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P03186 (DEN_EBVB9) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 69. 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):
Large tegument protein
Short name=LTP
Gene names
ORF Names:BPLF1
OrganismEpstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) [Reference proteome]
Taxonomic identifier10377 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeLymphocryptovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length3149 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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. Ref.3 Ref.4

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.

Subcellular location

Virion tegument. Host cytoplasm. Host nucleus By similarity Ref.2.

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 – 31493149Deneddylase
PRO_0000116038

Regions

Domain41 – 258218Peptidase C76
Repeat335 – 33951
Repeat340 – 34452
Repeat345 – 34953
Repeat350 – 35454
Repeat355 – 35955
Repeat360 – 36456
Repeat365 – 36957
Repeat370 – 37458
Region1 – 269269Deubiquitination activity By similarity
Region335 – 374408 X 5 AA repeats of P-A-S-A-A
Coiled coil1100 – 113031 Potential
Coiled coil1394 – 144653 Potential
Coiled coil1706 – 173530 Potential
Coiled coil1875 – 190430 Potential
Motif412 – 4187Nuclear localization signal By similarity
Compositional bias336 – 37641Ala-rich
Compositional bias527 – 5304Poly-Ala
Compositional bias532 – 5354Poly-Thr
Compositional bias1356 – 13594Poly-Asn
Compositional bias1475 – 14839Poly-Ala
Compositional bias1558 – 15636Poly-Gly
Compositional bias1656 – 16594Poly-Pro
Compositional bias1830 – 18334Poly-Ala
Compositional bias2085 – 20884Poly-Arg
Compositional bias2100 – 21034Poly-Ala
Compositional bias2845 – 2948104Ala-rich

Sites

Active site611 By similarity
Active site1931 By similarity
Active site1951 By similarity
Site481Important for catalytic activity By similarity

Experimental info

Mutagenesis611C → A: Complete loss of ubiquitin and NEDD8 binding. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P03186 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 3DD0C576587313D8

FASTA3,149337,959
        10         20         30         40         50         60 
MSNGDWGQSQ RTRGTGPVRG IRTMDVNAPG GGSGGSALRI LGTASCNQAH CKFGRFAGIQ 

        70         80         90        100        110        120 
CVSNCVLYLV KSFLAGRPLT SRPELDEVLD EGARLDALMR QSGILKGHEM AQLTDVPSSV 

       130        140        150        160        170        180 
VLRGGGRVHI YRSAEIFGLV LFPAQIANSA VVQSLAEVLH GSYNGVAQFI LYICDIYAGA 

       190        200        210        220        230        240 
IIIETDGSFY LFDPHCQKDA APGTPAHVRV STYAHDILQY VGAPGAQYTC VHLYFLPEAF 

       250        260        270        280        290        300 
ETEDPRIFML EHYGVYDFYE ANGSGFDLVG PELVSSDGEA AGTPGADSSP PVMLPFERRI 

       310        320        330        340        350        360 
IPYNLRPLPS RSFTSDSFPA ARYSPAKTNS PPSSPASAAP ASAAPASAAP ASAAPASAAP 

       370        380        390        400        410        420 
ASAAPASAAP ASAAPASSPP LFIPIPGLGH TPGVPAPSTP PRASSGAAPQ TPKRKKGLGK 

       430        440        450        460        470        480 
DSPHKKPTSG RRLPLSSTTD TEDDQLPRTH VPPHRPPSAA RLPPPVIPIP HQSPPASPTP 

       490        500        510        520        530        540 
HPAPVSTIAP SVTPSPRLPL QIPIPLPQAA PSNPKIPLTT PSPSPTAAAA PTTTTLSPPP 

       550        560        570        580        590        600 
TQQQPPQSAA PAPSPLLPQQ QPTPSAAPAP SPLLPQQQPP PSAARAPSPL PPQQQPLPSA 

       610        620        630        640        650        660 
TPAPPPAQQL PPSATTLEPE KNHPPAADRA GTEISPSPPF GQQPSFGDDA SGGSGLVRYL 

       670        680        690        700        710        720 
SDLEEPFLSM SDSEEAESDL ASDIPTTEDE DMFEDEVFSN SLESGSSAPT SPITLDTARS 

       730        740        750        760        770        780 
QYYQTTFDIE TPEMDFVPLE SNIARIAGHT YQEQAIVYDP ASNREVPEAD ALSMIDYLLV 

       790        800        810        820        830        840 
TVVLEQGLIR SRDRSSVLNL LEFLKDWSGH LQVPTLDLEQ LLTSELNIQN LANMLSENKG 

       850        860        870        880        890        900 
RAGEFHKHLA AKLEACLPSL ATKDAVRVDA GAKMLAEIPQ LAESDDGKFD LEAARRRLTD 

       910        920        930        940        950        960 
LLSGGDQEAG EGGGEPEDNS IYRGPHVDVP LVLDDESWKR LLSLAEAART AVARQQAGVD 

       970        980        990       1000       1010       1020 
EEDVRFLALL TAIEYGAPPA ASVPPFVHNV AVRSKNAALH VRRCTADIRD KVASAASDYL 

      1030       1040       1050       1060       1070       1080 
SYLEDPSLPT VMDFDDLLTH LRHTCQIIAS LPLLNIRYTS IEWDYRELLY LGTALSDMSG 

      1090       1100       1110       1120       1130       1140 
IPWPLERVEE DDPSIAPLPE FETVAKKQKE LETTRENEKR LRTILDDIEA MLGLAGVASA 

      1150       1160       1170       1180       1190       1200 
PGAPISPASP SATPANHDNP EATPPLADTA ALTIPVIEKY IANAGSIVGA AKNPTYIRLR 

      1210       1220       1230       1240       1250       1260 
DTIQQIVRSK KYLMNILKSI TFYTIDNYIA SFEESIDHLY RDLPVLDPEV QDGIDRILDP 

      1270       1280       1290       1300       1310       1320 
MVSEALHTFE MGNRLTLEPA RLVALQNFAT HSTLKETAAA VNLLPGLLAV YDATITGQAP 

      1330       1340       1350       1360       1370       1380 
EDALRLLSGL QNQLSQTLIP GKLKKRFLSY LQKLKNNNND QLRQKEVQAW RLEAEGFKPA 

      1390       1400       1410       1420       1430       1440 
TEEQLEAFLD TAPNKELKRQ YEKKLRQLME TGRKEKEKLR EQEDKERQER RAREANEAWA 

      1450       1460       1470       1480       1490       1500 
RIRKALGARP EPAPTSPDDW NTLLASLLPD NTDSAAAAAA AVARNTDILD SLTQILAAML 

      1510       1520       1530       1540       1550       1560 
LGITRVRRER LRSLLVDDGG AAERMEAAEP GWFTDIETGP LARLDAWPAT PAATAKEGGG 

      1570       1580       1590       1600       1610       1620 
GRGAEEAAGA LFRARTAADA IRSALAQTRQ ALQSPDMKSA VVNTDLEAPY AEYERGLAGL 

      1630       1640       1650       1660       1670       1680 
LEKRRAAEAA LTAIVSEYVD RTLPEATNDP GQANLPPPPT IPQATAPPRL ASDSALWPKK 

      1690       1700       1710       1720       1730       1740 
PQLLTRRERD DLLQATGDFF SELLTEAEAA EVRALEEQVR ESQTLMAKAH EMAASTRRGF 

      1750       1760       1770       1780       1790       1800 
HTALEAVLSR SRDEAPDDEL RSLLPSPPKA PVQAPLEAAL ARAAAGNGSW PYRKSLAAAK 

      1810       1820       1830       1840       1850       1860 
WIRGICEAVR GLSEGALALA GGAGAWLNLA AAADGEIHEL TRLLEVEGMA QNSMDGMEEL 

      1870       1880       1890       1900       1910       1920 
RLALATLDPK RVAGGKETVA DWKRRLSRLE AIIQEAQEES QLQGTLQDLV TQARGHTDPR 

      1930       1940       1950       1960       1970       1980 
QLKIVVEAAR GLALGASAGS QYALLKDKLL RYASAKQSFL AFYETAQPTV FVKHPLTNNL 

      1990       2000       2010       2020       2030       2040 
PLLITISAPP TGWGNGAPTR RAQFLAAAGP AKYAGTLWLE TESPCDPLNP AYVSADTQEP 

      2050       2060       2070       2080       2090       2100 
LNYIPVYHNF LEYVMPTVLE NPEAFSLTPA GRPQAIGPPQ DDQERRRRTL ASVASARLSA 

      2110       2120       2130       2140       2150       2160 
AAADSYWDTW PDVESNAGEL LREYVSAPKA LMEDLADNPI VAMTLLAHAS LIASRNHPPY 

      2170       2180       2190       2200       2210       2220 
PAPATDREVI LLEQREMMAL LVGTHPAYAA AFLGAPSFYA GLGLVSALAR DGGLGDLLSD 

      2230       2240       2250       2260       2270       2280 
SVLTYRLVRS PASGRGGMPS TTRGSNDGED ARRLTRHRIA GPPTGFIFFQ DAWEEMDTRA 

      2290       2300       2310       2320       2330       2340 
ALWPHPEFLG LVHNQSTARA RACMLLLARR CFAPEALQQL WHSLRPLEGP VAFQDYLRDF 

      2350       2360       2370       2380       2390       2400 
VKQAYTRGEE LPRAEGLEVP RETPSSYGTV TGRALRNLMP YGTPITGPKR GSGDTIPVSV 

      2410       2420       2430       2440       2450       2460 
FEAAVAAAFL GRPLTLFVSS QYLFNLKTLG QVRVVAPLLY CDGHSEPFRS LVETISLNFL 

      2470       2480       2490       2500       2510       2520 
QDLDGYSESF EPEMSIFARQ AVWLRELLTE ARAAKPKEAR PPTVAILANR KNIIWKCFTY 

      2530       2540       2550       2560       2570       2580 
RHNLPDVQFY FNAAGASRWP TDVLNPSFYE HEDPPLPVGY QLPPNPRNVQ ELFSGFPPRV 

      2590       2600       2610       2620       2630       2640 
GHGLVSGDGF QSADNTPASS DRLQQLGGGE TDQGEKGSTT AESEASGPPS PQSPLLEKVA 

      2650       2660       2670       2680       2690       2700 
PGRPRDWLSP TSSPRDVTVT PGLAAPITLP GPRLMARPYF GAETRASESP DRSPGSSPRP 

      2710       2720       2730       2740       2750       2760 
WPKDSLELLP QPAPQQPPSS PWASEQGPIV YTLSPHSTPS TASGSQKKHT IQIPGLVPSQ 

      2770       2780       2790       2800       2810       2820 
KPSYPPSAPY KPGQSTGGIA PTPSAASLTT FGLQPQDTQA SSQDPPYGHS IMQREKKQQG 

      2830       2840       2850       2860       2870       2880 
GREEAAEIRP SATRLPTAVG LRPRAPVVAA GAAASATPAF DPGEAPSGFP IPQAPALGSG 

      2890       2900       2910       2920       2930       2940 
LAAPAHTPVG ALAPRPQKTQ AQRPQDAAAL PTPTIKAVGA RPVPKATGAL AAGARPRGQP 

      2950       2960       2970       2980       2990       3000 
TAAPPSAASP PRVSLPVRSR QQQSPAIPLP PMHSGSEPGA RPEVRLSQYR HAGPQTYTVR 

      3010       3020       3030       3040       3050       3060 
KEAPPSAASQ LPKMPKCKDS MYYPPSGSAR YPAPFQALSF SQSVASPAPS SDQTTLLWNT 

      3070       3080       3090       3100       3110       3120 
PSVVTQFLSI EDIIREVVTG GSTSGDLVVP SGSPSSLSTA APEQDLRYSL TLSQASRVLS 

      3130       3140 
RFVSQLRRKL ERSTHRLIAD LERLKFLYL 

« Hide

References

« Hide 'large scale' references
[1]"DNA sequence and expression of the B95-8 Epstein-Barr virus genome."
Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J., Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C., Tuffnell P.S., Barrell B.G.
Nature 310:207-211(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"Proteins of purified Epstein-Barr virus."
Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E., Illanes D., Sarracino D., Kieff E.
Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[3]"The EBV deubiquitinating enzyme, BPLF1, reduces EBV ribonucleotide reductase activity."
Whitehurst C.B., Ning S., Bentz G.L., Dufour F., Gershburg E., Shackelford J., Langelier Y., Pagano J.S.
J. Virol. 83:4345-4353(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"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, MUTAGENESIS OF CYS-61.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V01555 Genomic DNA. Translation: CAA24839.1.
AJ507799 Genomic DNA. Translation: CAD53402.1.
PIRQQBE8. G93065.
RefSeqYP_401652.1. NC_007605.1.

3D structure databases

ProteinModelPortalP03186.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid971768. 7 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID3783726.

Phylogenomic databases

ProtClustDBCLSP2512080.

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_EBVB9
AccessionPrimary (citable) accession number: P03186
Secondary accession number(s): Q777G4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: February 19, 2014
This is version 69 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