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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 activity By similarity
Active sitei61 – 611 By similarity
Active sitei193 – 1931 By similarity
Active sitei195 – 1951 By similarity

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. Host cytoplasm. Host nucleus By similarity 1 Publication

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-SubCell
  2. host cell nucleus Source: UniProtKB-SubCell
  3. viral tegument Source: UniProtKB-SubCell
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 – 31493149Deneddylase
PRO_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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 258218Peptidase C76
Add
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 activity By similarity
Add
BLAST
Regioni335 – 374408 X 5 AA repeats of P-A-S-A-A
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1100 – 113031 Reviewed prediction
Add
BLAST
Coiled coili1394 – 144653 Reviewed prediction
Add
BLAST
Coiled coili1706 – 173530 Reviewed prediction
Add
BLAST
Coiled coili1875 – 190430 Reviewed prediction
Add
BLAST

Motif

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi336 – 37641Ala-rich
Add
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-rich
Add
BLAST

Sequence similaritiesi

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

MSNGDWGQSQ RTRGTGPVRG IRTMDVNAPG GGSGGSALRI LGTASCNQAH     50
CKFGRFAGIQ CVSNCVLYLV KSFLAGRPLT SRPELDEVLD EGARLDALMR 100
QSGILKGHEM AQLTDVPSSV VLRGGGRVHI YRSAEIFGLV LFPAQIANSA 150
VVQSLAEVLH GSYNGVAQFI LYICDIYAGA IIIETDGSFY LFDPHCQKDA 200
APGTPAHVRV STYAHDILQY VGAPGAQYTC VHLYFLPEAF ETEDPRIFML 250
EHYGVYDFYE ANGSGFDLVG PELVSSDGEA AGTPGADSSP PVMLPFERRI 300
IPYNLRPLPS RSFTSDSFPA ARYSPAKTNS PPSSPASAAP ASAAPASAAP 350
ASAAPASAAP ASAAPASAAP ASAAPASSPP LFIPIPGLGH TPGVPAPSTP 400
PRASSGAAPQ TPKRKKGLGK DSPHKKPTSG RRLPLSSTTD TEDDQLPRTH 450
VPPHRPPSAA RLPPPVIPIP HQSPPASPTP HPAPVSTIAP SVTPSPRLPL 500
QIPIPLPQAA PSNPKIPLTT PSPSPTAAAA PTTTTLSPPP TQQQPPQSAA 550
PAPSPLLPQQ QPTPSAAPAP SPLLPQQQPP PSAARAPSPL PPQQQPLPSA 600
TPAPPPAQQL PPSATTLEPE KNHPPAADRA GTEISPSPPF GQQPSFGDDA 650
SGGSGLVRYL SDLEEPFLSM SDSEEAESDL ASDIPTTEDE DMFEDEVFSN 700
SLESGSSAPT SPITLDTARS QYYQTTFDIE TPEMDFVPLE SNIARIAGHT 750
YQEQAIVYDP ASNREVPEAD ALSMIDYLLV TVVLEQGLIR SRDRSSVLNL 800
LEFLKDWSGH LQVPTLDLEQ LLTSELNIQN LANMLSENKG RAGEFHKHLA 850
AKLEACLPSL ATKDAVRVDA GAKMLAEIPQ LAESDDGKFD LEAARRRLTD 900
LLSGGDQEAG EGGGEPEDNS IYRGPHVDVP LVLDDESWKR LLSLAEAART 950
AVARQQAGVD EEDVRFLALL TAIEYGAPPA ASVPPFVHNV AVRSKNAALH 1000
VRRCTADIRD KVASAASDYL SYLEDPSLPT VMDFDDLLTH LRHTCQIIAS 1050
LPLLNIRYTS IEWDYRELLY LGTALSDMSG IPWPLERVEE DDPSIAPLPE 1100
FETVAKKQKE LETTRENEKR LRTILDDIEA MLGLAGVASA PGAPISPASP 1150
SATPANHDNP EATPPLADTA ALTIPVIEKY IANAGSIVGA AKNPTYIRLR 1200
DTIQQIVRSK KYLMNILKSI TFYTIDNYIA SFEESIDHLY RDLPVLDPEV 1250
QDGIDRILDP MVSEALHTFE MGNRLTLEPA RLVALQNFAT HSTLKETAAA 1300
VNLLPGLLAV YDATITGQAP EDALRLLSGL QNQLSQTLIP GKLKKRFLSY 1350
LQKLKNNNND QLRQKEVQAW RLEAEGFKPA TEEQLEAFLD TAPNKELKRQ 1400
YEKKLRQLME TGRKEKEKLR EQEDKERQER RAREANEAWA RIRKALGARP 1450
EPAPTSPDDW NTLLASLLPD NTDSAAAAAA AVARNTDILD SLTQILAAML 1500
LGITRVRRER LRSLLVDDGG AAERMEAAEP GWFTDIETGP LARLDAWPAT 1550
PAATAKEGGG GRGAEEAAGA LFRARTAADA IRSALAQTRQ ALQSPDMKSA 1600
VVNTDLEAPY AEYERGLAGL LEKRRAAEAA LTAIVSEYVD RTLPEATNDP 1650
GQANLPPPPT IPQATAPPRL ASDSALWPKK PQLLTRRERD DLLQATGDFF 1700
SELLTEAEAA EVRALEEQVR ESQTLMAKAH EMAASTRRGF HTALEAVLSR 1750
SRDEAPDDEL RSLLPSPPKA PVQAPLEAAL ARAAAGNGSW PYRKSLAAAK 1800
WIRGICEAVR GLSEGALALA GGAGAWLNLA AAADGEIHEL TRLLEVEGMA 1850
QNSMDGMEEL RLALATLDPK RVAGGKETVA DWKRRLSRLE AIIQEAQEES 1900
QLQGTLQDLV TQARGHTDPR QLKIVVEAAR GLALGASAGS QYALLKDKLL 1950
RYASAKQSFL AFYETAQPTV FVKHPLTNNL PLLITISAPP TGWGNGAPTR 2000
RAQFLAAAGP AKYAGTLWLE TESPCDPLNP AYVSADTQEP LNYIPVYHNF 2050
LEYVMPTVLE NPEAFSLTPA GRPQAIGPPQ DDQERRRRTL ASVASARLSA 2100
AAADSYWDTW PDVESNAGEL LREYVSAPKA LMEDLADNPI VAMTLLAHAS 2150
LIASRNHPPY PAPATDREVI LLEQREMMAL LVGTHPAYAA AFLGAPSFYA 2200
GLGLVSALAR DGGLGDLLSD SVLTYRLVRS PASGRGGMPS TTRGSNDGED 2250
ARRLTRHRIA GPPTGFIFFQ DAWEEMDTRA ALWPHPEFLG LVHNQSTARA 2300
RACMLLLARR CFAPEALQQL WHSLRPLEGP VAFQDYLRDF VKQAYTRGEE 2350
LPRAEGLEVP RETPSSYGTV TGRALRNLMP YGTPITGPKR GSGDTIPVSV 2400
FEAAVAAAFL GRPLTLFVSS QYLFNLKTLG QVRVVAPLLY CDGHSEPFRS 2450
LVETISLNFL QDLDGYSESF EPEMSIFARQ AVWLRELLTE ARAAKPKEAR 2500
PPTVAILANR KNIIWKCFTY RHNLPDVQFY FNAAGASRWP TDVLNPSFYE 2550
HEDPPLPVGY QLPPNPRNVQ ELFSGFPPRV GHGLVSGDGF QSADNTPASS 2600
DRLQQLGGGE TDQGEKGSTT AESEASGPPS PQSPLLEKVA PGRPRDWLSP 2650
TSSPRDVTVT PGLAAPITLP GPRLMARPYF GAETRASESP DRSPGSSPRP 2700
WPKDSLELLP QPAPQQPPSS PWASEQGPIV YTLSPHSTPS TASGSQKKHT 2750
IQIPGLVPSQ KPSYPPSAPY KPGQSTGGIA PTPSAASLTT FGLQPQDTQA 2800
SSQDPPYGHS IMQREKKQQG GREEAAEIRP SATRLPTAVG LRPRAPVVAA 2850
GAAASATPAF DPGEAPSGFP IPQAPALGSG LAAPAHTPVG ALAPRPQKTQ 2900
AQRPQDAAAL PTPTIKAVGA RPVPKATGAL AAGARPRGQP TAAPPSAASP 2950
PRVSLPVRSR QQQSPAIPLP PMHSGSEPGA RPEVRLSQYR HAGPQTYTVR 3000
KEAPPSAASQ LPKMPKCKDS MYYPPSGSAR YPAPFQALSF SQSVASPAPS 3050
SDQTTLLWNT PSVVTQFLSI EDIIREVVTG GSTSGDLVVP SGSPSSLSTA 3100
APEQDLRYSL TLSQASRVLS RFVSQLRRKL ERSTHRLIAD LERLKFLYL 3149
Length:3,149
Mass (Da):337,959
Last modified:July 21, 1986 - v1
Checksum:i3DD0C576587313D8
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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: July 9, 2014
This is version 71 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

Similar proteinsi