ID   UL38_HCMVA              Reviewed;         331 AA.
AC   P16779; Q7M6P5;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   02-JUN-2021, entry version 55.
DE   RecName: Full=Apoptosis inhibitor UL38;
GN   Name=UL38;
OS   Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX   NCBI_TaxID=10360;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
RA   Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
RA   Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
RA   Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
RT   "Analysis of the protein-coding content of the sequence of human
RT   cytomegalovirus strain AD169.";
RL   Curr. Top. Microbiol. Immunol. 154:125-169(1990).
RN   [2]
RP   GENOME REANNOTATION.
RX   PubMed=12533697; DOI=10.1099/vir.0.18606-0;
RA   Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA   McGeoch D.J., Hayward G.S.;
RT   "The human cytomegalovirus genome revisited: comparison with the chimpanzee
RT   cytomegalovirus genome.";
RL   J. Gen. Virol. 84:17-28(2003).
RN   [3]
RP   ERRATUM OF PUBMED:12533697.
RA   Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA   McGeoch D.J., Hayward G.S.;
RL   J. Gen. Virol. 84:1053-1053(2003).
RN   [4]
RP   IDENTIFICATION.
RX   PubMed=15452216; DOI=10.1128/jvi.78.20.10960-10966.2004;
RA   Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA   Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA   Shenk T., Smith R.D., Nelson J.A.;
RT   "Identification of proteins in human cytomegalovirus (HCMV) particles: the
RT   HCMV proteome.";
RL   J. Virol. 78:10960-10966(2004).
RN   [5]
RP   ERRATUM OF PUBMED:15452216.
RA   Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA   Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA   Shenk T., Smith R.D., Nelson J.A.;
RL   J. Virol. 78:13395-13395(2004).
CC   -!- FUNCTION: Plays a role in the inhibition of host apoptosis to
CC       facilitate efficient viral replication. Promotes stabilization and
CC       inactivation of host TP53 through interaction with host MDM2 (By
CC       similarity). Induces host mTORC1 activation by antagonizing the ability
CC       of host TSC1/2 to negatively regulate mTORC1. Thus, inhibits a growth
CC       regulatory pathway to facilitate viral replication (By similarity).
CC       {ECO:0000250|UniProtKB:F5HG98, ECO:0000250|UniProtKB:Q9WT45}.
CC   -!- SUBUNIT: Interacts with host MDM2; this interaction leads to the
CC       stabilization of host TP53 (By similarity). Interacts with host TSC2;
CC       this interaction prevents host cell stress responses (By similarity).
CC       {ECO:0000250|UniProtKB:F5HG98, ECO:0000250|UniProtKB:Q9WT45}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:F5HG98}.
CC       Host nucleus {ECO:0000250|UniProtKB:F5HG98}. Note=localized in the host
CC       nucleus at early times postinfection and then increases in both nuclear
CC       and cytoplasmic compartments during the course of infection.
CC       {ECO:0000250|UniProtKB:F5HG98}.
CC   -!- SIMILARITY: Belongs to the beta-herpesvirinae UL38 protein family.
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DR   EMBL; X17403; CAA35397.1; -; Genomic_DNA.
DR   EMBL; BK000394; DAA00143.1; -; Genomic_DNA.
DR   PIR; S09800; S09800.
DR   Proteomes; UP000008991; Genome.
DR   Proteomes; UP000008992; 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:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR   InterPro; IPR003360; US22-like.
DR   Pfam; PF02393; US22; 1.
PE   3: Inferred from homology;
KW   Host cytoplasm; Host nucleus; Host-virus interaction;
KW   Modulation of host cell apoptosis by virus; Reference proteome.
FT   CHAIN           1..331
FT                   /note="Apoptosis inhibitor UL38"
FT                   /id="PRO_0000115320"
FT   REGION          247..305
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        276..303
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   331 AA;  36737 MW;  B0AFAD6DA2FF2B49 CRC64;
     MTTTTHSTAA IMSLLDEAEW RQTQMDVGGL IQASALGKVA LRYAVRKLMK RGARLRHDSG
     LYVCICDPSY EFLQMNLSKI SWLERHCPPL DQELIMFGVI EAWEEASVRP TRQLVLFMTP
     KWDVFAYDSG ILFFLAPSMA QFWHGAIVLE YWNALFPVEV RSHVRQHAHT MDDLVMVFHQ
     LDYEKQVLEA RRDKNTEGPR TFAKSVNSYV RAILESERRI REGKIPMTFV DRDSLRANSL
     AHIQATGAQP SHAPAQRVLS APPSLPLPVS EEDPAAAATP SSSAATTPPS SVVPASVESE
     LSSSPPLPPV VVKDVVYTAG EGDVVQMVVV V