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O41965 (DEN_MHV68) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 38. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Deneddylase

EC=3.4.19.12
EC=3.4.22.-
Alternative name(s):
Tegument protein VP1-2
Tegument protein VP1/2
Gene names
ORF Names:ORF64
OrganismMurid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68)
Taxonomic identifier33708 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
Virus hostApodemus sylvaticus (European woodmouse) [TaxID: 10129]

Protein attributes

Sequence length2457 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)

Function

Deneddylase that deregulates the host cell cycle S phase to create a favorable environment allowing efficient viral genome replication. Interacts with and deneddylates host cullins including CUL1 and CUL4A, thereby reducing their E3 ubiquitin ligase activity. Inhibition of cullins leads to the stabilization of cullin-RING ligase substrates such as host CDN1A/p21, CDKN1B/p27kip and CDC25A, preventing S phase progression. Additionally, acts as a deubiquitinase and cleaves both 'Lys-48' and 'Lys-63'-linked ubiquitin chains By similarity. Ref.2

Catalytic activity

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).

Subunit structure

Interacts with host CUL1 and CUL4A; these interactions inhibit the E3 ligase activity of cullins By similarity.

Subcellular location

Virion tegument. Host cytoplasm. Host nucleus By similarity. Note: Tightly associated with the capsid By similarity.

Sequence similarities

Belongs to the herpesviridae deneddylase family.

Contains 8 LRR (leucine-rich) repeats.

Contains 1 peptidase C76 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 24572457Deneddylase
PRO_0000406915

Regions

Domain13 – 224212Peptidase C76
Repeat426 – 44924LRR 1
Repeat1017 – 104226LRR 2
Repeat1254 – 127724LRR 3
Repeat1662 – 168524LRR 4
Repeat1699 – 172123LRR 5
Repeat1740 – 176324LRR 6
Repeat1801 – 182727LRR 7
Repeat2046 – 207126LRR 8

Sites

Active site331 By similarity
Active site1631 By similarity
Active site1651 By similarity
Site201Important for catalytic activity By similarity

Sequences

Sequence LengthMass (Da)Tools
O41965 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 6AE1D5E1821BAAD1

FASTA2,457273,538
        10         20         30         40         50         60 
MALPASLAGF RIEGTASTNQ ADCKFGENAG AQCLSNCIIY LMSSYFNNEA PITETHDLNK 

        70         80         90        100        110        120 
VLKFGAELDS NLRKLGLLSP GQYAQLDHVP CYVQTRKWSG FIYTSAEMFG LLGMPADISD 

       130        140        150        160        170        180 
SCITSLRDLL TANYSNTIQY ILYICGQKSG AIIIQGGRYT MFDPHCLKDI PESPAHVLST 

       190        200        210        220        230        240 
SDPDALIKYV GGVSREYTAC FLYFVPGHIS PKNYIMSHYK VISFSDLHGS KIILEEYDLP 

       250        260        270        280        290        300 
TTNQSFCSSP QASSSPDPEV GSLLKYMSKA KRKRYPMSCG EEWTDANKKR KESGRTPPEK 

       310        320        330        340        350        360 
MTHPLPSPDI IDLTMDDDVI DLTGDDDMED ESEGDREAEP DRSGTSLPSV TLPNLAAVDQ 

       370        380        390        400        410        420 
LLNSLTLPGH VPSFPALVDT DTGESYRLTR ALHQLKNVLQ QVLEIGVVSD SDYTPTEALN 

       430        440        450        460        470        480 
VLNYLMAWSK QLQIKNDDIK LLINSNLQIE KLFTLLKNNL ISDPNLADHV QAKVCACLPA 

       490        500        510        520        530        540 
MHANRATDLQ KILLHCKNLT RALEISKSSL DIKDIITTFT ESFPQDFFCV CSVEEANNLV 

       550        560        570        580        590        600 
STVQDLKRVV SNNMALTSEQ DARFKALMLS VLNNTDPPAS LGPIYLETET RTPLLSSAIQ 

       610        620        630        640        650        660 
EAVKAIEKDT VETLSELISN IPSENAIETT FVPPVRTLLK NVTTLLTVIN ACVERAEIRT 

       670        680        690        700        710        720 
PEIDSSQQQL SYIGRELSKI IDETWPERAF REPVHVLDIF QKTSSHLNDL KKKMADSESL 

       730        740        750        760        770        780 
DKILSEINQT LKAIQDKAAS PALINTLSDY IKNATVLAQA SDPRLVEIQS QVTTLTTSTS 

       790        800        810        820        830        840 
YIESLLQKIN IRTLPEVIPQ LQAATKTEQG QLSLAAMNLS LIQITNSLIN EALSSIHARS 

       850        860        870        880        890        900 
HNHLSNTFFN SLNSLMGLAD IPGREDLIKT MESIMAVQEE LVDCDDMECV EKGLTTFKYI 

       910        920        930        940        950        960 
KSSIRQYKFD KSFKTKIYLI ITSEVRDLTK IKTDKQLEAW KQDVADFTPA SIDDLNLFLD 

       970        980        990       1000       1010       1020 
KAPTKTARSY ATRQLKHFRD DLIKEQEMET ETTPVPSTAE IERAIDLKIK ATWDKILTNL 

      1030       1040       1050       1060       1070       1080 
RDLTFHHIAP GDWQVLLTVF NDHKSALFTK MGGELLKALQ GLTAYVDSIL TPLLASQLPQ 

      1090       1100       1110       1120       1130       1140 
GQRYVAPNSD WVETFDQNVK YYLRTFHLPR VSEQLDDLER KTLLLTKLVK FTDLSQSLIG 

      1150       1160       1170       1180       1190       1200 
THLEKDWSIY QKLFNSLLTV YNDHLIKTKT EVHAFLDKIA SDPLLEPQAH PDLQKITQLF 

      1210       1220       1230       1240       1250       1260 
TEQEIIEINT LPDIFKESIK NNEKHYIASY QTEMKVFTSM VDAALAKKTQ STTEYNTHLL 

      1270       1280       1290       1300       1310       1320 
KIVNNMLVQA PPYAASHPIS SDAISYITSL VRDKHLLEKL SYAESLKNFN WLSRLITIIL 

      1330       1340       1350       1360       1370       1380 
TNCHPSHKQH LQTLLDEILS REQTLTPLVA LEDNANQSPT ERTLQAALTT LNVERVLGRA 

      1390       1400       1410       1420       1430       1440 
TTFQKWKSQL QELEEAVKTT TQVSLLIQTI SSLHDKTVTE MDPTILSSHS QALADKLKEL 

      1450       1460       1470       1480       1490       1500 
LALKPSLDET TMSLFHGMKA YAQFKHYFVQ HYVITQPKIF DAYPLSHHGT VSSSGGHQAT 

      1510       1520       1530       1540       1550       1560 
KFNPLMRLKA FSMVTDVKKM SVWREINTTV DPTGHTFIPA PPTPAMPPIH YNVLFSSFLQ 

      1570       1580       1590       1600       1610       1620 
AEAINLALNS NQPPTKKFGL LPGLMDARVG VQGAMLLDNQ WNDISTNSAK LLDHYVRSEL 

      1630       1640       1650       1660       1670       1680 
TPNSLTNSQF AAMTVFAHAM AMVTPHINST RATIFPSKAI VLNQLQFLKL CLTMWPKFSG 

      1690       1700       1710       1720       1730       1740 
GLLRAPSFER VVQLARATLP TLLLSAPRNT LNHFLANNYR PTDTLPNTEA LLFYPNQHPL 

      1750       1760       1770       1780       1790       1800 
VNLEKLLLTS SPFHALSTSV LNTRISMLVW GILSLSEAVL QQLWDSLYQE SATFTTYIDL 

      1810       1820       1830       1840       1850       1860 
LRHLSAMNHK NSTLTTSTSL PQNNGPVVYS YGHTAGTTVA TLEGSHPLDD GGQNIPMTLF 

      1870       1880       1890       1900       1910       1920 
EFVIFAIILK LKFHVFYTQE KALVNTQLGP LHLITHALDG TGDTEPFKTY ISIPPQKYNG 

      1930       1940       1950       1960       1970       1980 
LGNLQQFCSQ DEIQIFQRQH EWLVGVTKQT SFSNEDLFIV LASADNKVLS VHTFNPPINS 

      1990       2000       2010       2020       2030       2040 
LESETPEIVA APIQESWPKE ITTVSFWDKP ALEKSPQELI TEVSLVAEIF SGSAIFNTFP 

      2050       2060       2070       2080       2090       2100 
PSYKMVSHTP SLHVETHQLE NLSITEGTPP TSPPLPDSTT QDHMEEPDNK QAKPPYQMTS 

      2110       2120       2130       2140       2150       2160 
PMKENTSTSG RPARSPSPSP PVLTPIKPII PIPQATPTMP ILSPFTPRLL PAAVKKHQNG 

      2170       2180       2190       2200       2210       2220 
AVWGHSGSLP PTHIQSSTPG PAQNTRDSGR RQIVSPVITI LPGTKAGADS AGQNTSHKDI 

      2230       2240       2250       2260       2270       2280 
SAYSPPPASK KTDRPSDTHV TAPLFSKSKL VTPRPAAKTD TGTFGPLLGH EKPPVTDLTA 

      2290       2300       2310       2320       2330       2340 
PVEPGHPSKV SPIIHLKPSN TGDRDPHPIS DDEDSKQPPV PDTSRDKAQS RWKTPKQRPQ 

      2350       2360       2370       2380       2390       2400 
NIFPPPKHED DVPVTAPQPQ GRKILVGGRQ LPSLVYNPPT LRDIKTGMSD DKNPEPCVKE 

      2410       2420       2430       2440       2450 
NPPGVTHDPP LRIQHMEQTV NSSKYNVLLF IEKIIKSVHD HSSYMLSTLK RIKQLYI 

« Hide

References

« Hide 'large scale' references
[1]"Complete sequence and genomic analysis of murine gammaherpesvirus 68."
Virgin H.W. IV, Latreille P., Wamsley P., Hallsworth K., Weck K.E., Dal Canto A.J., Speck S.H.
J. Virol. 71:5894-5904(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: G2.4 and WUMS.
[2]"A functional ubiquitin-specific protease embedded in the large tegument protein (ORF64) of murine gammaherpesvirus 68 is active during the course of infection."
Gredmark S., Schlieker C., Quesada V., Spooner E., Ploegh H.L.
J. Virol. 81:10300-10309(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U97553 Genomic DNA. Translation: AAB66417.1.
AF105037 Genomic DNA. Translation: AAF19328.1.
RefSeqNP_044902.1. NC_001826.2.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-47224N.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID1497174.

Family and domain databases

InterProIPR006928. Pept_C76_UL36-USP.
[Graphical view]
PfamPF04843. Herpes_teg_N. 1 hit.
[Graphical view]
PROSITEPS51521. HTUSP. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameDEN_MHV68
AccessionPrimary (citable) accession number: O41965
Entry history
Integrated into UniProtKB/Swiss-Prot: April 5, 2011
Last sequence update: January 1, 1998
Last modified: May 14, 2014
This is version 38 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries