LTP_HHV11
ID LTP_HHV11 Reviewed; 3164 AA.
AC P10220; B9VQG4; Q09I97;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 116.
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:16109378};
DE EC=3.4.22.- {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:16109378};
GN ORFNames=UL36;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Nonneuroinvasive mutant HF10;
RX PubMed=17218138; DOI=10.1016/j.micinf.2006.10.019;
RA Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y.;
RT "Determination and analysis of the DNA sequence of highly attenuated herpes
RT simplex virus type 1 mutant HF10, a potential oncolytic virus.";
RL Microbes Infect. 9:142-149(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17 syn+;
RA Cunningham C., Davison A.J.;
RT "Herpes simplex virus type 1 bacterial artificial chromosome.";
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP CHARACTERIZATION, ACTIVE SITES, AND MUTAGENESIS OF CYS-65.
RC STRAIN=KOS;
RX PubMed=16109378; DOI=10.1016/j.molcel.2005.07.003;
RA Kattenhorn L.M., Korbel G.A., Kessler B.M., Spooner E., Ploegh H.L.;
RT "A deubiquitinating enzyme encoded by HSV-1 belongs to a family of cysteine
RT proteases that is conserved across the family Herpesviridae.";
RL Mol. Cell 19:547-557(2005).
RN [5]
RP FUNCTION.
RX PubMed=16306630; DOI=10.1128/jvi.79.24.15582-15585.2005;
RA Schlieker C., Korbel G.A., Kattenhorn L.M., Ploegh H.L.;
RT "A deubiquitinating activity is conserved in the large tegument protein of
RT the herpesviridae.";
RL J. Virol. 79:15582-15585(2005).
RN [6]
RP INTERACTION WITH UL25, AND SUBCELLULAR LOCATION.
RX PubMed=17715218; DOI=10.1128/jvi.01113-07;
RA Coller K.E., Lee J.I., Ueda A., Smith G.A.;
RT "The capsid and tegument of the alphaherpesviruses are linked by an
RT interaction between the UL25 and VP1/2 proteins.";
RL J. Virol. 81:11790-11797(2007).
RN [7]
RP INTERACTION WITH UL37.
RC STRAIN=KOS;
RX PubMed=18787001; DOI=10.1128/jvi.00956-08;
RA Desai P., Sexton G.L., Huang E., Person S.;
RT "Localization of herpes simplex virus type 1 UL37 in the Golgi complex
RT requires UL36 but not capsid structures.";
RL J. Virol. 82:11354-11361(2008).
RN [8]
RP SUBCELLULAR LOCATION.
RC STRAIN=F;
RX PubMed=18596102; DOI=10.1128/jvi.00904-08;
RA Loret S., Guay G., Lippe R.;
RT "Comprehensive characterization of extracellular herpes simplex virus type
RT 1 virions.";
RL J. Virol. 82:8605-8618(2008).
RN [9]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RC STRAIN=F;
RX PubMed=18216103; DOI=10.1128/jvi.01919-07;
RA Jovasevic V., Liang L., Roizman B.;
RT "Proteolytic cleavage of VP1-2 is required for release of herpes simplex
RT virus 1 DNA into the nucleus.";
RL J. Virol. 82:3311-3319(2008).
RN [10]
RP FUNCTION.
RX PubMed=18495763; DOI=10.1128/jvi.00225-08;
RA Shanda S.K., Wilson D.W.;
RT "UL36p is required for efficient transport of membrane-associated herpes
RT simplex virus type 1 along microtubules.";
RL J. Virol. 82:7388-7394(2008).
RN [11]
RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=18385239; DOI=10.1128/jvi.02497-07;
RA Abaitua F., O'Hare P.;
RT "Identification of a highly conserved, functional nuclear localization
RT signal within the N-terminal region of herpes simplex virus type 1 VP1-2
RT tegument protein.";
RL J. Virol. 82:5234-5244(2008).
RN [12]
RP FUNCTION.
RC STRAIN=17 syn+;
RX PubMed=18971278; DOI=10.1128/jvi.01032-08;
RA Roberts A.P., Abaitua F., O'Hare P., McNab D., Rixon F.J., Pasdeloup D.;
RT "Differing roles of inner tegument proteins pUL36 and pUL37 during entry of
RT herpes simplex virus type 1.";
RL J. Virol. 83:105-116(2009).
RN [13]
RP FUNCTION.
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 [14]
RP FUNCTION, AND INTERACTION WITH VP16.
RX PubMed=19923173; DOI=10.1128/jvi.01721-09;
RA Ko D.H., Cunningham A.L., Diefenbach R.J.;
RT "The major determinant for addition of tegument protein pUL48 (VP16) to
RT capsids in herpes simplex virus type 1 is the presence of the major
RT tegument protein pUL36 (VP1/2).";
RL J. Virol. 84:1397-1405(2010).
RN [15]
RP FUNCTION, AND INTERACTION WITH UL19.
RX PubMed=22345483; DOI=10.1128/jvi.00012-12;
RA Cardone G., Newcomb W.W., Cheng N., Wingfield P.T., Trus B.L., Brown J.C.,
RA Steven A.C.;
RT "The UL36 tegument protein of herpes simplex virus 1 has a composite
RT binding site at the capsid vertices.";
RL J. Virol. 86:4058-4064(2012).
RN [16]
RP FUNCTION, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=22718835; DOI=10.1128/jvi.01209-12;
RA Abaitua F., Hollinshead M., Bolstad M., Crump C.M., O'Hare P.;
RT "A Nuclear localization signal in herpesvirus protein VP1-2 is essential
RT for infection via capsid routing to the nuclear pore.";
RL J. Virol. 86:8998-9014(2012).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23186167; DOI=10.1111/cmi.12075;
RA Sandbaumhueter M., Doehner K., Schipke J., Binz A., Pohlmann A., Sodeik B.,
RA Bauerfeind R.;
RT "Cytosolic herpes simplex virus capsids not only require binding inner
RT tegument protein pUL36 but also pUL37 for active transport prior to
RT secondary envelopment.";
RL Cell. Microbiol. 15:248-269(2013).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1625-1757, AND SUBUNIT.
RX PubMed=25678705; DOI=10.1074/jbc.m114.612838;
RA Scrima N., Lepault J., Boulard Y., Pasdeloup D., Bressanelli S., Roche S.;
RT "Insights into herpesvirus tegument organization from structural analyses
RT of the 970 central residues of HSV-1 UL36 protein.";
RL J. Biol. Chem. 290:8820-8833(2015).
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.
CC {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:16306630,
CC ECO:0000269|PubMed:18216103, ECO:0000269|PubMed:18495763,
CC ECO:0000269|PubMed:18971278, ECO:0000269|PubMed:19923173,
CC ECO:0000269|PubMed:20190741, ECO:0000269|PubMed:22345483,
CC ECO:0000269|PubMed:22718835, ECO:0000269|PubMed:23186167}.
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:16109378};
CC -!- SUBUNIT: Interacts with host CUL1 and CUL4A; these interactions inhibit
CC the E3 ligase activity of cullins. Interacts with inner tegument
CC protein. Interacts with capsid vertex specific component CVC2.
CC Interacts with the major capsid protein/MCP (By similarity). Interacts
CC with VP16; this interaction is important for outer tegument association
CC to the capsid. May form homodimers. {ECO:0000250|UniProtKB:P03186,
CC ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:17715218,
CC ECO:0000269|PubMed:18787001, ECO:0000269|PubMed:19923173,
CC ECO:0000269|PubMed:22345483, ECO:0000269|PubMed:25678705}.
CC -!- INTERACTION:
CC P10220; P10221: UL37; NbExp=2; IntAct=EBI-7694334, EBI-6880600;
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000255|HAMAP-Rule:MF_04044,
CC ECO:0000269|PubMed:18596102}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04044, ECO:0000269|PubMed:17715218,
CC ECO:0000269|PubMed:18385239, ECO:0000269|PubMed:23186167}. Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:17715218,
CC ECO:0000269|PubMed:18385239}. Note=Tightly associated with the capsid.
CC {ECO:0000255|HAMAP-Rule:MF_04044}.
CC -!- PTM: Proteolytically processed, possibly into several polypeptides.
CC Enzymatic activity is only detectable following cleavage of the UL36
CC protein, which occurs late during viral replication.
CC {ECO:0000269|PubMed:18216103}.
CC -!- SIMILARITY: Belongs to the herpesviridae large tegument protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04044}.
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DR EMBL; X14112; CAA32311.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63498.1; -; Genomic_DNA.
DR EMBL; FJ593289; ACM62259.1; -; Genomic_DNA.
DR PIR; I30085; WMBEH6.
DR RefSeq; YP_009137111.1; NC_001806.2.
DR PDB; 4TT0; X-ray; 2.60 A; A/B=1625-1757.
DR PDB; 4TT1; X-ray; 2.75 A; A/B=1625-1757.
DR PDBsum; 4TT0; -.
DR PDBsum; 4TT1; -.
DR SMR; P10220; -.
DR BioGRID; 971402; 8.
DR IntAct; P10220; 3.
DR MINT; P10220; -.
DR MEROPS; C76.001; -.
DR PRIDE; P10220; -.
DR GeneID; 2703357; -.
DR KEGG; vg:2703357; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180652; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:AgBase.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IDA:CAFA.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0019784; F:deNEDDylase activity; IEA:InterPro.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0039708; P:nuclear capsid assembly; IMP:AgBase.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039693; P:viral DNA genome replication; IEA:InterPro.
DR HAMAP; MF_04044; HSV_LTP; 1.
DR InterPro; IPR005210; Herpes_LT_deneddylase.
DR InterPro; IPR006928; Herpes_teg_USP.
DR InterPro; IPR034702; HSV_LTP.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR Pfam; PF04843; Herpes_teg_N; 1.
DR Pfam; PF03586; Herpes_UL36; 1.
DR SUPFAM; SSF54001; SSF54001; 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..3164
FT /note="Large tegument protein deneddylase"
FT /id="PRO_0000116035"
FT DOMAIN 45..263
FT /note="Peptidase C76"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REPEAT 2911..2912
FT /note="1"
FT REPEAT 2913..2914
FT /note="2"
FT REPEAT 2915..2916
FT /note="3"
FT REPEAT 2917..2918
FT /note="4"
FT REPEAT 2919..2920
FT /note="5"
FT REPEAT 2921..2922
FT /note="6"
FT REPEAT 2923..2924
FT /note="7"
FT REPEAT 2925..2926
FT /note="8"
FT REPEAT 2927..2928
FT /note="9"
FT REPEAT 2929..2930
FT /note="10"
FT REPEAT 2931..2932
FT /note="11"
FT REPEAT 2933..2934
FT /note="12"
FT REPEAT 2935..2936
FT /note="13"
FT REPEAT 2937..2938
FT /note="14"
FT REPEAT 2939..2940
FT /note="15"
FT REPEAT 2941..2942
FT /note="16"
FT REPEAT 2943..2944
FT /note="17"
FT REPEAT 2945..2946
FT /note="18"
FT REPEAT 2947..2948
FT /note="19"
FT REPEAT 2949..2950
FT /note="20"
FT REPEAT 2951..2952
FT /note="21"
FT REPEAT 2953..2954
FT /note="22"
FT REPEAT 2955..2956
FT /note="23"
FT REPEAT 2957..2958
FT /note="24"
FT REPEAT 2959..2960
FT /note="25"
FT REPEAT 2961..2962
FT /note="26"
FT REPEAT 2963..2964
FT /note="27"
FT REPEAT 2965..2966
FT /note="28"
FT REPEAT 2967..2968
FT /note="29"
FT REPEAT 2969..2970
FT /note="30"
FT REPEAT 2971..2972
FT /note="31"
FT REPEAT 2973..2974
FT /note="32"
FT REPEAT 2975..2976
FT /note="33"
FT REPEAT 2977..2978
FT /note="34"
FT REPEAT 2979..2980
FT /note="35"
FT REGION 1..273
FT /note="Deubiquitination activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 289..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 426..432
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:18385239,
FT ECO:0000269|PubMed:22718835"
FT REGION 579..609
FT /note="Interaction with inner tegument protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 579..609
FT /note="Interaction with UL37"
FT /evidence="ECO:0000269|PubMed:18787001"
FT REGION 2296..2318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2518..2552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2583..3020
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2911..2980
FT /note="35 X 2 AA tandem repeats of P-Q"
FT COMPBIAS 366..392
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2719..2736
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2840..2865
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2885..2911
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2912..2980
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3001..3020
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 65
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044,
FT ECO:0000269|PubMed:16109378"
FT ACT_SITE 197
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT ACT_SITE 199
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT SITE 52
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT VARIANT 234
FT /note="A -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 307
FT /note="P -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 375..379
FT /note="Missing (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 392
FT /note="T -> P (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 620
FT /note="N -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 624
FT /note="W -> R (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 671
FT /note="A -> V (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 885
FT /note="I -> M (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1023
FT /note="A -> V (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1244
FT /note="V -> G (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1373
FT /note="G -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1389
FT /note="G -> D (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1419
FT /note="T -> M (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1470
FT /note="A -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1604
FT /note="A -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1605
FT /note="H -> D (in strain: 17 syn+ and Nonneuroinvasive
FT mutant HF10)"
FT VARIANT 1642
FT /note="E -> D (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1695
FT /note="V -> L (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1729
FT /note="G -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1777
FT /note="R -> C (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1888
FT /note="V -> M (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 1973
FT /note="E -> K (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2267
FT /note="V -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2540
FT /note="V -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2545
FT /note="A -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2646
FT /note="F -> V (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2666
FT /note="P -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2748
FT /note="A -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2856
FT /note="A -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2875
FT /note="A -> T (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2894
FT /note="T -> A (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 2973..2978
FT /note="Missing (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 3095
FT /note="V -> A (in strain: Nonneuroinvasive mutant HF10)"
FT MUTAGEN 65
FT /note="C->A: Complete loss of deubiquitination activity."
FT /evidence="ECO:0000269|PubMed:16109378"
FT HELIX 1625..1665
FT /evidence="ECO:0007829|PDB:4TT0"
FT HELIX 1672..1678
FT /evidence="ECO:0007829|PDB:4TT0"
FT HELIX 1684..1720
FT /evidence="ECO:0007829|PDB:4TT0"
FT TURN 1723..1725
FT /evidence="ECO:0007829|PDB:4TT0"
FT STRAND 1729..1731
FT /evidence="ECO:0007829|PDB:4TT1"
FT HELIX 1736..1738
FT /evidence="ECO:0007829|PDB:4TT0"
FT HELIX 1739..1746
FT /evidence="ECO:0007829|PDB:4TT0"
SQ SEQUENCE 3164 AA; 335862 MW; CC5D31FF4F9FE3F4 CRC64;
MGGGNNTNPG GPVHKQAGSL ASRAHMIAGT PPHSTMERGG DRDIVVTGAR NQFAPDLEPG
GSVSCMRSSL SFLSLIFDVG PRDVLSAEAI EGCLVEGGEW TRATAGPGPP RMCSIVELPN
FLEYPGARGG LRCVFSRVYG EVGFFGEPAA GLLETQCPAH TFFAGPWALR PLSYTLLTIG
PLGMGLFRDG DTAYLFDPHG LPEGTPAFIA KVRAGDMYPY LTYYTRDRPD VRWAGAMVFF
VPSGPEPAAP ADLTAAALHL YGASETYLQD EAFSERRVAI THPLRGEIAG LGEPCVGVGP
REGVGGPGPH PPTAAQSPPP TRARRDDRAS ETSRGTAGPS AKPEAKRPNR APDDVWAVAL
KGTPPTDPPS ADPPSADPPS AIPPPPPSAP KTPAAEAAEE DDDDMRVLEM GVVPVGRHRA
RYSAGLPKRR RPTWTPPSSV EDLTSGEKTK RSAPPAKTKK KSTPKGKTPV GAAVPASVPE
PVLASAPPDP AGPPVAEAGE DDGPTVPASS QALEALKTRR SPEPPGADLA QLFEAHPNVA
ATAVKFTACS AALAREVAAC SRLTISALRS PYPASPGLLE LCVIFFFERV LAFLIENGAR
THTQAGVAGP AAALLEFTLN MLPWKTAVGD FLASTRLSLA DVAAHLPLVQ HVLDENSLIG
RLALAKLILV ARDVIRETDA FYGELADLEL QLRAAPPANL YTRLGEWLLE RSQAHPDTLF
APATPTHPEP LLYRVQALAK FARGEEIRVE AEDRQMREAL DALARGVDAV SQHAGPLGVM
PAPAGAAPQG APRPPPLGPE AVQVRLEEVR TQARRAIEGA VKEYFYRGAV YSAKALQASD
NNDRRFHVAS AAVVPVVQLL ESLPVFDQHT RDIAQRAAIP APPPIATSPT AILLRDLIQR
GQTLDAPEDL AAWLSVLTDA ANQGLIERKP LDELARSIRD INDQQARRSS GLAELRRFDA
LDAALGQQLD SDAAFVPAPG ASPYPDDGGL SPEATRMAEE ALRQARAMDA AKLTAELAPD
ARARLRERAR SLEAMLEGAR ERAKVARDAR EKFLHKLQGV LRPLPDFVGL KACPAVLATL
RASLPAGWSD LPEAVRGAPP EVTAALRADM WGLLGQYRDA LEHPTPDTAT ALSGLHPSFV
VVLKNLFADA PETPFLLQFF ADHAPIIAHA VSNAINAGSA AVATADPAST VDAAVRAHRV
LVDAVTALGA AASDPASPLA FLAAMADSAA GYVKATRLAL DARVAIAQLT TLGSAAADLV
VQVRRAANQP EGEHASLIQA ATRATTGARE SLAGHEGRFG GLLHAEGTAG DHSPSGRALQ
ELGKVIGATR RRADELEAAT ADLREKMAAQ RARSSHERWA ADVEAVLDRV ESGAEFDVVE
LRRLQALAGT HGYNPRDFRK RAEQALGTNA KAVTLALETA LAFNPYTPEN QRHPMLPPLA
AIHRIDWSAA FGAAADTYAD MFRVDTEPLA RLLRLAGGLL ERAQANDGFI DYHEAVLHLS
EDLGGVPALR QYVPFFQKGY AEYVDIRDRL DALRADARRA IGSVALDLAA AAEEISAVRN
DPAAAAELVR AGVTLPCPSE DALVACVAAL ERVDQSPVKD TAYAHYVAFV TRQDLADTKD
AVVRAKQQRA EATERVTAGL REVLAARERR AQLEAEGLAN LKTLLKVVAV PATVAKTLDQ
ARSAEEIADQ VEILVDQTEK ARELDVQAVA WLEHAQRTFE THPLSAASGD GPGLLTRQGA
RLQALFDTRR RVEALRRSLE EAEAEWDEVW GRFGRVRGGA WKSPEGFRAA CEQLRALQDT
TNTVSGLRAQ RDYERLPAKY QGVLGAKSAE RAGAVEELGG RVAQHADLSA RLRDEVVPRV
AWEMNFDTLG GLLAEFDAVA GDLAPWAVEE FRGARELIQR RMGLYSAYAK ATGQTGAGAA
AAPAPLLVDL RALDARARAS APPGQEADPQ MLRRRGEAYL RVSGGPGPLV LREATSTLDR
PFAPSFLVPD GTPLQYALCF PAVTDKLGAL LMCPEAACIR PPLPTDTLES ASTVTAMYVL
TVINRLQLAL SDAQAANFQL FGRFVRHRQA RWGASMDAAA ELYVALVATT LTREFGCRWA
QLEWGGDAAA PGPPLGPQSS TRHRVSFNEN DVLVALVASS PEHIYTFWRL DLVRQHEYMH
LTLPRAFQNA ADSMLFVQRL TPHPDARIRV LPAFSAGGPP TRGLMFGTRL ADWRRGKLSE
TDPLAPWRSV PELGTERGAA LGKLSPAQAL AAVSVLGRMC LPSTALVALW TCMFPDDYTE
YDSFDALLTA RLESGQTLSP SGGREASPPA PPNALYRPTG QHVAVPAAAT HRTPAARVTA
MDLVLAAVLL GAPVVVALRN TTAFSRESEL ELCLTLFDSR ARGPDAALRD AVSSDIETWA
VRLLHADLNP IENACLAAQL PRLSALIAER PLARGPPCLV LVDISMTPVA VLWENPDPPG
PPDVRFVGSE ATEELPFVAG GEDVLAASAT DEDPFLARAI LGRPFDASLL SGELFPGHPV
YQRAPDDQSP SVPNPTPGPV DLVGAEGSLG PGSLAPTLFT DATPGEPVPP RMWAWIHGLE
ELASDDSGGP APLLAPDPLS PTADQSVPTS QCAPRPPGPA VTAREARPGV PAESTRPAPV
GPRDDFRRLP SPQSSPAPPD ATAPRPPASS RASAASSSGS RARRHRRARS LARATQASAT
TQGWRPPALP DTVAPVTDFA RPPAPPKPPE PAPHALVSGV PLPLGPQAAG QASPALPIDP
VPPPVATGTV LPGGENRRPP LTSGPAPTPP RVPVGGPQRR LTRPAVASLS ESRESLPSPW
DPADPTAPVL GRNPAEPTSS SPAGPSPPPP AVQPVAPPPT SGPPPTYLTL EGGVAPGGPV
SRRPTTRQPV ATPTTSARPR GHLTVSRLSA PQPQPQPQPQ PQPQPQPQPQ PQPQPQPQPQ
PQPQPQPQPQ PQPQPQPQPQ PQPQPQPQPQ PQPQPQPQPQ NGHVAPGEYP AVRFRAPQNR
PSVPASASST NPRTGSSLSG VSSWASSLAL HIDATPPPVS LLQTLYVSDD EDSDATSLFL
SDSEAEALDP LPGEPHSPIT NEPFSALSAD DSQEVTRLQF GPPPVSANAV LSRRYVQRTG
RSALAVLIRA CYRLQQQLQR TRRALLHHSD AVLTSLHHVR MLLG
