LTP_HCMVT
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 03-AUG-2022, entry version 33.
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; Herpesviridae; Betaherpesvirinae; 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 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 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