ID   LTP_SHV21               Reviewed;        2469 AA.
AC   Q01056;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1993, sequence version 1.
DT   24-JAN-2024, entry version 90.
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; Synonyms=EERF2;
OS   Saimiriine herpesvirus 2 (strain 11) (SaHV-2) (Herpesvirus saimiri).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Rhadinovirus;
OC   Rhadinovirus saimiriinegamma2; Saimiriine herpesvirus 2.
OX   NCBI_TaxID=10383;
OH   NCBI_TaxID=9521; Saimiri sciureus (Common squirrel monkey).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=1321287; DOI=10.1128/jvi.66.8.5047-5058.1992;
RA   Albrecht J.-C., Nicholas J., Biller D., Cameron K.R., Biesinger B.,
RA   Newman C., Wittmann S., Craxton M.A., Coleman H., Fleckenstein B.,
RA   Honess R.W.;
RT   "Primary structure of the herpesvirus saimiri genome.";
RL   J. Virol. 66:5047-5058(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1314457; DOI=10.1016/0042-6822(92)90759-i;
RA   Nicholas J., Cameron K.R., Coleman H., Newman C., Honess R.W.;
RT   "Analysis of nucleotide sequence of the rightmost 43 kbp of herpesvirus
RT   saimiri (HVS) L-DNA: general conservation of genetic organization between
RT   HVS and Epstein-Barr virus.";
RL   Virology 188:296-310(1992).
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; X64346; CAA45687.1; -; Genomic_DNA.
DR   EMBL; M86409; AAA46140.1; -; Genomic_DNA.
DR   RefSeq; NP_040266.1; NC_001350.1.
DR   SMR; Q01056; -.
DR   GeneID; 1682468; -.
DR   KEGG; vg:1682468; -.
DR   Proteomes; UP000000587; 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:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-UniRule.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 3.90.70.120; -; 1.
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; 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..2469
FT                   /note="Large tegument protein deneddylase"
FT                   /id="PRO_0000116039"
FT   DOMAIN          13..225
FT                   /note="Peptidase C76"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          1..237
FT                   /note="Deubiquitination activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          244..318
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          286
FT                   /note="Interaction with inner tegument protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT   REGION          346..377
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        252..276
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        278..297
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        346..365
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        33
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            20
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
SQ   SEQUENCE   2469 AA;  280168 MW;  D2B4B8DC08644CDB CRC64;
     MDIHPLFKKL NLEGIASTHQ ADEKYGQYAG SQCLSNCVMF LVSSYYNDET PVTSLHGLNE
     ILKYGAKIDF ILRRSGQLGH NQYAQLHHIP GYIAGPKWAC FIYQSIEMFG MLGHESPINE
     PFVASLKSLL SKNYNTTVQY FLAICNSKSM GILIKDKKIF IFDPHSCPLV PNSPAHVFST
     SNVNDAIEYL SPPNVQYTGS FLYFVPKEYI GHSHYIMNHY RVINYEKLHG PNIDLTSQEG
     LIIEISPPNT PKPTSTQKPP KTPRTPKPAT PKAPKTPRKP KTPKESTIPY DKSKKPPKIP
     KTSKKSKKVL TKDTALTPQH KTIEEHLREL LPPITETVED NTLFNHPVER TTPGTDSLLS
     GINSTTKRED DLEDDDNVTS KLKEDEDDWI DDIPIPEVLD TETTHSDQET IYMIGDENIH
     DWSYSDDDID DTLDISFIQL DNLITSLDNI PKNNTFPRII DKTSNQPIKE GKALHSIDRI
     LKNIVLEHGL ITSSSISISK CKSLLQFVIL WGEKLSIPTR DLKTILKTEL IITEIAEIAL
     TKLTNDTFRN NVITKLNKCM LKLKSESVDS YKHLSALLNN IILKIQTIDT EIELKTLSTV
     FTSELGKDFS VVCTKKESET IMAAIKNLKE KISTRKQELH TEENYFQSVL IAMETFQPIP
     LPTRVIEIQP SKKAQQLHEK SKLVEQKLTI DANNVLTDLL HTMKQDKTDI SPAPDFTTVL
     KNIQSTLQLL QTCVTDLNID KKFISNTVQQ LSYIGWEVAE LSHSQWNFPK ADPVIPLKIL
     DDIKKEIQQV TTKQKNEETL SKILADVQTL LENAKQSDTL SIPILQHYIT KAGTLVGERE
     NQKFESLKNT VQKLSTSEEF LKTLIDSTTL ENVQLQIQEI SDILQSNQYI HQSETIKQAF
     FDKSNTIINN ILQLINQQKY TTVTQPMLIA VKRFLSEAKF RESNTICEII STLVSLGSLL
     SKSTTVEALK DALKSIDTLK EKLTAVDRPL KRELYNVIRK LQKQLKTLLE QQEFDNWKME
     VDSFVPTPSR DVKTFIQNAP SMKAKQYAKK ALKDQIQAME IDVDPESVIE DNIKANGQKA
     WQKIQSAFQD LNFSILIPDD WLSLAKEYTR PKSTLFTVIG PILLKFVEEV LESVKNLKEA
     KLKSLLPNGP VFTPPKFDWI HYYESNVNFH LKTINLPKVS TVAHNIGHEL SLLSQALNSK
     TLPEAVVGTS LEQHAAKFSC MFKTLEATWH DHQVDTRTKI DEYIEDLRND TKKHIVAPQI
     QSPNRFLSPE DIQEINSLPK LFRDSLLENE SRLLASQKNE FQMLENTVKA AELQYKATQE
     DIISNMSEAI NSLLPLAPAY ILAIPTIPTD PLKYVENIIQ DKRLLNTEPY QITIECLNWL
     NTACKTLLSI CPKSQKQRLV VLDQSINTHL NITQQFYNLE KTANTTDDLS VLQNAISTLD
     LKRVQGGKAT VDSWQSKLQQ MKAMLDNISK SAQTLASLDI LWGTALTSVS TAHLGELLQK
     ADPLQKDIES LSSTNTDLLS RVTELIHFIK FKRGFLSYYE EGQKEVFQRY PLTQNIRPSQ
     PTEINNLLRL ALFVLLKNKD ASAWIWTETL PLVDSNKLAY VPPNKGPLYT CSQYLKLLEA
     QLLDPSLSKV ILSDNRPLAG IAQARLGIDS TVLLARAFPD IQKHAEEVLT AYKNSIVSHT
     QNEFMAMTIV CHMIKIIMND FYPQNFNINT VPIYVNHTKL LQIILTMWPR LIKASLCQQS
     FQEATSLLQT TLKPLFLKIT DLTLENNIYN PASHCSDALL FFPQKWKSIN IQSIMWEHPS
     FLAICKNKSR ARITFLALAF KIIDPTILNQ LWTSLNPANT SDSTSYSLLL NHLVATEFDK
     NVPSTFLEPG NPSLAYAYGT QTGNIIGTKS YVPQKSPPIS VTAFEIALGA LIFQVPVKLF
     VTDKTPVLSS PELGDMLIVS ELLDCTGTTE PFKTMIEAPK SSLSTNLNKQ YVSPPHELEV
     FSRQASWLQH ILSSSNFKNN IVATIDYSTT FLNAYVVPEK LPFKQESFCF IPKIDSLQWP
     NNTFTTFLPL VEMPSNIELH YAKVTEPFNK TVLSTMFNVF PTHILPTQEE HDQSISSKSP
     TFKIEHDYNT NSVYNNHINN INLTNNSTYH QYKDVLPQPL ADKLSYEPKD LQNLASTTEP
     QIEDIFSELS IKETDNTAKA PLLYPQKQPK TKKFLSPVHT KHKTSNSIIF EENTTVKVQP
     NTCIQHSDLH KDTNTPRQQI SNAPCFIPNH KVPVIIKPSQ EKLKANTVHT NTDDLSPKKP
     QILIANNNNI FKQSDKQHKH QYTQISKPKI FINQDSNNPI KQPHHNPPQP LIKPTDPQQL
     TLSNDIISSD QTTKNLNVQR KPIIVIPNNN YALNQVQKLS NLPSIKTKPY ITLKDIQSNS
     KTLYDESPIT IPILEHLDIE PIVSISYLEK RVDETKFIIL EFIKHTKQNI IKTTNLLIHQ
     IMKIKTLYL
//