LTP_HHV6G
ID LTP_HHV6G Reviewed; 2077 AA.
AC P30002;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 69.
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 6A (strain GS) (HHV-6 variant A) (Human B lymphotropic
OS virus).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Roseolovirus.
OX NCBI_TaxID=10369;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1654455; DOI=10.1128/jvi.65.10.5597-5604.1991;
RA Josephs S.F., Ablashi D.V., Salahuddin S.Z., Jagodzinski L.L.,
RA Wong-Staal F., Gallo R.C.;
RT "Identification of the human herpesvirus 6 glycoprotein H and putative
RT large tegument protein genes.";
RL J. Virol. 65:5597-5604(1991).
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; S57540; AAB19786.1; -; Genomic_DNA.
DR PIR; H40511; WZBEZ4.
DR SMR; P30002; -.
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; Repeat;
KW Thiol protease; Ubl conjugation pathway; Virion; Virion tegument.
FT CHAIN 1..2077
FT /note="Large tegument protein deneddylase"
FT /id="PRO_0000116040"
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..2003
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; 239910 MW; 28E297FDC2FAD2AE CRC64;
MKIITSSTNQ NDSKYGPRAG KQCMSNSFSF LHTVYLNGIN NSLNAGTIDA IMEEGYHLDT
AGTLALMLNN SDSQDYRLPT EIPKRIHSRY GVTQHELSRP FNGTLDTQKI DNEVYLGLID
LILYGKSKNG 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 RLNDILLILK DGQFSSLETM HLNLLETFLK QLQDNNVIIH
FTHALLPVLK DIETTISKII SDVIEKILIK TPLNPEQMSK EEQKYTPLLS FLSKFKKTTF
CTEDVKTEID QMQKSITFLK KIATSANKHT RLSHSIYGQE LNLYEERITE LRKETNKMKE
QLSKEYALAE KKILLSSQDA KTDKIYLVLN THTLKEIKNT QFRETAFAKA LTVEVNNKEN
QLQELLNHFN AHLKAKMDQN HITKLSFDTK WTAFVSDSRL YIPDFINIKL QDFISDPFKV
ISQLMNKATN EMPYIQAEIT LKWLTKLIHD INKFCLSAIS EFGKEAIPFN YAALRDLEYQ
INTKYVEIEN KVICNETVEN TKNIPKLTKL LKQLVPKRVA GGQEQYQTLM NKILSSETSM
QQTYEKEQLK KEYFEIVNNV ASFKLAFNFP QQLQNVERLI EKFKSLPKSQ PFEKFPQEND
LLSDSLNTEN YINGLRALLN FITAAQNYIQ NTLLKQWAVF QQQNFIPIDY SVANVKPISD
LYARLRIERE RQVFYQVNSV FGTHLIVDDT GVPLQFHNIF NNAIVKFFSL NYKQIHVPED
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 TFAMYIDTIE KTYLLCMRHL
ENVLHDKDFQ SVLRARTFDI DYILKQSWTK NIVEHSLFSV QLDKIVSYLN HTNRATPNIP
LILFNYDNEV VNVYLPPMST NPKKVAFYIK NPFHFPVQEY EATNLISFHL YPKTTDILNQ
LPPNNTESTR PGKQTSETLT TKNLSEPKFK KPAVTGLMPK SQSIILSTDT NVPETSPDVK
ANTASAAIKD VTLAREKINE FSESINTTIS KLKSMYL
