LTP_HHV2H
ID LTP_HHV2H Reviewed; 3122 AA.
AC P89459;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 83.
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 ORFNames=UL36;
OS Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10315;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=9499055; DOI=10.1128/jvi.72.3.2010-2021.1998;
RA Dolan A., Jamieson F.E., Cunningham C., Barnett B.C., McGeoch D.J.;
RT "The genome sequence of herpes simplex virus type 2.";
RL J. Virol. 72:2010-2021(1998).
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 -!- PTM: Proteolytically processed, possibly into several polypeptides.
CC Enzymatic activity is only detectable following cleavage of the UL36
CC protein, which occurs late during viral replication (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the herpesviridae large tegument protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04044}.
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DR EMBL; Z86099; CAB06722.1; -; Genomic_DNA.
DR PDB; 6M6G; EM; 5.39 A; n/o=1-3122.
DR PDB; 6M6H; EM; 4.50 A; P/Q=1-3122.
DR PDBsum; 6M6G; -.
DR PDBsum; 6M6H; -.
DR SMR; P89459; -.
DR MEROPS; C76.001; -.
DR PRIDE; P89459; -.
DR Proteomes; UP000001874; 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:0019784; F:deNEDDylase activity; IEA:InterPro.
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 GO; GO:0039693; P:viral DNA genome replication; IEA:InterPro.
DR HAMAP; MF_04044; HSV_LTP; 1.
DR InterPro; IPR005210; Herpes_LT_deneddylase.
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 Pfam; PF03586; Herpes_UL36; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51521; HTUSP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Host nucleus; Host-virus interaction;
KW Hydrolase; 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..3122
FT /note="Large tegument protein deneddylase"
FT /id="PRO_0000385478"
FT DOMAIN 20..238
FT /note="Peptidase C76"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REPEAT 2891..2895
FT /note="1"
FT REPEAT 2896..2900
FT /note="2"
FT REPEAT 2901..2905
FT /note="3"
FT REPEAT 2906..2910
FT /note="4"
FT REPEAT 2911..2915
FT /note="5"
FT REPEAT 2916..2920
FT /note="6"
FT REPEAT 2921..2925
FT /note="7"
FT REPEAT 2926..2930
FT /note="8"
FT REPEAT 2931..2935
FT /note="9"
FT REPEAT 2936..2940
FT /note="10"
FT REPEAT 2941..2945
FT /note="11"
FT REGION 1..248
FT /note="Deubiquitination activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 281..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..578
FT /note="Interaction with inner tegument protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 2494..2539
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2570..2974
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2891..2945
FT /note="11 X 5 AA tandem repeats of P-Q-P-P-L"
FT REGION 3006..3059
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2632..2651
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2687..2728
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2827..2851
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2891..2950
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2951..2974
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3006..3024
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3030..3044
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 40
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT ACT_SITE 172
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT ACT_SITE 174
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT SITE 27
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ SEQUENCE 3122 AA; 330051 MW; 6EBF94B51BFE8C0B CRC64;
MIPAALPHPT MKRQGDRDIV VTGVRNQFAT DLEPGGSVSC MRSSLSFLSL LFDVGPRDVL
SAEAIEGCLV EGGEWTRAAA GSGPPRMCSI IELPNFLEYP AARGGLRCVF SRVYGEVGFF
GEPTAGLLET QCPAHTFFAG PWAMRPLSYT LLTIGPLGMG LYRDGDTAYL FDPHGLPAGT
PAFIAKVRAG DVYPYLTYYA HDRPKVRWAG AMVFFVPSGP GAVAPADLTA AALHLYGASE
TYLQDEPFVE RRVAITHPLR GEIGGLGALF VGVVPRGDGE GSGPVVPALP APTHVQTPGA
DRPPEAPRGA SGPPDTPQAG HPNRPPDDVW AAALEGTPPA KPSAPDAAAS GPPHAAPPPQ
TPAGDAAEEA EDLRVLEVGA VPVGRHRARY STGLPKRRRP TWTPPSSVED LTSGERPAPK
APPAKAKKKS APKKKAPVAA EVPASSPTPI AATVPPAPDT PPQSGQGGGD DGPASPSSPS
VLETLGARRP PEPPGADLAQ LFEVHPNVAA TAVRLAARDA ALAREVAACS QLTINALRSP
YPAHPGLLEL CVIFFFERVL AFLIENGART HTQAGVAGPA AALLDFTLRM LPRKTAVGDF
LASTRMSLAD VAAHRPLIQH VLDENSQIGR LALAKLVLVA RDVIRETDAF YGDLADLDLQ
LRAAPPANLY ARLGEWLLER SRAHPNTLFA PATPTHPEPL LHRIQALAQF ARGEEMRVEA
EAREMREALD ALARGVDSVS QRAGPLTVMP VPAAPGAGGR APCPPALGPE AIQARLEDVR
IQARRAIESA VKEYFHRGAV YSAKALQASD SHDCRFHVAS AAVVPMVQLL ESLPAFDQHT
RDVAQRAALP PPPPLATSPQ AILLRDLLQR GQPLDAPEDL AAWLSVLTDA ATQGLIERKP
LEELARSIHG INDQQARRSS GLAELQRFDA LDAALAQQLD SDAAFVPATG PAPYVDGGGL
SPEATRMAED ALRQARAMEA AKMTAELAPE ARSRLRERAH ALEAMLNDAR ERAKVAHDAR
EKFLHKLQGV LRPLPDFVGL KACPAVLATL RASLPAGWTD LADAVRGPPP EVTAALRADL
WGLLGQYREA LEHPTPDTAT ALAGLHPAFV VVLKTLFADA PETPVLVQFF SDHAPTIAKA
VSNAINAGSA AVATASPAAT VDAAVRAHGA LADAVSALGA AARDPASPLS FLAVLADSAA
GYVKATRLAL EARGAIDELT TLGSAAADLV VQARRACAQP EGDHAALIDA AARATTAARE
SLAGHEAGFG GLLHAEGTAG DHSPSGRALQ ELGKVIGATR RRADELEAAV ADLTAKMAAQ
RARGSSERWA AGVEAALDRV ENRAEFDVVE LRRLQALAGT HGYNPRDFRK RAEQALAANA
EAVTLALDTA FAFNPYTPEN QRHPMLPPLA AIHRLGWSAA FHAAAETYAD MFRVDAEPLA
RLLRIAEGLL EMAQAGDGFI DYHEAVGRLA DDMTSVPGLR RYVPFFQHGY ADYVELRDRL
DAIRADVHRA LGGVPLDLAA AAEQISAARN DPEATAELVR TGVTLPCPSE DALVACAAAL
ERVDQSPVKN TAYAEYVAFV TRQDTAETKD AVVRAKQQRA EATERVMAGL REALAARERR
AQIEAEGLAN LKTMLKVVAV PATVAKTLDQ ARSVAEIADQ VEVLLDQTEK TRELDVPAVI
WLEHAQRTFE THPLSAARGD GPGPLARHAG RLGALFDTRR RVDALRRSLE EAEAEWDEVW
GRFGRVRGGA WKSPEGFRAM HEQLRALQDT TNTVSGLRAQ PAYERLSARY QGVLGAKGAE
RAEAVEELGA RVTKHTALCA RLRDEVVRRV PWEMNFDALG GLLAEFDAAA ADLAPWAVEE
FRGARELIQY RMGLYSAYAR AGGQTGAGAE SAPAPLLVDL RALDARARAS SSPEGHEVDP
QLLRRRGEAY LRAGGDPGPL VLREAVSALD LPFATSFLAP DGTPLQYALC FPAVTDKLGA
LLMRPEAACV RPPLPTDVLE SAPTVTAMYV LTVVNRLQLA LSDAQAANFQ LFGRFVRHRQ
ATWGASMDAA AELYVALVAT TLTREFGCRW AQLGWASGAA APRPPPGPRG SQRHCVAFNE
NDVLVALVAG VPEHIYNFWR LDLVRQHEYM HLTLERAFED AAESMLFVQR LTPHPDARIR
VLPTFLDGGP PTRGLLFGTR LADWRRGKLS ETDPLAPWRS ALELGTQRRD VPALGKLSPA
QALAAVSVLG RMCLPSAALA ALWTCMFPDD YTEYDSFDAL LAARLESGQT LGPAGGREAS
LPEAPHALYR PTGQHVAVLA AATHRTPAAR VTAMDLVLAA VLLGAPVVVA LRNTTAFSRE
SELELCLTLF DSRPGGPDAA LRDVVSSDIE TWAVGLLHTD LNPIENACLA AQLPRLSALI
AERPLADGPP CLVLVDISMT PVAVLWEAPE PPGPPDVRFV GSEATEELPF VATAGDVLAA
SAADADPFFA RAILGRPFDA SLLTGELFPG HPVYQRPLAD EAGPSAPTAA RDPRDLAGGD
GGSGPEDPAA PPARQADPGV LAPTLLTDAT TGEPVPPRMW AWIHGLEELA SDDAGGPTPN
PAPALLPPPA TDQSVPTSQY APRPIGPAAT ARETRPSVPP QQNTGRVPVA PRDDPRPSPP
TPSPPADAAL PPPAFSGSAA AFSAAVPRVR RSRRTRAKSR APRASAPPEG WRPPALPAPV
APVAASARPP DQPPTPESAP PAWVSALPLP PGPASARGAF PAPTLAPIPP PPAEGAVVPG
GDRRRGRRQT TAGPSPTPPR GPAAGPPRRL TRPAVASLSA SLNSLPSPRD PADHAAAVSA
AAAAVPPSPG LAPPTSAVQT SPPPLAPGPV APSEPLCGWV VPGGPVARRP PPQSPATKPA
ARTRIRARSV PQPPLPQPPL PQPPLPQPPL PQPPLPQPPL PQPPLPQPPL PQPPLPQPPL
PQPPLPPVTR TLTPQSRDSV PTPESPTHTN THLPVSAVTS WASSLALHVD SAPPPASLLQ
TLHISSDDEH SDADSLRFSD SDDTEALDPL PPEPHLPPAD EPPGPLAADH LQSPHSQFGP
LPVQANAVLS RRYVRSTGRS ALAVLIRACR RIQQQLQRTR RALFQRSNAV LTSLHHVRML
LG
