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P10220 (DEN_HHV11) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 75. 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):
Tegument protein VP1-2
Tegument protein VP1/2
Gene names
ORF Names:UL36
OrganismHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]
Taxonomic identifier10299 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length3164 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 By similarity. Ref.5 Ref.9 Ref.11 Ref.12

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. Interacts with UL37. Ref.6

Subcellular location

Virion tegument. Host cytoplasm. Host nucleus. Note: Tightly associated with the capsid. Ref.7 Ref.10

Post-translational modification

Proteolytically processed, possibly into several polypeptides. Enzymatic activity is only detectable following cleavage of the UL36 protein, which occurs late during viral replication.

Sequence similarities

Belongs to the herpesviridae deneddylase family.

Contains 1 peptidase C76 domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UL37P102212EBI-7694334,EBI-6880600

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 31643164Deneddylase
PRO_0000116035

Regions

Domain45 – 263219Peptidase C76
Repeat2911 – 291221
Repeat2913 – 291422
Repeat2915 – 291623
Repeat2917 – 291824
Repeat2919 – 292025
Repeat2921 – 292226
Repeat2923 – 292427
Repeat2925 – 292628
Repeat2927 – 292829
Repeat2929 – 2930210
Repeat2931 – 2932211
Repeat2933 – 2934212
Repeat2935 – 2936213
Repeat2937 – 2938214
Repeat2939 – 2940215
Repeat2941 – 2942216
Repeat2943 – 2944217
Repeat2945 – 2946218
Repeat2947 – 2948219
Repeat2949 – 2950220
Repeat2951 – 2952221
Repeat2953 – 2954222
Repeat2955 – 2956223
Repeat2957 – 2958224
Repeat2959 – 2960225
Repeat2961 – 2962226
Repeat2963 – 2964227
Repeat2965 – 2966228
Repeat2967 – 2968229
Repeat2969 – 2970230
Repeat2971 – 2972231
Repeat2973 – 2974232
Repeat2975 – 2976233
Repeat2977 – 2978234
Repeat2979 – 2980235
Region1 – 273273Deubiquitination activity By similarity
Region579 – 60931Interaction with UL37
Region2911 – 29807035 X 2 AA tandem repeats of P-Q
Coiled coil1020 – 105334 Potential
Coiled coil1317 – 135438 Potential
Coiled coil1741 – 176929 Potential
Motif426 – 4338Nuclear localization signal By similarity
Compositional bias307 – 494188Pro-rich
Compositional bias1161 – 1288128Ala-rich

Sites

Active site651 Ref.4
Active site1971 By similarity
Active site1991 By similarity
Site521Important for catalytic activity By similarity

Natural variations

Natural variant2341A → T in strain: Nonneuroinvasive mutant HF10.
Natural variant3071P → T in strain: Nonneuroinvasive mutant HF10.
Natural variant375 – 3795Missing in strain: Nonneuroinvasive mutant HF10.
Natural variant3921T → P in strain: Nonneuroinvasive mutant HF10.
Natural variant6201N → S in strain: Nonneuroinvasive mutant HF10.
Natural variant6241W → R in strain: Nonneuroinvasive mutant HF10.
Natural variant6711A → V in strain: Nonneuroinvasive mutant HF10.
Natural variant8851I → M in strain: Nonneuroinvasive mutant HF10.
Natural variant10231A → V in strain: Nonneuroinvasive mutant HF10.
Natural variant12441V → G in strain: Nonneuroinvasive mutant HF10.
Natural variant13731G → S in strain: Nonneuroinvasive mutant HF10.
Natural variant13891G → D in strain: Nonneuroinvasive mutant HF10.
Natural variant14191T → M in strain: Nonneuroinvasive mutant HF10.
Natural variant14701A → T in strain: Nonneuroinvasive mutant HF10.
Natural variant16041A → S in strain: Nonneuroinvasive mutant HF10.
Natural variant16051H → D in strain: 17 syn+ and Nonneuroinvasive mutant HF10.
Natural variant16421E → D in strain: Nonneuroinvasive mutant HF10.
Natural variant16951V → L in strain: Nonneuroinvasive mutant HF10.
Natural variant17291G → S in strain: Nonneuroinvasive mutant HF10.
Natural variant17771R → C in strain: Nonneuroinvasive mutant HF10.
Natural variant18881V → M in strain: Nonneuroinvasive mutant HF10.
Natural variant19731E → K in strain: Nonneuroinvasive mutant HF10.
Natural variant22671V → A in strain: Nonneuroinvasive mutant HF10.
Natural variant25401V → A in strain: Nonneuroinvasive mutant HF10.
Natural variant25451A → T in strain: Nonneuroinvasive mutant HF10.
Natural variant26461F → V in strain: Nonneuroinvasive mutant HF10.
Natural variant26661P → T in strain: Nonneuroinvasive mutant HF10.
Natural variant27481A → S in strain: Nonneuroinvasive mutant HF10.
Natural variant28561A → T in strain: Nonneuroinvasive mutant HF10.
Natural variant28751A → T in strain: Nonneuroinvasive mutant HF10.
Natural variant28941T → A in strain: Nonneuroinvasive mutant HF10.
Natural variant2973 – 29786Missing in strain: Nonneuroinvasive mutant HF10.
Natural variant30951V → A in strain: Nonneuroinvasive mutant HF10.

Experimental info

Mutagenesis651C → A: Complete loss of deubiquitination activity. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P10220 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: CC5D31FF4F9FE3F4

FASTA3,164335,862
        10         20         30         40         50         60 
MGGGNNTNPG GPVHKQAGSL ASRAHMIAGT PPHSTMERGG DRDIVVTGAR NQFAPDLEPG 

        70         80         90        100        110        120 
GSVSCMRSSL SFLSLIFDVG PRDVLSAEAI EGCLVEGGEW TRATAGPGPP RMCSIVELPN 

       130        140        150        160        170        180 
FLEYPGARGG LRCVFSRVYG EVGFFGEPAA GLLETQCPAH TFFAGPWALR PLSYTLLTIG 

       190        200        210        220        230        240 
PLGMGLFRDG DTAYLFDPHG LPEGTPAFIA KVRAGDMYPY LTYYTRDRPD VRWAGAMVFF 

       250        260        270        280        290        300 
VPSGPEPAAP ADLTAAALHL YGASETYLQD EAFSERRVAI THPLRGEIAG LGEPCVGVGP 

       310        320        330        340        350        360 
REGVGGPGPH PPTAAQSPPP TRARRDDRAS ETSRGTAGPS AKPEAKRPNR APDDVWAVAL 

       370        380        390        400        410        420 
KGTPPTDPPS ADPPSADPPS AIPPPPPSAP KTPAAEAAEE DDDDMRVLEM GVVPVGRHRA 

       430        440        450        460        470        480 
RYSAGLPKRR RPTWTPPSSV EDLTSGEKTK RSAPPAKTKK KSTPKGKTPV GAAVPASVPE 

       490        500        510        520        530        540 
PVLASAPPDP AGPPVAEAGE DDGPTVPASS QALEALKTRR SPEPPGADLA QLFEAHPNVA 

       550        560        570        580        590        600 
ATAVKFTACS AALAREVAAC SRLTISALRS PYPASPGLLE LCVIFFFERV LAFLIENGAR 

       610        620        630        640        650        660 
THTQAGVAGP AAALLEFTLN MLPWKTAVGD FLASTRLSLA DVAAHLPLVQ HVLDENSLIG 

       670        680        690        700        710        720 
RLALAKLILV ARDVIRETDA FYGELADLEL QLRAAPPANL YTRLGEWLLE RSQAHPDTLF 

       730        740        750        760        770        780 
APATPTHPEP LLYRVQALAK FARGEEIRVE AEDRQMREAL DALARGVDAV SQHAGPLGVM 

       790        800        810        820        830        840 
PAPAGAAPQG APRPPPLGPE AVQVRLEEVR TQARRAIEGA VKEYFYRGAV YSAKALQASD 

       850        860        870        880        890        900 
NNDRRFHVAS AAVVPVVQLL ESLPVFDQHT RDIAQRAAIP APPPIATSPT AILLRDLIQR 

       910        920        930        940        950        960 
GQTLDAPEDL AAWLSVLTDA ANQGLIERKP LDELARSIRD INDQQARRSS GLAELRRFDA 

       970        980        990       1000       1010       1020 
LDAALGQQLD SDAAFVPAPG ASPYPDDGGL SPEATRMAEE ALRQARAMDA AKLTAELAPD 

      1030       1040       1050       1060       1070       1080 
ARARLRERAR SLEAMLEGAR ERAKVARDAR EKFLHKLQGV LRPLPDFVGL KACPAVLATL 

      1090       1100       1110       1120       1130       1140 
RASLPAGWSD LPEAVRGAPP EVTAALRADM WGLLGQYRDA LEHPTPDTAT ALSGLHPSFV 

      1150       1160       1170       1180       1190       1200 
VVLKNLFADA PETPFLLQFF ADHAPIIAHA VSNAINAGSA AVATADPAST VDAAVRAHRV 

      1210       1220       1230       1240       1250       1260 
LVDAVTALGA AASDPASPLA FLAAMADSAA GYVKATRLAL DARVAIAQLT TLGSAAADLV 

      1270       1280       1290       1300       1310       1320 
VQVRRAANQP EGEHASLIQA ATRATTGARE SLAGHEGRFG GLLHAEGTAG DHSPSGRALQ 

      1330       1340       1350       1360       1370       1380 
ELGKVIGATR RRADELEAAT ADLREKMAAQ RARSSHERWA ADVEAVLDRV ESGAEFDVVE 

      1390       1400       1410       1420       1430       1440 
LRRLQALAGT HGYNPRDFRK RAEQALGTNA KAVTLALETA LAFNPYTPEN QRHPMLPPLA 

      1450       1460       1470       1480       1490       1500 
AIHRIDWSAA FGAAADTYAD MFRVDTEPLA RLLRLAGGLL ERAQANDGFI DYHEAVLHLS 

      1510       1520       1530       1540       1550       1560 
EDLGGVPALR QYVPFFQKGY AEYVDIRDRL DALRADARRA IGSVALDLAA AAEEISAVRN 

      1570       1580       1590       1600       1610       1620 
DPAAAAELVR AGVTLPCPSE DALVACVAAL ERVDQSPVKD TAYAHYVAFV TRQDLADTKD 

      1630       1640       1650       1660       1670       1680 
AVVRAKQQRA EATERVTAGL REVLAARERR AQLEAEGLAN LKTLLKVVAV PATVAKTLDQ 

      1690       1700       1710       1720       1730       1740 
ARSAEEIADQ VEILVDQTEK ARELDVQAVA WLEHAQRTFE THPLSAASGD GPGLLTRQGA 

      1750       1760       1770       1780       1790       1800 
RLQALFDTRR RVEALRRSLE EAEAEWDEVW GRFGRVRGGA WKSPEGFRAA CEQLRALQDT 

      1810       1820       1830       1840       1850       1860 
TNTVSGLRAQ RDYERLPAKY QGVLGAKSAE RAGAVEELGG RVAQHADLSA RLRDEVVPRV 

      1870       1880       1890       1900       1910       1920 
AWEMNFDTLG GLLAEFDAVA GDLAPWAVEE FRGARELIQR RMGLYSAYAK ATGQTGAGAA 

      1930       1940       1950       1960       1970       1980 
AAPAPLLVDL RALDARARAS APPGQEADPQ MLRRRGEAYL RVSGGPGPLV LREATSTLDR 

      1990       2000       2010       2020       2030       2040 
PFAPSFLVPD GTPLQYALCF PAVTDKLGAL LMCPEAACIR PPLPTDTLES ASTVTAMYVL 

      2050       2060       2070       2080       2090       2100 
TVINRLQLAL SDAQAANFQL FGRFVRHRQA RWGASMDAAA ELYVALVATT LTREFGCRWA 

      2110       2120       2130       2140       2150       2160 
QLEWGGDAAA PGPPLGPQSS TRHRVSFNEN DVLVALVASS PEHIYTFWRL DLVRQHEYMH 

      2170       2180       2190       2200       2210       2220 
LTLPRAFQNA ADSMLFVQRL TPHPDARIRV LPAFSAGGPP TRGLMFGTRL ADWRRGKLSE 

      2230       2240       2250       2260       2270       2280 
TDPLAPWRSV PELGTERGAA LGKLSPAQAL AAVSVLGRMC LPSTALVALW TCMFPDDYTE 

      2290       2300       2310       2320       2330       2340 
YDSFDALLTA RLESGQTLSP SGGREASPPA PPNALYRPTG QHVAVPAAAT HRTPAARVTA 

      2350       2360       2370       2380       2390       2400 
MDLVLAAVLL GAPVVVALRN TTAFSRESEL ELCLTLFDSR ARGPDAALRD AVSSDIETWA 

      2410       2420       2430       2440       2450       2460 
VRLLHADLNP IENACLAAQL PRLSALIAER PLARGPPCLV LVDISMTPVA VLWENPDPPG 

      2470       2480       2490       2500       2510       2520 
PPDVRFVGSE ATEELPFVAG GEDVLAASAT DEDPFLARAI LGRPFDASLL SGELFPGHPV 

      2530       2540       2550       2560       2570       2580 
YQRAPDDQSP SVPNPTPGPV DLVGAEGSLG PGSLAPTLFT DATPGEPVPP RMWAWIHGLE 

      2590       2600       2610       2620       2630       2640 
ELASDDSGGP APLLAPDPLS PTADQSVPTS QCAPRPPGPA VTAREARPGV PAESTRPAPV 

      2650       2660       2670       2680       2690       2700 
GPRDDFRRLP SPQSSPAPPD ATAPRPPASS RASAASSSGS RARRHRRARS LARATQASAT 

      2710       2720       2730       2740       2750       2760 
TQGWRPPALP DTVAPVTDFA RPPAPPKPPE PAPHALVSGV PLPLGPQAAG QASPALPIDP 

      2770       2780       2790       2800       2810       2820 
VPPPVATGTV LPGGENRRPP LTSGPAPTPP RVPVGGPQRR LTRPAVASLS ESRESLPSPW 

      2830       2840       2850       2860       2870       2880 
DPADPTAPVL GRNPAEPTSS SPAGPSPPPP AVQPVAPPPT SGPPPTYLTL EGGVAPGGPV 

      2890       2900       2910       2920       2930       2940 
SRRPTTRQPV ATPTTSARPR GHLTVSRLSA PQPQPQPQPQ PQPQPQPQPQ PQPQPQPQPQ 

      2950       2960       2970       2980       2990       3000 
PQPQPQPQPQ PQPQPQPQPQ PQPQPQPQPQ PQPQPQPQPQ NGHVAPGEYP AVRFRAPQNR 

      3010       3020       3030       3040       3050       3060 
PSVPASASST NPRTGSSLSG VSSWASSLAL HIDATPPPVS LLQTLYVSDD EDSDATSLFL 

      3070       3080       3090       3100       3110       3120 
SDSEAEALDP LPGEPHSPIT NEPFSALSAD DSQEVTRLQF GPPPVSANAV LSRRYVQRTG 

      3130       3140       3150       3160 
RSALAVLIRA CYRLQQQLQR TRRALLHHSD AVLTSLHHVR MLLG 

« Hide

References

« Hide 'large scale' references
[1]"The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1."
McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P.
J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus."
Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y.
Microbes Infect. 9:142-149(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Nonneuroinvasive mutant HF10.
[3]"Herpes simplex virus type 1 bacterial artificial chromosome."
Cunningham C., Davison A.J.
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: 17 syn+.
[4]"A deubiquitinating enzyme encoded by HSV-1 belongs to a family of cysteine proteases that is conserved across the family Herpesviridae."
Kattenhorn L.M., Korbel G.A., Kessler B.M., Spooner E., Ploegh H.L.
Mol. Cell 19:547-557(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, ACTIVE SITES, MUTAGENESIS OF CYS-65.
Strain: KOS.
[5]"A deubiquitinating activity is conserved in the large tegument protein of the herpesviridae."
Schlieker C., Korbel G.A., Kattenhorn L.M., Ploegh H.L.
J. Virol. 79:15582-15585(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Localization of herpes simplex virus type 1 UL37 in the Golgi complex requires UL36 but not capsid structures."
Desai P., Sexton G.L., Huang E., Person S.
J. Virol. 82:11354-11361(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UL37.
Strain: KOS.
[7]"Comprehensive characterization of extracellular herpes simplex virus type 1 virions."
Loret S., Guay G., Lippe R.
J. Virol. 82:8605-8618(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
Strain: F.
[8]"Proteolytic cleavage of VP1-2 is required for release of herpes simplex virus 1 DNA into the nucleus."
Jovasevic V., Liang L., Roizman B.
J. Virol. 82:3311-3319(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC CLEAVAGE.
Strain: F.
[9]"UL36p is required for efficient transport of membrane-associated herpes simplex virus type 1 along microtubules."
Shanda S.K., Wilson D.W.
J. Virol. 82:7388-7394(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Identification of a highly conserved, functional nuclear localization signal within the N-terminal region of herpes simplex virus type 1 VP1-2 tegument protein."
Abaitua F., O'Hare P.
J. Virol. 82:5234-5244(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL.
[11]"Differing roles of inner tegument proteins pUL36 and pUL37 during entry of herpes simplex virus type 1."
Roberts A.P., Abaitua F., O'Hare P., McNab D., Rixon F.J., Pasdeloup D.
J. Virol. 83:105-116(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
Strain: 17 syn+.
[12]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14112 Genomic DNA. Translation: CAA32311.1.
DQ889502 Genomic DNA. Translation: ABI63498.1.
FJ593289 Genomic DNA. Translation: ACM62259.1.
PIRWMBEH6. I30085.
RefSeqNP_044638.2. NC_001806.1.

3D structure databases

ProteinModelPortalP10220.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP10220. 2 interactions.
MINTMINT-6732711.

Protein family/group databases

MEROPSC76.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2703357.

Family and domain databases

InterProIPR005210. Herpes_UL36.
IPR006928. Pept_C76_UL36-USP.
[Graphical view]
PfamPF04843. Herpes_teg_N. 1 hit.
PF03586. Herpes_UL36. 1 hit.
[Graphical view]
PROSITEPS51521. HTUSP. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameDEN_HHV11
AccessionPrimary (citable) accession number: P10220
Secondary accession number(s): B9VQG4, Q09I97
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: June 11, 2014
This is version 75 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