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Protein

Large tegument protein deneddylase

Gene

ORF64

Organism
Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi

Functioni

Large tegument protein that plays multiple roles in the viral cycle. During viral entry, remains associated with the capsid while most of the tegument is detached and participates in the capsid transport toward the host nucleus. Plays a role in the routing of the capsid at the nuclear pore complex and subsequent uncoating. Within the host nucleus, acts as a deneddylase and promotes the degradation of nuclear CRLs (cullin-RING ubiquitin ligases) and thereby stabilizes nuclear CRL substrates, while cytoplasmic CRLs remain unaffected. These modifications prevent host cell cycle S-phase progression and create a favorable environment allowing efficient viral genome replication. Participates later in the secondary envelopment of capsids. Indeed, plays a linker role for the association of the outer viral tegument to the capsids together with the inner tegument protein.UniRule annotation1 Publication

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei20Important for catalytic activityUniRule annotation1
Active sitei33UniRule annotation1
Active sitei163UniRule annotation1
Active sitei165UniRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Host-virus interaction, Modulation of host ubiquitin pathway by viral deubiquitinase, Modulation of host ubiquitin pathway by virus, Ubl conjugation pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Large tegument protein deneddylaseUniRule annotation (EC:3.4.19.12UniRule annotation, EC:3.4.22.-UniRule annotation)
Gene namesi
ORF Names:ORF64
OrganismiMurid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68)
Taxonomic identifieri33708 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
Virus hostiApodemus sylvaticus (European woodmouse) [TaxID: 10129]

Subcellular locationi

  • Virion tegument UniRule annotation
  • Host cytoplasm UniRule annotation
  • Host nucleus UniRule annotation

  • Note: Tightly associated with the capsid.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Virion, Virion tegument

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004069151 – 2457Large tegument protein deneddylaseAdd BLAST2457

Interactioni

Subunit structurei

Interacts with host CUL1 and CUL4A; these interactions inhibit the E3 ligase activity of cullins. Interacts with inner tegument protein. Interacts with capsid vertex specific component CVC2. Interacts with the major capsid protein/MCP.UniRule annotation

Protein-protein interaction databases

DIPiDIP-47224N.
IntActiO41965. 1 interactor.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 224Peptidase C76UniRule annotationAdd BLAST212

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 234Deubiquitination activityUniRule annotationAdd BLAST234

Sequence similaritiesi

Belongs to the herpesviridae large tegument protein family.UniRule annotation
Contains 1 peptidase C76 domain.UniRule annotation

Keywords - Domaini

Repeat

Family and domain databases

HAMAPiMF_04044. HSV_LTP. 1 hit.
InterProiIPR006928. htUSP.
[Graphical view]
PfamiPF04843. Herpes_teg_N. 1 hit.
[Graphical view]
PROSITEiPS51521. HTUSP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O41965-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALPASLAGF RIEGTASTNQ ADCKFGENAG AQCLSNCIIY LMSSYFNNEA
60 70 80 90 100
PITETHDLNK VLKFGAELDS NLRKLGLLSP GQYAQLDHVP CYVQTRKWSG
110 120 130 140 150
FIYTSAEMFG LLGMPADISD SCITSLRDLL TANYSNTIQY ILYICGQKSG
160 170 180 190 200
AIIIQGGRYT MFDPHCLKDI PESPAHVLST SDPDALIKYV GGVSREYTAC
210 220 230 240 250
FLYFVPGHIS PKNYIMSHYK VISFSDLHGS KIILEEYDLP TTNQSFCSSP
260 270 280 290 300
QASSSPDPEV GSLLKYMSKA KRKRYPMSCG EEWTDANKKR KESGRTPPEK
310 320 330 340 350
MTHPLPSPDI IDLTMDDDVI DLTGDDDMED ESEGDREAEP DRSGTSLPSV
360 370 380 390 400
TLPNLAAVDQ LLNSLTLPGH VPSFPALVDT DTGESYRLTR ALHQLKNVLQ
410 420 430 440 450
QVLEIGVVSD SDYTPTEALN VLNYLMAWSK QLQIKNDDIK LLINSNLQIE
460 470 480 490 500
KLFTLLKNNL ISDPNLADHV QAKVCACLPA MHANRATDLQ KILLHCKNLT
510 520 530 540 550
RALEISKSSL DIKDIITTFT ESFPQDFFCV CSVEEANNLV STVQDLKRVV
560 570 580 590 600
SNNMALTSEQ DARFKALMLS VLNNTDPPAS LGPIYLETET RTPLLSSAIQ
610 620 630 640 650
EAVKAIEKDT VETLSELISN IPSENAIETT FVPPVRTLLK NVTTLLTVIN
660 670 680 690 700
ACVERAEIRT PEIDSSQQQL SYIGRELSKI IDETWPERAF REPVHVLDIF
710 720 730 740 750
QKTSSHLNDL KKKMADSESL DKILSEINQT LKAIQDKAAS PALINTLSDY
760 770 780 790 800
IKNATVLAQA SDPRLVEIQS QVTTLTTSTS YIESLLQKIN IRTLPEVIPQ
810 820 830 840 850
LQAATKTEQG QLSLAAMNLS LIQITNSLIN EALSSIHARS HNHLSNTFFN
860 870 880 890 900
SLNSLMGLAD IPGREDLIKT MESIMAVQEE LVDCDDMECV EKGLTTFKYI
910 920 930 940 950
KSSIRQYKFD KSFKTKIYLI ITSEVRDLTK IKTDKQLEAW KQDVADFTPA
960 970 980 990 1000
SIDDLNLFLD KAPTKTARSY ATRQLKHFRD DLIKEQEMET ETTPVPSTAE
1010 1020 1030 1040 1050
IERAIDLKIK ATWDKILTNL RDLTFHHIAP GDWQVLLTVF NDHKSALFTK
1060 1070 1080 1090 1100
MGGELLKALQ GLTAYVDSIL TPLLASQLPQ GQRYVAPNSD WVETFDQNVK
1110 1120 1130 1140 1150
YYLRTFHLPR VSEQLDDLER KTLLLTKLVK FTDLSQSLIG THLEKDWSIY
1160 1170 1180 1190 1200
QKLFNSLLTV YNDHLIKTKT EVHAFLDKIA SDPLLEPQAH PDLQKITQLF
1210 1220 1230 1240 1250
TEQEIIEINT LPDIFKESIK NNEKHYIASY QTEMKVFTSM VDAALAKKTQ
1260 1270 1280 1290 1300
STTEYNTHLL KIVNNMLVQA PPYAASHPIS SDAISYITSL VRDKHLLEKL
1310 1320 1330 1340 1350
SYAESLKNFN WLSRLITIIL TNCHPSHKQH LQTLLDEILS REQTLTPLVA
1360 1370 1380 1390 1400
LEDNANQSPT ERTLQAALTT LNVERVLGRA TTFQKWKSQL QELEEAVKTT
1410 1420 1430 1440 1450
TQVSLLIQTI SSLHDKTVTE MDPTILSSHS QALADKLKEL LALKPSLDET
1460 1470 1480 1490 1500
TMSLFHGMKA YAQFKHYFVQ HYVITQPKIF DAYPLSHHGT VSSSGGHQAT
1510 1520 1530 1540 1550
KFNPLMRLKA FSMVTDVKKM SVWREINTTV DPTGHTFIPA PPTPAMPPIH
1560 1570 1580 1590 1600
YNVLFSSFLQ AEAINLALNS NQPPTKKFGL LPGLMDARVG VQGAMLLDNQ
1610 1620 1630 1640 1650
WNDISTNSAK LLDHYVRSEL TPNSLTNSQF AAMTVFAHAM AMVTPHINST
1660 1670 1680 1690 1700
RATIFPSKAI VLNQLQFLKL CLTMWPKFSG GLLRAPSFER VVQLARATLP
1710 1720 1730 1740 1750
TLLLSAPRNT LNHFLANNYR PTDTLPNTEA LLFYPNQHPL VNLEKLLLTS
1760 1770 1780 1790 1800
SPFHALSTSV LNTRISMLVW GILSLSEAVL QQLWDSLYQE SATFTTYIDL
1810 1820 1830 1840 1850
LRHLSAMNHK NSTLTTSTSL PQNNGPVVYS YGHTAGTTVA TLEGSHPLDD
1860 1870 1880 1890 1900
GGQNIPMTLF EFVIFAIILK LKFHVFYTQE KALVNTQLGP LHLITHALDG
1910 1920 1930 1940 1950
TGDTEPFKTY ISIPPQKYNG LGNLQQFCSQ DEIQIFQRQH EWLVGVTKQT
1960 1970 1980 1990 2000
SFSNEDLFIV LASADNKVLS VHTFNPPINS LESETPEIVA APIQESWPKE
2010 2020 2030 2040 2050
ITTVSFWDKP ALEKSPQELI TEVSLVAEIF SGSAIFNTFP PSYKMVSHTP
2060 2070 2080 2090 2100
SLHVETHQLE NLSITEGTPP TSPPLPDSTT QDHMEEPDNK QAKPPYQMTS
2110 2120 2130 2140 2150
PMKENTSTSG RPARSPSPSP PVLTPIKPII PIPQATPTMP ILSPFTPRLL
2160 2170 2180 2190 2200
PAAVKKHQNG AVWGHSGSLP PTHIQSSTPG PAQNTRDSGR RQIVSPVITI
2210 2220 2230 2240 2250
LPGTKAGADS AGQNTSHKDI SAYSPPPASK KTDRPSDTHV TAPLFSKSKL
2260 2270 2280 2290 2300
VTPRPAAKTD TGTFGPLLGH EKPPVTDLTA PVEPGHPSKV SPIIHLKPSN
2310 2320 2330 2340 2350
TGDRDPHPIS DDEDSKQPPV PDTSRDKAQS RWKTPKQRPQ NIFPPPKHED
2360 2370 2380 2390 2400
DVPVTAPQPQ GRKILVGGRQ LPSLVYNPPT LRDIKTGMSD DKNPEPCVKE
2410 2420 2430 2440 2450
NPPGVTHDPP LRIQHMEQTV NSSKYNVLLF IEKIIKSVHD HSSYMLSTLK

RIKQLYI
Length:2,457
Mass (Da):273,538
Last modified:January 1, 1998 - v1
Checksum:i6AE1D5E1821BAAD1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U97553 Genomic DNA. Translation: AAB66417.1.
AF105037 Genomic DNA. Translation: AAF19328.1.
RefSeqiNP_044902.1. NC_001826.2.

Genome annotation databases

GeneIDi1497174.
KEGGivg:1497174.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U97553 Genomic DNA. Translation: AAB66417.1.
AF105037 Genomic DNA. Translation: AAF19328.1.
RefSeqiNP_044902.1. NC_001826.2.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-47224N.
IntActiO41965. 1 interactor.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1497174.
KEGGivg:1497174.

Family and domain databases

HAMAPiMF_04044. HSV_LTP. 1 hit.
InterProiIPR006928. htUSP.
[Graphical view]
PfamiPF04843. Herpes_teg_N. 1 hit.
[Graphical view]
PROSITEiPS51521. HTUSP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLTP_MHV68
AccessioniPrimary (citable) accession number: O41965
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 5, 2011
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 46 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.