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P03186

- DEN_EBVB9

UniProt

P03186 - DEN_EBVB9

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Protein

Deneddylase

Gene

BPLF1

Organism
Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

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).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei48 – 481Important for catalytic activityPROSITE-ProRule annotation
Active sitei61 – 611PROSITE-ProRule annotation
Active sitei193 – 1931PROSITE-ProRule annotation
Active sitei195 – 1951PROSITE-ProRule annotation

GO - Molecular functioni

  1. cysteine-type peptidase activity Source: UniProtKB-KW

GO - Biological processi

  1. modulation by virus of host protein ubiquitination Source: UniProtKB-KW
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:
Deneddylase (EC:3.4.19.12, EC:3.4.22.-)
Alternative name(s):
Large tegument protein
Short name:
LTP
Gene namesi
ORF Names:BPLF1
OrganismiEpstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4)
Taxonomic identifieri10377 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeLymphocryptovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000007640: Genome

Subcellular locationi

Virion tegument 1 Publication. Host cytoplasm 1 Publication. Host nucleus By similarity

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell nucleus Source: UniProtKB-KW
  3. viral tegument Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Virion, Virion tegument

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi61 – 611C → A: Complete loss of ubiquitin and NEDD8 binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 31493149DeneddylasePRO_0000116038Add
BLAST

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi971768. 10 interactions.

Structurei

3D structure databases

ProteinModelPortaliP03186.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 258218Peptidase C76PROSITE-ProRule annotationAdd
BLAST
Repeati335 – 33951
Repeati340 – 34452
Repeati345 – 34953
Repeati350 – 35454
Repeati355 – 35955
Repeati360 – 36456
Repeati365 – 36957
Repeati370 – 37458

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 269269Deubiquitination activityBy similarityAdd
BLAST
Regioni335 – 374408 X 5 AA repeats of P-A-S-A-AAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1100 – 113031Sequence AnalysisAdd
BLAST
Coiled coili1394 – 144653Sequence AnalysisAdd
BLAST
Coiled coili1706 – 173530Sequence AnalysisAdd
BLAST
Coiled coili1875 – 190430Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi412 – 4187Nuclear localization signalBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi336 – 37641Ala-richAdd
BLAST
Compositional biasi527 – 5304Poly-Ala
Compositional biasi532 – 5354Poly-Thr
Compositional biasi1356 – 13594Poly-Asn
Compositional biasi1475 – 14839Poly-Ala
Compositional biasi1558 – 15636Poly-Gly
Compositional biasi1656 – 16594Poly-Pro
Compositional biasi1830 – 18334Poly-Ala
Compositional biasi2085 – 20884Poly-Arg
Compositional biasi2100 – 21034Poly-Ala
Compositional biasi2845 – 2948104Ala-richAdd
BLAST

Sequence similaritiesi

Belongs to the herpesviridae deneddylase family.Curated
Contains 1 peptidase C76 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Family and domain databases

InterProiIPR006928. Pept_C76_UL36-USP.
[Graphical view]
PfamiPF04843. Herpes_teg_N. 1 hit.
[Graphical view]
PROSITEiPS51521. HTUSP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P03186-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSNGDWGQSQ RTRGTGPVRG IRTMDVNAPG GGSGGSALRI LGTASCNQAH
60 70 80 90 100
CKFGRFAGIQ CVSNCVLYLV KSFLAGRPLT SRPELDEVLD EGARLDALMR
110 120 130 140 150
QSGILKGHEM AQLTDVPSSV VLRGGGRVHI YRSAEIFGLV LFPAQIANSA
160 170 180 190 200
VVQSLAEVLH GSYNGVAQFI LYICDIYAGA IIIETDGSFY LFDPHCQKDA
210 220 230 240 250
APGTPAHVRV STYAHDILQY VGAPGAQYTC VHLYFLPEAF ETEDPRIFML
260 270 280 290 300
EHYGVYDFYE ANGSGFDLVG PELVSSDGEA AGTPGADSSP PVMLPFERRI
310 320 330 340 350
IPYNLRPLPS RSFTSDSFPA ARYSPAKTNS PPSSPASAAP ASAAPASAAP
360 370 380 390 400
ASAAPASAAP ASAAPASAAP ASAAPASSPP LFIPIPGLGH TPGVPAPSTP
410 420 430 440 450
PRASSGAAPQ TPKRKKGLGK DSPHKKPTSG RRLPLSSTTD TEDDQLPRTH
460 470 480 490 500
VPPHRPPSAA RLPPPVIPIP HQSPPASPTP HPAPVSTIAP SVTPSPRLPL
510 520 530 540 550
QIPIPLPQAA PSNPKIPLTT PSPSPTAAAA PTTTTLSPPP TQQQPPQSAA
560 570 580 590 600
PAPSPLLPQQ QPTPSAAPAP SPLLPQQQPP PSAARAPSPL PPQQQPLPSA
610 620 630 640 650
TPAPPPAQQL PPSATTLEPE KNHPPAADRA GTEISPSPPF GQQPSFGDDA
660 670 680 690 700
SGGSGLVRYL SDLEEPFLSM SDSEEAESDL ASDIPTTEDE DMFEDEVFSN
710 720 730 740 750
SLESGSSAPT SPITLDTARS QYYQTTFDIE TPEMDFVPLE SNIARIAGHT
760 770 780 790 800
YQEQAIVYDP ASNREVPEAD ALSMIDYLLV TVVLEQGLIR SRDRSSVLNL
810 820 830 840 850
LEFLKDWSGH LQVPTLDLEQ LLTSELNIQN LANMLSENKG RAGEFHKHLA
860 870 880 890 900
AKLEACLPSL ATKDAVRVDA GAKMLAEIPQ LAESDDGKFD LEAARRRLTD
910 920 930 940 950
LLSGGDQEAG EGGGEPEDNS IYRGPHVDVP LVLDDESWKR LLSLAEAART
960 970 980 990 1000
AVARQQAGVD EEDVRFLALL TAIEYGAPPA ASVPPFVHNV AVRSKNAALH
1010 1020 1030 1040 1050
VRRCTADIRD KVASAASDYL SYLEDPSLPT VMDFDDLLTH LRHTCQIIAS
1060 1070 1080 1090 1100
LPLLNIRYTS IEWDYRELLY LGTALSDMSG IPWPLERVEE DDPSIAPLPE
1110 1120 1130 1140 1150
FETVAKKQKE LETTRENEKR LRTILDDIEA MLGLAGVASA PGAPISPASP
1160 1170 1180 1190 1200
SATPANHDNP EATPPLADTA ALTIPVIEKY IANAGSIVGA AKNPTYIRLR
1210 1220 1230 1240 1250
DTIQQIVRSK KYLMNILKSI TFYTIDNYIA SFEESIDHLY RDLPVLDPEV
1260 1270 1280 1290 1300
QDGIDRILDP MVSEALHTFE MGNRLTLEPA RLVALQNFAT HSTLKETAAA
1310 1320 1330 1340 1350
VNLLPGLLAV YDATITGQAP EDALRLLSGL QNQLSQTLIP GKLKKRFLSY
1360 1370 1380 1390 1400
LQKLKNNNND QLRQKEVQAW RLEAEGFKPA TEEQLEAFLD TAPNKELKRQ
1410 1420 1430 1440 1450
YEKKLRQLME TGRKEKEKLR EQEDKERQER RAREANEAWA RIRKALGARP
1460 1470 1480 1490 1500
EPAPTSPDDW NTLLASLLPD NTDSAAAAAA AVARNTDILD SLTQILAAML
1510 1520 1530 1540 1550
LGITRVRRER LRSLLVDDGG AAERMEAAEP GWFTDIETGP LARLDAWPAT
1560 1570 1580 1590 1600
PAATAKEGGG GRGAEEAAGA LFRARTAADA IRSALAQTRQ ALQSPDMKSA
1610 1620 1630 1640 1650
VVNTDLEAPY AEYERGLAGL LEKRRAAEAA LTAIVSEYVD RTLPEATNDP
1660 1670 1680 1690 1700
GQANLPPPPT IPQATAPPRL ASDSALWPKK PQLLTRRERD DLLQATGDFF
1710 1720 1730 1740 1750
SELLTEAEAA EVRALEEQVR ESQTLMAKAH EMAASTRRGF HTALEAVLSR
1760 1770 1780 1790 1800
SRDEAPDDEL RSLLPSPPKA PVQAPLEAAL ARAAAGNGSW PYRKSLAAAK
1810 1820 1830 1840 1850
WIRGICEAVR GLSEGALALA GGAGAWLNLA AAADGEIHEL TRLLEVEGMA
1860 1870 1880 1890 1900
QNSMDGMEEL RLALATLDPK RVAGGKETVA DWKRRLSRLE AIIQEAQEES
1910 1920 1930 1940 1950
QLQGTLQDLV TQARGHTDPR QLKIVVEAAR GLALGASAGS QYALLKDKLL
1960 1970 1980 1990 2000
RYASAKQSFL AFYETAQPTV FVKHPLTNNL PLLITISAPP TGWGNGAPTR
2010 2020 2030 2040 2050
RAQFLAAAGP AKYAGTLWLE TESPCDPLNP AYVSADTQEP LNYIPVYHNF
2060 2070 2080 2090 2100
LEYVMPTVLE NPEAFSLTPA GRPQAIGPPQ DDQERRRRTL ASVASARLSA
2110 2120 2130 2140 2150
AAADSYWDTW PDVESNAGEL LREYVSAPKA LMEDLADNPI VAMTLLAHAS
2160 2170 2180 2190 2200
LIASRNHPPY PAPATDREVI LLEQREMMAL LVGTHPAYAA AFLGAPSFYA
2210 2220 2230 2240 2250
GLGLVSALAR DGGLGDLLSD SVLTYRLVRS PASGRGGMPS TTRGSNDGED
2260 2270 2280 2290 2300
ARRLTRHRIA GPPTGFIFFQ DAWEEMDTRA ALWPHPEFLG LVHNQSTARA
2310 2320 2330 2340 2350
RACMLLLARR CFAPEALQQL WHSLRPLEGP VAFQDYLRDF VKQAYTRGEE
2360 2370 2380 2390 2400
LPRAEGLEVP RETPSSYGTV TGRALRNLMP YGTPITGPKR GSGDTIPVSV
2410 2420 2430 2440 2450
FEAAVAAAFL GRPLTLFVSS QYLFNLKTLG QVRVVAPLLY CDGHSEPFRS
2460 2470 2480 2490 2500
LVETISLNFL QDLDGYSESF EPEMSIFARQ AVWLRELLTE ARAAKPKEAR
2510 2520 2530 2540 2550
PPTVAILANR KNIIWKCFTY RHNLPDVQFY FNAAGASRWP TDVLNPSFYE
2560 2570 2580 2590 2600
HEDPPLPVGY QLPPNPRNVQ ELFSGFPPRV GHGLVSGDGF QSADNTPASS
2610 2620 2630 2640 2650
DRLQQLGGGE TDQGEKGSTT AESEASGPPS PQSPLLEKVA PGRPRDWLSP
2660 2670 2680 2690 2700
TSSPRDVTVT PGLAAPITLP GPRLMARPYF GAETRASESP DRSPGSSPRP
2710 2720 2730 2740 2750
WPKDSLELLP QPAPQQPPSS PWASEQGPIV YTLSPHSTPS TASGSQKKHT
2760 2770 2780 2790 2800
IQIPGLVPSQ KPSYPPSAPY KPGQSTGGIA PTPSAASLTT FGLQPQDTQA
2810 2820 2830 2840 2850
SSQDPPYGHS IMQREKKQQG GREEAAEIRP SATRLPTAVG LRPRAPVVAA
2860 2870 2880 2890 2900
GAAASATPAF DPGEAPSGFP IPQAPALGSG LAAPAHTPVG ALAPRPQKTQ
2910 2920 2930 2940 2950
AQRPQDAAAL PTPTIKAVGA RPVPKATGAL AAGARPRGQP TAAPPSAASP
2960 2970 2980 2990 3000
PRVSLPVRSR QQQSPAIPLP PMHSGSEPGA RPEVRLSQYR HAGPQTYTVR
3010 3020 3030 3040 3050
KEAPPSAASQ LPKMPKCKDS MYYPPSGSAR YPAPFQALSF SQSVASPAPS
3060 3070 3080 3090 3100
SDQTTLLWNT PSVVTQFLSI EDIIREVVTG GSTSGDLVVP SGSPSSLSTA
3110 3120 3130 3140
APEQDLRYSL TLSQASRVLS RFVSQLRRKL ERSTHRLIAD LERLKFLYL
Length:3,149
Mass (Da):337,959
Last modified:July 21, 1986 - v1
Checksum:i3DD0C576587313D8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01555 Genomic DNA. Translation: CAA24839.1.
AJ507799 Genomic DNA. Translation: CAD53402.1.
PIRiG93065. QQBE8.
RefSeqiYP_401652.1. NC_007605.1.

Genome annotation databases

GeneIDi3783726.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01555 Genomic DNA. Translation: CAA24839.1 .
AJ507799 Genomic DNA. Translation: CAD53402.1 .
PIRi G93065. QQBE8.
RefSeqi YP_401652.1. NC_007605.1.

3D structure databases

ProteinModelPortali P03186.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 971768. 10 interactions.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 3783726.

Family and domain databases

InterProi IPR006928. Pept_C76_UL36-USP.
[Graphical view ]
Pfami PF04843. Herpes_teg_N. 1 hit.
[Graphical view ]
PROSITEi PS51521. HTUSP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. 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.

Entry informationi

Entry nameiDEN_EBVB9
AccessioniPrimary (citable) accession number: P03186
Secondary accession number(s): Q777G4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 29, 2014
This is version 73 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3