LTP_EBVB9
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 03-AUG-2022, entry version 105.
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};
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; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
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 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 [3]
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 [4]
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 [5]
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).
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:0000250|UniProtKB:P10220, ECO:0000255|HAMAP-Rule:MF_04044,
CC ECO:0000269|PubMed:19244336, ECO:0000269|PubMed:20190741,
CC ECO:0000269|PubMed:22474075}.
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};
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.
CC {ECO:0000250|UniProtKB:P10220, ECO:0000255|HAMAP-Rule:MF_04044,
CC ECO:0000269|PubMed:22474075}.
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}. Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04044}. Note=Tightly associated with the
CC capsid. {ECO:0000255|HAMAP-Rule:MF_04044}.
CC -!- SIMILARITY: Belongs to the herpesviridae large tegument protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04044}.
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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 SMR; P03186; -.
DR BioGRID; 971768; 78.
DR IntAct; P03186; 1.
DR MINT; P03186; -.
DR PRIDE; P03186; -.
DR DNASU; 3783726; -.
DR GeneID; 3783726; -.
DR KEGG; vg:3783726; -.
DR BRENDA; 3.4.19.12; 2112.
DR SIGNOR; P03186; -.
DR Proteomes; UP000153037; Genome.
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 virus of host protein ubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 Pfam; PF04843; Herpes_teg_N; 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..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 /evidence="ECO:0000269|PubMed:20190741"
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
