon response by herpesvirus deconjugases.";
RL   PLoS Pathog. 15:e1008146-e1008146(2019).
RN   [10]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=33509017; DOI=10.1080/15548627.2021.1874660;
RA   Ylae-Anttila P., Gupta S., Masucci M.G.;
RT   "The Epstein-Barr virus deubiquitinase BPLF1 targets SQSTM1/p62 to inhibit
RT   selective autophagy.";
RL   Autophagy 17:3461-3474(2021).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP   CYS-61.
RX   PubMed=34543352; DOI=10.1371/journal.ppat.1009954;
RA   Li J., Nagy N., Liu J., Gupta S., Frisan T., Hennig T., Cameron D.P.,
RA   Baranello L., Masucci M.G.;
RT   "The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the
RT   activity of topoisomerase II during productive infection.";
RL   PLoS Pathog. 17:e1009954-e1009954(2021).
RN   [12]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=36802409; DOI=10.1371/journal.ppat.1011186;
RA   Lui W.Y., Bharti A., Wong N.M., Jangra S., Botelho M.G., Yuen K.S.,
RA   Jin D.Y.;
RT   "Suppression of cGAS- and RIG-I-mediated innate immune signaling by
RT   Epstein-Barr virus deubiquitinase BPLF1.";
RL   PLoS Pathog. 19:e1011186-e1011186(2023).
CC   -!- FUNCTION: Large tegument protein that plays multiple roles in the viral
CC       cycle. During viral entry, remains associated with the capsid while
CC       most of the tegument is detached and participates in the capsid
CC       transport toward the host nucleus. Plays a role in the routing of the
CC       capsid at the nuclear pore complex and subsequent uncoating. Within the
CC       host nucleus, acts as a deneddylase and promotes the degradation of
CC       nuclear CRLs (cullin-RING ubiquitin ligases) and thereby stabilizes
CC       nuclear CRL substrates, while cytoplasmic CRLs remain unaffected. These
CC       modifications prevent host cell cycle S-phase progression and create a
CC       favorable environment allowing efficient viral genome replication.
CC       Participates later in the secondary envelopment of capsids. Indeed,
CC       plays a linker role for the association of the outer viral tegument to
CC       the capsids together with the inner tegument protein (By similarity).
CC       Counteracts host TLR-mediated NF-kappa-B activation through both MYD88
CC       and TICAM1-dependent pathways by interfering with 'Lys-63'- and 'Lys-
CC       48'-linked ubiquitination of signaling intermediates such as TRAF6 and
CC       IKBKG (PubMed:24586164). Inhibits type I interferon production by
CC       forming a tri-molecular complex with host TRIM25 and 14-3-3 thereby
CC       promoting TRIM25 autoubiquitination and sequestration of the ligase
CC       into inactive protein aggregates (PubMed:31710640). In turn, host RIGI
CC       is recruited to the complex but ubiquitination is severely impaired
CC       leading to inhibition of the pathway (PubMed:29357390). Catalyzes also
CC       the removal of 'Lys-48'- and 'Lys-63'-linked ubiquitin chains on host
CC       TBK1 and STING1 suppressing cGAS-STING signaling in addition to the
CC       RIGI-MAVS pathway (PubMed:36802409). Inhibits selective autophagy by
CC       deubiquitinating host SQSTM1. In turn, decreased SQSTM1 ubiquitination
CC       fails to recruit LC3 to SQSTM1-positive aggregates (PubMed:34543352).
CC       In the host nucleus, deubiquitinates topoisomerase II subunits TOP2A
CC       and TOP2B thereby stabilizing SUMOylated TOP2 which halts the DNA
CC       damage response to TOP2-induced double strand DNA breaks and promotes
CC       cell survival (PubMed:34543352). {ECO:0000255|HAMAP-Rule:MF_04044,
CC       ECO:0000269|PubMed:19244336, ECO:0000269|PubMed:20190741,
CC       ECO:0000269|PubMed:22474075, ECO:0000269|PubMed:24586164,
CC       ECO:0000269|PubMed:34543352, ECO:0000269|PubMed:36802409}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000255|HAMAP-Rule:MF_04044,
CC         ECO:0000269|PubMed:20190741, ECO:0000269|PubMed:24586164,
CC         ECO:0000269|PubMed:33509017};
CC   -!- SUBUNIT: Interacts with host CUL1 and CUL4A; these interactions inhibit
CC       the E3 ligase activity of cullins (PubMed:22474075). Interacts with
CC       inner tegument protein. Interacts with capsid vertex specific component
CC       CVC2. Interacts with the major capsid protein/MCP (By similarity).
CC       Interacts with host TRIM25 and YWHAZ (PubMed:29357390,
CC       PubMed:31710640). {ECO:0000255|HAMAP-Rule:MF_04044,
CC       ECO:0000269|PubMed:22474075, ECO:0000269|PubMed:29357390,
CC       ECO:0000269|PubMed:31710640}.
CC   -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000255|HAMAP-Rule:MF_04044,
CC       ECO:0000269|PubMed:15534216}. Host cytoplasm {ECO:0000255|HAMAP-
CC       Rule:MF_04044, ECO:0000269|PubMed:15534216,
CC       ECO:0000269|PubMed:24586164, ECO:0000269|PubMed:29357390,
CC       ECO:0000269|PubMed:31710640, ECO:0000269|PubMed:34543352}. Host nucleus
CC       {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:34543352}.
CC       Note=Tightly associated with the capsid. {ECO:0000255|HAMAP-
CC       Rule:MF_04044}.
CC   -!- SIMILARITY: Belongs to the herpesviridae large tegument protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04044}.
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; V01555; CAA24839.1; -; Genomic_DNA.
DR   EMBL; AJ507799; CAD53402.1; -; Genomic_DNA.
DR   PIR; G93065; QQBE8.
DR   RefSeq; YP_401652.1; NC_007605.1.
DR   PDB; 6W2D; EM; 4.00 A; y/z=1-3149.
DR   PDB; 6W2E; EM; 4.40 A; y/z=1-3149.
DR   PDB; 7BQX; EM; 4.20 A; B/O=1-3149.
DR   PDB; 7BR7; EM; 4.30 A; B/O=1-3149.
DR   PDBsum; 6W2D; -.
DR   PDBsum; 6W2E; -.
DR   PDBsum; 7BQX; -.
DR   PDBsum; 7BR7; -.
DR   EMDB; EMD-21525; -.
DR   EMDB; EMD-21526; -.
DR   EMDB; EMD-30157; -.
DR   EMDB; EMD-30158; -.
DR   SMR; P03186; -.
DR   BioGRID; 971768; 78.
DR   IntAct; P03186; 1.
DR   MINT; P03186; -.
DR   DNASU; 3783726; -.
DR   GeneID; 3783726; -.
DR   KEGG; vg:3783726; -.
DR   BRENDA; 3.4.19.12; 2112.
DR   SIGNOR; P03186; -.
DR   Proteomes; UP000153037; Segment.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-UniRule.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 3.90.70.120; -; 1.
DR   HAMAP; MF_04044; HSV_LTP; 1.
DR   InterPro; IPR006928; Herpes_teg_USP.
DR   InterPro; IPR034702; HSV_LTP.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   PANTHER; PTHR24216:SF65; PAXILLIN-LIKE PROTEIN 1; 1.
DR   PANTHER; PTHR24216; PAXILLIN-RELATED; 1.
DR   Pfam; PF04843; Herpes_teg_N; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS51521; HTUSP; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Host cytoplasm; Host nucleus; Host-virus interaction;
KW   Hydrolase; Modulation of host ubiquitin pathway by viral deubiquitinase;
KW   Modulation of host ubiquitin pathway by virus; Protease;
KW   Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway;
KW   Virion; Virion tegument.
FT   CHAIN           1..3149
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000116038"
FT   DOMAIN          41..258
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REPEAT          335..339
FT                   /note="1"
FT   REPEAT          340..344
FT                   /note="2"
FT   REPEAT          345..349
FT                   /note="3"
FT   REPEAT          350..354
FT                   /note="4"
FT   REPEAT          355..359
FT                   /note="5"
FT   REPEAT          360..364
FT                   /note="6"
FT   REPEAT          365..369
FT                   /note="7"
FT   REPEAT          370..374
FT                   /note="8"
FT   REGION          1..268
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..30
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          319..341
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          335..374
FT                   /note="8 X 5 AA repeats of P-A-S-A-A"
FT   REGION          382..656
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          554..584
FT                   /note="Interaction with inner tegument protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          901..923
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1143..1166
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1412..1434
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1644..1677
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2583..2839
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2852..2981
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2995..3019
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..16
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        319..337
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        382..399
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        414..428
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        451..489
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        496..521
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        522..537
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        538..612
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1651..1665
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2589..2630
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2705..2721
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2722..2757
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2777..2808
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2815..2829
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2955..2969
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        61
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044,
FT                   ECO:0000269|PubMed:20190741"
FT   ACT_SITE        193
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        195
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   SITE            48
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   MUTAGEN         61
FT                   /note="C->A: Complete loss of ubiquitin and NEDD8 binding
FT                   as well as deubiquitinase activity."
FT                   /evidence="ECO:0000269|PubMed:20190741,
FT                   ECO:0000269|PubMed:24586164, ECO:0000269|PubMed:29357390,
FT                   ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34543352"
SQ   SEQUENCE   3149 AA;  337959 MW;  3DD0C576587313D8 CRC64;
     MSNGDWGQSQ RTRGTGPVRG IRTMDVNAPG GGSGGSALRI LGTASCNQAH CKFGRFAGIQ
     CVSNCVLYLV KSFLAGRPLT SRPELDEVLD EGARLDALMR QSGILKGHEM AQLTDVPSSV
     VLRGGGRVHI YRSAEIFGLV LFPAQIANSA VVQSLAEVLH GSYNGVAQFI LYICDIYAGA
     IIIETDGSFY LFDPHCQKDA APGTPAHVRV STYAHDILQY VGAPGAQYTC VHLYFLPEAF
     ETEDPRIFML EHYGVYDFYE ANGSGFDLVG PELVSSDGEA AGTPGADSSP PVMLPFERRI
     IPYNLRPLPS RSFTSDSFPA ARYSPAKTNS PPSSPASAAP ASAAPASAAP ASAAPASAAP
     ASAAPASAAP ASAAPASSPP LFIPIPGLGH TPGVPAPSTP PRASSGAAPQ TPKRKKGLGK
     DSPHKKPTSG RRLPLSSTTD TEDDQLPRTH VPPHRPPSAA RLPPPVIPIP HQSPPASPTP
     HPAPVSTIAP SVTPSPRLPL QIPIPLPQAA PSNPKIPLTT PSPSPTAAAA PTTTTLSPPP
     TQQQPPQSAA PAPSPLLPQQ QPTPSAAPAP SPLLPQQQPP PSAARAPSPL PPQQQPLPSA
     TPAPPPAQQL PPSATTLEPE KNHPPAADRA GTEISPSPPF GQQPSFGDDA SGGSGLVRYL
     SDLEEPFLSM SDSEEAESDL ASDIPTTEDE DMFEDEVFSN SLESGSSAPT SPITLDTARS
     QYYQTTFDIE TPEMDFVPLE SNIARIAGHT YQEQAIVYDP ASNREVPEAD ALSMIDYLLV
     TVVLEQGLIR SRDRSSVLNL LEFLKDWSGH LQVPTLDLEQ LLTSELNIQN LANMLSENKG
     RAGEFHKHLA AKLEACLPSL ATKDAVRVDA GAKMLAEIPQ LAESDDGKFD LEAARRRLTD
     LLSGGDQEAG EGGGEPEDNS IYRGPHVDVP LVLDDESWKR LLSLAEAART AVARQQAGVD
     EEDVRFLALL TAIEYGAPPA ASVPPFVHNV AVRSKNAALH VRRCTADIRD KVASAASDYL
     SYLEDPSLPT VMDFDDLLTH LRHTCQIIAS LPLLNIRYTS IEWDYRELLY LGTALSDMSG
     IPWPLERVEE DDPSIAPLPE FETVAKKQKE LETTRENEKR LRTILDDIEA MLGLAGVASA
     PGAPISPASP SATPANHDNP EATPPLADTA ALTIPVIEKY IANAGSIVGA AKNPTYIRLR
     DTIQQIVRSK KYLMNILKSI TFYTIDNYIA SFEESIDHLY RDLPVLDPEV QDGIDRILDP
     MVSEALHTFE MGNRLTLEPA RLVALQNFAT HSTLKETAAA VNLLPGLLAV YDATITGQAP
     EDALRLLSGL QNQLSQTLIP GKLKKRFLSY LQKLKNNNND QLRQKEVQAW RLEAEGFKPA
     TEEQLEAFLD TAPNKELKRQ YEKKLRQLME TGRKEKEKLR EQEDKERQER RAREANEAWA
     RIRKALGARP EPAPTSPDDW NTLLASLLPD NTDSAAAAAA AVARNTDILD SLTQILAAML
     LGITRVRRER LRSLLVDDGG AAERMEAAEP GWFTDIETGP LARLDAWPAT PAATAKEGGG
     GRGAEEAAGA LFRARTAADA IRSALAQTRQ ALQSPDMKSA VVNTDLEAPY AEYERGLAGL
     LEKRRAAEAA LTAIVSEYVD RTLPEATNDP GQANLPPPPT IPQATAPPRL ASDSALWPKK
     PQLLTRRERD DLLQATGDFF SELLTEAEAA EVRALEEQVR ESQTLMAKAH EMAASTRRGF
     HTALEAVLSR SRDEAPDDEL RSLLPSPPKA PVQAPLEAAL ARAAAGNGSW PYRKSLAAAK
     WIRGICEAVR GLSEGALALA GGAGAWLNLA AAADGEIHEL TRLLEVEGMA QNSMDGMEEL
     RLALATLDPK RVAGGKETVA DWKRRLSRLE AIIQEAQEES QLQGTLQDLV TQARGHTDPR
     QLKIVVEAAR GLALGASAGS QYALLKDKLL RYASAKQSFL AFYETAQPTV FVKHPLTNNL
     PLLITISAPP TGWGNGAPTR RAQFLAAAGP AKYAGTLWLE TESPCDPLNP AYVSADTQEP
     LNYIPVYHNF LEYVMPTVLE NPEAFSLTPA GRPQAIGPPQ DDQERRRRTL ASVASARLSA
     AAADSYWDTW PDVESNAGEL LREYVSAPKA LMEDLADNPI VAMTLLAHAS LIASRNHPPY
     PAPATDREVI LLEQREMMAL LVGTHPAYAA AFLGAPSFYA GLGLVSALAR DGGLGDLLSD
     SVLTYRLVRS PASGRGGMPS TTRGSNDGED ARRLTRHRIA GPPTGFIFFQ DAWEEMDTRA
     ALWPHPEFLG LVHNQSTARA RACMLLLARR CFAPEALQQL WHSLRPLEGP VAFQDYLRDF
     VKQAYTRGEE LPRAEGLEVP RETPSSYGTV TGRALRNLMP YGTPITGPKR GSGDTIPVSV
     FEAAVAAAFL GRPLTLFVSS QYLFNLKTLG QVRVVAPLLY CDGHSEPFRS LVETISLNFL
     QDLDGYSESF EPEMSIFARQ AVWLRELLTE ARAAKPKEAR PPTVAILANR KNIIWKCFTY
     RHNLPDVQFY FNAAGASRWP TDVLNPSFYE HEDPPLPVGY QLPPNPRNVQ ELFSGFPPRV
     GHGLVSGDGF QSADNTPASS DRLQQLGGGE TDQGEKGSTT AESEASGPPS PQSPLLEKVA
     PGRPRDWLSP TSSPRDVTVT PGLAAPITLP GPRLMARPYF GAETRASESP DRSPGSSPRP
     WPKDSLELLP QPAPQQPPSS PWASEQGPIV YTLSPHSTPS TASGSQKKHT IQIPGLVPSQ
     KPSYPPSAPY KPGQSTGGIA PTPSAASLTT FGLQPQDTQA SSQDPPYGHS IMQREKKQQG
     GREEAAEIRP SATRLPTAVG LRPRAPVVAA GAAASATPAF DPGEAPSGFP IPQAPALGSG
     LAAPAHTPVG ALAPRPQKTQ AQRPQDAAAL PTPTIKAVGA RPVPKATGAL AAGARPRGQP
     TAAPPSAASP PRVSLPVRSR QQQSPAIPLP PMHSGSEPGA RPEVRLSQYR HAGPQTYTVR
     KEAPPSAASQ LPKMPKCKDS MYYPPSGSAR YPAPFQALSF SQSVASPAPS SDQTTLLWNT
     PSVVTQFLSI EDIIREVVTG GSTSGDLVVP SGSPSSLSTA APEQDLRYSL TLSQASRVLS
     RFVSQLRRKL ERSTHRLIAD LERLKFLYL
//