ID   LTP_HCMVT               Reviewed;        2242 AA.
AC   D5LX59;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   15-JUN-2010, sequence version 1.
DT   24-JAN-2024, entry version 38.
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, ECO:0000269|PubMed:19759126};
DE            EC=3.4.22.- {ECO:0000255|HAMAP-Rule:MF_04044, ECO:0000269|PubMed:19759126};
GN   ORFNames=UL48;
OS   Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Betaherpesvirinae; Cytomegalovirus;
OC   Cytomegalovirus humanbeta5; Human cytomegalovirus.
OX   NCBI_TaxID=10363;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CINCY+Towne;
RA   Davison A.J.;
RT   "Human cytomegalovirus RL11 gene family: variation, recombination and
RT   transcription.";
RL   Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, AND MUTAGENESIS OF CYS-24 AND HIS-162.
RX   PubMed=19759126; DOI=10.1128/jvi.00411-09;
RA   Kim E.T., Oh S.E., Lee Y.O., Gibson W., Ahn J.H.;
RT   "Cleavage specificity of the UL48 deubiquitinating protease activity of
RT   human cytomegalovirus and the growth of an active-site mutant virus in
RT   cultured cells.";
RL   J. Virol. 83:12046-12056(2009).
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:19759126}.
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         ECO:0000269|PubMed:19759126};
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; GU980198; ADE88055.1; -; Genomic_DNA.
DR   SMR; D5LX59; -.
DR   Proteomes; UP000149703; 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   1: Evidence at protein level;
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; Repeat;
KW   Thiol protease; Ubl conjugation pathway; Virion; Virion tegument.
FT   CHAIN           1..2242
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000406913"
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..318
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          328..332
FT                   /note="Interaction with inner tegument protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1173..1229
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..318
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1173..1188
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        24
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044,
FT                   ECO:0000269|PubMed:19759126"
FT   ACT_SITE        160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        162
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044,
FT                   ECO:0000269|PubMed:19759126"
FT   MUTAGEN         24
FT                   /note="C->S: Complete loss of DUB activity."
FT                   /evidence="ECO:0000269|PubMed:19759126"
FT   MUTAGEN         162
FT                   /note="H->A: Complete loss of DUB activity."
FT                   /evidence="ECO:0000269|PubMed:19759126"
SQ   SEQUENCE   2242 AA;  253365 MW;  209FE3CF7502FDAA 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 LATASSSSPS AIAAASSSSA VPPSYSCGEG ALPALGRYQQ LVDEVEQELK
     ALTLPPLPAN TSAWTLHAAG TESGANAATA TAPSFDEAFL TDRLQQLIIH AVNQRSCLRR
     PCGPQSAAQQ AVRAYLGLSK KLDAFLLNWL HHGLDLRRMH DYLSHKTTKG TYSTLDRALL
     EKMQVVFDPY GRQHGPALIA WVEEMLRYVE SKPTNELSQR LQRFVTKRPM PVSDSFVCLR
     PVDFQRLTQV IEQRRRVLQR QREEYHGVYE HLAGLITSID IHDLDASDLN RREILKALQP
     LDDNAKQELF RLGNAKMLEL QMDLDRLSTQ LLTRVHNHIL NGFLPVEDLK QMERVVEQVL
     RLFYDLRDLK LCDGSYEEGF VVIREQLSYL MTGTVRDNVP LLQEILQLRH AYQQATQQNE
     GRLTQIHDLL HVIETLVRDP GSRGSALTLA LVQEQLAQLE ALGGLQLPEV QQRLQNAQLA
     LSRLYEEEEE TQRFLDGLSY DDPPTEQTIK RHPQLREMLR RDEQTRLRLI NAVLSMFHTL
     VMRLARDESP RPTFFDAVSL LLQQLPPDSH EREDLRAANA TYAQMVKKLE QIEKAGTGAS
     EKRFQALREL VYFFRNHEYF FQHMVGRLGV GPQVTELYER YQHEMEEQHL ERLEREWQEE
     AGKLTVTSVE DVQRVLARAP SHRVMHQMQQ TLTTKMQDFL DKEKRKQEEQ QRQLLDGYQK
     KVQQDLQRVV DAVKGEMLST IPHQPLEATL ELLLGLDQRA QPLLDKFNQD LLSALQQLSK
     KLDGRINECL HGVLTGDVER RCHPHREAAM QTQASLNHLD QVLGPQLLIH ETQQALQHAV
     HQAQFIEKCQ QGDPTTAITG SEFESDFARY RSSQQKMEGQ LQETRQQMTE TSERLDRSLR
     QDPGSSSVTR VPEKPFKGQE LAGRITPPPV DFQRPVFKTL LDQQADAARK ALSDEADLLN
     QKVQTQLRQR DEQLSTAQNL WTDLVTRHKM SGGLDVTTPD AKALMEKPLE TLRELLGKAT
     QQLPYLSAER TVRWMLAFLE EALAQITADP THPHHGSRTH YRNLQQQAVE SAVTLAHQIE
     QNAACENFIA QHQEATANGA STPRVDMVQA VEAVWQRLEP GRVAGGAARH QKVQELLQRL
     GQTLGDLELQ ETLATEYFAL LHGIQTFSYG LDFRSQLEKI RDLRTRFAEL AKRRGTRLSN
     EGALPNPRKP QATTSLGAFT RGLNALERHV QLGHQYLLNK LNGSSLVYRL EDIPSVLPPT
     HETDPALIMR DRLRRLCFAR HHDTFLEVVD VFGMRQIVTQ AGEPIHLVTD YGNVAFKYLA
     LRDDGRPLAW RRRCSGGGLK NVVTTRYKAI TVAVAVCQTL RTFWPQISQY DLRPYLTQHQ
     SHTHPAETHT LHNLKLFCYL VSTAWHQRID TQQELTAADR VGSGEGGDVG EQRPGRGTVL
     RLSLQEFCVL IAALYPEYIY TVLKYPVQMS LPSLTAHLHQ DVIHAVVNNT HKMPPDHLPE
     QVKAFCITPT QWPAMQLNKL FWENKLVQQL CQVGPQKSTP PLGKLWLYAM ATLVFPQDML
     QCLWLELKPQ YAETYASVSE LVQTLFQIFT QQCEMVTEGY TQPQLPTGEP VLQMIRVRRQ
     DTTTTDTNTT TEPGLLDVFI QTETALDYAL GSWLFGIPVC LGVHVADLLK GQRVLVARHL
     EYTSRDRDFL RIQRSRDLNL SQLLQDTWTE TPLEHCWLQA QIRRLRDYLR FPTRLEFIPL
     VIYNAQDHTV VRVLRPPSTF EQDHSRLVLD EAFPIFPLYD QDDNSSADNV AASGAAPTPP
     VPFNRVPVNI QFLRENPPPI ARVQQPPRRH RHRAAAAADD DGQIDHVQDD TSRTADSALV
     STAFGGSVFQ ENRLGETPLC RDELVAVAPG AASTSFASPP ITVLTQNVLS ALEILRLVRL
     NLRQLAQSVQ DTIQHMRFLY LL
//