ID   VPAP_HCMVM              Reviewed;         433 AA.
AC   F5HC97;
DT   11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 1.
DT   03-AUG-2022, entry version 32.
DE   RecName: Full=DNA polymerase processivity factor;
DE   AltName: Full=Polymerase accessory protein;
DE            Short=PAP;
DE   AltName: Full=Protein ICP36;
GN   Name=UL44;
OS   Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX   NCBI_TaxID=295027;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA   Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA   Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA   Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT   "Genetic content of wild-type human cytomegalovirus.";
RL   J. Gen. Virol. 85:1301-1312(2004).
CC   -!- FUNCTION: Accessory subunit of the DNA polymerase that plays an
CC       essential role in viral DNA replication and acts by increasing the
CC       processivity of polymerization. Forms dimers that binds to double-
CC       stranded DNA and UL54 specifically to stimulates long chain DNA
CC       synthesis efficiently. Plays an important role in maintaining the
CC       structure of viral replication compartments by interacting with host
CC       nucleolin/NUC. In addition, suppresses innate immune responses through
CC       effects on host IRF3 and NF-kappa-B. Mechanistically, interfere with
CC       the binding of IRF3 and the p65 NF-kappa-B subunit to the promoters of
CC       antiviral genes, thereby inhibiting the expression of these genes.
CC       {ECO:0000250|UniProtKB:P16790}.
CC   -!- SUBUNIT: Forms homodimers. Interacts with host SMARCB1. Interacts with
CC       host NCL/nucleolin; this interaction is important for the organization
CC       of proteins within viral replication compartments. Interacts with
CC       UL112/UL113; this interaction is necessary for efficient viral DNA
CC       replication. Interacts with UL84. Interacts with the uracil DNA
CC       glycosylase UL114. Interacts with the DNA polymerase catalytic subunit
CC       UL54. Interacts with host IRF3. Interacts with host RELA.
CC       {ECO:0000250|UniProtKB:P16790}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P16790}. Host
CC       nucleus {ECO:0000250|UniProtKB:P16790}.
CC   -!- DOMAIN: The C-terminal region is required for viral DNA synthesis.
CC       {ECO:0000250|UniProtKB:P16790}.
CC   -!- PTM: Phosphorylated by UL97 on serine residues, phosphorylation seems
CC       important for UL44 nuclear entry but does not directly affect its role
CC       in replication. {ECO:0000250|UniProtKB:P16790}.
CC   -!- PTM: Sumoylated. Sumoylation on Lys-410 increases viral DNA
CC       replication. {ECO:0000250|UniProtKB:P16790}.
CC   -!- SIMILARITY: Belongs to the herpesviridae polymerase accessory protein
CC       family. {ECO:0000305}.
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DR   EMBL; AY446894; AAR31608.1; -; Genomic_DNA.
DR   RefSeq; YP_081502.1; NC_006273.2.
DR   SMR; F5HC97; -.
DR   BioGRID; 1678013; 1.
DR   PRIDE; F5HC97; -.
DR   DNASU; 3077460; -.
DR   GeneID; 3077460; -.
DR   KEGG; vg:3077460; -.
DR   Reactome; R-HSA-9609690; HCMV Early Events.
DR   Reactome; R-HSA-9610379; HCMV Late Events.
DR   Proteomes; UP000000938; Genome.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0019033; C:viral tegument; TAS:Reactome.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0030337; F:DNA polymerase processivity factor activity; IEA:InterPro.
DR   GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR   GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039693; P:viral DNA genome replication; IEA:UniProtKB-KW.
DR   InterPro; IPR004997; Herpes_PAP.
DR   Pfam; PF03325; Herpes_PAP; 1.
PE   3: Inferred from homology;
KW   DNA replication; DNA-binding; Host nucleus; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host IRF3 by virus; Inhibition of host NF-kappa-B by virus;
KW   Inhibition of host RLR pathway by virus; Isopeptide bond; Phosphoprotein;
KW   Reference proteome; Ubl conjugation; Viral DNA replication;
KW   Viral immunoevasion; Virion.
FT   CHAIN           1..433
FT                   /note="DNA polymerase processivity factor"
FT                   /id="PRO_0000418258"
FT   REGION          274..433
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        363..377
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   433 AA;  46263 MW;  DC7669CA7121B2C0 CRC64;
     MDRKTRLSEP PTLALRLKPY KTAIQQLRSV IRALKENTTV TFLPTPSLIL QTVRSHCVSK
     ITFNSSCLYI TDKSFQPKTI NNSTPLLGNF MYLTSSKDLT KFYVQDISDL SAKISMCAPD
     FNMEFSSACV HGQDIVRESE NSAVHVDLDF GVVADLLKWI GPHTRVKRNV KKAPCPTGTV
     QILVHAGPPA IKFILTNGSE LEFTANNRVS FHGVKNMRIN VQLKNFYQTL LNCAVTKLPC
     TLRIVTEHDT LLYVASRNGL FAVENFLTEE PFQRGDPFDK NYVGNSGKSR GGGGGSGSLS
     SLANAGGLHD DGPGLDNDIM NEPMGLGGLG GGGGGGGKKH DRGGGGGSGT RKMSSGGGGG
     DHDHGLSSKE KYEQHKITSY LTSKGGSGGG GGGGGGGLDR NSGNYFNDAK EESDSEDSVT
     FEFVPNTKKQ KCG