ID   LTP_HCMVM               Reviewed;        2241 AA.
AC   Q6SW84; D2K3L5;
DT   18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 76.
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=UL48;
OS   Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Betaherpesvirinae; Cytomegalovirus;
OC   Cytomegalovirus humanbeta5; Human cytomegalovirus.
OX   NCBI_TaxID=295027;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA   Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA   Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA   Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT   "Genetic content of wild-type human cytomegalovirus.";
RL   J. Gen. Virol. 85:1301-1312(2004).
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; AY446894; AAR31613.1; -; Genomic_DNA.
DR   RefSeq; YP_081506.1; NC_006273.2.
DR   SMR; Q6SW84; -.
DR   BioGRID; 1678057; 8.
DR   DNASU; 3077504; -.
DR   GeneID; 3077504; -.
DR   KEGG; vg:3077504; -.
DR   Reactome; R-HSA-9609690; HCMV Early Events.
DR   Reactome; R-HSA-9610379; HCMV Late Events.
DR   Proteomes; UP000000938; Segment.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0072517; C:host cell viral assembly compartment; TAS:Reactome.
DR   GO; GO:0019033; C:viral tegument; TAS:Reactome.
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..2241
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000416709"
FT   DOMAIN          4..226
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..238
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          239..314
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          327..331
FT                   /note="Interaction with inner tegument protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1187..1230
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2118..2152
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        251..272
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        300..314
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2131..2151
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        24
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        162
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ   SEQUENCE   2241 AA;  253174 MW;  83C76E6D72FA039B CRC64;
     MKVTQASCHQ GDIARFGARA GNQCVCNGIM FLHALHLGGT SAVLQTEALD AIMEEGARLD
     ARLERELQKK LPAGGRLPVY RLGDEVPRRL ESRFGRTVHA LSRPFNGTTE TCDLDGYMCP
     GIFDFLRYAH AKPRPTYVLV TVNSLARAVV FTEDHMLVFD PHSSAECHNA AVYHCEGLHQ
     VLMVLTGFGV QLSPAFYYEA LFLYMLDVAT VPEAEIAARL VSTYRDRDID LTGVVRESAD
     TAATTTTAAP SLPPLPDPIV DPGCPPGVAP SIPVYDPSSS PKKTPEKRRK DLSGSKHGGK
     KKPPSTTSKT LATASSSPSA IAAASSSSAV PPSYSCGEGA LPALGRYQQL VDEVEQELKA
     LTLPPLPANT SAWTLHAAGT ESGANAATAT APSFDEAFLT DRLQQLIIHA VNQRSCLRRP
     CGPQSAAQQA VRAYLGLSKK LDAFLLNWLH HGLDLQRMHD YLSHKTTKGT YSTLDRALLE
     KMQVVFDPYG RQHGPALIAW VEEMLRYVES KPTNELSQRL QRFVTKRPMP VSDSFVCLRP
     VDFQRLTQVI EQRRRVLQRQ REEYHGVYEH LAGLITSIDI HDLDASDLNR REILKALQPL
     DDNAKQELFR LGNAKMLELQ MDLDRLSTQL LTRVHNHILN GFLPVEDLKQ MERVVEQVLR
     LFYDLRDLKL CDGSYEEGFV VIREQLSYLM TGTVRDNVPL LQEILQLRHA YQQATQQNEG
     RLTQIHDLLH VIETLVRDPG SRGSALTLAL VQEQLAQLEA LGGLQLPEVQ QRLQNAQLAL
     SRLYEEEEET QRFLDGLSYD DPPTEQTIKR HPQLREMLRR DEQTRLRLIN AVLSMFHTLV
     MRLARDESPR PTFFDAVSLL LQQLPPDSHE REDLRAANAT YAQMVKKLEQ IEKAGTGASE
     KRFQALRELV YFFRNHEYFF QHMVGRLGVG PQVTELYERY QHEMEEQHLE RLEREWQEEA
     GKLTVTSVED VQRVLARAPS HRVMHQMQQT LTTKMQDFLD KEKRKQEEQQ RQLLDGYQKK
     VQQDLQRVVD AVKGEMLSTI PHQPLEATLE LLLGLDQRAQ PLLDKFNQDL LSALQQLSKK
     LDGRINECLH GVLTGDVERR CHPHREAAMQ TQASLNHLDQ ILGPQLLIHE TQQALQHAVH
     QAQFIEKCQQ GDPTTAITGS EFESDFARYR SSQQKMEGQL QETRQQMTET SERLDRSLRQ
     DPGSSSVTRV PEKPFKGQEL AGRITPPPAD FQRPVFKTLL DQQADAARKA LSDEADLLNQ
     KVQTQLRQRD EQLSTAQNLW TDLVTRHKMS GGLDVTTPDA KALMEKPLET LRELLGKATQ
     QLPYLSAERT VRWMLAFLEE ALAQITADPT HPHHGSRTHY RNLQQQAVES AVTLAHQIEQ
     NAACENFIAQ HQEATANGAS TPRVDMVQAV EAVWQRLEPG RVAGGAARHQ KVQELLQRLG
     QTLGDLELQE TLATEYFALL HGIQTFSYGL DFRSQLEKIR DLRTRFAELA KRCGTRLSNE
     GALPNPRKPQ ATTSLGAFTR GLNALERHVQ LGHQYLLNKL NGSSLVYRLE DIPSVLPPTH
     ETDPALIMRD RLRRLCFARH HDTFLEVVDV FGMRQIVTQA GEPIYLVTDY GNVAFKYLAL
     RDDGRPLAWR RRCSGGGLKN VVTTRYKAIT VAVAVCQTLR TFWPQISQYD LRPYLTQHQS
     HTHPAETHTL HNLKLFCYLV STAWHQRIDT QQELTAADRV GSGEGGDVGE QRPGRGTVLR
     LSLQEFCVLI AALYPEYIYT VLKYPVQMSL PSLTAHLHQD VIHAVVNNTH KMPPDHLPEQ
     VKAFCITPTQ WPAMQLNKLF WENKLVQQLC QVGPQKSTPS LGKLWLYAMA TLVFPQDMLQ
     CLWLELKPQY AETYASVSEL VQTLFQIFTQ QCEMVTEGYT QPQLPTGEPV LQMIRVRRQD
     TTTTDTNTTT EPGLLDVFIQ TETALDYALG SWLFGIPVCL GVHVADLLKG QRVLVARHLE
     YTSRDRDFLR IQRSRDLNLS QLLQDTWTET PLEHCWLQAQ IRRLRDYLRF PTRLEFIPLV
     IYNAQDHTVV RVLRPPSTFE QDHSRLVLDE AFPTFPLYDQ DDNTSADNVA ASGAAPTPPV
     PFNRVPVNIQ FLRENPPPIA RVQQPPRRHR HRAAAAADDD GQIDHAQDDT SRTADSALVS
     TAFGGSVFQE NRLGETPLCR DELVAVAPGA ASTSFASPPI TVLTQNVLSA LEILRLVRLD
     LRQLAQSVQD TIQHMRFLYL L
//