ID LTP_VZVO Reviewed; 2763 AA. AC Q4JQX9; Q4JQV3; DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot. DT 22-SEP-2009, sequence version 2. DT 27-MAR-2024, 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 ORFNames=ORF22; OS Varicella-zoster virus (strain Oka vaccine) (HHV-3) (Human herpesvirus 3). OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes; OC Herpesvirales; Orthoherpesviridae; Alphaherpesvirinae; Varicellovirus; OC Varicellovirus humanalpha3; Human herpesvirus 3. OX NCBI_TaxID=341980; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Isolate Human/Japan/P-Oka/1970, and Oka varicella vaccine Biken RC (V-Oka-Biken); RX PubMed=12388706; DOI=10.1128/jvi.76.22.11447-11459.2002; RA Gomi Y., Sunamachi H., Mori Y., Nagaike K., Takahashi M., Yamanishi K.; RT "Comparison of the complete DNA sequences of the Oka varicella vaccine and RT its parental virus."; RL J. Virol. 76:11447-11459(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Oka varicella vaccine VarilRix (V-Oka-GSK), and Oka varicella RC vaccine Varivax (V-Oka-Merck); RX PubMed=18787000; DOI=10.1128/jvi.00777-08; RA Tillieux S.L., Halsey W.S., Thomas E.S., Voycik J.J., Sathe G.M., RA Vassilev V.; RT "Complete DNA sequences of two oka strain varicella-zoster virus genomes."; RL J. Virol. 82:11023-11044(2008). 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB097932; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB097933; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; DQ008355; AAY57708.1; -; Genomic_DNA. DR EMBL; DQ008354; AAY57637.1; -; Genomic_DNA. DR SMR; Q4JQX9; -. DR IntAct; Q4JQX9; 20. DR MINT; Q4JQX9; -. DR Proteomes; UP000002603; Genome. DR Proteomes; UP000008504; Genome. DR Proteomes; UP000008505; Genome. DR Proteomes; UP000008506; 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 Pfam; PF04843; Herpes_teg_N; 1. DR Pfam; PF03586; Herpes_UL36; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00116; DNA_POLYMERASE_B; 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; Repeat; KW Thiol protease; Ubl conjugation pathway; Virion; Virion tegument. FT CHAIN 1..2763 FT /note="Large tegument protein deneddylase" FT /id="PRO_0000385479" FT DOMAIN 12..237 FT /note="Peptidase C76" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT REPEAT 2455..2457 FT /note="1" FT REPEAT 2458..2460 FT /note="2" FT REPEAT 2461..2463 FT /note="3" FT REPEAT 2464..2466 FT /note="4" FT REPEAT 2467..2469 FT /note="5" FT REPEAT 2470..2472 FT /note="6" FT REPEAT 2473..2475 FT /note="7" FT REPEAT 2476..2478 FT /note="8" FT REGION 1..247 FT /note="Deubiquitination activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT REGION 495..523 FT /note="Interaction with inner tegument protein" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT REGION 2455..2478 FT /note="8 X 3 AA repeats of P-A/V-Q" FT REGION 2630..2651 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 32 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT ACT_SITE 168 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT ACT_SITE 170 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT SITE 19 FT /note="Important for catalytic activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT VARIANT 2468 FT /note="A -> V (in strain: Oka varicella vaccine VarilRix FT (V-Oka-GSK))" SQ SEQUENCE 2763 AA; 306336 MW; C0E4F5AC0A599529 CRC64; MDIIPPIAVT VAGVGSRNQF DGALGPASGL SCLRTSLSFL HMTYAHGINA TLSSDMIDGC LQEGAAWTTD LSNMGRGVPD MCALVDLPNR ISYIKLGDTT STCCVLSRIY GDSHFFTVPD EGFMCTQIPA RAFFDDVWMG REESYTIITV DSTGMAIYRQ GNISFIFDPH GHGTIGQAVV VRVNTTDVYS YIASEYTHRP DNVESQWAAA LVFFVTANDG PVSEEALSSA VTLIYGSCDT YFTDEQYCEK LVTAQHPLLL SPPNSTTIVL NKSSIVPLHQ NVGESVSLEA TLHSTLTNTV ALDPRCSYSE VDPWHAVLET TSTGSGVLDC RRRRRPSWTP PSSEENLACI DDGLVNNTHS TDNLHKPAKK VLKFKPTVDV PDKTQVAHVL PRLREVANTP DVVLNVSNVD TPESSPTFSR NMNVGSSLKD RKPFLFEQSG DVNMVVEKLL QHGHEISNGY VQNAVGTLDT VITGHTNVPI WVTRPLVMPD EKDPLELFIN LTILRLTGFV VENGTRTHHG ATSVVSDFIG PLGEILTGFP SAAELIRVTS LILTNMPGAE YAIKTVLRKK CTIGMLIIAK FGLVAMRVQD TTGALHAELD VLEADLGGSS PIDLYSRLST GLISILNSPI ISHPGLFAEL IPTRTGSLSE RIRLLCELVS ARETRYMREH TALVSSVKAL ENALRSTRNK IDAIQIPEVP QEPPEETDIP PEELIRRVYE IRSEVTMLLT SAVTEYFTRG VLYSTRALIA EQSPRRFRVA TASTAPIQRL LDSLPEFDAK LTAIISSLSI HPPPETIQNL PVVSLLKELI KEGEDLNTDT ALVSWLSVVG EAQTAGYLSR REFDELSRTI KTINTRATQR ASAEAELSCF NTLSAAVDQA VKDYETYNNG EVKYPEITRD DLLATIVRAT DDLVRQIKIL SDPMIQSGLQ PSIKRRLETR LKEVQTYANE ARTTQDTIKS RKQAAYNKLG GLLRPVTGFV GLRAAVDLLP ELASELDVQG ALVNLRTKVL EAPVEIRSQL TGDFWALFNQ YRDILEHPGN ARTSVLGGLG ACFTAIIEIV PIPTEYRPSL LAFFGDVADV LASDIATVST NPESESAINA VVATLSKATL VSSTVPALSF VLSLYKKYQA LQQEITNTHK LTELQKQLGD DFSTLAVSSG HLKFISSSNV DDYEINDAIL SIQTNVHALM DTVKLVEVEL QKLPPHCIAG TSTLSRVVKD LHKLVTMAHE KKEQAKVLIT DCERAHKQQT TRVLYERWTR DIIACLEAME TRHVFNGTEL ARLRDMAAAG GFDIHAVYPQ ARQVVAACET TAVTALDTVF RHNPHTPENT NIPPPLALLR GLTWFDDFSI TAPVFTVMFP GVSIEGLLLL MRIRAVVLLS ADTSINGIPN YRDMILRTSG DLLQIPALAG YVDFYTRSYD QFITESVTLS ELRADIRQAA GAKLTEANKA LEEVTHVRAH ETAKLALKEG VFITLPSEGL LIRAIEYFTT FDHKRFIGTA YERVLQTMVD RDLKEANAEL AQFRMVCQAT KNRAIQILQN IVDTANATEQ QEDVDFTNLK TLLKLTPPPK TIALAIDRST SVQDIVTQFA LLLGRLEEET GTLDIQAVDW MYQARNIIDS HPLSVRIDGT GPLHTYKDRV DKLYALRTKL DLLRRRIETG EVTWDDAWTT FKRETGDMLA SGDTYATSVD SIKALQASAS VVDMLCSEPE FFLLPVETKN RLQKKQQERK TALDVVLQKQ RQFEETASRL RALIERIPTE SDHDVLRMLL HDFDQFTHLP IWIKTQYMTF RNLLMVRLGL YASYAEIFPP ASPNGVFAPI PAMSGVCLED QSRCIRARVA AFMGEASVVQ TFREARSSID ALFGKNLTFY LDTDGVPLRY RVCYKSVGVK LGTMLCSQGG LSLRPALPDE GIVEETTLSA LRVANEVNEL RIEYESAIKS GFSAFSTFVR HRHAEWGKTN ARRAIAEIYA GLITTTLTRQ YGVHWDKLIY SFEKHHLTSV MGNGLTKPIQ RRGDVRVLEL TLSDIVTILV ATTPVHLLNF ARLDLIKQHE YMARTLRPVI EAAFRGRLLV RSLDGDPKGN ARAFFNAAPS KHKLPLALGS NQDPTGGRIF AFRMADWKLV KMPQKITDPF APWQLSPPPG VKANVDAVTR IMATDRLATI TVLGRMCLPP ISLVSMWNTL QPEEFAYRTQ DDVDIIVDAR LDLSSTLNAR FDTAPSNTTL EWNTDRKVIT DAYIQTGATT VFTVTGAAPT HVSNVTAFDI ATTAILFGAP LVIAMELTSV FSQNSGLTLG LKLFDSRHMA TDSGISSAVS PDIVSWGLRL LHMDPHPIEN ACLIVQLEKL SALIANKPLT NNPPCLLLLD EHMNPSYVLW ERKDSIPAPD YVVFWGPESL IDLPYIDSDE DSFPSCPDDP FYSQIIAGYA PQGPPNLDTT DFYPTEPLFK SPVQVVRSSK CKKMPVQPVQ PAQPVQPAQP AQPVQPAQPI EPGTQIVVQN FKKPQSVKTT LSQKDIPLYV ETESETAVLI PKQLTTSIKT TVCKSITPPN NQLSDWKNNP QQNQTLNQAF NKPILEITSI PTDDSISYRT WIEKSNQTQK RHQNDPRMYN SKTVFHPVNN QLPSWVDTAA DAPQTDLLTN YKTRQPSPNF PRDVHTWGVS SNPFNSPNRD LYESDFSEPS DGYSSESENS IVLSLDEHRS CRVPRHVRVV NADVVTGRRY VRGTALGALA LLSQACRRMI DNVRYTRKLL MDHTEDIFQG LGYVKLLLDG TYI //