LTP_VZVD
ID LTP_VZVD Reviewed; 2763 AA.
AC P09278;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 100.
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 Dumas) (HHV-3) (Human herpesvirus 3).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Varicellovirus.
OX NCBI_TaxID=10338;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=3018124; DOI=10.1099/0022-1317-67-9-1759;
RA Davison A.J., Scott J.E.;
RT "The complete DNA sequence of varicella-zoster virus.";
RL J. Gen. Virol. 67:1759-1816(1986).
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}.
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DR EMBL; X04370; CAA27905.1; -; Genomic_DNA.
DR PIR; D27343; WZBE22.
DR SMR; P09278; -.
DR PRIDE; P09278; -.
DR Proteomes; UP000002602; 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; 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;
KW Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway;
KW Virion; Virion tegument.
FT CHAIN 1..2763
FT /note="Large tegument protein deneddylase"
FT /id="PRO_0000116037"
FT DOMAIN 12..237
FT /note="Peptidase C76"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REPEAT 2458..2460
FT /note="1"
FT REPEAT 2461..2463
FT /note="2"
FT REPEAT 2464..2466
FT /note="3"
FT REPEAT 2467..2469
FT /note="4"
FT REPEAT 2470..2472
FT /note="5"
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 2456..2476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2458..2472
FT /note="5 X 3 AA repeats of P-A-Q"
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"
SQ SEQUENCE 2763 AA; 306343 MW; 0995F7745B9542F5 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 TRHIFNGTEL ARLRDMAAAG GFDIHAVYPQ ARQVVAACET TAVTALDTVF
RHNPYTPENT 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 RDFDQFTHLP 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 CKKMPVRPAQ
PAQPAQPAQP AQTVQPAQPI EPGTQIVVQN FKKPQSVKTT LSQKDIPLYV ETESETAVLI
PKQLTTSIKT TVCKSITPPN NQLSDWKNNP QQNQTLNQAF SKPILEITSI PTDDSISYRT
WIEKSNQTQK RHQNDPRMYN SKTVFHPVNN QLPSWVDTAA DAPQTDLLTN YKTRQPSPNF
PRDVHTWGVS SNPFNSPNRD LYQSDFSEPS DGYSSESENS IVLSLDEHRS CRVPRHVRVV
NADVVTGRRY VRGTALGALA LLSQACRRMI DNVRYTRKLL MDHTEDIFQG LGYVKLLLDG
TYI
