P10220 (DEN_HHV11) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Deneddylase UL36
Short name=pUL36
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

Organism

Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]

Taxonomic identifier

10299 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 1

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	3164 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 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 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 endopeptidase activity Inferred from electronic annotation. Source: InterPro omega peptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 3164	3164	Deneddylase UL36		PRO_0000116035
Regions
	Domain	45 – 263	219	Peptidase C76
	Repeat	2911 – 2912	2	1
	Repeat	2913 – 2914	2	2
	Repeat	2915 – 2916	2	3
	Repeat	2917 – 2918	2	4
	Repeat	2919 – 2920	2	5
	Repeat	2921 – 2922	2	6
	Repeat	2923 – 2924	2	7
	Repeat	2925 – 2926	2	8
	Repeat	2927 – 2928	2	9
	Repeat	2929 – 2930	2	10
	Repeat	2931 – 2932	2	11
	Repeat	2933 – 2934	2	12
	Repeat	2935 – 2936	2	13
	Repeat	2937 – 2938	2	14
	Repeat	2939 – 2940	2	15
	Repeat	2941 – 2942	2	16
	Repeat	2943 – 2944	2	17
	Repeat	2945 – 2946	2	18
	Repeat	2947 – 2948	2	19
	Repeat	2949 – 2950	2	20
	Repeat	2951 – 2952	2	21
	Repeat	2953 – 2954	2	22
	Repeat	2955 – 2956	2	23
	Repeat	2957 – 2958	2	24
	Repeat	2959 – 2960	2	25
	Repeat	2961 – 2962	2	26
	Repeat	2963 – 2964	2	27
	Repeat	2965 – 2966	2	28
	Repeat	2967 – 2968	2	29
	Repeat	2969 – 2970	2	30
	Repeat	2971 – 2972	2	31
	Repeat	2973 – 2974	2	32
	Repeat	2975 – 2976	2	33
	Repeat	2977 – 2978	2	34
	Repeat	2979 – 2980	2	35
	Region	1 – 273	273	Deubiquitination activity By similarity
	Region	579 – 609	31	Interaction with UL37
	Region	2911 – 2980	70	35 X 2 AA tandem repeats of P-Q
	Coiled coil	1020 – 1053	34	Potential
	Coiled coil	1317 – 1354	38	Potential
	Coiled coil	1741 – 1769	29	Potential
	Motif	426 – 433	8	Nuclear localization signal By similarity
	Compositional bias	307 – 494	188	Pro-rich
	Compositional bias	1161 – 1288	128	Ala-rich
Sites
	Active site	65	1	Ref.4
	Active site	197	1	By similarity
	Active site	199	1	By similarity
	Site	52	1	Important for catalytic activity By similarity
Natural variations
	Natural variant	234	1	A → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	307	1	P → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	375 – 379	5	Missing in strain: Nonneuroinvasive mutant HF10.
	Natural variant	392	1	T → P in strain: Nonneuroinvasive mutant HF10.
	Natural variant	620	1	N → S in strain: Nonneuroinvasive mutant HF10.
	Natural variant	624	1	W → R in strain: Nonneuroinvasive mutant HF10.
	Natural variant	671	1	A → V in strain: Nonneuroinvasive mutant HF10.
	Natural variant	885	1	I → M in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1023	1	A → V in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1244	1	V → G in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1373	1	G → S in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1389	1	G → D in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1419	1	T → M in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1470	1	A → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1604	1	A → S in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1605	1	H → D in strain: 17 syn+ and Nonneuroinvasive mutant HF10.
	Natural variant	1642	1	E → D in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1695	1	V → L in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1729	1	G → S in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1777	1	R → C in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1888	1	V → M in strain: Nonneuroinvasive mutant HF10.
	Natural variant	1973	1	E → K in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2267	1	V → A in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2540	1	V → A in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2545	1	A → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2646	1	F → V in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2666	1	P → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2748	1	A → S in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2856	1	A → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2875	1	A → T in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2894	1	T → A in strain: Nonneuroinvasive mutant HF10.
	Natural variant	2973 – 2978	6	Missing in strain: Nonneuroinvasive mutant HF10.
	Natural variant	3095	1	V → A in strain: Nonneuroinvasive mutant HF10.
Experimental info
	Mutagenesis	65	1	C → A: Complete loss of deubiquitination activity. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P10220 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: CC5D31FF4F9FE3F4	FASTA	3,164	335,862
	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

References

	« Hide 'large scale' referencesShow '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.
PIR	WMBEH6. I30085.
RefSeq	NP_044638.2. NC_001806.1.
3D structure databases
ProteinModelPortal	P10220.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-6732711.
Protein family/group databases
MEROPS	C76.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	2703357.
Phylogenomic databases
ProtClustDB	PHA3247.
Family and domain databases
InterPro	IPR005210. Herpes_UL36. IPR006928. Pept_C76_UL36-USP. [Graphical view]
Pfam	PF04843. Herpes_teg_N. 1 hit. PF03586. Herpes_UL36. 1 hit. [Graphical view]
PROSITE	PS51521. HTUSP. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

DEN_HHV11

Accession

Primary (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:	April 3, 2013
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program