LTP_MHV68
ID LTP_MHV68 Reviewed; 2457 AA.
AC O41965;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 66.
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 ORFNames=ORF64;
OS Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=33708;
OH NCBI_TaxID=10129; Apodemus sylvaticus (European woodmouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=G2.4, and WUMS;
RX PubMed=9223479; DOI=10.1128/jvi.71.8.5894-5904.1997;
RA Virgin H.W., Latreille P., Wamsley P., Hallsworth K., Weck K.E.,
RA Dal Canto A.J., Speck S.H.;
RT "Complete sequence and genomic analysis of murine gammaherpesvirus 68.";
RL J. Virol. 71:5894-5904(1997).
RN [2]
RP FUNCTION.
RX PubMed=17634221; DOI=10.1128/jvi.01149-07;
RA Gredmark S., Schlieker C., Quesada V., Spooner E., Ploegh H.L.;
RT "A functional ubiquitin-specific protease embedded in the large tegument
RT protein (ORF64) of murine gammaherpesvirus 68 is active during the course
RT of infection.";
RL J. Virol. 81:10300-10309(2007).
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, ECO:0000269|PubMed:17634221}.
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; U97553; AAB66417.1; -; Genomic_DNA.
DR EMBL; AF105037; AAF19328.1; -; Genomic_DNA.
DR RefSeq; NP_044902.1; NC_001826.2.
DR SMR; O41965; -.
DR DIP; DIP-47224N; -.
DR IntAct; O41965; 1.
DR MINT; O41965; -.
DR PRIDE; O41965; -.
DR GeneID; 1497174; -.
DR KEGG; vg:1497174; -.
DR Proteomes; UP000099649; Genome.
DR Proteomes; UP000175018; 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..2457
FT /note="Large tegument protein deneddylase"
FT /id="PRO_0000406915"
FT DOMAIN 13..224
FT /note="Peptidase C76"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 1..234
FT /note="Deubiquitination activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04044"
FT REGION 281..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2064..2131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2164..2360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2387..2407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..298
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..336
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2093..2113
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2114..2131
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2169..2192
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2208..2222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2300..2333
FT /note="Basic and acidic 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 2457 AA; 273538 MW; 6AE1D5E1821BAAD1 CRC64;
MALPASLAGF RIEGTASTNQ ADCKFGENAG AQCLSNCIIY LMSSYFNNEA PITETHDLNK
VLKFGAELDS NLRKLGLLSP GQYAQLDHVP CYVQTRKWSG FIYTSAEMFG LLGMPADISD
SCITSLRDLL TANYSNTIQY ILYICGQKSG AIIIQGGRYT MFDPHCLKDI PESPAHVLST
SDPDALIKYV GGVSREYTAC FLYFVPGHIS PKNYIMSHYK VISFSDLHGS KIILEEYDLP
TTNQSFCSSP QASSSPDPEV GSLLKYMSKA KRKRYPMSCG EEWTDANKKR KESGRTPPEK
MTHPLPSPDI IDLTMDDDVI DLTGDDDMED ESEGDREAEP DRSGTSLPSV TLPNLAAVDQ
LLNSLTLPGH VPSFPALVDT DTGESYRLTR ALHQLKNVLQ QVLEIGVVSD SDYTPTEALN
VLNYLMAWSK QLQIKNDDIK LLINSNLQIE KLFTLLKNNL ISDPNLADHV QAKVCACLPA
MHANRATDLQ KILLHCKNLT RALEISKSSL DIKDIITTFT ESFPQDFFCV CSVEEANNLV
STVQDLKRVV SNNMALTSEQ DARFKALMLS VLNNTDPPAS LGPIYLETET RTPLLSSAIQ
EAVKAIEKDT VETLSELISN IPSENAIETT FVPPVRTLLK NVTTLLTVIN ACVERAEIRT
PEIDSSQQQL SYIGRELSKI IDETWPERAF REPVHVLDIF QKTSSHLNDL KKKMADSESL
DKILSEINQT LKAIQDKAAS PALINTLSDY IKNATVLAQA SDPRLVEIQS QVTTLTTSTS
YIESLLQKIN IRTLPEVIPQ LQAATKTEQG QLSLAAMNLS LIQITNSLIN EALSSIHARS
HNHLSNTFFN SLNSLMGLAD IPGREDLIKT MESIMAVQEE LVDCDDMECV EKGLTTFKYI
KSSIRQYKFD KSFKTKIYLI ITSEVRDLTK IKTDKQLEAW KQDVADFTPA SIDDLNLFLD
KAPTKTARSY ATRQLKHFRD DLIKEQEMET ETTPVPSTAE IERAIDLKIK ATWDKILTNL
RDLTFHHIAP GDWQVLLTVF NDHKSALFTK MGGELLKALQ GLTAYVDSIL TPLLASQLPQ
GQRYVAPNSD WVETFDQNVK YYLRTFHLPR VSEQLDDLER KTLLLTKLVK FTDLSQSLIG
THLEKDWSIY QKLFNSLLTV YNDHLIKTKT EVHAFLDKIA SDPLLEPQAH PDLQKITQLF
TEQEIIEINT LPDIFKESIK NNEKHYIASY QTEMKVFTSM VDAALAKKTQ STTEYNTHLL
KIVNNMLVQA PPYAASHPIS SDAISYITSL VRDKHLLEKL SYAESLKNFN WLSRLITIIL
TNCHPSHKQH LQTLLDEILS REQTLTPLVA LEDNANQSPT ERTLQAALTT LNVERVLGRA
TTFQKWKSQL QELEEAVKTT TQVSLLIQTI SSLHDKTVTE MDPTILSSHS QALADKLKEL
LALKPSLDET TMSLFHGMKA YAQFKHYFVQ HYVITQPKIF DAYPLSHHGT VSSSGGHQAT
KFNPLMRLKA FSMVTDVKKM SVWREINTTV DPTGHTFIPA PPTPAMPPIH YNVLFSSFLQ
AEAINLALNS NQPPTKKFGL LPGLMDARVG VQGAMLLDNQ WNDISTNSAK LLDHYVRSEL
TPNSLTNSQF AAMTVFAHAM AMVTPHINST RATIFPSKAI VLNQLQFLKL CLTMWPKFSG
GLLRAPSFER VVQLARATLP TLLLSAPRNT LNHFLANNYR PTDTLPNTEA LLFYPNQHPL
VNLEKLLLTS SPFHALSTSV LNTRISMLVW GILSLSEAVL QQLWDSLYQE SATFTTYIDL
LRHLSAMNHK NSTLTTSTSL PQNNGPVVYS YGHTAGTTVA TLEGSHPLDD GGQNIPMTLF
EFVIFAIILK LKFHVFYTQE KALVNTQLGP LHLITHALDG TGDTEPFKTY ISIPPQKYNG
LGNLQQFCSQ DEIQIFQRQH EWLVGVTKQT SFSNEDLFIV LASADNKVLS VHTFNPPINS
LESETPEIVA APIQESWPKE ITTVSFWDKP ALEKSPQELI TEVSLVAEIF SGSAIFNTFP
PSYKMVSHTP SLHVETHQLE NLSITEGTPP TSPPLPDSTT QDHMEEPDNK QAKPPYQMTS
PMKENTSTSG RPARSPSPSP PVLTPIKPII PIPQATPTMP ILSPFTPRLL PAAVKKHQNG
AVWGHSGSLP PTHIQSSTPG PAQNTRDSGR RQIVSPVITI LPGTKAGADS AGQNTSHKDI
SAYSPPPASK KTDRPSDTHV TAPLFSKSKL VTPRPAAKTD TGTFGPLLGH EKPPVTDLTA
PVEPGHPSKV SPIIHLKPSN TGDRDPHPIS DDEDSKQPPV PDTSRDKAQS RWKTPKQRPQ
NIFPPPKHED DVPVTAPQPQ GRKILVGGRQ LPSLVYNPPT LRDIKTGMSD DKNPEPCVKE
NPPGVTHDPP LRIQHMEQTV NSSKYNVLLF IEKIIKSVHD HSSYMLSTLK RIKQLYI
