AN_HHV8P
ID AN_HHV8P Reviewed; 486 AA.
AC Q2HR95;
DT 24-JUL-2013, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 02-JUN-2021, entry version 69.
DE RecName: Full=Shutoff alkaline exonuclease {ECO:0000255|HAMAP-Rule:MF_04009};
DE Short=SOX {ECO:0000255|HAMAP-Rule:MF_04009};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04009};
GN Name=ORF37;
OS Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's
OS sarcoma-associated herpesvirus).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=868565;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16760382; DOI=10.1099/vir.0.81919-0;
RA Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.;
RT "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.";
RL J. Gen. Virol. 87:1781-1804(2006).
RN [2]
RP FUNCTION.
RX PubMed=15023341; DOI=10.1016/s1097-2765(04)00091-7;
RA Glaunsinger B., Ganem D.;
RT "Lytic KSHV infection inhibits host gene expression by accelerating global
RT mRNA turnover.";
RL Mol. Cell 13:713-723(2004).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF GLU-184; ASP-221; GLU-244 AND LYS-246.
RX PubMed=22046136; DOI=10.1371/journal.ppat.1002339;
RA Covarrubias S., Gaglia M.M., Kumar G.R., Wong W., Jackson A.O.,
RA Glaunsinger B.A.;
RT "Coordinated destruction of cellular messages in translation complexes by
RT the gammaherpesvirus host shutoff factor and the mammalian exonuclease
RT Xrn1.";
RL PLoS Pathog. 7:E1002339-E1002339(2011).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19587049; DOI=10.1128/jvi.01051-09;
RA Covarrubias S., Richner J.M., Clyde K., Lee Y.J., Glaunsinger B.A.;
RT "Host shutoff is a conserved phenotype of gammaherpesvirus infection and is
RT orchestrated exclusively from the cytoplasm.";
RL J. Virol. 83:9554-9566(2009).
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. Also acts as a cytoplasmic RNA
CC endonuclease that induces degradation of the majority of the cellular
CC messenger RNAs during early lytic infection. The resulting inhibition
CC of cellular protein synthesis serves to ensure maximal viral gene
CC expression and evasion from host immune response. Internally cleaves
CC host mRNAs which are then degraded by the cellular exonuclease XRN1.
CC Bypasses therefore the regulatory steps of deadenylation and decapping
CC normally required for XRN1 activation. {ECO:0000255|HAMAP-
CC Rule:MF_04009, ECO:0000269|PubMed:15023341,
CC ECO:0000269|PubMed:19587049, ECO:0000269|PubMed:22046136}.
CC -!- SUBUNIT: Forms a complex with the DNA polymerase, the DNA polymerase
CC processivity factor, and the major DNA binding protein.
CC {ECO:0000255|HAMAP-Rule:MF_04009}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04009,
CC ECO:0000269|PubMed:19587049}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04009, ECO:0000269|PubMed:19587049}.
CC -!- SIMILARITY: Belongs to the herpesviridae alkaline nuclease family.
CC {ECO:0000255|HAMAP-Rule:MF_04009}.
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DR EMBL; AF148805; ABD28888.1; -; Genomic_DNA.
DR RefSeq; YP_001129390.1; NC_009333.1.
DR SMR; Q2HR95; -.
DR BioGRID; 1777015; 5.
DR PRIDE; Q2HR95; -.
DR DNASU; 4961512; -.
DR GeneID; 4961512; -.
DR KEGG; vg:4961483; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; 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:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-UniRule.
DR GO; GO:0039657; P:suppression by virus of host gene expression; 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 Decay of host mRNAs by virus; Early protein; Endonuclease;
KW Eukaryotic host gene expression shutoff by virus; Exonuclease;
KW Host cytoplasm; Host gene expression shutoff by virus;
KW Host mRNA suppression by virus; Host nucleus; Host-virus interaction;
KW Hydrolase; Nuclease; Reference proteome; RNA-binding.
FT CHAIN 1..486
FT /note="Shutoff alkaline exonuclease"
FT /id="PRO_0000423145"
FT SITE 184
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT SITE 221
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT SITE 244
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT SITE 246
FT /note="Required for function"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04009"
FT MUTAGEN 184
FT /note="E->A: Complete loss of ability to deplete cellular
FT mRNAs."
FT /evidence="ECO:0000269|PubMed:22046136"
FT MUTAGEN 221
FT /note="D->A,S: Complete loss of ability to deplete cellular
FT mRNAs."
FT /evidence="ECO:0000269|PubMed:22046136"
FT MUTAGEN 244
FT /note="E->A: Complete loss of ability to deplete cellular
FT mRNAs."
FT /evidence="ECO:0000269|PubMed:22046136"
FT MUTAGEN 246
FT /note="K->I: Complete loss of ability to deplete cellular
FT mRNAs."
FT /evidence="ECO:0000269|PubMed:22046136"
SQ SEQUENCE 486 AA; 55076 MW; D7E0FA2FCB04AACF CRC64;
MEATPTPADL FSEDYLVDTL DGLTVDDQQA VLASLSFSKF LKHAKVRDWC AQAKIQPSMP
ALRMAYNYFL FSKVGEFIGS EDVCNFFVDR VFGGVRLLDV ASVYAACSQM NAHQRHHICC
LVERATSSQS LNPVWDALRD GIISSSKFHW AVKQQNTSKK IFSPWPITNN HFVAGPLAFG
LRCEEVVKTL LATLLHPDEA NCLDYGFMQS PQNGIFGVSL DFAANVKTDT EGRLQFDPNC
KVYEIKCRFK YTFAKMECDP IYAAYQRLYE APGKLALKDF FYSISKPAVE YVGLGKLPSE
SDYLVAYDQE WEACPRKKRK LTPLHNLIRE CILHNSTTES DVYVLTDPQD TRGQISIKAR
FKANLFVNVR HSYFYQVLLQ SSIVEEYIGL DSGIPRLGSP KYYIATGFFR KRGYQDPVNC
TIGGDALDPH VEIPTLLIVT PVYFPRGAKH RLLHQAANFW SRSAKDTFPY IKWDFSYLSA
NVPHSP
