ID   LTP_HHV6U               Reviewed;        2077 AA.
AC   P52340; Q69055;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 86.
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; Synonyms=HHRF1;
OS   Human herpesvirus 6A (strain Uganda-1102) (HHV-6 variant A) (Human B
OS   lymphotropic virus).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Betaherpesvirinae; Roseolovirus;
OC   Roseolovirus humanbeta6a; Human betaherpesvirus 6A.
OX   NCBI_TaxID=10370;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8289364; DOI=10.1128/jvi.68.2.597-610.1994;
RA   Nicholas J., Martin M.E.D.;
RT   "Nucleotide sequence analysis of a 38.5-kilobase-pair region of the genome
RT   of human herpesvirus 6 encoding human cytomegalovirus immediate-early gene
RT   homologs and transactivating functions.";
RL   J. Virol. 68:597-610(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=7747482; DOI=10.1006/viro.1995.1228;
RA   Gompels U.A., Nicholas J., Lawrence G.L., Jones M., Thomson B.J.,
RA   Martin M.E.D., Efstathiou S., Craxton M.A., Macaulay H.A.;
RT   "The DNA sequence of human herpesvirus-6: structure, coding content, and
RT   genome evolution.";
RL   Virology 209:29-51(1995).
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   -!- SEQUENCE CAUTION:
CC       Sequence=AAA16739.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; L25528; AAA16739.1; ALT_INIT; Genomic_DNA.
DR   EMBL; X83413; CAA58411.1; -; Genomic_DNA.
DR   PIR; T09326; T09326.
DR   RefSeq; NP_042924.1; NC_001664.2.
DR   SMR; P52340; -.
DR   GeneID; 1487907; -.
DR   KEGG; vg:1487907; -.
DR   Proteomes; UP000009295; 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_0000116041"
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   REGION          1982..2004
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
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;  239947 MW;  C1CA4BDC26650511 CRC64;
     MKIITSSTNQ NDSKYGPRAG KQCMSNSFSF LHTVYLNGIN NSLNAGTIDA IMEEGYHLDT
     AGTLALMLNN SDSQDYRLPT EIPKRIHSRY GVTQHELSRP FNGTLDTQKI DNEVYLGLID
     FILYGKSKNG PTFAVITIGV LSRALFFLNN TLYLFDSHPT EREATAAIYI CQNIEEVYEL
     LTTHGTEGFY YDASLIFFIE TSNLSLSSHD AELLILKTYK DPDIAIALDK FSSTEIHEIK
     KTDDIGSQQD LVADKTTDLE HAPHKRKKNS HSLELELNDK KKKDTASLTY YATEVDLIPS
     FYELRSQFQS LFHDLKSFPI MKSNFNWTIY LQDSPINPNQ PFATPFLWNR VFHLLCQIID
     VFVGVGSTND DSSKQQQQTI FINYLLPFKD FSEVFNEALA ACQENNLDII FIYNNYLCKT
     TTFRTLERIL LSKFLAIVDN DHKKHYEWVK SWTTQMFQGM PKKLDDIENY LKAYVDHNPV
     KHFHEFICLN KAEKYKVAVL LNEKRKEIQE AIEREKNSFA QLSNFIDKLG ETPALPIESE
     NVHKVHTSDI TEGIVPRFIT ESIELPNIST LNNTQQISLD KQLNEKLTNT IHTLTNKFTK
     IVQDNYNNIA AGFMPVTELN CLFAYLVNLY FNIEVLKHSG LNINTVLLQE VEKLYDNTQF
     LRFGTSHFNI NNLSNFTLSI RKMFVDFYNS QKPSDRASEI LAAIESILAD PSKNKTVVNI
     EMIKSQLEEL GKMEISTTEN KQTAAITKQI LGDQELTPIY DFLHHLSAYN LPNTTTVKNL
     HLHFILEQRP DIAMTLHDKI QSILDIYVDD MLNDITVPEQ TFSTVLFLVD LFPNSTEKTA
     LFESVLTLRQ LAKKCANLKT LDEFDDLAQF ITTNSEQLQN MMRQHFGKKI PTLMGHIKFL
     YSQKIITTEE KNWIQRAKTV VITSPEELTA FLATAPTKHA LQTCKPDLDK ALQRHMEEQM
     KQTAENDKKH ILTIRSTLEK RLTDILLILK DGQFSSLETM HLNLLETFLK QLQDNNVIIH
     FTHALLPVLK DIETTISKII SDVIEKILIK TPLNPEQMSK EEQKYTPLLS FLSKFKKTTF
     CTEDVKTEIE QVQKSITFLK KIATSTNKHT RLSHSIYGQE LNLYEERITE LRKETNKMKE
     QLSKEYALAE KKILLSSQDA KTDKIYLVLN THTLKEIKNT QFKETAFAKA LTVEVNNKEN
     QLQELLNHFN AHLKAKMDQN HITKLSFDTK WTAFVSDSRL YIPDFINIKL QDFISDPFKV
     ISQLMNKATN EMPYIQAEIT LKWLTKLIHD INKFCLSAIS EFGKEAIPFN YAALRDLEYQ
     INTKYVEIEN KVICNETVEN TKNIPKLTKL LKQLDPKRVA GGQEQYQTLM NKILTSETSM
     QQTYEKEQLK KEYFEIVNNV ASFKLAFNFP QQLQNVERLI EKFKSLPKSQ PFEKFPQEND
     LLSDSLNTEN YINGLRALLN FITAAQNYIQ NTLLKQWAVF QQQNFIPIDY SVANVKPISD
     LYARLRIERE RQVFYQVNSV FGTHLIVDDT GVPLQFHNIF NNAIVKFFSL NYKQINVPED
     TPRLVSSQYK LLSVCKSFIM ILQQFWENII TLDLGPYLRD GTQNFKRELI PIVNLKLFIY
     CITQAWTASE DSTVSTAFEL PIKQFTLLIL CSHPEYLYGC LSHSTDLVIN SLAKSIDKNS
     LYNTFVVSHN PPEKPMHLMR NICIDTQLWQ PAKLMKDTFQ QTFFTQLCPK NEKFFIYLTA
     FLILPYKFMN YIWIQYKPAI FTQRSYQNLI KDLCSEYVHQ NKITTSSVTP HEPDTIKSGE
     RITSKITVHK AQNTPTLTRL QAQEYVFDYI LYSFLTGYEM TFAMYIDIIE KTYLLCMRHL
     ENVLHDKDFQ SVLRARTFDI DYILKQSWTK NIVEHSLFSV QLDKIVSYLN HTNRATPNIP
     LILFNYDNEV VNVYLPPMST NPKKVAFYIK NPFHFPVQEY EATNLISFHL YPKTTDILNQ
     LPPNNTESTR PGKQTSETLT NKNLSEPKFK KPAVTGLMPK SQSIILSTDT NVPETSPDVK
     ANTASAAIKD VTLAREKINE FSESINTTIS KLKSMYL
//