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A8E1C4 (DEN_MUHVK) Reviewed, UniProtKB/Swiss-Prot

Last modified June 26, 2013. Version 14. 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.-
Gene names
Name:M48
OrganismMurid herpesvirus 1 (strain K181) (MuHV-1) (Mouse cytomegalovirus)
Taxonomic identifier69156 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeBetaherpesvirinaeMuromegalovirus
Virus hostMus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length2147 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 CDKN1A/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.3

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.

Sequence similarities

Belongs to the herpesviridae deneddylase family.

Contains 1 peptidase C76 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 21472147Deneddylase
PRO_0000396954

Regions

Domain3 – 223221Peptidase C76
Coiled coil649 – 68638 Potential
Coiled coil937 – 96428 Potential
Coiled coil1184 – 121936 Potential
Motif296 – 3038Nuclear localization signal By similarity
Compositional bias233 – 2386Poly-Gly
Compositional bias465 – 4684Poly-Thr
Compositional bias536 – 5394Poly-Ala
Compositional bias687 – 6904Poly-Ser
Compositional bias691 – 6944Poly-Pro
Compositional bias1567 – 15704Poly-Ser
Compositional bias2046 – 20494Poly-Ser

Sites

Active site231 By similarity
Active site1561 By similarity
Active site1581 By similarity
Site101Important for catalytic activity By similarity

Sequences

Sequence LengthMass (Da)Tools
A8E1C4 [UniParc].

Last modified November 13, 2007. Version 1.
Checksum: 4C5DB3F99EF1A63A

FASTA2,147238,457
        10         20         30         40         50         60 
MKIVRASRDQ SAPVYGPRAG SQCMSNCFTF LHTCYLMGID PVLDTTSLDA VLDSGARLDA 

        70         80         90        100        110        120 
IADEKVKRQA LTDHPYRLGT EIPTVIETPA GITGHALSRP FNGTAETQDL GGYKCLGILD 

       130        140        150        160        170        180 
FLTYARGKPL PVYIIVTVGV HTRGVIVARG ATYVFDPHTT DLSAEAAVYV CDDFTEAISA 

       190        200        210        220        230        240 
LSFFGAMIGD FYYDAVLVYF TRCRTTLISP SELLVQIMDQ YKDPDIDASV MSGSGGGGPS 

       250        260        270        280        290        300 
ISSSAASASA SVSPLPSGAA SDGVTNGAGA QTSSKSGKKR RAPDVPPQQK GTAKTLRRSR 

       310        320        330        340        350        360 
RPIRLPERLS EVIVEDVQTI EHFRTATQSL PVKPPQEWTM YCGEEPFYRQ YFVDVGRQLL 

       370        380        390        400        410        420 
AHAIDTYVSL DKTTDESAVQ RFESLMGLSD ELDAVIAAAR ATELSAPPLY KTYLSQRVSA 

       430        440        450        460        470        480 
SAVTRTDRLL ASKILALFEE GSATDFETVS SWLRELLQQL PVENTTTTEA KIAAFVAQHP 

       490        500        510        520        530        540 
IPGERAFVCL RNSQVKSLGE LLSVKRETLK VKYMENDATY RKILDAISKL GLASNAAAAI 

       550        560        570        580        590        600 
QSADTSHLDS EQLASLAQAA EAYAQSAYES CQAKMTELLS TNHNRILTGS LPDSDIAAVL 

       610        620        630        640        650        660 
AAFKAVSENV RALREVELLK SQVHVQLAQL TEDLLYLQTA EVKLEVTPSA EIKKLRAEYE 

       670        680        690        700        710        720 
TARKQISDEE MRIKELIENM EDMITDSSSS PPPPEMLDML RTQIEEVESM TVDEQDARRA 

       730        740        750        760        770        780 
DKVLGKLSTL DEAEAKATEF AQSLSTVNIP SLNEIKGVKM LKSVLETNAD LRRAYVQAVT 

       790        800        810        820        830        840 
GMLENALKQL AEGNLPSDDM MSRITALAEQ LPTGRQVRAD LLDSTDIVSQ MSRRLRYAAN 

       850        860        870        880        890        900 
QKNSTQSLED VLNFFSENDD MIRKLLKTSW GKPVATVYRR VQVEYDRKME ELRESEWLKR 

       910        920        930        940        950        960 
VKETDIDSPQ TLERLLKTAP NETILAKHAP DMHARLKKRM QSEAEKRTAD MKRLYEEMRK 

       970        980        990       1000       1010       1020 
KVDTDLKVVS DSFSSQTPSM FSSIDLKSCG TSLVRLTKED RKAAIATFNA NLTKSLNSLL 

      1030       1040       1050       1060       1070       1080 
ASLVTVETAT IAAILKGADP EATSSTGSAG GGADRQKHTS TLENNISTLL GWQQKVLLPE 

      1090       1100       1110       1120       1130       1140 
TERDLLTIAH LLTALTHMRK NWRNPAAAFS STPHTAAYRN FAELANEIES RRTETLARYK 

      1150       1160       1170       1180       1190       1200 
SKYAELNASI HDNTKANDVT IKPEDTFTAA FRDTVKAMAA PFSTELQARL QARENELKDE 

      1210       1220       1230       1240       1250       1260 
LSDLNVKLKT KLERYLAKRS SQDARWRDLI TQHRIRLPEG LDVDTNRLRT DTVVTLNGII 

      1270       1280       1290       1300       1310       1320 
RSAATTLPYI TAKRGLEWTT EFILAAIEEK KDADPGMFAQ LATLLDNSQA IARKIEEKIV 

      1330       1340       1350       1360       1370       1380 
YNTKVEAEML ETAPEHTRES LSNLQLMLGQ LEAKRVVGGE ARYKILSDAI LTKQNKLAFA 

      1390       1400       1410       1420       1430       1440 
EDLEKLSARY FELARDIRSS KYGLDFDAQL LKTSLLKSEI GQHKKDPPST GEEVGLPEES 

      1450       1460       1470       1480       1490       1500 
TTAAKISISS LLLGIAALEK YIVAHRTLLD NFVSSQPLIS QAENIPALVG GPGEDDKPGQ 

      1510       1520       1530       1540       1550       1560 
EPFDWTRIDL SRLSACDVST ALYRGTDVFG ERRVMTARGI QLYLYATHGN FVFEAFSHVR 

      1570       1580       1590       1600       1610       1620 
GTKGLLSSSS GGGNGSGASS RQKDQQNATV TRRYRSVTVL ASIAATLQTF WSEISRYDIR 

      1630       1640       1650       1660       1670       1680 
ELLVESGRDP ESAADQRDRR LNTVMNLKLF VYVMTVAWSE ATPPVEPGSP EATHALEVSL 

      1690       1700       1710       1720       1730       1740 
LDFSTLMAAL HPEYVYAITT QPVDATLRGL IARLDRRTVD AAMNTQENPP PYDMRELKAF 

      1750       1760       1770       1780       1790       1800 
CLDTKQWTQE DIRPQMWMSD LVKQICTSHP RNRDASTSTK LFLYMLATKV LPRDILRCLW 

      1810       1820       1830       1840       1850       1860 
VQFRPAYASS IASLEELVSA LCDSFFKIYG TTSETVSARL KTGEKVERQV VLRHKPTMSL 

      1870       1880       1890       1900       1910       1920 
LDEFSQQEAV LDYILGSYVF AIPMTVGIHV TNIVNGRYRL IVRHLENLPS DPDFVKVVRS 

      1930       1940       1950       1960       1970       1980 
RDLSFDRFGW SYTVQNPVER SWFSLQEDRL RHLLTNPPQQ DRTPLVVYDS NTNYAVNAMM 

      1990       2000       2010       2020       2030       2040 
PPLKAPPATS RVHLTVKNPF STMRMIPHED EGDDAATSET PFTSLPINID FLRRDPPRLK 

      2050       2060       2070       2080       2090       2100 
RASGDSSSSV PAEDRDPDAR PQDSVPDQSL SEPLFSQTKV SSIVPKDAVT TLSNESISQT 

      2110       2120       2130       2140 
FQIHPFRALS SAIMAAIEIL QETRLQLDTF ESDMCEAIRR IKILYLH 

« Hide

References

« Hide 'large scale' references
[1]"Laboratory strains of murine cytomegalovirus are genetically similar to but phenotypically distinct from wild strains of virus."
Smith L.M., McWhorter A.R., Masters L.L., Shellam G.R., Redwood A.J.
J. Virol. 82:6689-6696(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K181.
[2]"Use of a murine cytomegalovirus K181-derived bacterial artificial chromosome as a vaccine vector for immunocontraception."
Redwood A.J., Messerle M., Harvey N.L., Hardy C.M., Kozinowski U.H., Lawson M.A., Shellam G.R.
J. Virol. 79:2998-3008(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K181.
[3]"A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases."
Gastaldello S., Hildebrand S., Faridani O., Callegari S., Palmkvist M., Di Guglielmo C., Masucci M.G.
Nat. Cell Biol. 12:351-361(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AM886412 Genomic DNA. Translation: CAP08095.1.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActA8E1C4. 29 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

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_MUHVK
AccessionPrimary (citable) accession number: A8E1C4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: November 13, 2007
Last modified: June 26, 2013
This is version 14 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