LTP_HCMVM
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 03-AUG-2022, entry version 70.
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; Herpesviridae; Betaherpesvirinae; 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; 7.
DR PRIDE; Q6SW84; -.
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; Genome.
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 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..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
