Gene ID:HHVTW063
GenBank Locus Tag:
DNA Molecule Name:
1
GenBank ID:
1869883
Gene Name:
RS1 alpha4
Definition:
positive and negative gene regulator, ICP4
Cellular Location:
[Evidence]
Gene Start:
132032
Gene Stop:
128076
Gene Length:
3957
Molecular Weight*:
135104
pI*:
6.60
Net Charge*:
-3.94
EC:
Functional Class:
transcription regulation; early factor
transcription regulation; immediate-early factor
transcription regulation; late factor
virulence factor; blocks apoptosis
Gene Ontology:
Pathway: pathway table
Secondary Evidence:
Brehm M, Samaniego LA, Bonneau RH, DeLuca NA, Tevethia SS,
Immunogenicity of herpes simplex virus type 1 mutants containing deletions in one or more alpha-genes: ICP4, ICP27, ICP22, and ICP0, Virology 1999 Apr 10;256(2):258-69, Medline: 99208821.
de Bruyn Kops A, Uprichard SL, Chen M, Knipe DM, Comparison of the intranuclear distributions of herpes simplex virus proteins involved in various viral functions, Virology 1998 Dec 5;252(1):162-78, Medline: 99092485.
Jameson HL, Arnott CH, Lillycrop KA , Regulation of herpes simplex virus immediate early gene expression, Biochem Soc Trans 1998 Aug;26(3):S258, Medline: 9843911.
Randall G, Lagunoff M, Roizman B, The product of ORF O located within the domain of herpes simplex virus 1 genome transcribed during latent infection inds to and inhibits in vitro binding of infected cell protein 4 to its cognate DNA site, Proc Natl Acad Sci U S A 1997 Sep 16;94(19):10379-84, Medline: 97439873.
Leopardi R, Roizman B, The herpes simplex virus major regulatory protein ICP4, blocks apoptosis induced by the virus or by hyperthermia, Proc Natl Acad Sci U S A 1996 Sep 3;93(18):9583-7, Medline: 96382509.
Leopardi R, Michael N, Roizman B, Repression of the herpes simplex virus 1 alpha 4 gene by its gene product (ICP4) within the context of the viral genome is conditioned by the distance and stereoaxial alignment of the ICP4 DNA binding site relative to the TATA box, J Virol 1995 May;69(5):3042-8, Medline: 95222756.
Papavassiliou AG, Wilcox KW, Silverstein SJ, The interaction of ICP4 with cell/infected-cell factors and its state of phosphorylation modulate differential recognition of leader sequences in herpes simplex virus DNA, EMBO J 1991 Feb;10(2):397-406, Medline: 91122047.
Michael N, Roizman B, Binding of the herpes simplex virus major regulatory protein, to viral DNA, Proc Natl Acad Sci U S A 1989 Dec;86(24):9808-12, Medline: 90099354.
Kristie TM, Roizman B, Alpha 4, the major regulatory protein of herpes simplex virus type 1, is stably and specifically associated with promoter-regulatory domains of alpha genes and of selected
other viral genes, Proc Natl Acad Sci U S A 1986 May;83(10):3218-22, Medline: 86205868.
McGeoch DJ, Dolan A, Donald S, Brauer DH, Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1, Nucleic Acids Res 1986 Feb 25;14(4):1727-45, Medline: 86148504.
Comment:
Alpha4 lies wholly within the long terminal repeat which borders the S region, so there are two identical copies in the genome.
Alpha4 contains one tandem nucleotide repeat at genome coodinates 131514 - 131548 with period(unit size) 3, copy # 11.7, 93% matches and no inserts/deletes.
de Bruyn Kops et.al.(1998) report that using dual label immunofluorescence and confocal microscopy HSV proteins ICP4 and ICP27 show a diffuse distribution within replication compartments and remain within the compartments when viral DNA replication is inhibited. They conclude that the sites of viral DNA replication and late transcription appear to be distinct but codistribute
within the boundaries of replication compartments.
In his review article (PNAS 93:11307,1996, Medline: 97030190) Roizman summarizes that ICP4 is multifunctional in HSV-1; it represses it´s own synthesis and positively regulates (transcriptionally activates) most beta and gamma genes; binds with high affinity to the sequence 5´-ATCGTC-3'; is nucleotidylated and poly ADP-ribosylated; the long serine stretch is a major phosphorylation site; only phosphorylated ICP4 interacts with alpha and gamma genes; blocks apoptosis. ICP4 is essential for growth in cell culture and has alpha expression regulation.
Blast Summary: PSI-Blast Search
Residues 35-1316 of ICP4 are 73% similar using gapped BLAST to residues 2-1292 of both copies of ICP4 in Human herpesvirus 1 (strain 17) and significantly similar to Bovine herpesvirus 1 (AAA03610), Equine herpesvirus 1 and 4 (P17473 and AAC59583) and
other Alphaherpesvirinae.
Top Blast Hits: Updated monthly
Click here to view the entire PsiBlast results.
COGS Summary: COGS Search
None.
Blocks Summary: Blocks Search
Residues 821-864 and 901-938 represent blocks BL00415N and O (Synapsins proteins) with a combined E value of 0.00058.
Residues 614-625 represent block BL00964A (Syndecans proteins) with an E value of 0.0061.
ProDom Summary: Protein Domain Search
ProDom produced >1700 high scoring segment pairs. Residues 16-73, 94-201, 298-368, 369-534, 535-608, 686-747 and 849-1314 constitute ICP4 domains as seen in P90493_VVVVV. Residues 342-988 are 29% similar to a hypothetical protein domain as seen in O41971_VVVVV (murine herpesvirus).
Paralogs: Local Blast Search
The 1318 residues of ICP4 at this location (HHVTW063) are identical to the 1318 residues of ICP4 in the other segment
of the inverted repeat (HHVTW077).
Pfam Summary: Pfam Search
None.
Structural Feature(s):
| Feature Type | Start | Stop |
| non-globular |
Top PDB Hits:
None.
Gene Protein Sequence:
MSAEQRKKKKTTTTTQGRGAEVAMADEDGGRLRAAAETTGGPGSPDPADG
PPPTPNPDRRPAARPGFGWHGGPEENEDEADDAAADADADEAAPASGEAV
DEPAADGVVSPRQLALLASMVDEAVRTIPSPPPERDGAQEEAARSPSPPR
TPSMRADYGEENDDDDDDDDDDDRDAGRWVRGPETTSAVRGAYPDPMASL
SPRPPAPRRHHHHHHHRRRRAPRRRSAASDSSKSGSSSSASSASSSASSS
SSASASSSDDDDDDDAARAPASAADHAAGGTLGADDEEAGVPARAPGAAP
RPSPPRAEPAPARTPAATAGRLERRRARAAVAGRDATGRFTAGRPRRVEL
DADAASGAFYARYRDGYVSGEPWPGAGPPPPGRVLYGGLGDSRPGLWGAP
EAEEARARFEASGAPAPVWAPELGDAAQQYALITRLLYTPDAEAMGWLQN
PRVAPGDVALDQACFRISGAARNSSSFISGSVARAVPHLGYAMAAGRFGW
GLAHVAAAVAMSRRYDRAQKGFLLTSLRRAYAPLLARENAALTGARTPDD
GGDANRHDGDDARGKPAAAAAPLPSAAASPADERAVPAGYGAAGVLAALG
RLSAAPASAPAGADDDDDDDGAGGGGGGRRAEAGRVAVECLAACRGILEA
LAEGFDGDLAAVPGLAGARPAAPPRPGPAGAAAPPHADAPRLRAWLRELR
FVRDALVLMRLRGDLRVAGGSEAAVAAVRAVSLVAGALGPALPRSPRLLS
SAAAAAADLLFQNQSLRPLLADTVAAADSLAAPASAPREARKRKSPAPAR
APPGGAPRPPKKSRADAPRPAAAPPAGAAPPAPPTPPPRPPRPAALTRRP
AEGPDPQGGWRRQPPGPSHTPAPSAAALEAYCAPRAVAELTDHPLFPAPW
RPALMFDPRALASLAARCAAPPPGGAPAAFGPLRASGPLRRAAAWMRQVP
DPEDVRVVILYSPLPGEDLAAGRAGGGPPPEWSAERGGLSCLLAALGNRL
CGPATAAWAGNWTGAPDVSALGAQGVLLLSTRDLAFAGAVEFLGLLAGAC
DRRLIVVNAVRAADWPADGPVVSRQHAYLACEVLPAVQCAVRWPAARDLR
RTVLASGRVFGPGVFARVEAAHARLYPDAPPLRLCRGANVRYRVRTRFGP
DTLVPMSPREYRRAVLPALDGRAAASGAGDAMAPGAPDFCEDEAHSHRAC
ARWGLGAPLRPVYVALGRDAVRGGPAELRGPRREFCARALLEPDGDAPPL
VLRDDADAGPPPQIRWASAAGRAGTVLAAAGGGVEVVGTAAGLATPPRRE
PVDMDAELEDDDDGLFGE$
Gene Nucleotide Sequence: Sequence Viewer
ATGTCGGCGGAGCAGCGGAAGAAGAAGAAGACGACGACGACGACGCAGGG
CCGCGGGGCCGAGGTCGCGATGGCGGACGAGGACGGGGGACGTCTCCGGG
CCGCGGCGGAGACGACCGGCGGCCCCGGATCTCCGGATCCAGCCGACGGA
CCGCCGCCCACCCCGAACCCGGACCGTCGCCCCGCCGCGCGGCCCGGGTT
CGGGTGGCACGGTGGGCCGGAGGAGAACGAAGACGAGGCCGACGACGCCG
CCGCCGATGCCGATGCCGACGAGGCGGCCCCGGCGTCCGGGGAGGCCGTC
GACGAGCCTGCCGCGGACGGCGTCGTCTCGCCGCGGCAGCTGGCCCTGCT
GGCCTCGATGGTGGACGAGGCCGTTCGCACGATCCCGTCGCCCCCCCCGG
AGCGCGACGGCGCGCAAGAAGAAGCGGCCCGCTCGCCTTCTCCGCCGCGG
ACCCCCTCCATGCGCGCCGATTATGGCGAGGAGAACGACGACGACGACGA
CGACGACGATGACGACGACCGCGACGCGGGCCGCTGGGTCCGCGGACCGG
AGACGACGTCCGCGGTCCGCGGGGCGTACCCGGACCCCATGGCCAGCCTG
TCGCCGCGACCCCCGGCGCCCCGCCGACACCACCACCACCACCACCACCG
CCGCCGGCGCGCCCCCCGCCGGCGCTCGGCCGCCTCTGACTCATCAAAAT
CCGGATCCTCGTCGTCGGCGTCCTCCGCCTCCTCCTCCGCCTCCTCCTCC
TCGTCTGCATCCGCCTCCTCGTCTGACGACGACGACGACGACGACGCCGC
CCGCGCCCCCGCCAGCGCCGCAGACCACGCCGCGGGCGGGACCCTCGGCG
CGGACGACGAGGAGGCGGGGGTGCCCGCGAGGGCCCCGGGGGCGGCGCCC
CGGCCGAGCCCGCCCAGGGCCGAGCCCGCCCCGGCCCGGACCCCCGCGGC
GACCGCGGGCCGCCTGGAGCGCCGCCGGGCCCGCGCGGCGGTGGCCGGCC
GCGACGCCACGGGCCGCTTCACGGCCGGGCGGCCCCGGCGGGTCGAGCTG
GACGCCGACGCGGCCTCCGGCGCCTTCTACGCGCGCTACCGCGACGGGTA
CGTCAGCGGGGAGCCGTGGCCCGGGGCCGGCCCCCCGCCCCCGGGGCGCG
TGCTGTACGGCGGGCTGGGCGACAGCCGCCCCGGCCTCTGGGGGGCGCCC
GAGGCGGAGGAGGCGCGGGCCCGGTTCGAGGCCTCGGGCGCCCCGGCGCC
CGTGTGGGCGCCCGAGCTGGGCGACGCGGCGCAGCAGTACGCCCTGATCA
CGCGGCTGCTGTACACGCCGGACGCGGAGGCGATGGGGTGGCTCCAGAAC
CCGCGCGTGGCGCCCGGGGACGTGGCGCTGGACCAGGCCTGCTTCCGGAT
CTCGGGCGCGGCGCGCAACAGCAGCTCCTTCATCTCCGGCAGCGTGGCGC
GGGCCGTGCCCCACCTGGGGTACGCCATGGCGGCGGGCCGCTTCGGCTGG
GGCCTGGCGCACGTGGCGGCCGCCGTGGCCATGAGCCGCCGCTACGACCG
CGCGCAGAAGGGCTTCCTGCTGACCAGCCTGCGCCGCGCCTACGCGCCCC
TGCTGGCGCGCGAGAACGCGGCGCTGACCGGGGCGCGAACCCCCGACGAC
GGCGGCGACGCCAACCGCCACGACGGCGACGACGCCCGCGGGAAGCCCGC
CGCCGCCGCCGCCCCGTTGCCGTCGGCGGCGGCGTCGCCGGCCGACGAGC
GCGCGGTGCCCGCCGGCTACGGCGCCGCGGGGGTGCTCGCCGCCCTGGGG
CGCCTGAGCGCCGCGCCCGCCTCCGCGCCGGCCGGGGCCGACGACGACGA
CGACGACGACGGCGCCGGCGGTGGTGGCGGCGGCCGGCGCGCGGAGGCGG
GCCGCGTGGCCGTGGAGTGCCTGGCCGCCTGCCGCGGGATCCTGGAGGCG
CTGGCGGAGGGCTTCGACGGCGACCTGGCGGCCGTGCCGGGGCTGGCCGG
AGCCCGGCCCGCCGCGCCCCCGCGCCCGGGGCCCGCGGGCGCGGCCGCCC
CGCCGCACGCCGACGCGCCCCGCCTGCGCGCCTGGCTGCGCGAGCTGCGG
TTCGTGCGCGACGCGCTGGTGCTGATGCGCCTGCGCGGGGACCTGCGCGT
GGCCGGCGGCAGCGAGGCCGCCGTGGCCGCCGTGCGCGCCGTGAGCCTGG
TCGCCGGGGCCCTGGGCCCGGCGCTGCCGCGGAGCCCGCGCCTGCTGAGC
TCCGCCGCCGCCGCCGCCGCGGACCTGCTCTTCCAGAACCAGAGCCTGCG
CCCCCTGCTGGCCGACACCGTCGCCGCGGCCGACTCGCTCGCCGCGCCCG
CCTCCGCGCCGCGGGAGGCGCGCAAGCGCAAGAGCCCCGCCCCGGCCAGG
GCGCCGCCGGGCGGCGCCCCGCGCCCCCCGAAGAAGAGCCGCGCGGACGC
CCCCCGCCCCGCGGCCGCCCCTCCCGCGGGGGCCGCGCCCCCCGCCCCGC
CGACGCCGCCGCCGCGGCCGCCGCGCCCCGCGGCGCTGACCCGCCGGCCC
GCCGAGGGCCCCGACCCGCAGGGCGGCTGGCGCCGCCAGCCGCCGGGGCC
CAGCCACACGCCGGCGCCCTCGGCCGCCGCCCTGGAGGCCTACTGCGCCC
CGCGGGCCGTGGCCGAGCTCACGGACCACCCGCTCTTCCCCGCGCCGTGG
CGCCCGGCCCTCATGTTCGACCCGCGCGCGCTGGCCTCGCTGGCCGCGCG
CTGCGCCGCCCCGCCCCCCGGCGGCGCGCCCGCCGCCTTCGGCCCGCTGC
GCGCCTCGGGCCCGCTGCGCCGCGCGGCGGCCTGGATGCGCCAGGTGCCC
GACCCGGAGGACGTGCGCGTGGTGATCCTCTACTCGCCGCTGCCGGGCGA
GGACCTGGCCGCGGGCCGCGCCGGGGGCGGGCCCCCCCCGGAGTGGTCCG
CCGAGCGCGGCGGGCTGTCCTGCCTGCTGGCGGCCCTGGGCAACCGGCTC
TGCGGGCCCGCCACGGCCGCCTGGGCGGGCAACTGGACCGGCGCCCCCGA
CGTCTCGGCGCTGGGCGCGCAGGGCGTGCTGCTGCTGTCCACGCGGGACC
TGGCCTTCGCCGGCGCCGTGGAGTTCCTGGGGCTGCTGGCCGGCGCCTGC
GACCGCCGCCTCATCGTCGTCAACGCCGTGCGCGCCGCGGACTGGCCCGC
CGACGGGCCCGTGGTCTCGCGGCAGCACGCCTACCTGGCCTGCGAGGTGC
TGCCCGCCGTGCAGTGCGCCGTGCGCTGGCCGGCGGCGCGGGACCTGCGC
CGCACCGTGCTGGCCTCCGGCCGCGTGTTCGGGCCGGGGGTCTTCGCGCG
CGTGGAGGCCGCGCACGCGCGCCTGTACCCCGACGCGCCGCCGCTGCGCC
TCTGCCGCGGGGCCAACGTGCGGTACCGCGTGCGCACGCGCTTCGGCCCC
GACACGCTGGTGCCCATGTCCCCGCGCGAGTACCGCCGCGCCGTGCTCCC
GGCGCTGGACGGCCGGGCCGCCGCCTCGGGCGCGGGCGACGCCATGGCGC
CCGGCGCGCCGGACTTCTGCGAGGACGAGGCGCACTCGCACCGCGCCTGC
GCGCGCTGGGGCCTGGGCGCGCCGCTGCGGCCCGTCTACGTGGCGCTGGG
GCGCGACGCCGTGCGCGGCGGCCCGGCGGAGCTGCGCGGGCCGCGGCGGG
AGTTCTGCGCGCGGGCGCTGCTCGAGCCCGACGGCGACGCGCCCCCGCTG
GTGCTGCGCGACGACGCGGACGCGGGCCCGCCCCCGCAGATACGCTGGGC
GTCGGCCGCGGGCCGCGCGGGGACGGTGCTGGCCGCGGCGGGCGGCGGCG
TGGAGGTGGTGGGGACCGCCGCGGGGCTGGCCACGCCGCCGAGGCGCGAG
CCCGTGGACATGGACGCGGAGCTGGAGGACGACGACGACGGACTGTTTGG
GGAGTGA