ID   LTP_GAHVM               Reviewed;        3342 AA.
AC   Q9E6N3;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 81.
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   Name=MDV049;
OS   Gallid herpesvirus 2 (strain Chicken/Md5/ATCC VR-987) (GaHV-2) (Marek's
OS   disease herpesvirus type 1).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Alphaherpesvirinae; Mardivirus;
OC   Mardivirus gallidalpha2; Gallid alphaherpesvirus 2.
OX   NCBI_TaxID=10389;
OH   NCBI_TaxID=9031; Gallus gallus (Chicken).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10933706; DOI=10.1128/jvi.74.17.7980-7988.2000;
RA   Tulman E.R., Afonso C.L., Lu Z., Zsak L., Rock D.L., Kutish G.F.;
RT   "The genome of a very virulent Marek's disease virus.";
RL   J. Virol. 74:7980-7988(2000).
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; AF243438; AAG14229.1; -; Genomic_DNA.
DR   RefSeq; YP_001033965.1; NC_002229.3.
DR   GeneID; 4811510; -.
DR   KEGG; vg:4811510; -.
DR   Proteomes; UP000008072; Segment.
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; 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..3342
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000406498"
FT   DOMAIN          78..298
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..302
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          472..554
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          630..656
FT                   /note="Interaction with inner tegument protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          2584..2603
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2654..2987
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          3196..3279
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        477..493
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        509..530
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        538..554
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2586..2600
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2699..2903
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2905..2942
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        3222..3252
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        3265..3279
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        98
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        232
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        234
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   SITE            85
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ   SEQUENCE   3342 AA;  367314 MW;  49B6E04418E54890 CRC64;
     MTDSTDSRQA TTNCRKYSRT TSNAPMLAAN VLRDKSTSGL CSLDRKHDPY FGQIMDNPEV
     ILDEWAKMVI DTTDVTVVAV GIRNQFAPDL SPASSVSCLR SSLAFLRIVF AYGLDTVISS
     DAIDRLLLQG KAWTIATSED GTYTTCVPHD LPNRIISKDA GGNLCVAFSS SYGEFEFYLE
     ENTPTILDTQ ISARTFIEQI WKKKRGDVYC LIVVGVLGIG VYRSGDGIYI FDPHGHGHIG
     QACIVRVSEG YFYQYLTSYA DPSATPDWSA TFVYFVSTVS ICPPRDEIIS TVSRIYGTSD
     IVLDLGRARE EDNRKVVSAD FDPPSRPQPR LTKLVIGSTD TTIQGSDYPC IQAEDLNGED
     SRPLDHNLSY NDAPTNTESV APPSTKDCRD CINIQNPGET LDDTHSTIVD PSTKDSISVT
     AWQGVFSDVI EDPPPKTNFQ FSFGTFAKVA ENKIGTTSVE GCIRNYARHK RRRPLWTPQS
     SSENISLDGS SSSLSRKHSR KSKRTLESRI VEAVTSTESS DVTENVDTYP PVISNIPDEP
     TLGSSPTTSN RGEDTTVEHL LKNRPLFNFK SLTEDEDGLV QDRLWSDEYL SHYPLADIRD
     KIEDVACSID SGLRIIVHVG SPYDSDGGLL YVCMMDIFAR LFNYIIENGA RTTSDRESVV
     GYEMAALLKA FTIPVYFTTF IASTGMVLSE ASESIDLIER VLAENSKIGN LALSKMILVA
     LEVEEVTDEL HKSLDAIEKE VGTADPYGIY ERMAAILVDT LYHNSGKLYS EKTSSNSNQT
     LTDRVISLCT LIRDIEAVAI RKAELILAEM EALEAGVRWM NTTLDAFIMG GSGSSPMIDA
     ADIVAKTSSA VVTQRLGDIG KTVIDVVGHS LREYYLKVAL YSVKALTASS SDVSRFKIVV
     TDQYEKINRF ASSLSVIDDV MVLIASRSNA RVPSPVSQAF ESELLGNLLE IGSDLDVPEK
     LTTWKNLMTS MQVGGWISRR ELDMLMKEID IVNEKATRHE TVLTELERLN ELETRFGSYT
     DLDTTVELQK LDEAIKIGED IVKLAIVLED KKNATSLSSD VREKLRDTRR KNETFITHLR
     ERYQEVKSTI EDLYSSIRKI LRPLPKFVGL RALDSKVKVI TESIPRGMGS FENFLASAPS
     DIIGSLQSDL WVLFIQYKTI LSRPTTEVAA ELSGLGVPFA LAIRLVFGPQ GSYPAASVFF
     GKHADVLSAT IAAAAVEPMS VEKTMAVVST LKAAISDIDR ANAIAPPQGI MSISSTERSD
     AFLFLKALLS TAEIAADVAN RGQHLESLIQ SVRTILDNLI TSNHKIRSLN PREVISENDT
     SVVASAKVEF SNAIQTVGNV TATLSTFEGL TYTSNPHIQR KIAELSKLIR SANQRAGELD
     IAIQTYEHNR ISAERSRSED LWISSINSLL LNAEVKSEFD AMEINRLEDA ARTGGYDTIR
     YKSRAEKIVI AHARVLESSI ESVLKFNPYS TQNMVHGLSP PIAALKSITW GDSFMTAAPY
     YTKLFGVNCD TVMDLLHISI AILRHANANS GNVDYYLLMG ELESALKSYP NLVKYVNFYR
     SGYVKFMSFL AHLEQRRVEA HHASGRVALE ISAALEDLAR THSPEGARRA LEYGVSIIIP
     SVNTIMSIAE ELKKDHVEEL EGTAYSEYGA HLLRRDTDAM TSLIHRVTTA IEDAKTRGEA
     ILKNLAEASY AADRESAELL ANLKNLLRLV SMPSHIAKAI DRSETVNDIV TQAALLLTKV
     EETKELDSQT VEWLRHAESV IDSHDLTVRI DESGPMSIYA DRIDALVNLS KRLEELKSEL
     ALAEVAWDDT WATFVHDKDR IDKSSEGFSS ARESAARTKV SVNMINALRS NAEYPRLPAK
     IIGLIDTKYR DRVVVLDAFL TTVKEIEATQ KQMEGLCEKI PSTFAINDLK KIYTQFEDIA
     KRLPKWYTKR VARYSRLLTL RLALYAGYSN TFEGNVGDPM LLPFDAGDAN NGANHTSNVG
     VVNRYLKHRV ASWIRPKVVA TLQEAFSEID SPGCLTYLDS TDKPLRYSLC FRTVGEKLAA
     CLCEPAAIGI KPQIPIQPIT TEETEAAAGM LSDIMTFRLG FVHDMANHLY SFTKYVRTKR
     HNWMQSDYIK ALGTIYCALI AITLTRKNRS NLSDIYFIPG RRTPIVDKKE LKKNAANGRG
     KQVVRLDPAD VMVTIMANIP GHMLTFSKLD LIDQYDFMDK TIYEVMTDSI STVAFVNCLS
     VQLSKDNIPD PNCRPLSLTG SVWDPAGGSL FSVRYSDWRQ GKLSDTDPLK LWEDLDGDAA
     DGLAKIRAAI PSSLLTTTTV LARMCIPPTA LAVIWSSLLP DGLEQNCKSY DDVVTARGDL
     ASSLDVTTSL LSCSENKNIS SITDSPNLYD LTGNVTTFTV VSTPPSRVLR VNAMDIATTA
     TLFGARIVIA AECPEAYSSE SGLSLCIRLF DSRHGSRGCF LEPTAVSSDM TSWGTKLLIT
     DNNPIENACL GQQLEHLSRI VASKPLASAP PCLLIVDSGM APIKVLWSKE ILDPIPIIRL
     ISEDDALISE LPYVDAGIRK EPELANEHMV IADVQEASKF FSDESRIYPC PIYNKCVSPD
     LSRDGDADIS SNRIDSEDDT YADSMGSGYL SIDPESMWDR VVENDMEGAQ VQLLLPGDII
     HHNDRHVSEN MNYPQIGHLD ISPNYRDPID ETSSNPPPFP KHSNLFPSDH DPTSESSSKP
     TPAPKPTPAP KPTPAPKPTP APKPTPAPKP TPAPKPTPAP KPKPPPDPDF KPSPAPKPSP
     ASKPTPAPKP SPAPKPKPPP DPDFKPTPAP KPSPASKPKP PPDPDFKPTP APKPKPPPDP
     DFKPSPAPKP SPAPKPKPPP DPDFKPTPAP KPSPASKPSP ASKPKPPPAP DSKPSPAPKP
     KPPPTPDSKP SPAPKPKSPS ASKPLPVLFP NSDSKTSPVP NPNTFSASKI PPTSSIAEET
     KPCQSNLPAI PLITKPDSVK NGYTTLKTDD KRKGSQSRYR NEKSRKHMHN THTAVYNTTF
     NWTGTAAASS RHDMELNQYS PGIVTFDNLI DKEGYRHESE TIPRESYSEH RKDLDWMSTP
     TVIANASSSL ITNNDYGGIG GIDLKKYRFK NGTGLLRQGS PTTRLHCRKN NSSRSITDIL
     VGTASPTNEP SPLLQRLKAH TISGDKKANM DAGTIRGRLY DYSSFWPPCI QGACSTSPKT
     IDLKYLSSEQ ATVAYPKHDD THHQTPTGLA PNDKHSDMHI SSIITETDTK ENSIPGYNNI
     PMRHSSESES LTSLDSDSDD SHLHVSGSTD TTTDGSSTSR VIPADALLTR RDFRNASRGA
     LYALTKACKK VARQIVYVRE QLRTKVATLA IELFKIKMIL TG
//