VIE1_HCMVT
ID VIE1_HCMVT Reviewed; 491 AA.
AC P03169; Q00677;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 02-JUN-2021, entry version 78.
DE RecName: Full=Immediate early protein IE1;
DE Short=IE1;
DE AltName: Full=55 kDa immediate-early protein 1;
DE AltName: Full=IE1p72 {ECO:0000250|UniProtKB:P13202};
DE AltName: Full=IE72 {ECO:0000303|PubMed:22158879};
GN Name=UL123;
OS Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10363;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6317889; DOI=10.1128/jvi.49.1.190-199.1984;
RA Stenberg R.M., Thomsen D.R., Stinski M.F.;
RT "Structural analysis of the major immediate early gene of human
RT cytomegalovirus.";
RL J. Virol. 49:190-199(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-48.
RX PubMed=1650459; DOI=10.1093/nar/19.14.3979;
RA Chapman B.S., Thayer R.M., Vincent K.A., Haigwood N.L.;
RT "Effect of intron A from human cytomegalovirus (Towne) immediate early gene
RT on heterologous expression in mammalian cells.";
RL Nucleic Acids Res. 19:3979-3986(1991).
RN [3]
RP INTERACTION WITH HOST E2F1.
RX PubMed=7494286; DOI=10.1128/jvi.69.12.7759-7767.1995;
RA Margolis M.J., Pajovic S., Wong E.L., Wade M., Jupp R., Nelson J.A.,
RA Azizkhan J.C.;
RT "Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product
RT with E2F1 coincides with E2F-dependent activation of dihydrofolate
RT reductase transcription.";
RL J. Virol. 69:7759-7767(1995).
RN [4]
RP FUNCTION.
RX PubMed=8876134; DOI=10.1073/pnas.93.21.11321;
RA Mocarski E.S., Kemble G.W., Lyle J.M., Greaves R.F.;
RT "A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is
RT replication defective due to a failure in autoregulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:11321-11326(1996).
RN [5]
RP INTERACTION WITH HUMAN RB1, AND FUNCTION.
RX PubMed=8892909; DOI=10.1128/jvi.70.11.7867-7877.1996;
RA Poma E.E., Kowalik T.F., Zhu L., Sinclair J.H., Huang E.S.;
RT "The human cytomegalovirus IE1-72 protein interacts with the cellular p107
RT protein and relieves p107-mediated transcriptional repression of an E2F-
RT responsive promoter.";
RL J. Virol. 70:7867-7877(1996).
RN [6]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=9151854; DOI=10.1128/jvi.71.6.4599-4613.1997;
RA Ahn J.H., Hayward G.S.;
RT "The major immediate-early proteins IE1 and IE2 of human cytomegalovirus
RT colocalize with and disrupt PML-associated nuclear bodies at very early
RT times in infected permissive cells.";
RL J. Virol. 71:4599-4613(1997).
RN [7]
RP FUNCTION.
RX PubMed=10233977; DOI=10.1128/jvi.73.6.5137-5143.1999;
RA Mueller S., Dejean A.;
RT "Viral immediate-early proteins abrogate the modification by SUMO-1 of PML
RT and Sp100 proteins, correlating with nuclear body disruption.";
RL J. Virol. 73:5137-5143(1999).
RN [8]
RP SUMOYLATION AT LYS-450, AND MUTAGENESIS OF LYS-450.
RX PubMed=11861864; DOI=10.1128/jvi.76.6.2990-2996.2002;
RA Spengler M.L., Kurapatwinski K., Black A.R., Azizkhan-Clifford J.;
RT "SUMO-1 modification of human cytomegalovirus IE1/IE72.";
RL J. Virol. 76:2990-2996(2002).
RN [9]
RP FUNCTION, DOMAIN, MUTAGENESIS OF LEU-174, AND INTERACTION WITH HOST PML.
RX PubMed=15163746; DOI=10.1128/jvi.78.12.6527-6542.2004;
RA Lee H.R., Kim D.J., Lee J.M., Choi C.Y., Ahn B.Y., Hayward G.S., Ahn J.H.;
RT "Ability of the human cytomegalovirus IE1 protein to modulate sumoylation
RT of PML correlates with its functional activities in transcriptional
RT regulation and infectivity in cultured fibroblast cells.";
RL J. Virol. 78:6527-6542(2004).
RN [10]
RP MUTAGENESIS OF LYS-450, AND SUBCELLULAR LOCATION.
RX PubMed=15220454; DOI=10.1128/jvi.78.14.7803-7812.2004;
RA Nevels M., Brune W., Shenk T.;
RT "SUMOylation of the human cytomegalovirus 72-kilodalton IE1 protein
RT facilitates expression of the 86-kilodalton IE2 protein and promotes viral
RT replication.";
RL J. Virol. 78:7803-7812(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOST HDAC3.
RC STRAIN=CR208, and Towne;
RX PubMed=15572445; DOI=10.1073/pnas.0407933101;
RA Nevels M., Paulus C., Shenk T.;
RT "Human cytomegalovirus immediate-early 1 protein facilitates viral
RT replication by antagonizing histone deacetylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17234-17239(2004).
RN [12]
RP FUNCTION, INTERACTION WITH HOST STAT1, INTERACTION WITH HOST STAT2, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=CR208, and Towne;
RX PubMed=16497831; DOI=10.1073/pnas.0600007103;
RA Paulus C., Krauss S., Nevels M.;
RT "A human cytomegalovirus antagonist of type I IFN-dependent signal
RT transducer and activator of transcription signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:3840-3845(2006).
RN [13]
RP NUCLEAR LOCALIZATION SIGNAL, DOMAIN, AND FUNCTION.
RX PubMed=17367754; DOI=10.1016/j.bbrc.2007.03.007;
RA Lee H.R., Huh Y.H., Kim Y.E., Lee K., Kim S., Ahn J.H.;
RT "N-terminal determinants of human cytomegalovirus IE1 protein in nuclear
RT targeting and disrupting PML-associated subnuclear structures.";
RL Biochem. Biophys. Res. Commun. 356:499-504(2007).
RN [14]
RP FUNCTION.
RX PubMed=17331553; DOI=10.1016/j.virol.2007.01.036;
RA Yee L.F., Lin P.L., Stinski M.F.;
RT "Ectopic expression of HCMV IE72 and IE86 proteins is sufficient to induce
RT early gene expression but not production of infectious virus in
RT undifferentiated promonocytic THP-1 cells.";
RL Virology 363:174-188(2007).
RN [15]
RP INTERACTION WITH HOST STAT2, SUMOYLATION AT LYS-450, AND FUNCTION.
RX PubMed=18701593; DOI=10.1128/jvi.00833-08;
RA Huh Y.H., Kim Y.E., Kim E.T., Park J.J., Song M.J., Zhu H., Hayward G.S.,
RA Ahn J.H.;
RT "Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes
RT viral growth and is negatively regulated by SUMO.";
RL J. Virol. 82:10444-10454(2008).
RN [16]
RP INTERACTION WITH HOST STAT2, AND FUNCTION.
RX PubMed=19812155; DOI=10.1128/jvi.01164-09;
RA Krauss S., Kaps J., Czech N., Paulus C., Nevels M.;
RT "Physical requirements and functional consequences of complex formation
RT between the cytomegalovirus IE1 protein and human STAT2.";
RL J. Virol. 83:12854-12870(2009).
RN [17]
RP INTERACTION WITH HUMAN TP53.
RX PubMed=19776115; DOI=10.1128/jvi.00304-09;
RA Hwang E.S., Zhang Z., Cai H., Huang D.Y., Huong S.M., Cha C.Y., Huang E.S.;
RT "Human cytomegalovirus IE1-72 protein interacts with p53 and inhibits p53-
RT dependent transactivation by a mechanism different from that of IE2-86
RT protein.";
RL J. Virol. 83:12388-12398(2009).
RN [18]
RP INTERACTION WITH HUMAN DAXX.
RX PubMed=20444888; DOI=10.1128/jvi.02231-09;
RA Reeves M., Woodhall D., Compton T., Sinclair J.;
RT "Human cytomegalovirus IE72 protein interacts with the transcriptional
RT repressor hDaxx to regulate LUNA gene expression during lytic infection.";
RL J. Virol. 84:7185-7194(2010).
RN [19]
RP INTERACTION WITH HUMAN SP100, AND FUNCTION.
RX PubMed=21880768; DOI=10.1128/jvi.00758-11;
RA Kim Y.E., Lee J.H., Kim E.T., Shin H.J., Gu S.Y., Seol H.S., Ling P.D.,
RA Lee C.H., Ahn J.H.;
RT "Human cytomegalovirus infection causes degradation of Sp100 proteins that
RT suppress viral gene expression.";
RL J. Virol. 85:11928-11937(2011).
RN [20]
RP DOMAIN.
RX PubMed=22158879; DOI=10.1099/vir.0.037986-0;
RA Shin H.J., Kim Y.E., Kim E.T., Ahn J.H.;
RT "The chromatin-tethering domain of human cytomegalovirus IE1 mediates
RT associations of IE1, PML, and STAT2 with mitotic chromosomes, but is not
RT essential for viral replication.";
RL J. Gen. Virol. 93:716-721(2012).
RN [21]
RP FUNCTION.
RC STRAIN=TB40/E;
RX PubMed=23878222; DOI=10.1073/pnas.1305548110;
RA Zalckvar E., Paulus C., Tillo D., Asbach-Nitzsche A., Lubling Y.,
RA Winterling C., Strieder N., Muecke K., Goodrum F., Segal E., Nevels M.;
RT "Nucleosome maps of the human cytomegalovirus genome reveal a temporal
RT switch in chromatin organization linked to a major IE protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:13126-13131(2013).
RN [22]
RP DOMAIN.
RX PubMed=24227840; DOI=10.1128/jvi.02606-13;
RA Muecke K., Paulus C., Bernhardt K., Gerrer K., Schoen K., Fink A.,
RA Sauer E.M., Asbach-Nitzsche A., Harwardt T., Kieninger B., Kremer W.,
RA Kalbitzer H.R., Nevels M.;
RT "Human cytomegalovirus major immediate early 1 protein targets host
RT chromosomes by docking to the acidic pocket on the nucleosome surface.";
RL J. Virol. 88:1228-1248(2014).
RN [23]
RP FUNCTION, INTERACTION WITH HOST STAT1, INTERACTION WITH HOST STAT2,
RP INTERACTION WITH HOST HDAC1, INTERACTION WITH HOST HDAC2, AND INTERACTION
RP WITH HOST PML.
RC STRAIN=Toledo;
RX PubMed=25812002; DOI=10.1371/journal.ppat.1004785;
RA Kim Y.E., Ahn J.H.;
RT "Positive role of promyelocytic leukemia protein in type I interferon
RT response and its regulation by human cytomegalovirus.";
RL PLoS Pathog. 11:e1004785-e1004785(2015).
RN [24]
RP FUNCTION, AND INTERACTION WITH HOST STAT3.
RC STRAIN=TB40/E;
RX PubMed=27387064; DOI=10.1371/journal.ppat.1005748;
RA Harwardt T., Lukas S., Zenger M., Reitberger T., Danzer D., Uebner T.,
RA Munday D.C., Nevels M., Paulus C.;
RT "Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to
RT Downstream STAT1 Signaling Switching an IL6-Type to an IFNgamma-Like
RT Response.";
RL PLoS Pathog. 12:e1005748-e1005748(2016).
RN [25] {ECO:0007744|PDB:5E5A}
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 476-491.
RX PubMed=26812545; DOI=10.7554/elife.11911;
RA Fang Q., Chen P., Wang M., Fang J., Yang N., Li G., Xu R.M.;
RT "Human cytomegalovirus IE1 protein alters the higher-order chromatin
RT structure by targeting the acidic patch of the nucleosome.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Plays an important role in transactivating viral early genes
CC as well as activating its own promoter, probably by altering the viral
CC chromatin structure (PubMed:17331553, PubMed:8876134, PubMed:23878222,
CC PubMed:15572445, PubMed:26812545). Expression of IE1 and IE2 proteins
CC is critical for the establishment of lytic infection and reactivation
CC from viral latency (By similarity). Disrupts PML-associated ND10
CC nuclear bodies by interfering with host PML and SP100 sumoylation
CC thereby altering the regulation of type I and type II interferon-
CC induced gene expression (PubMed:9151854, PubMed:15163746,
CC PubMed:17367754, PubMed:10233977). Promotes efficient viral growth by
CC interacting with and directing host SP100 to degradation, leading to
CC enhanced acetylation level of histones (PubMed:21880768). In addition,
CC functions in counteracting the host innate antiviral response. Inhibits
CC the type I interferon pathway by directly interacting with and
CC sequestrating host STAT2 (PubMed:18701593, PubMed:19812155,
CC PubMed:16497831). Also targets type II interferon pathway by repressing
CC IL6- and STAT3 target genes (PubMed:27387064). Repression of STAT3
CC genes is due to STAT3 nuclear accumulation and disruption of IL6-
CC induced STAT3 phosphorylation by IE1 (By similarity). This repression
CC is followed by phosphorylation and activation of STAT1
CC (PubMed:27387064). Inhibits host ISG transcription by sequestering host
CC ISGF3 in a PML- and STAT2- binding dependent manner (PubMed:25812002).
CC Alters host cell cycle progression, probably through its interaction
CC with host E2F1 or RB1 that overcomes the RB1-mediated repression of
CC E2F-responsive promoters (PubMed:8892909).
CC {ECO:0000250|UniProtKB:P13202, ECO:0000269|PubMed:10233977,
CC ECO:0000269|PubMed:15163746, ECO:0000269|PubMed:15572445,
CC ECO:0000269|PubMed:16497831, ECO:0000269|PubMed:17331553,
CC ECO:0000269|PubMed:17367754, ECO:0000269|PubMed:18701593,
CC ECO:0000269|PubMed:19812155, ECO:0000269|PubMed:21880768,
CC ECO:0000269|PubMed:23878222, ECO:0000269|PubMed:25812002,
CC ECO:0000269|PubMed:26812545, ECO:0000269|PubMed:27387064,
CC ECO:0000269|PubMed:8876134, ECO:0000269|PubMed:8892909,
CC ECO:0000269|PubMed:9151854}.
CC -!- SUBUNIT: Interacts with human p53/TP53; this interaction inhibits
CC p53/TP53-dependent transactivation activity (PubMed:19776115).
CC Interacts with host STAT1 (PubMed:16497831, PubMed:25812002). Interacts
CC with host STAT2; this interaction promotes viral growth and counteracts
CC the antiviral interferon response (PubMed:16497831, PubMed:18701593,
CC PubMed:19812155, PubMed:25812002). May also interact with the host
CC STAT1-STAT2 heterodimer (PubMed:16497831). Interacts with host STAT3;
CC this interaction leads to STAT3 nuclear accumulation and disruption of
CC IL6-induced STAT3 phosphorylation (PubMed:27387064). Interacts with
CC host PML; this interaction inhibits host PML de novo sumoylation and
CC probably inhibits PML regulation of type I and type II interferon-
CC induced gene expression (PubMed:25812002) (Probable). Interacts with
CC host DAXX (PubMed:20444888). Interacts with host SP100
CC (PubMed:21880768). Interacts with host E2F1 (PubMed:7494286). Interacts
CC with host RB1 (PubMed:8892909). Interacts with host HDAC1; this
CC interaction inhibits histone deacetylation and promotes viral
CC transcription (PubMed:25812002). Interacts with host HDAC2; this
CC interaction inhibits histone deacetylation and promotes viral
CC transcription (PubMed:25812002). Interacts with host HDAC3; this
CC interaction inhibits histone deacetylation and promotes viral
CC transcription (PubMed:15572445). {ECO:0000269|PubMed:15572445,
CC ECO:0000269|PubMed:16497831, ECO:0000269|PubMed:18701593,
CC ECO:0000269|PubMed:19776115, ECO:0000269|PubMed:19812155,
CC ECO:0000269|PubMed:20444888, ECO:0000269|PubMed:21880768,
CC ECO:0000269|PubMed:25812002, ECO:0000269|PubMed:27387064,
CC ECO:0000269|PubMed:7494286, ECO:0000269|PubMed:8892909,
CC ECO:0000305|PubMed:15163746}.
CC -!- INTERACTION:
CC P03169; P23497: SP100; Xeno; NbExp=4; IntAct=EBI-6691147, EBI-751145;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:15220454,
CC ECO:0000269|PubMed:16497831, ECO:0000269|PubMed:9151854}.
CC Note=Colocalizes with host PML-associated nuclear bodies very early
CC post infection. {ECO:0000269|PubMed:15220454,
CC ECO:0000269|PubMed:9151854}.
CC -!- DOMAIN: The N-terminal region is required for nuclear targeting
CC (PubMed:17367754). The C-terminal 16-amino acid is termed the
CC chromosome-tethering domain (CTD) and is required for the association
CC of IE1, host PML and host STAT2 with the mitotic chromosomes
CC (PubMed:22158879). Targets host nucleosomes by directly binding to the
CC acidic pocket of core histones (PubMed:24227840).
CC {ECO:0000269|PubMed:17367754, ECO:0000269|PubMed:22158879,
CC ECO:0000269|PubMed:24227840}.
CC -!- PTM: Sumoylated by host PML/nuclear domain 10 (By similarity).
CC Sumoylation abolishes the interaction with host STAT2 and thus the IE1-
CC mediated repression of interferon-stimulated genes (PubMed:18701593).
CC {ECO:0000250|UniProtKB:P13202, ECO:0000269|PubMed:18701593}.
CC -!- SIMILARITY: Belongs to the HHV-5 IE1 protein family. {ECO:0000305}.
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DR EMBL; M11630; AAA45979.1; -; Genomic_DNA.
DR EMBL; M11628; AAA45979.1; JOINED; Genomic_DNA.
DR EMBL; M11629; AAA45979.1; JOINED; Genomic_DNA.
DR EMBL; M60321; AAA45982.1; -; Genomic_DNA.
DR PIR; A03722; EDBEIC.
DR PDB; 4QRU; X-ray; 1.60 A; C=199-207.
DR PDB; 5E5A; X-ray; 2.81 A; K=476-491.
DR PDBsum; 4QRU; -.
DR PDBsum; 5E5A; -.
DR SMR; P03169; -.
DR IntAct; P03169; 1.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0039695; P:DNA-templated viral transcription; IDA:UniProtKB.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR010855; Cytomega_IE1/IE2.
DR Pfam; PF07340; Herpes_IE1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus; Isopeptide bond;
KW Modulation of host cell cycle by virus; Ubl conjugation;
KW Viral immunoevasion.
FT CHAIN 1..491
FT /note="Immediate early protein IE1"
FT /id="PRO_0000115356"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..24
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:18701593"
FT REGION 132..346
FT /note="Interaction with host PML, interference with PML
FT sumoylation and disruption of PML-associated nuclear
FT bodies"
FT /evidence="ECO:0000269|PubMed:15163746"
FT REGION 373..445
FT /note="Interaction with host STAT2"
FT /evidence="ECO:0000269|PubMed:19812155"
FT REGION 410..445
FT /note="Interaction with host STAT3"
FT /evidence="ECO:0000269|PubMed:27387064"
FT REGION 410..420
FT /note="Modulation of STAT3/STAT1 signaling"
FT /evidence="ECO:0000269|PubMed:27387064"
FT REGION 421..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..472
FT /note="Acidic"
FT /evidence="ECO:0000269|PubMed:18701593,
FT ECO:0000269|PubMed:19812155"
FT REGION 449..452
FT /note="Interaction with host SUMO1"
FT REGION 475..491
FT /note="Chromosome-tethering domain (CTD), binding to
FT histones"
FT /evidence="ECO:0000269|PubMed:22158879,
FT ECO:0000269|PubMed:24227840"
FT COMPBIAS 1..19
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..442
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 450
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:11861864,
FT ECO:0000269|PubMed:18701593"
FT MUTAGEN 174
FT /note="L->P: Complete loss of interference with PML
FT sumoylation, disruption of PML-associated nuclear bodies
FT and transactivation activity."
FT /evidence="ECO:0000269|PubMed:15163746"
FT MUTAGEN 450
FT /note="K->R: Complete loss of SUMO-1 modification, no
FT effect on nuclear localization and function of IE72,
FT reduced levels of IE2 transcription."
FT /evidence="ECO:0000269|PubMed:11861864,
FT ECO:0000269|PubMed:15220454"
FT CONFLICT 96
FT /note="V -> L (in Ref. 1; AAA45979)"
FT /evidence="ECO:0000305"
FT TURN 486..489
FT /evidence="ECO:0007829|PDB:5E5A"
SQ SEQUENCE 491 AA; 55179 MW; E6041928A91A5867 CRC64;
MESSAKRKMD PDNPDEGPSS KVPRPETPVT KATTFLQTML RKEVNSQLSL GDPLFPELAE
ESLKTFERVT EDCNENPEKD VLAELVKQIK VRVDMVRHRI KEHMLKKYTQ TEEKFTGAFN
MMGGCLQNAL DILDKVHEPF EEMKCIGLTM QSMYENYIVP EDKREMWMAC IKELHDVSKG
AANKLGGALQ AKARAKKDEL RRKMMYMCYR NIEFFTKNSA FPKTTNGCSQ AMAALQNLPQ
CSPDEIMAYA QKIFKILDEE RDKVLTHIDH IFMDILTTCV ETMCNEYKVT SDACMMTMYG
GISLLSEFCR VLSCYVLEET SVMLAKRPLI TKPEVISVMK RRIEEICMKV FAQYILGADP
LRVCSPSVDD LRAIAEESDE EEAIVAYTLA TRGASSSDSL VSPPESPVPA TIPLSSVIVA
ENSDQEESEQ SDEEEEEGAQ EEREDTVSVK SEPVSEIEEV APEEEEDGAE EPTASGGKST
HPMVTRSKAD Q
