ID   LTP_ALHV1               Reviewed;        2606 AA.
AC   O36414;
DT   08-MAR-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 63.
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=64;
OS   Alcelaphine herpesvirus 1 (strain C500) (AlHV-1) (Malignant catarrhal fever
OS   virus).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Gammaherpesvirinae; Macavirus.
OX   NCBI_TaxID=654901;
OH   NCBI_TaxID=9927; Connochaetes taurinus (Blue wildebeest).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=9261371; DOI=10.1128/jvi.71.9.6517-6525.1997;
RA   Ensser A., Pflanz R., Fleckenstein B.;
RT   "Primary structure of the alcelaphine herpesvirus 1 genome.";
RL   J. Virol. 71:6517-6525(1997).
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; AF005370; AAC58111.1; -; Genomic_DNA.
DR   PIR; T03159; T03159.
DR   RefSeq; NP_065563.1; NC_002531.1.
DR   SMR; O36414; -.
DR   GeneID; 911802; -.
DR   KEGG; vg:911802; -.
DR   Proteomes; UP000000941; 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:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-UniRule.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   HAMAP; MF_04044; HSV_LTP; 1.
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   SUPFAM; SSF54001; SSF54001; 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..2606
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000405760"
FT   DOMAIN          14..225
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..235
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          318..349
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          390..411
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1020..1135
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2253..2316
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2434..2458
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1048..1064
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1083..1135
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2280..2316
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        34
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        163
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   ACT_SITE        165
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   SITE            21
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ   SEQUENCE   2606 AA;  290017 MW;  0D3604B55D673082 CRC64;
     MAFQAQTDTG LQLLATASSH QGDCKYGPFA GSQCLSVCVY YLASSFMNNA PVDSREGLDD
     VLLHGSTLDR LMRTHNFIPM NEFAQLSSVP KVLITHLWSC AIETSPELYG LLSDECVVCA
     PFIMSLRKAL EMNYFEIPQY ILYICNGKSG AIIIKNKTYF IFDPHCTSSR DTAAVYASAS
     ASSVVAYVGE ASREYTACHL YFIPAESSDE PVNEYLLANY GIASALKRSG AYVNLKTLQT
     HAISESTQPI APPVPAAPSG MQFFPTQASF PSSQSFVATS TPVPTKALKP TPSHQPSIPG
     AASLKTALHM ATVKRKRIAI SPLHSNTESD DSETGKKNTP VKITKPNEAD VGEVETFWLD
     DDISTKQMLS ETSSSEKNLP ESIFSSSDWD TDSLLSTHES PPATPSLKSG QVNYTSTFSL
     DNEELGGSNL QLQDKTYKLD STTFENLPQL LTSLEEHIEK VSKYPHKNDM PVIVDHSVNK
     CYREAVALYT IDSLLSHVIE QGLISKPEHK SQALNILRYI AIWLNKLSIY TNQVQELINT
     ELYIPYIYQA LFATKFDGKL EAMLIEKITK CFQTLHGTSL QDMKNLSKMI QASIKNTPYY
     DKAVNVQEET ENLKSAVSLP YFITTEEELK KIQALAANLW KVIQDHNNSV SHEDSEFHRA
     VNSVKNFLPI PSDIQPLDYT LSDKADYLGD TVQQLVASIT QECQTISNHM LSSMQSNVSF
     SADIPDFYSL RGKICTTLNN IQTSKDHLGL YNDKLQKARQ QLAYLGYEIS SITNSQWSTD
     YTEPVTPIPE LGEIQSQLKI FNTNQQNQQM LQNILDEVES MLQAAKSEQT EQGLQKLAML
     LPSIEAYLEN AGTLLGPEGN AQFDRLRKEI TDLIGSVDVM LAYVKNISAH TLATDAQTIS
     NFPTDAKQQR VFQQALTQKV KDLFTQVNAS LKTDRPPTFT ENDMAALESL AVMSNDSTLS
     TAAAFYTKIT LLLKSKPDCT VPLYDIAHLK SQLATANINS STKRSLYMLL AQLNKETVSK
     KGLEQTQAPA PKGPTADTPV TDSKLIQDSQ QNDRHQKEKP LKPKKPQAIS LPAVKDTTKH
     LKPSKPQNLS LPVSTNKAPV EESPESSPIE STSPSHSPVS SMESQNGSFS LESSEEELMD
     TFAVDDHELS DTDHHMDVDK TTTSVAMDDK PSTSPEPPSQ SLSAIVQQEE RLGEEQAWKK
     IQIAFKTLDF TDITYSDWVH VTGITQHHDL KVSETFGPTL ESLMSPLLQK LKKMTIGAAL
     SLTTYGQAFK WPSIDWMTPY KNNVLFYLST VRYPSLVDLA EQSRAEIDVL LQLRSSDALL
     KGTAGTYLES DSRNMLDIVS SIEDAASDYK LNVHTEVEKW THQVHNIVNT GDSLPPKPDV
     ILPSHLLNPA FEQTIASLNK DFRDYVYTVE KHLLAELSND FQLLKVLISE TENGFQAWEK
     ETANKLLQLI SHSLQNAPPE VRQYTVSHTD PLTLFDKLIH DSEVSSKLTY SEASAALHWV
     ESTCAHIATQ CQYPAVGAKL QAIIALVAKV KPKLESLVSL ENQANNTDDI NIIKQAISSL
     DPKRITGGTS KVQEWTQKVK DLEKLLADTE LEASVVQNIQ LLRHMALTAR STNLLANLKQ
     KTTSLYEKWV KEHKTGPTSP ITGTIKELDL YLTFKLKFIE YYETNQACIF STFALPASKI
     DAKDALTPLT PQSPVFDFNT SGPSPPPPIN FQQRLEAMCH LNYAPTQPIW LQVFPTVDNL
     SMDYIPIKNA SPLSLQVIFN NFIETYFVQA PQGPQKDTSQ YRGSTVLPNV LQAHFGTIAT
     HLINSHWNNI LENSTQALQS YTTVHSLHGT AKQNEFMAII VAVHGLLQSL STIYLDTPAN
     SSDIPVVLSF RATLEIILWI WPKIIFYFLK MKSFQSGVSF LQIMINRCLI NLTSAFVIQH
     ITNSLIMAGV PEPNGYLFCP KYWTQLEPQA YLWGDEKFLQ LCSNSQEKAR VCFFVCALES
     INPVVLGQLW RSLKPTFLPD VHTPYDFLKV LVEAAYKPAY DCQVVSKARV DETPPYSYGF
     PGNSVLRVES KTTKPQGVTT IPISGFEMAA AAILQKFNPV IYLSTKKPVF SNEFTGEIFV
     VSPLLDCTGN EEPFSSLLTA PLQPVSENTT LASLYTQLEK DIFRSQKLWL QQHLSSPNNL
     SHLKHPIVLL DSEKKLTGAY SLTNNAPPPQ LLNLRFAYDG KGLPNWPMEI LQASTLSYSH
     QQALEDKTKD WIIDIEDLDD SLCIQNMFSA YPPEIHSGPS RSDSEDSEDS LSPTSPTPHL
     PKAEFTPLPD SPKPPQDPKD KSTPNPPRPT TFPTPLLPCY PLSEAYATLP KPISIKPSAR
     VHFVVPPKSN LAADQLLRDF ESLSLQDRPE RPKDGPPDIN YLVPPHGSYI NLQPPNPRMA
     VIGTLRAADQ KSVFTPTRPA GVGSRAKWVS RQLPPHDFVE PVENGDPPGP PGSEERKYSI
     RQESYQDPTV SLLLRQPPII EAVRLFPDKS LTAAQMQQAF KQKQLHVCEK SHRKRLLSAP
     PTIAPNHLSI HEILADRASL VAPRPPFIPI DENLDIEPLF VQFIMEVSIE EAKNVLITFI
     KKIRQAVTHN AQLLASSIQR LAALYL