AN_HHV11
ID AN_HHV11 Reviewed; 626 AA.
AC P04294;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=Alkaline nuclease {ECO:0000255|HAMAP-Rule:MF_04009};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04009};
GN ORFNames=UL12;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3010237; DOI=10.1093/nar/14.8.3435;
RA McGeoch D.J., Dolan A., Frame M.C.;
RT "DNA sequence of the region in the genome of herpes simplex virus type 1
RT containing the exonuclease gene and neighbouring genes.";
RL Nucleic Acids Res. 14:3435-3448(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Nonneuroinvasive mutant HF10;
RX PubMed=17218138; DOI=10.1016/j.micinf.2006.10.019;
RA Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y.;
RT "Determination and analysis of the DNA sequence of highly attenuated herpes
RT simplex virus type 1 mutant HF10, a potential oncolytic virus.";
RL Microbes Infect. 9:142-149(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17 syn+;
RA Cunningham C., Davison A.J.;
RT "Herpes simplex virus type 1 bacterial artificial chromosome.";
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP ALTERNATIVE SPLICING (ISOFORM UL12.5).
RX PubMed=8560762; DOI=10.1006/viro.1996.0018;
RA Martinez R., Shao L., Bronstein J.C., Weber P.C., Weller S.K.;
RT "The product of a 1.9-kb mRNA which overlaps the HSV-1 alkaline nuclease
RT gene (UL12) cannot relieve the growth defects of a null mutant.";
RL Virology 215:152-164(1996).
RN [6]
RP SUBCELLULAR LOCATION (ISOFORM UL12).
RX PubMed=3032315; DOI=10.1111/j.1768-322x.1986.tb00485.x;
RA Puvion-Dutilleul F., Pichard E.;
RT "Viral alkaline nuclease in intranuclear dense bodies induced by herpes
RT simplex infection.";
RL Biol. Cell 58:15-22(1986).
RN [7]
RP FUNCTION.
RX PubMed=9601512; DOI=10.1006/viro.1998.9129;
RA Goldstein J.N., Weller S.K.;
RT "The exonuclease activity of HSV-1 UL12 is required for in vivo function.";
RL Virology 244:442-457(1998).
RN [8]
RP INTERACTION WITH ICP8, AND SUBCELLULAR LOCATION.
RX PubMed=15078942; DOI=10.1128/jvi.78.9.4599-4608.2004;
RA Reuven N.B., Antoku S., Weller S.K.;
RT "The UL12.5 gene product of herpes simplex virus type 1 exhibits nuclease
RT and strand exchange activities but does not localize to the nucleus.";
RL J. Virol. 78:4599-4608(2004).
RN [9]
RP FUNCTION.
RX PubMed=15994834; DOI=10.1128/jvi.79.14.9356-9358.2005;
RA Reuven N.B., Weller S.K.;
RT "Herpes simplex virus type 1 single-strand DNA binding protein ICP8
RT enhances the nuclease activity of the UL12 alkaline nuclease by increasing
RT its processivity.";
RL J. Virol. 79:9356-9358(2005).
RN [10]
RP SUBCELLULAR LOCATION (ISOFORM UL12.5), AND FUNCTION (ISOFORM UL12.5).
RX PubMed=19129438; DOI=10.1128/jvi.02087-08;
RA Corcoran J.A., Saffran H.A., Duguay B.A., Smiley J.R.;
RT "Herpes simplex virus UL12.5 targets mitochondria through a mitochondrial
RT localization sequence proximal to the N terminus.";
RL J. Virol. 83:2601-2610(2009).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOST RAD50; NBN AND MRE11.
RX PubMed=20943970; DOI=10.1128/jvi.01506-10;
RA Balasubramanian N., Bai P., Buchek G., Korza G., Weller S.K.;
RT "Physical interaction between the herpes simplex virus type 1 exonuclease,
RT UL12, and the DNA double-strand break-sensing MRN complex.";
RL J. Virol. 84:12504-12514(2010).
RN [12]
RP INTERACTION WITH HOST MSH6.
RX PubMed=21957315; DOI=10.1128/jvi.05487-11;
RA Mohni K.N., Mastrocola A.S., Bai P., Weller S.K., Heinen C.D.;
RT "DNA mismatch repair proteins are required for efficient herpes simplex
RT virus 1 replication.";
RL J. Virol. 85:12241-12253(2011).
RN [13]
RP FUNCTION.
RX PubMed=24335305; DOI=10.1128/jvi.03621-13;
RA Fujii H., Mugitani M., Koyanagi N., Liu Z., Tsuda S., Arii J., Kato A.,
RA Kawaguchi Y.;
RT "Role of the nuclease activities encoded by herpes simplex virus 1 UL12 in
RT viral replication and neurovirulence.";
RL J. Virol. 88:2359-2364(2014).
CC -!- FUNCTION: Plays a role in processing non linear or branched viral DNA
CC intermediates in order to promote the production of mature packaged
CC unit-length linear progeny viral DNA molecules. Exhibits endonuclease
CC and exonuclease activities and accepts both double-stranded and single-
CC stranded DNA as substrate. Exonuclease digestion of DNA is in the 5'->
CC 3' direction and the products are 5'-monophosphate nucleosides.
CC Additionally, forms a recombinase with the major DNA-binding protein,
CC which displays strand exchange activity. {ECO:0000255|HAMAP-
CC Rule:MF_04009, ECO:0000269|PubMed:15994834,
CC ECO:0000269|PubMed:20943970, ECO:0000269|PubMed:24335305,
CC ECO:0000269|PubMed:9601512}.
CC -!- FUNCTION: [Isoform UL12.5]: Degrades host mitochondrial DNA.
CC {ECO:0000269|PubMed:19129438}.
CC -!- SUBUNIT: Forms a complex with the DNA polymerase, the DNA polymerase
CC processivity factor, and the major DNA binding protein (By similarity).
CC Interacts with the host MRN complex composed of MRE11, RAD50 and NBN;
CC these interactions may help in recombination or repair of the viral
CC DNA. Interacts with host MSH6, a component of the post-replicative DNA
CC mismatch repair system (MMR). {ECO:0000255|HAMAP-Rule:MF_04009,
CC ECO:0000269|PubMed:15078942, ECO:0000269|PubMed:20943970,
CC ECO:0000269|PubMed:21957315}.
CC -!- SUBCELLULAR LOCATION: [Isoform UL12.5]: Host mitochondrion
CC {ECO:0000269|PubMed:19129438}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04009,
CC ECO:0000269|PubMed:15078942, ECO:0000269|PubMed:3032315}. Host
CC cytoplasm {ECO:0000255|HAMAP-Rule:MF_04009}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=UL12;
CC IsoId=P04294-1; Sequence=Displayed;
CC Name=UL12.5;
CC IsoId=P04294-2; Sequence=VSP_038098;
CC -!- MISCELLANEOUS: [Isoform UL12.5]: Produced by alternative initiation at
CC Met-127 of isoform UL12. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the herpesviridae alkaline nuclease family.
CC {ECO:0000255|HAMAP-Rule:MF_04009}.
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DR EMBL; X14112; CAA32325.1; -; Genomic_DNA.
DR EMBL; X03839; CAA27453.1; -; Genomic_DNA.
DR PIR; A00781; NDBE61.
DR RefSeq; YP_009137086.1; NC_001806.2.
DR SMR; P04294; -.
DR BioGRID; 971420; 5.
DR IntAct; P04294; 1.
DR MINT; P04294; -.
DR PRIDE; P04294; -.
DR GeneID; 24271463; -.
DR KEGG; vg:24271463; -.
DR Proteomes; UP000009294; Genome.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004518; F:nuclease activity; IDA:CACAO.
DR GO; GO:0016032; P:viral process; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04009; HSV_AN; 1.
DR InterPro; IPR001616; Herpes_alk_exo.
DR InterPro; IPR011335; Restrct_endonuc-II-like.
DR InterPro; IPR034720; Viral_alk_exo.
DR Pfam; PF01771; Viral_alk_exo; 1.
DR PRINTS; PR00924; ALKEXNUCLASE.
DR SUPFAM; SSF52980; SSF52980; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Endonuclease; Exonuclease; Host cytoplasm;
KW Host mitochondrion; Host nucleus; Host-virus interaction; Hydrolase;
KW Nuclease; Reference proteome.
FT CHAIN 1..626
FT /note="Alkaline nuclease"
FT /id="PRO_0000115690"
FT REGION 1..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 601..626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..59
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..626
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 280
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT SITE 340
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT SITE 364
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT SITE 366
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT VAR_SEQ 1..126
FT /note="Missing (in isoform UL12.5)"
FT /evidence="ECO:0000305"
FT /id="VSP_038098"
SQ SEQUENCE 626 AA; 67508 MW; 7B86C941A0105035 CRC64;
MESTVGPACP PGRTVTKRPW ALAEDTPRGP DSPPKRPRPN SLPLTTTFRP LPPPPQTTSA
VDPSSHSPVN PPRDQHATDT ADEKPRAASP ALSDASGPPT PDIPLSPGGT HARDPDADPD
SPDLDSMWSA SVIPNALPSH ILAETFERHL RGLLRGVRAP LAIGPLWARL DYLCSLAVVL
EEAGMVDRGL GRHLWRLTRR GPPAAADAVA PRPLMGFYEA ATQNQADCQL WALLRRGLTT
ASTLRWGPQG PCFSPQWLKH NASLRPDVQS SAVMFGRVNE PTARSLLFRY CVGRADDGGE
AGADTRRFIF HEPSDLAEEN VHTCGVLMDG HTGMVGASLD ILVCPRDIHG YLAPVPKTPL
AFYEVKCRAK YAFDPMDPSD PTASAYEDLM AHRSPEAFRA FIRSIPKPSV RYFAPGRVPG
PEEALVTQDQ AWSEAHASGE KRRCSAADRA LVELNSGVVS EVLLFGAPDL GRHTISPVSW
SSGDLVRREP VFANPRHPNF KQILVQGYVL DSHFPDCPPH PHLVTFIGRH RTSAEEGVTF
RLEDGAGALG AAGPSKASIL PNQAVPIALI ITPVRIDPEI YKAIQRSSRL AFDDTLAELW
ASRSPGPGPA AAETTSSSPT TGRSSR
