P03186 (DEN_EBVB9) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Deneddylase BPLF1
EC=3.4.19.12
EC=3.4.22.-

Alternative name(s):
Large tegument protein
Short name=LTP

Gene names

ORF Names:

BPLF1

Organism

Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) [Reference proteome]

Taxonomic identifier

10377 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Gammaherpesvirinae › Lymphocryptovirus › Epstein-Barr virus (strain GD1)

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	3149 AA.
Sequence status	Complete.
Protein existence	Evidence 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 large tegument protein family. Contains 1 peptidase C76 domain.

Ontologies

Keywords
Biological process	Host-virus interaction Modulation of host ubiquitin pathway by viral deubiquitinase Modulation of host ubiquitin pathway by virus Ubl conjugation pathway
Cellular component	Host cytoplasm Host nucleus Virion Virion tegument
Domain	Coiled coil Repeat
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	modulation by virus of host protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell viral tegument Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 3149	3149	Deneddylase BPLF1		PRO_0000116038
Regions
	Domain	41 – 258	218	Peptidase C76
	Repeat	335 – 339	5	1
	Repeat	340 – 344	5	2
	Repeat	345 – 349	5	3
	Repeat	350 – 354	5	4
	Repeat	355 – 359	5	5
	Repeat	360 – 364	5	6
	Repeat	365 – 369	5	7
	Repeat	370 – 374	5	8
	Region	1 – 269	269	Deubiquitination activity By similarity
	Region	335 – 374	40	8 X 5 AA repeats of P-A-S-A-A
	Coiled coil	1100 – 1130	31	Potential
	Coiled coil	1394 – 1446	53	Potential
	Coiled coil	1706 – 1735	30	Potential
	Coiled coil	1875 – 1904	30	Potential
	Motif	412 – 418	7	Nuclear localization signal By similarity
	Compositional bias	336 – 376	41	Ala-rich
	Compositional bias	527 – 530	4	Poly-Ala
	Compositional bias	532 – 535	4	Poly-Thr
	Compositional bias	1356 – 1359	4	Poly-Asn
	Compositional bias	1475 – 1483	9	Poly-Ala
	Compositional bias	1558 – 1563	6	Poly-Gly
	Compositional bias	1656 – 1659	4	Poly-Pro
	Compositional bias	1830 – 1833	4	Poly-Ala
	Compositional bias	2085 – 2088	4	Poly-Arg
	Compositional bias	2100 – 2103	4	Poly-Ala
	Compositional bias	2845 – 2948	104	Ala-rich
Sites
	Active site	61	1	By similarity
	Active site	193	1	By similarity
	Active site	195	1	By similarity
	Site	48	1	Important for catalytic activity By similarity
Experimental info
	Mutagenesis	61	1	C → A: Complete loss of ubiquitin and NEDD8 binding. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P03186 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 3DD0C576587313D8	FASTA	3,149	337,959
	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

References

	« Hide 'large scale' referencesShow '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.
PIR	QQBE8. G93065.
RefSeq	YP_401652.1. NC_007605.1.
3D structure databases
ProteinModelPortal	P03186.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	3783726.
Phylogenomic databases
ProtClustDB	CLSP2512080.
Family and domain databases
InterPro	IPR006928. Pept_C76_UL36-USP. [Graphical view]
Pfam	PF04843. Herpes_teg_N. 1 hit. [Graphical view]
PROSITE	PS51521. HTUSP. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

DEN_EBVB9

Accession

Primary (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:	April 3, 2013
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program