ID   VIL6_HHV8P              Reviewed;         204 AA.
AC   Q2HRC7;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   03-AUG-2022, entry version 75.
DE   RecName: Full=Viral interleukin-6 homolog;
DE            Short=vIL-6;
DE   Flags: Precursor;
GN   Name=K2;
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=10400794; DOI=10.1128/jvi.73.8.6953-6963.1999;
RA   Glenn M., Rainbow L., Aurade F., Davison A., Schulz T.F.;
RT   "Identification of a spliced gene from Kaposi's sarcoma-associated
RT   herpesvirus encoding a protein with similarities to latent membrane
RT   proteins 1 and 2A of Epstein-Barr virus.";
RL   J. Virol. 73:6953-6963(1999).
RN   [2]
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   [3]
RP   FUNCTION, AND INTERACTION WITH HOST IL6ST.
RX   PubMed=11238858; DOI=10.1128/jvi.75.7.3325-3334.2001;
RA   Li H., Wang H., Nicholas J.;
RT   "Detection of direct binding of human herpesvirus 8-encoded interleukin-6
RT   (vIL-6) to both gp130 and IL-6 receptor (IL-6R) and identification of amino
RT   acid residues of vIL-6 important for IL-6R-dependent and -independent
RT   signaling.";
RL   J. Virol. 75:3325-3334(2001).
RN   [4]
RP   FUNCTION.
RX   PubMed=12434062; DOI=10.1126/science.1074883;
RA   Chatterjee M., Osborne J., Bestetti G., Chang Y., Moore P.S.;
RT   "Viral IL-6-induced cell proliferation and immune evasion of interferon
RT   activity.";
RL   Science 298:1432-1435(2002).
RN   [5]
RP   REVIEW ON FUNCTION.
RX   PubMed=21767154; DOI=10.1089/jir.2011.0043;
RA   Sakakibara S., Tosato G.;
RT   "Viral interleukin-6: role in Kaposi's sarcoma-associated herpesvirus:
RT   associated malignancies.";
RL   J. Interferon Cytokine Res. 31:791-801(2011).
RN   [6]
RP   FUNCTION.
RX   PubMed=22521915; DOI=10.1016/j.virol.2012.03.013;
RA   Morris V.A., Punjabi A.S., Wells R.C., Wittkopp C.J., Vart R., Lagunoff M.;
RT   "The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic
RT   endothelial cell differentiation.";
RL   Virology 428:112-120(2012).
CC   -!- FUNCTION: Initiates signal transduction through binding to interleukin-
CC       6 receptor subunit beta IL6ST, independently of the cognate IL6
CC       receptor IL6R. In infected primary effusion lymphoma cells, promotes
CC       proliferation of cells, protects them from apoptosis, and promotes
CC       immune evasion of interferon activity. Drives also blood to lymphatic
CC       endothelial cell differentiation. {ECO:0000269|PubMed:11238858,
CC       ECO:0000269|PubMed:12434062, ECO:0000269|PubMed:22521915}.
CC   -!- SUBUNIT: Interacts with host IL6ST. {ECO:0000269|PubMed:11238858}.
CC   -!- INTERACTION:
CC       Q2HRC7; P08887: IL6R; Xeno; NbExp=3; IntAct=EBI-9007403, EBI-299383;
CC       Q2HRC7; P40189: IL6ST; Xeno; NbExp=2; IntAct=EBI-9007403, EBI-1030834;
CC   -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR   EMBL; AF148805; ABD28856.1; -; Genomic_DNA.
DR   RefSeq; YP_001129358.1; NC_009333.1.
DR   SMR; Q2HRC7; -.
DR   BioGRID; 1776952; 5.
DR   IntAct; Q2HRC7; 2.
DR   PRIDE; Q2HRC7; -.
DR   DNASU; 4961449; -.
DR   GeneID; 4961449; -.
DR   KEGG; vg:4961449; -.
DR   Proteomes; UP000000942; Genome.
DR   GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR   GO; GO:0005125; F:cytokine activity; IEA:InterPro.
DR   GO; GO:0005138; F:interleukin-6 receptor binding; IEA:InterPro.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR003574; IL-6.
DR   InterPro; IPR030474; IL-6/GCSF/MGF.
DR   PANTHER; PTHR10511; PTHR10511; 1.
DR   PANTHER; PTHR10511:SF3; PTHR10511:SF3; 1.
DR   Pfam; PF00489; IL6; 1.
DR   PRINTS; PR00433; IL6GCSFMGF.
DR   SMART; SM00126; IL6; 1.
DR   SUPFAM; SSF47266; SSF47266; 1.
PE   1: Evidence at protein level;
KW   Evasion of host immunity by viral interleukin-like protein;
KW   Host-virus interaction; Reference proteome; Signal; Viral immunoevasion.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..204
FT                   /note="Viral interleukin-6 homolog"
FT                   /id="PRO_0000423843"
SQ   SEQUENCE   204 AA;  23460 MW;  722A16644C6835A5 CRC64;
     MRWFKLWSIL LVGSLLVSGT RGKLPDAPEF EKDLLIQRLN WMLWVIDECF RDLCYRTGIC
     KGILEPAAIF HLKLPAINDT DHCGLIGFNE TSCLKKLADG FFEFEVLFKF LTTEFGKSVI
     NVDVMELLTK TLGWDIQEEL NKLTKTHYSP PKFDRGLLGR LQGLKYWVRH FASFYVLSAM
     EKFAGQAVRV LNSIPDVTPD VHDK