ID   LTP_MHV68               Reviewed;        2457 AA.
AC   O41965;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   24-JAN-2024, entry version 72.
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=ORF64;
OS   Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Rhadinovirus;
OC   Rhadinovirus muridgamma4.
OX   NCBI_TaxID=33708;
OH   NCBI_TaxID=10129; Apodemus sylvaticus (European woodmouse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=G2.4, and WUMS;
RX   PubMed=9223479; DOI=10.1128/jvi.71.8.5894-5904.1997;
RA   Virgin H.W., Latreille P., Wamsley P., Hallsworth K., Weck K.E.,
RA   Dal Canto A.J., Speck S.H.;
RT   "Complete sequence and genomic analysis of murine gammaherpesvirus 68.";
RL   J. Virol. 71:5894-5904(1997).
RN   [2]
RP   FUNCTION.
RX   PubMed=17634221; DOI=10.1128/jvi.01149-07;
RA   Gredmark S., Schlieker C., Quesada V., Spooner E., Ploegh H.L.;
RT   "A functional ubiquitin-specific protease embedded in the large tegument
RT   protein (ORF64) of murine gammaherpesvirus 68 is active during the course
RT   of infection.";
RL   J. Virol. 81:10300-10309(2007).
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:17634221}.
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; U97553; AAB66417.1; -; Genomic_DNA.
DR   EMBL; AF105037; AAF19328.1; -; Genomic_DNA.
DR   RefSeq; NP_044902.1; NC_001826.2.
DR   SMR; O41965; -.
DR   DIP; DIP-47224N; -.
DR   IntAct; O41965; 1.
DR   MINT; O41965; -.
DR   GeneID; 1497174; -.
DR   KEGG; vg:1497174; -.
DR   Proteomes; UP000099649; Genome.
DR   Proteomes; UP000175018; 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 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   Pfam; PF04843; Herpes_teg_N; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 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..2457
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000406915"
FT   DOMAIN          13..224
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..234
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          281..350
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2064..2131
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2164..2360
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2387..2407
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        281..298
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        314..336
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2093..2113
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2114..2131
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2169..2192
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2208..2222
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2300..2333
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        33
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        163
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        165
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   SITE            20
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ   SEQUENCE   2457 AA;  273538 MW;  6AE1D5E1821BAAD1 CRC64;
     MALPASLAGF RIEGTASTNQ ADCKFGENAG AQCLSNCIIY LMSSYFNNEA PITETHDLNK
     VLKFGAELDS NLRKLGLLSP GQYAQLDHVP CYVQTRKWSG FIYTSAEMFG LLGMPADISD
     SCITSLRDLL TANYSNTIQY ILYICGQKSG AIIIQGGRYT MFDPHCLKDI PESPAHVLST
     SDPDALIKYV GGVSREYTAC FLYFVPGHIS PKNYIMSHYK VISFSDLHGS KIILEEYDLP
     TTNQSFCSSP QASSSPDPEV GSLLKYMSKA KRKRYPMSCG EEWTDANKKR KESGRTPPEK
     MTHPLPSPDI IDLTMDDDVI DLTGDDDMED ESEGDREAEP DRSGTSLPSV TLPNLAAVDQ
     LLNSLTLPGH VPSFPALVDT DTGESYRLTR ALHQLKNVLQ QVLEIGVVSD SDYTPTEALN
     VLNYLMAWSK QLQIKNDDIK LLINSNLQIE KLFTLLKNNL ISDPNLADHV QAKVCACLPA
     MHANRATDLQ KILLHCKNLT RALEISKSSL DIKDIITTFT ESFPQDFFCV CSVEEANNLV
     STVQDLKRVV SNNMALTSEQ DARFKALMLS VLNNTDPPAS LGPIYLETET RTPLLSSAIQ
     EAVKAIEKDT VETLSELISN IPSENAIETT FVPPVRTLLK NVTTLLTVIN ACVERAEIRT
     PEIDSSQQQL SYIGRELSKI IDETWPERAF REPVHVLDIF QKTSSHLNDL KKKMADSESL
     DKILSEINQT LKAIQDKAAS PALINTLSDY IKNATVLAQA SDPRLVEIQS QVTTLTTSTS
     YIESLLQKIN IRTLPEVIPQ LQAATKTEQG QLSLAAMNLS LIQITNSLIN EALSSIHARS
     HNHLSNTFFN SLNSLMGLAD IPGREDLIKT MESIMAVQEE LVDCDDMECV EKGLTTFKYI
     KSSIRQYKFD KSFKTKIYLI ITSEVRDLTK IKTDKQLEAW KQDVADFTPA SIDDLNLFLD
     KAPTKTARSY ATRQLKHFRD DLIKEQEMET ETTPVPSTAE IERAIDLKIK ATWDKILTNL
     RDLTFHHIAP GDWQVLLTVF NDHKSALFTK MGGELLKALQ GLTAYVDSIL TPLLASQLPQ
     GQRYVAPNSD WVETFDQNVK YYLRTFHLPR VSEQLDDLER KTLLLTKLVK FTDLSQSLIG
     THLEKDWSIY QKLFNSLLTV YNDHLIKTKT EVHAFLDKIA SDPLLEPQAH PDLQKITQLF
     TEQEIIEINT LPDIFKESIK NNEKHYIASY QTEMKVFTSM VDAALAKKTQ STTEYNTHLL
     KIVNNMLVQA PPYAASHPIS SDAISYITSL VRDKHLLEKL SYAESLKNFN WLSRLITIIL
     TNCHPSHKQH LQTLLDEILS REQTLTPLVA LEDNANQSPT ERTLQAALTT LNVERVLGRA
     TTFQKWKSQL QELEEAVKTT TQVSLLIQTI SSLHDKTVTE MDPTILSSHS QALADKLKEL
     LALKPSLDET TMSLFHGMKA YAQFKHYFVQ HYVITQPKIF DAYPLSHHGT VSSSGGHQAT
     KFNPLMRLKA FSMVTDVKKM SVWREINTTV DPTGHTFIPA PPTPAMPPIH YNVLFSSFLQ
     AEAINLALNS NQPPTKKFGL LPGLMDARVG VQGAMLLDNQ WNDISTNSAK LLDHYVRSEL
     TPNSLTNSQF AAMTVFAHAM AMVTPHINST RATIFPSKAI VLNQLQFLKL CLTMWPKFSG
     GLLRAPSFER VVQLARATLP TLLLSAPRNT LNHFLANNYR PTDTLPNTEA LLFYPNQHPL
     VNLEKLLLTS SPFHALSTSV LNTRISMLVW GILSLSEAVL QQLWDSLYQE SATFTTYIDL
     LRHLSAMNHK NSTLTTSTSL PQNNGPVVYS YGHTAGTTVA TLEGSHPLDD GGQNIPMTLF
     EFVIFAIILK LKFHVFYTQE KALVNTQLGP LHLITHALDG TGDTEPFKTY ISIPPQKYNG
     LGNLQQFCSQ DEIQIFQRQH EWLVGVTKQT SFSNEDLFIV LASADNKVLS VHTFNPPINS
     LESETPEIVA APIQESWPKE ITTVSFWDKP ALEKSPQELI TEVSLVAEIF SGSAIFNTFP
     PSYKMVSHTP SLHVETHQLE NLSITEGTPP TSPPLPDSTT QDHMEEPDNK QAKPPYQMTS
     PMKENTSTSG RPARSPSPSP PVLTPIKPII PIPQATPTMP ILSPFTPRLL PAAVKKHQNG
     AVWGHSGSLP PTHIQSSTPG PAQNTRDSGR RQIVSPVITI LPGTKAGADS AGQNTSHKDI
     SAYSPPPASK KTDRPSDTHV TAPLFSKSKL VTPRPAAKTD TGTFGPLLGH EKPPVTDLTA
     PVEPGHPSKV SPIIHLKPSN TGDRDPHPIS DDEDSKQPPV PDTSRDKAQS RWKTPKQRPQ
     NIFPPPKHED DVPVTAPQPQ GRKILVGGRQ LPSLVYNPPT LRDIKTGMSD DKNPEPCVKE
     NPPGVTHDPP LRIQHMEQTV NSSKYNVLLF IEKIIKSVHD HSSYMLSTLK RIKQLYI
//