Gene ID:HHVTW002
GenBank Locus Tag:
DNA Molecule Name:
1
GenBank ID:
124135
Gene Name:
RL2 alpha0 ICP0
Definition:
promiscuous transactivator, cellular homolog, ICP0, VMW118 (ICP0_HSV2H)
Cellular Location:
[Evidence]
Gene Start:
2303
Gene Stop:
5368
Gene Length:
3066
Molecular Weight*:
81980
pI*:
8.00
Net Charge*:
6.61
EC:
Functional Class:
transcription regulation; immediate-early factor
zinc finger; zinc RING finger, C3HC4-class
Gene Ontology:
Pathway: pathway table
Primary Evidence:
Holzerlandt R, Orengo C, Kellam P, Alba MM.
Identification of new herpesvirus gene homologs in the human genome,
Genome Res. 2002 Nov;12(11):1739-48,
PMID: 12421761.
McGeoch,D.J., Cunningham,C., McIntyre,G. and Dolan,
Comparative sequence analysis of the long repeat region adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2,
J. Gen. Virol. 72 (Pt 12), 3057-3075 (1991),
Medline: 92113549.
Secondary Evidence:
Poon AP, Silverstein SJ, Roizman B.
An early regulatory function required in a cell type-dependent manner is expressed by the genomic but not the cDNA copy of the herpes simplex virus 1 gene encoding infected cell
protein 0,
J Virol. 2002 Oct;76(19):9744-55,
PMID: 12208953.
Hagglund R, Roizman B.
Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes simplex virus-1-infected cell protein 0,
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7889-94,
PMID: 12060736.
Hagglund R, Van Sant C, Lopez P, Roizman B.
Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes,
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):631-6,
PMID: 11805320.
Hagglund R, Munger J, Poon AP, Roizman B.
U(S)3 protein kinase of herpes simplex virus 1 blocks caspase 3 activation induced by the products of U(S)1.5 and U(L)13 genes and modulates expression of transduced U(S)1.5 open reading frame in a cell type-specific manner,
J Virol. 2002 Jan;76(2):743-54,
PMID: 11752164.
Mossman,K.L. and Smiley,J.R., Herpes simplex virus ICP0 and ICP34.5 counteract distinct interferon-induced barriers to virus replication,
J Virol 2002 Feb; 76 (4):1995-8,
PMID: 11799195.
Van Sant C, Hagglund R, Lopez P, Roizman B.
The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity,
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8815-20,
PMID: 11447293.
Advani SJ, Hagglund R, Weichselbaum RR, Roizman B, Posttranslational processing of infected cell proteins 0 and 4 of herpes simplex virus 1 is sequential and reflects the subcellular compartment in which the proteins localize,
J Virol. 2001 Sep;75(17):7904-12,
Medline: 11483735.
Lopez P, Van Sant C, Roizman B., Requirements for the nuclear-cytoplasmic translocation of infected-cell protein 0 of herpes simplex virus 1,
J Virol. 2001 Apr;75(8):3832-40.
Medline: 11264372.
Everett RD.
ICP0, a regulator of herpes simplex virus during lytic and latent infection,
Bioessays. 2000 Aug;22(8):761-70. Review,
PMID: 10918307.
Mossman KL, Smiley JR, Truncation of the C-terminal acidic transcriptional activation domain of herpes simplex virus VP16 renders expression of the immediate-early genes almost entirely dependent on ICP0,
J Virol 1999 Dec;73(12):9726-33,
Medline: 20027193.
Hobbs WE 2nd, DeLuca NA, Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0,
J Virol 1999 Oct;73(10):8245-55,
Medline: 99412340.
Lachmann RH, Sadarangani M, Atkinson HR, Efstathiou S, An analysis of herpes simplex virus gene expression during latency establishment and reactivation,
J Gen Virol 1999 May;80 ( Pt 5):1271-82,
Medline: 99281905.
Lium EK, Panagiotidis CA, Wen X, Silverstein SJ, The NH2 terminus of the herpes simplex virus type 1 regulatory rotein ICP0 contains a promoter-specific transcription activation domain,
J Virol 1998 Oct;72(10):7785-95,
Medline: 98406178.
Lium EK, Silverstein S, Mutational analysis of the herpes simplex virus type 1 ICP0 C3HC4 zinc ring finger reveals a requirement for
ICP0 in the expression of the essential alpha27 gene,
J Virol 1997 Nov;71(11):8602-14,
Medline: 98001383.
Carter KL, Roizman B, Alternatively spliced mRNAs predicted to yield frame-shift proteins and stable intron 1 RNAs of the herpes simplex virus 1 regulatory gene alpha 0 accumulate in the cytoplasm of infected cells,
Proc Natl Acad Sci U S A 1996 Oct 29;93(22):12535-40,
Medline: 97057278.
Barlow PN, Luisi B, Milner A, Elliott M, Everett R, Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger,
J Mol Biol. 1994 Mar 25;237(2):201-11,
Medline: 94172642.
Everett RD, Barlow P, Milner A, Luisi B, Orr A, Hope G, Lyon D A novel arrangement of zinc-binding residues and secondary structure in the C3HCr motif of an alpha herpes virus protein family,
J Mol Biol 1993 Dec 20;234(4):1038-47,
Medline: 94087718.
Wirth,U.V., Fraefel,C., Vogt,B., Vlcek,C., Paces,V. and Schwyzer,M
Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3' coterminal and encode a putative zinc finger transactivator,
J. Virol. 66 (5), 2763-2772 (1992),
Medline: 92219360.
Perry,L.J. and McGeoch,D.J, The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1,
J. Gen. Virol. 69 (Pt 11), 2831-2846 (1988),
Medline: 89036163.
McGeoch,D.J., Dalrymple,M.A., Davison,A.J., Dolan,A., Frame,M.C., McNab,D., Perry,L.J., Scott,J.E. and Taylor,P., The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1,
J. Gen. Virol. 69 (Pt 7), 1531-1574 (1988),
Medline: 88274327.
Perry LJ, Rixon FJ, Everett RD, Frame MC, McGeoch DJ, Characterization of the IE110 gene of herpes simplex virus type 1,
J Gen Virol 1986 Nov;67 ( Pt 11):2365-80,
Medline: 87059760.
Everett RD, Trans activation of transcription by herpes virus
products: requirement for two HSV-1 immediate-early
polypeptides for maximum activity,
EMBO J. 1984 Dec 20;3(13):3135-41,
PMID: 6098466.
Comment:
The HSV-2 genome contains two copies of alpha0, one wholly within the long terminal repeat, RL region, (this location) and one in the inverted repeat region separating the long and short unique regions. Alpha0 displays similarity to other Alphaherpesvirinae ICP0 proteins and residues ~126-166 form a C3HC4-class zinc finger. Like it's counterpart in HSV-1, alpha0 in HSV-2 has two introns. Holzerlandt et al.(2002) identify RL2 as a cellular homolog.
Alpha0 contains 3 tandem nucleotide repeats at genome coordinates:
1) 3471-3607, period/unit size 11, copy # 12.5, 98% matches, no insert/deletes, 2) 4653-4770, period/unit size 15, copy # 7.9, 99% matches, no insert/deletes and 3) 4656-4770, period/unit size 3, copy # 38.3, 85% matches, no insert/deletes.
ICPO is dispensable in cell culture, Roizman, PNAS 93:11307, 1996, Medline: 97030190. However, Mossman and Smiley (1999) report that ICP0 and VP16 play key roles in stimulating the onset of the viral lytic cycle. Using mutants of one and both genes they demonstrate that expression of immediate-early genes requires ICP0 when the C-terminal activation domain of VP16 is deleted.
Using replication-incompetent HSV-1 Hobbs and DeLuca (1999) report
experiments that suggest expression of ICP0 is crucial for cell
cycle arrest.
In his review of HSV-1 (PNAS 93:11307,1996, Medline: 97030190) Roizman summarizes that ICP0 is a promiscuous transactivator of all three classes of HSV genes; requires ICP4 for optimal activity and may take part in the reactivation of latent HSV; it is nucleotidylated and phosphorylated by UL13. ICP0 has both nuclear (early) and cytoplasmic (late) locations during infection.
Blast Summary: PSI-Blast Search
Residues 1-812 of ICP0 are 56% similar using gapped BLAST to residues 1-767 of both copies of ICP0 (HHVONE002 and HHVONE061) in Human herpesirus 1 (strain 17). It shows 43% similarity to a 53 aa segment overlapping the zinc finger region of Bovine herpesvirus 1 (strains K22 and Jura at ICP0_HSVBK and ICP0_HSVBJ), and less similarity to the zinc finger region of Suid herpesvirus 1(P29129) and other Alphaherpesvirinae and weak similarity to other eukaryotic zinc finger proteins.
Top Blast Hits: Updated monthly
Click here to view the entire PsiBlast results.
COGS Summary: COGS Search
None.
Blocks Summary: Blocks Search
Residues 144-152 are 100% similar to block BL00518, Zinc finger, C3HC4 type (RING finger), with E value 0.03.
Residues 591-620 represent block PF00624I, Flocculin repeat, with an E value 0.0018 and residues 392-429 may represent block BP03591A, neurofilament repeat, with E value 0.01.
ProDom Summary: Protein Domain Search
Residues 1-112, 167-242, 277-382, 421-478 and 644-812 constitute trans-acting transcriptional protein domains seen in ICP0_HSV2H. Residues 126-166 constitute a zinc finger domain as seen in ICP0_HSV2H. Residues 396-558 are 53% similar to a trans-acting transcriptional protein domain as seen in ICP0_HSV11. Residues 177-696 are 26% similar to a submaxillary apomucin ice domain as seen in O18758_EEEEE.
Paralogs: Local Blast Search
Residues 1-825 of HHVTW002 are 99% identical to residues 1-826 of HHVTW061 (a single glycine added to HHVTW061 at aa 252 is the only difference).
Pfam Summary: Pfam Search
Residues 126-166 (E-value 5.8e-10) place ICP0 in the zf-C3HC4 family, described as Zinc finger, C3HC4 type (RING finger).
See Prosite PDOC00449.
Structural Feature(s):
| Feature Type | Start | Stop |
| non-globular | ||
| non-globular |
Top PDB Hits:
Round 1 hit structure pdb|1CHC|1CHC (Equine herpesvirus-1 C3HC4, or ring domain) with score 46.1, E value 0.001000 (17 of 43 aa matching).
Gene Protein Sequence:
MEPRPGTSSRADPGPERPPRQTPGTQPAAPHAWGMLNDMQWLASSDSEEE
TEVGISDDDLHRDSTSEAGSTDTEMFEAGLMDAATPPARPPAERQGSPTP
ADAQGSCGGGPVGEEEAEAGGGGDVCAVCTDEIAPPLRCQSFPCLHPFCI
PCMKTWIPLRNTCPLCNTPVAYLIVGVTASGSFSTIPIVNDPRTRVEAEA
AVRAGTAVDFIWTGNPRTAPRSLSLGGHTVRALSPTPPWPGTDDEDDDLA
DVDYVPPAPRRAPRRGGGGAGATRGTSQPAATRPAPPGAPRSSSSGGAPL
RAGVGSGSGGGPAVAAVVPRVASLPPAAGGGRAQARRVGEDAAAAEGRTP
PARQPRAAQEPPIVISDSPPPSPRRPAGPGPLSFVSSSSAQVSSGPGGGG
LPQSSGRAARPRAAVAPRVRSPPRAAAAPVVSASADAAGPAPPAVPVDAH
RAPRSRMTQAQTDTQAQSLGRAGATDARGSGGPGAEGGPGVPRGTNTPGA
APHAAEGAAARPRKRRGSDSGPAASSSASSSAAPRSPLAPQGVGAKRAAP
RRAPDSDSGDRGHGPLAPASAGAAPPSASPSSQAAVAAASSSSASSSSAS
SSSASSSSASSSSASSSSASSSSASSSAGGAGGSVASASGAGERRETSLG
PRAAAPRGPRKCARKTRHAEGGPEPGARDPAPGLTRYLPIAGVSSVVALA
PYVNKTVTGDCLPVLDMETGHIGAYVVLVDQTGNVADLLRAAAPAWSRRT
LLPEHARNCVRPPDYPTPPASEWNSLWMTPVGNMLFDQGTLVGALDFHGL
RSRHPWSREQGAPAPAGDAPAGHGE
Gene Nucleotide Sequence: Sequence Viewer
ATGGAACCCCGGCCCGGCACGAGCTCCCGGGCGGACCCCGGCCCCGAGCG
GCCGCCGCGGCAGACCCCCGGCACGGTGAGAGGGCGACCCCCGGGTCTCA
GGCCCCCCCTTTTCCCCGGACCACCCGGCTGCGGGTTGGGGGTGGTCGCG
GGCGGTGGGCTCGGGGGCGGGGACGCTTGACGGGGCCGACCCCCGGCCCG
CTTAAGCGGTCGGGGGACCCCCGTGGGCCGTGCGCCGCCCCCCGACCCTC
TGGGGGGGCGAGGGAGGCAGGGAGGAGCCCGAGAGCGGGGGACAGGGGGG
GAGACGAGGGGTCGGAATCCAAAGGACGCAGACCACCTTTGGTTACGGAC
CCCTTTCTCCCCCCCTTCCGAACAAAAAGCAGCGGGCGGGGGGCCGGGGT
GAGGGAGGGACACGGGGGACACGGCGCGGGGGTCCCGCCTCACGCCCCGC
GCCCTCTAAATCCCCCCCGTTGCTTTGTCAAGCAGCCCGCCGCCCCGCAC
GCCTGGGGGATGCTCAACGACATGCAGTGGCTCGCCAGCAGCGACTCGGA
GGAGGAGACCGAGGTGGGAATCTCTGACGACGACCTTCACCGCGACTCCA
CCTCCGAGGCGGGCAGCACGGACACGGAGATGTTCGAGGCGGGCCTGATG
GACGCGGCCACGCCCCCGGCCCGGCCCCCGGCCGAGCGCCAGGGCAGCCC
CACGCCCGCCGACGCGCAGGGATCCTGTGGGGGTGGGCCCGTGGGTGAGG
AGGAAGCGGAAGCGGGAGGGGGGGGCGACGTGTGTGCCGTGTGCACGGAC
GAGATCGCCCCGCCCCTGCGCTGCCAGAGTTTTCCCTGCCTGCACCCCTT
CTGCATCCCGTGCATGAAGACCTGGATTCCGTTGCGCAACACGTGTCCCC
TGTGCAACACCCCGGTGGCGTACCTGATAGTGGGCGTGACCGCCAGCGGG
TCGTTCAGCACCATCCCGATAGTGAACGACCCCCGGACCCGCGTGGAGGC
CGAGGCGGCCGTGCGGGCCGGCACGGCCGTGGACTTTATCTGGACGGGCA
ACCCGCGGACGGCCCCGCGCTCCCTGTCGCTGGGGGGACACACGGTCCGC
GCCCTGTCGCCCACCCCCCCGTGGCCCGGCACGGACGACGAGGACGATGA
CCTGGCCGACGGTGAGGGCGGGCGGGGGTCGGGCGGGGGGCGGGCGGGGG
TCGGGCGGGGGTCGGGCGGGGGTCGGGCGGGGGTCGGGCGGGGGTCGGGC
GGGGGTCGGGCGGGGGTCGGGCGGGGGTCGGGCGGGGGTCGGGCGGGGGT
CGGGCACTAACCGGGGGCTCCCGTCTCTGTCTCCCTCTGCAGTGGACTAC
GTCCCGCCCGCCCCCCGAAGAGCGCCCCGGCGCGGGGGCGGCGGTGCGGG
GGCGACCCGCGGAACCTCCCAGCCCGCCGCGACCCGACCGGCGCCCCCTG
GCGCCCCGCGGAGCAGCAGCAGCGGCGGCGCCCCGTTGCGGGCGGGGGTG
GGATCTGGGTCTGGGGGCGGCCCTGCCGTCGCGGCCGTCGTGCCGAGAGT
GGCCTCTCTTCCCCCTGCGGCCGGCGGGGGGCGCGCGCAGGCGCGGCGGG
TGGGCGAAGACGCCGCGGCGGCGGAGGGCAGGACGCCCCCCGCGAGACAG
CCCCGCGCGGCCCAGGAGCCCCCCATAGTCATCAGCGACTCTCCCCCGCC
GTCTCCGCGCCGCCCCGCGGGCCCCGGGCCGCTCTCCTTTGTCTCCTCCT
CCTCCGCACAGGTGTCCTCGGGCCCCGGGGGGGGAGGTCTGCCACAGTCG
TCGGGGCGCGCCGCGCGCCCCCGCGCGGCCGTCGCCCCGCGCGTCCGGAG
TCCGCCCCGCGCCGCCGCCGCCCCCGTGGTGTCTGCGAGCGCGGACGCGG
CCGGGCCCGCGCCGCCCGCCGTGCCGGTGGACGCGCACCGCGCGCCCCGG
TCGCGCATGACCCAGGCTCAGACCGACACCCAAGCACAGAGTCTGGGCCG
GGCAGGCGCGACCGACGCGCGCGGGTCGGGAGGGCCGGGCGCGGAGGGAG
GACCCGGGGTCCCCCGCGGCACCAACACCCCCGGTGCCGCCCCCCACGCC
GCGGAGGGGGCGGCGGCCCGCCCCCGGAAGAGGCGCGGGTCGGACTCGGG
CCCCGCGGCCTCGTCCTCCGCCTCTTCCTCCGCCGCCCCGCGCTCGCCCC
TCGCCCCCCAGGGGGTGGGGGCCAAGAGGGCGGCGCCGCGCCGGGCCCCG
GACTCGGACTCGGGCGACCGCGGCCACGGGCCGCTCGCCCCGGCGTCCGC
GGGCGCCGCGCCCCCGTCGGCGTCTCCGTCGTCCCAGGCCGCGGTCGCCG
CCGCCTCCTCCTCCTCCGCCTCCTCCTCCTCCGCCTCCTCCTCCTCCGCC
TCCTCCTCCTCCGCCTCCTCCTCCTCCGCCTCCTCCTCCTCCGCCTCCTC
CTCCTCCGCCTCTTCCTCTGCGGGCGGGGCTGGTGGGAGCGTCGCGTCCG
CGTCCGGCGCTGGGGAGAGACGAGAAACCTCCCTCGGCCCCCGCGCTGCT
GCGCCGCGGGGGCCGAGGAAGTGTGCCAGGAAGACGCGCCACGCGGAGGG
CGGCCCCGAGCCCGGGGCCCGCGACCCGGCGCCCGGCCTCACGCGCTACC
TGCCCATCGCGGGGGTCTCGAGCGTCGTGGCCCTGGCGCCTTACGTGAAC
AAGACGGTCACGGGGGACTGCCTGCCCGTCCTGGACATGGAGACGGGCCA
CATAGGGGCCTACGTGGTCCTCGTGGACCAGACGGGGAACGTGGCGGACC
TGCTGCGGGCCGCGGCCCCCGCGTGGAGCCGCCGCACCCTGCTCCCCGAG
CACGCGCGCAACTGCGTGAGGCCCCCCGACTACCCGACGCCCCCCGCGTC
GGAGTGGAACAGCCTCTGGATGACCCCGGTGGGCAACATGCTCTTTGACC
AGGGCACCCTGGTGGGCGCGCTGGACTTCCACGGCCTCCGGTCGCGCCAC
CCGTGGTCTCGGGAGCAGGGCGCGCCCGCGCCGGCCGGCGACGCCCCCGC
GGGCCACGGGGAGTAG