ID   VICA_HCMVM              Reviewed;         476 AA.
AC   F5HAY6;
DT   11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 1.
DT   23-FEB-2022, entry version 30.
DE   RecName: Full=Viral inhibitor of caspase-8-induced apoptosis;
DE            Short=vICA;
GN   Name=UL36;
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).
RN   [2]
RP   FUNCTION, INTERACTION WITH HOST CASP8, AND MUTAGENESIS OF CYS-131.
RC   STRAIN=Towne;
RX   PubMed=11427719; DOI=10.1073/pnas.141108798;
RA   Skaletskaya A., Bartle L.M., Chittenden T., McCormick A.L., Mocarski E.S.,
RA   Goldmacher V.S.;
RT   "A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8
RT   activation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:7829-7834(2001).
CC   -!- FUNCTION: Plays a role in the inhibition of apoptosis by interacting
CC       with the pro-domain of pro-caspase-8/CASP8 and thus preventing its
CC       activation. {ECO:0000269|PubMed:11427719}.
CC   -!- SUBUNIT: Interacts with host pro-caspase-8/CASP8; this interaction
CC       inhibits CASP8 activation. {ECO:0000269|PubMed:11427719}.
CC   -!- SIMILARITY: Belongs to the herpesviridae US22 family. {ECO:0000305}.
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DR   EMBL; AY446894; AAR31601.1; -; Genomic_DNA.
DR   RefSeq; YP_081495.1; NC_006273.2.
DR   PRIDE; F5HAY6; -.
DR   GeneID; 3077442; -.
DR   KEGG; vg:3077442; -.
DR   Reactome; R-HSA-9609690; HCMV Early Events.
DR   Reactome; R-HSA-9610379; HCMV Late Events.
DR   Proteomes; UP000000938; Genome.
DR   GO; GO:0019033; C:viral tegument; TAS:Reactome.
DR   GO; GO:0039650; P:suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process; IEA:UniProtKB-KW.
DR   InterPro; IPR003360; US22-like.
DR   Pfam; PF02393; US22; 2.
PE   1: Evidence at protein level;
KW   Host-virus interaction; Inhibition of host caspases by virus;
KW   Modulation of host cell apoptosis by virus; Reference proteome.
FT   CHAIN           1..476
FT                   /note="Viral inhibitor of caspase-8-induced apoptosis"
FT                   /id="PRO_0000418299"
FT   MUTAGEN         131
FT                   /note="C->R: Complete loss of interaction with Pro-caspase
FT                   8."
FT                   /evidence="ECO:0000269|PubMed:11427719"
SQ   SEQUENCE   476 AA;  54924 MW;  BEF2E05AA58785FA CRC64;
     MDDLRDTLMA YGCIAIRAGD FNGLNDFLEQ ECGTRLHVAW PERCFIQLRS RSALGPFVGK
     MGTVCSQGAY VCCQEYLHPF GFVEGPGFMR YQLIVLIGQR GGIYCYDDLR DCIYELAPTM
     KDFLRHGFRH CDHFHTMRDY QRPMVQYDDY WNAVMLYRGD VESLSAEVTK RGYASYSIDD
     PFDECPDTHF AFWTHNTEVM KFKETSFSVV RAGGSIQTME LMIRTVPRIT CYHQLLGALG
     HEVPERKEFL VRQYVLVDTF GVVYGYDPAM DAVYRLAEDV VMFTCVMGKK GHRNHRFSGR
     REAIVRLEKT PTCQHPKKTP DPMIMFDEDD DDELSLPRNV MTHEEAESRL YDAITENLMH
     CVKLVTTDSP LATHLWPQEL QALCDSPALS LCTDDVEGVR QKLRARTGSL HHFELSYRFH
     DEDPETYMGF LWDIPSCDRC VRRRRFKVCD VGRRHIIPGA ANGMPPLTPP HAYMNN