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   27-MAR-2024, entry version 89.
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; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus;
OC   Simplexvirus humanalpha2; Human herpesvirus 2.
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   EMDB; EMD-30123; -.
DR   EMDB; EMD-30124; -.
DR   SMR; P89459; -.
DR   MEROPS; C76.001; -.
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 symbiont 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   Gene3D; 3.90.70.120; -; 1.
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   PANTHER; PTHR24216:SF65; PAXILLIN-LIKE PROTEIN 1; 1.
DR   PANTHER; PTHR24216; PAXILLIN-RELATED; 1.
DR   Pfam; PF04843; Herpes_teg_N; 1.
DR   Pfam; PF03586; Herpes_UL36; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 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
//