ID   LTP_MUHVK               Reviewed;        2147 AA.
AC   A8E1C4;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 1.
DT   03-AUG-2022, entry version 46.
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   Name=M48;
OS   Murid herpesvirus 1 (strain K181) (MuHV-1) (Mouse cytomegalovirus).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Betaherpesvirinae; Muromegalovirus.
OX   NCBI_TaxID=69156;
OH   NCBI_TaxID=10090; Mus musculus (Mouse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K181;
RX   PubMed=18417589; DOI=10.1128/jvi.00160-08;
RA   Smith L.M., McWhorter A.R., Masters L.L., Shellam G.R., Redwood A.J.;
RT   "Laboratory strains of murine cytomegalovirus are genetically similar to
RT   but phenotypically distinct from wild strains of virus.";
RL   J. Virol. 82:6689-6696(2008).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K181;
RX   PubMed=15709020; DOI=10.1128/jvi.79.5.2998-3008.2005;
RA   Redwood A.J., Messerle M., Harvey N.L., Hardy C.M., Kozinowski U.H.,
RA   Lawson M.A., Shellam G.R.;
RT   "Use of a murine cytomegalovirus K181-derived bacterial artificial
RT   chromosome as a vaccine vector for immunocontraception.";
RL   J. Virol. 79:2998-3008(2005).
RN   [3]
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).
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:20190741}.
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; AM886412; CAP08095.1; -; Genomic_DNA.
DR   SMR; A8E1C4; -.
DR   IntAct; A8E1C4; 29.
DR   PRIDE; A8E1C4; -.
DR   Proteomes; UP000158680; 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..2147
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000396954"
FT   DOMAIN          3..223
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..233
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          228..301
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          292
FT                   /note="Interaction with inner tegument protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1419..1438
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1567..1589
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2034..2072
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        235..276
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        23
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        156
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        158
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   SITE            10
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ   SEQUENCE   2147 AA;  238457 MW;  4C5DB3F99EF1A63A CRC64;
     MKIVRASRDQ SAPVYGPRAG SQCMSNCFTF LHTCYLMGID PVLDTTSLDA VLDSGARLDA
     IADEKVKRQA LTDHPYRLGT EIPTVIETPA GITGHALSRP FNGTAETQDL GGYKCLGILD
     FLTYARGKPL PVYIIVTVGV HTRGVIVARG ATYVFDPHTT DLSAEAAVYV CDDFTEAISA
     LSFFGAMIGD FYYDAVLVYF TRCRTTLISP SELLVQIMDQ YKDPDIDASV MSGSGGGGPS
     ISSSAASASA SVSPLPSGAA SDGVTNGAGA QTSSKSGKKR RAPDVPPQQK GTAKTLRRSR
     RPIRLPERLS EVIVEDVQTI EHFRTATQSL PVKPPQEWTM YCGEEPFYRQ YFVDVGRQLL
     AHAIDTYVSL DKTTDESAVQ RFESLMGLSD ELDAVIAAAR ATELSAPPLY KTYLSQRVSA
     SAVTRTDRLL ASKILALFEE GSATDFETVS SWLRELLQQL PVENTTTTEA KIAAFVAQHP
     IPGERAFVCL RNSQVKSLGE LLSVKRETLK VKYMENDATY RKILDAISKL GLASNAAAAI
     QSADTSHLDS EQLASLAQAA EAYAQSAYES CQAKMTELLS TNHNRILTGS LPDSDIAAVL
     AAFKAVSENV RALREVELLK SQVHVQLAQL TEDLLYLQTA EVKLEVTPSA EIKKLRAEYE
     TARKQISDEE MRIKELIENM EDMITDSSSS PPPPEMLDML RTQIEEVESM TVDEQDARRA
     DKVLGKLSTL DEAEAKATEF AQSLSTVNIP SLNEIKGVKM LKSVLETNAD LRRAYVQAVT
     GMLENALKQL AEGNLPSDDM MSRITALAEQ LPTGRQVRAD LLDSTDIVSQ MSRRLRYAAN
     QKNSTQSLED VLNFFSENDD MIRKLLKTSW GKPVATVYRR VQVEYDRKME ELRESEWLKR
     VKETDIDSPQ TLERLLKTAP NETILAKHAP DMHARLKKRM QSEAEKRTAD MKRLYEEMRK
     KVDTDLKVVS DSFSSQTPSM FSSIDLKSCG TSLVRLTKED RKAAIATFNA NLTKSLNSLL
     ASLVTVETAT IAAILKGADP EATSSTGSAG GGADRQKHTS TLENNISTLL GWQQKVLLPE
     TERDLLTIAH LLTALTHMRK NWRNPAAAFS STPHTAAYRN FAELANEIES RRTETLARYK
     SKYAELNASI HDNTKANDVT IKPEDTFTAA FRDTVKAMAA PFSTELQARL QARENELKDE
     LSDLNVKLKT KLERYLAKRS SQDARWRDLI TQHRIRLPEG LDVDTNRLRT DTVVTLNGII
     RSAATTLPYI TAKRGLEWTT EFILAAIEEK KDADPGMFAQ LATLLDNSQA IARKIEEKIV
     YNTKVEAEML ETAPEHTRES LSNLQLMLGQ LEAKRVVGGE ARYKILSDAI LTKQNKLAFA
     EDLEKLSARY FELARDIRSS KYGLDFDAQL LKTSLLKSEI GQHKKDPPST GEEVGLPEES
     TTAAKISISS LLLGIAALEK YIVAHRTLLD NFVSSQPLIS QAENIPALVG GPGEDDKPGQ
     EPFDWTRIDL SRLSACDVST ALYRGTDVFG ERRVMTARGI QLYLYATHGN FVFEAFSHVR
     GTKGLLSSSS GGGNGSGASS RQKDQQNATV TRRYRSVTVL ASIAATLQTF WSEISRYDIR
     ELLVESGRDP ESAADQRDRR LNTVMNLKLF VYVMTVAWSE ATPPVEPGSP EATHALEVSL
     LDFSTLMAAL HPEYVYAITT QPVDATLRGL IARLDRRTVD AAMNTQENPP PYDMRELKAF
     CLDTKQWTQE DIRPQMWMSD LVKQICTSHP RNRDASTSTK LFLYMLATKV LPRDILRCLW
     VQFRPAYASS IASLEELVSA LCDSFFKIYG TTSETVSARL KTGEKVERQV VLRHKPTMSL
     LDEFSQQEAV LDYILGSYVF AIPMTVGIHV TNIVNGRYRL IVRHLENLPS DPDFVKVVRS
     RDLSFDRFGW SYTVQNPVER SWFSLQEDRL RHLLTNPPQQ DRTPLVVYDS NTNYAVNAMM
     PPLKAPPATS RVHLTVKNPF STMRMIPHED EGDDAATSET PFTSLPINID FLRRDPPRLK
     RASGDSSSSV PAEDRDPDAR PQDSVPDQSL SEPLFSQTKV SSIVPKDAVT TLSNESISQT
     FQIHPFRALS SAIMAAIEIL QETRLQLDTF ESDMCEAIRR IKILYLH