ID LTP_HHV6Z Reviewed; 2077 AA. AC Q9QJ37; DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 24-JAN-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 Name=U31; OS Human herpesvirus 6B (strain Z29) (HHV-6 variant B) (Human B lymphotropic OS virus). OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes; OC Herpesvirales; Orthoherpesviridae; Betaherpesvirinae; Roseolovirus; OC Roseolovirus humanbeta6b; Human herpesvirus 6B. OX NCBI_TaxID=36351; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10482553; DOI=10.1128/jvi.73.10.8040-8052.1999; RA Dominguez G., Dambaugh T.R., Stamey F.R., Dewhurst S., Inoue N., RA Pellett P.E.; RT "Human herpesvirus 6B genome sequence: coding content and comparison with RT human herpesvirus 6A."; RL J. Virol. 73:8040-8052(1999). 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; AF157706; AAD49645.1; -; Genomic_DNA. DR RefSeq; NP_050212.1; NC_000898.1. DR SMR; Q9QJ37; -. DR GeneID; 1497033; -. DR KEGG; vg:1497033; -. DR Proteomes; UP000006930; 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..2077 FT /note="Large tegument protein deneddylase" FT /id="PRO_0000408401" FT DOMAIN 3..221 FT /note="Peptidase C76" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT REGION 1..231 FT /note="Deubiquitination activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT REGION 287 FT /note="Interaction with inner tegument protein" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT ACT_SITE 23 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT ACT_SITE 156 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT ACT_SITE 158 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" FT SITE 10 FT /note="Important for catalytic activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044" SQ SEQUENCE 2077 AA; 240285 MW; 49D4C3F872A5BDF8 CRC64; MKIITSSTNQ NDSKYGPRAG KQCMSNSFSF LHTVYLNGIN NSLNAGTIDA IMEEGYHLDT ASTLALMLDN SDSQDYRLLT EIPRRIHSRY GVTQHELSRP FNGTLDTQKI DNEVYFGLID FILYGKTKNC PAFAVITIGV LSRAIFFLNN TLYLFDSHPT EREATAAIYI CQDIEEAYEL LTAHGTEGFY YDASFIFFIE TSNLSLSSHD AELLILKTYK DPDIAITLDK FSSTEIHDIK KTDDIGSQQD LVAAKTTYLE RAPQKRKKNS HSLELELNDK KKKDTASLTY YATEVDLIPS FYELRSQFQS LFHDLKSFPI MKSQFNWTIY LQDSPMNPNQ PFATPFLWNR VFHLLCQIVD VFVGVGSTND DSSKQKQQTI FINYLLPFKD FSEVFNEALT ACQENNLDIL LIYNNYLCKT TTFRTLERIL LSKFLAIADN EHEKHYEWVK SWTTQMLQEM PKKLDDIENY LKAYVSQNPV KHFHEFVCLN KAEKHNIAVL LNEKRKEIQE DIERDKNIFA QLSNFIDKLG ETPALPIESE NVHKVHTSDI TEAIVPRFMT ESIELPNIST LNNTQQLSLE KQISEKLTNT IHTLRNKFTK IVQDNYNNLA AGFMPVTELN CLFAYLVNLY FNIEVLKHSG LNINTELLQE VEKLYDNTQF LRFGTSHFNI NNLSNFTLSI RKMFVDFYNS QKPSDRASEI LAAIESILAD PSKNKTIVNI EMIKSQLEEL GKMEISTTEN KQTAEITKQI LGDQELTPIY DFLHHLSAYN LPNTTTVKNL HLHFILEKRP DIAAILHDKI QSILDICIDD MLNDITVPEQ TFSTVLFLVD LFPNSTEKTA LFESVLTLRQ LAKKCANLKT LEEFDDLAQF ITTNSEQLQN MMKQHFGKKI PTLMDHIKFL YSQKIITAEE KNWIQRAKTA VITSPEELTA FLATAPTKHA LQTCKPELDK ALQRHMEEQM KQTAENDKKH ILTIRNTLEK RLNDILLILK DGQFSSLETV HLNLLETFLK QLQDNDLIIH FTHALLPVLK DIETTISKTI SDILEKILIK TPLNPEQMSK EEQKYTPLLS FLSKFKKTTF CTEDVKTEID QMQKSITFLT KIATSTNKYT RISHSVYGQE LNLYEERITE LKKETNKIKE QLSKEYAVAE KKILLSSQDA KTNKIYLVLN THTLKEIKNT QFRETAFAKA LTVEVNNKEN QLQELLNHFN AHLKAKMDQN HITKLSFDTK WTAFVSDSRL YFPDFVDIKL QDFISDPFKV ISQLMNKAAN EMPYIQAEIT LKWLTQLVHD INKFCLSAIS EFGKEAIPFN YAALRDLEYQ INTKYVEIEN KVICNETVEN TKNIPKLTKL LKELDPKRVA GGQKQYQTLM NKILTSETSM QQTYEKEQLK KEYFETVNNV ASFKLAFNFP KQRQNVERLM EKFKSLPKGQ PFEKFPEEND LFSDSLITEN YINGLRALLN FITAAQNYIQ NTLLKQWAVF QQQNFIPIDY SVANVKPISD LYARLRIERD RQVFYQVNSV FGTQLIVDET GVPLQFHNIF YNAVVKFFSL NYKQIHVPED TPRLVSSQYK LLSVCKSFII ILQQFWENII TLDLGPYLRD GTQNFKRELI PIVNLKLFIY IITQAWTASE DSTVSTAFEL PIKQFTLLIL CSHPEYLYGC LSHPTDLVIN SLAKSIDKDS LYDTFVVSHN PPEKPMHLMR SICIDTQLWQ SAKLMKDTFQ QTFFTQLCPQ NEKFFIYLTA FLILPYKFLN YIWIQYKPIT FTQRSYQNLI KDLCSEYVHQ NKITMSSVTP HEPDTIKSGE KITSKITVHK AQNTPTLTRL QAQEYVFDYI LYSFLTGYEM TFAMYIDTIE KTYLLCMRHL ENVLHDKDFQ SVLRARTFDI NYILKQSWTK NIVEHSIFSV QLNKIVSYLN HTNRATPNIP LILFNYDNEV VNVYLPPMST DPKKVAFYIK NPFHFPVQEY EATDLISFHL YPKTTDILNQ LPPNKTVSTR PYNLSSETLT TKNLSEPKFK QPTVTGLMPK SQSIILSTDT NVLETSPDIK ANTASAAIKD VTLAREQISE FSESINTTLS KLKSLYL //