LTP_EBVA8
ID LTP_EBVA8 Reviewed; 3154 AA.
AC Q1HVH9;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 1.
DT 03-AUG-2022, entry version 55.
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};
DE EC=3.4.22.- {ECO:0000255|HAMAP-Rule:MF_04044};
GN ORFNames=BPLF1;
OS Epstein-Barr virus (strain AG876) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=82830;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16490228; DOI=10.1016/j.virol.2006.01.015;
RA Dolan A., Addison C., Gatherer D., Davison A.J., McGeoch D.J.;
RT "The genome of Epstein-Barr virus type 2 strain AG876.";
RL Virology 350:164-170(2006).
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}.
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 -!- 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. {ECO:0000255|HAMAP-
CC Rule:MF_04044}.
CC -!- SUBCELLULAR LOCATION: Virion tegument {ECO:0000255|HAMAP-
CC Rule:MF_04044}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04044}. Host
CC nucleus {ECO:0000255|HAMAP-Rule:MF_04044}. Note=Tightly associated with
CC the 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; DQ279927; ABB89229.1; -; Genomic_DNA.
DR RefSeq; YP_001129449.1; NC_009334.1.
DR SMR; Q1HVH9; -.
DR PRIDE; Q1HVH9; -.
DR GeneID; 5176165; -.
DR KEGG; vg:5176165; -.
DR Proteomes; UP000007639; 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 3: Inferred from homology;
KW Host cytoplasm; Host nucleus; Host-virus interaction; Hydrolase;
KW 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..3154
FT /note="Large tegument protein deneddylase"
FT /id="PRO_0000375969"
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 REPEAT 375..379
FT /note="9"
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..379
FT /note="9 X 5 AA repeats of P-A-S-A-A"
FT REGION 387..661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 559..589
FT /note="Interaction with inner tegument protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 906..928
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1148..1171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1413..1439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1649..1682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2588..2844
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2859..2986
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3000..3024
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 387..404
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..433
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..494
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..526
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..542
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..614
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1656..1670
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2594..2635
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2710..2726
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2727..2762
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2782..2813
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2820..2834
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2960..2974
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 61
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
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"
SQ SEQUENCE 3154 AA; 338449 MW; BFD719F4742849CB 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 ASAAPASAAP ASSPPLFIPI PGLGHTPGVP APSTPPRASG GAAPQTPKRK
KGLGKDSPHK KPTSGRRLPL SSTTDTEDDQ LPRTHVPPHR PPSAARLPPP VIPIPHQSPP
ASPTPRPAPV STIAPSVTPS PRLPLQIPIP LPQAAPSNPE IPLTTPSPSP TAAAAPTATT
LSPPPTQQQP PQSAAPAPSP PPTQQQPPQS AAPAPSPLLP QQQPPPSAAR APSPLPPQQQ
PLPSATPAPP HAQQLPPSAT TLEPEKNNPS AADRAGTEIS PSPPFGQQPS FGDDASGGSG
LVRYLSDLEE PFLSMSDSEE AESDLASDIP TTEDEDMFED EVFSNSLESG SSAPTSPITL
DTARSQYYQT TFDIETPEMD FVPLESNIAR IAGHTYQEQA IVYDPASNRE VPEADALSMI
DYLLVTVVLE QGLIRSRDRS AVLNLLEFLK DWSGHLQVPT LDLEQLLTSE LNIQNLANML
SENKGRAGEF HEHLAAKLEA CLPSLATKDA VRVDAGAKML AEIPQLAESG DGKFDLEAAR
RRLTDLLSGG DQEGEEGGGE PEDHSIYRGP HVDVPLVLDD ESWKRLLSLA EAARTAVARQ
QAGVDEEDVR FLALLTAIEY GAPPAASVPP FVHNVPVRSK NAALHVRRCT ADIRDKVASA
ASDYLSYLED PSLPTVMDFD DLLTHLRHTC QIIASLPLLN IRYTSIEWDY RELLYLGTAL
SDMSGIPWPL ERVEEDDPSI APLPEFETVA KKQKELETTR ENEKRLRTIL DDIEAMLGLA
GVASAPGAPI SPASPSATPA NHDNPEATPP LADTAALTIP VIEKYIANAG SIVGAAKNPT
YIRLRDTIQQ IVRSKKYLMN ILKSITFYTI DNYIASFEES IDHLYRDLPV LDPEVQDGID
RILDPMVSEA LHTFEMGNRL TLEPARLVAL QNFATHSTLK ETAAAVNLLP GLLAVYDATV
TGQAPEDALR LLSGLQNQLS QTLIPGKLKK RFLSYLQKLK NNNNDQLRQK EVQAWRLEAE
GFKPATEEQL EAFLDTAPNK ELKRQYEKKL RQLMETGRKE KEKLREQEDK ERRERRAREA
NEAWARIRKA LGARPEPAPT SPDDWNTLLA SLLPDNTDSA AAAAAAVARN TDILDSLTQI
LAAMLLGITR VRRERLRSLL VDDGGAAERM EAVEPGWFTE IETGPLARLD AWPATPAATA
KEGGGGRGAE EAAGALFRAR TAADAIRSAL AQTRQALQSP DMKSAVVNTD LEAPYAEYER
GLAGLLEKRR SAEAALTAIV SEYVDRTLPE ATNDPGQANL PPPPTIPQAT APPRLASDSA
LWPKKPQLLT RRERDDLLQA TGDFFSELLT EAEAAEVRAL EEQVRESQTL MAKAHEMAAS
TRRGFHTALE AVLSRSRDEA PDDELRSLLP SPPKAPVQAP LEAALARAAA GNGSWPYRKS
LAAAKWIRGI CEAVRGLSEG ALALAGGVGA WLNLAAAADG EIHELTRLLE VEGMAQNSMD
GMEELRLALA TLDPKRVAGG KETVADWKRR LSRLEAIIQE AQEESQLQGT LQDLVTQARG
HTDPRQLKIV VEAARGLALG ASAGSQYALL KDKLLRYASA KQSFLAFYET AQPTVFVKHP
LTNNLPLLIT ISAPPTGWGN GAPTRRAQFL AAAGPAKYAG TLWLETESPC DPLNPAYVSA
DTQEPLNYIP VYHNFLEYVM PTVLENPEAF SLTPAGRPQA IGPPQDDQER RRRTLASVAS
ARLSAAAADS YWDTWPDVES NAGELLREYV SAPKALMEDL ADNPIVAMTL LAHASLIASR
NHPPYPAPAT DREVILLEQR EMMALLVGTH PAYAAAFLGA PSFYAGLGLV SALARDGGLG
DLLSDSVLTY RLVRSPASGR GGMPSTTRGS NDGEDARRLT RHRIAGPPTG FIFFQDAWEE
MDTRAALWPH PEFLGLVHNQ STARARACML LLARRCFAPE ALQQLWHSLR PLEGPVAFQD
YLRDFVKQAY TRGEELPRAE GLEVPRETPS SYGTVTGRAL RNLMPYGTPI TGPKRGSGDT
IPVSVFEAAV AAAFLGRPLT LFVSSQYLFN LKTLGQVRVV APLLYCDGHS EPFRSLVETI
SLNFLQDLDG YSESFEPEMS IFARQAVWLR ELLTEARAAK PKEARPPTVA ILANRKNIIW
KCFTYRHNLP DVQFYFNAAG ASRWPTDVLN PSFYEHEDPP LPVGYQLPPN PRNVQELFSG
FPPRVGHGLV SGDGFQSADN TPASSDRLQQ LGGGETDQGE EGSTTAESEA SGPPSPQSPL
LEKVAPGRPR DWLSPTSSPR DVTVTPGLAA PITLPGPRLM ARPYFGAETR ASESPDRSPG
TSPRPWPKDS LELLPQPAPQ QPPSSPWASE QGPIVYTLSP NSTPSTASGS QKKHTIQIPG
LVPSQKPSYP PSAPYKPGQS TGGIAPTPSA ASLTTFGLQP QDTQASSQDP PYGHSIMQRE
KKQQGGREEA AEIRPSATRL PTAVGLRPRA PVVAAGAAAS ATPAFDPGEA PSGFPIPQAP
ALGSGLAAPA HTPVGALAPR PQKTQAQRPQ DAAALPTPTI KAVGARPVPK ATGALAAGAR
PRGQPTAAPP SAASPPRVSL PVRSRQQQSP AIPLPPMHSG SEPGARPEVR LSQYRHAGPQ
TYTVRKEAPP SAASQLPKMP KCKDSMYYPP SGSARYPAPF QALSFSQSVA SPAPSSDQTT
LLWNTPSVVT QFLSIEDIIR EVVTGGSTSG DLVVPSGSPS SLSTAAPEQD LRYSLTLSQA
SRVLSRFVSQ LRRKLERSTH RLIADLERLK FLYL
