Gene ID:KSHV009
DNA Molecule Name:
1
GenBank ID:
1718260
Gene Name:
K2 vIL-6
Definition:
interleukin-6 cellular homolog
Gene Start:
46116
Gene Stop:
45502
Gene Length:
615
Molecular Weight*:
23393
pI*:
6.70
Net Charge*:
-1.08
EC:
Functional Class:
cell signaling pathways
virulence factor; blocks apoptosis
virulence factor; cell cycle regulation and in vitro transformation
Gene Ontology:
Pathway: pathway table
Primary Evidence:
Li H, Wang H, Nicholas J, Detection of direct binding of human herpesvirus 8-encoded interleukin-6 (vIL-6) to both gp130 and IL-6 receptor (IL-6R) and identification of amino acid residues of vIL-6 important for IL-6R-dependent and -independent signaling, J Virol 2001 Apr;75(7):3325-34,
PMID: 11238858.
Chow D, He X, Snow AL, Rose-John S, Garcia KC, Structure of an extracellular gp130 cytokine receptor signaling complex, Science 2001 Mar 16;291(5511):2150-5,
PMID: 11251120.
Katano H, Sato Y, Kurata T, Mori S, Sata T.
Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease.
Virology. 2000 Apr 10;269(2):335-44.
PMID: 10753712.
Hideshima T, Chauhan D, Teoh G, Raje N, Treon SP, Tai YT, Shima Y, Anderson KC.
Characterization of signaling cascades triggered by human interleukin-6 versus Kaposi's sarcoma-associated herpes virus-encoded viral interleukin 6.
Clin Cancer Res. 2000 Mar;6(3):1180-9.
PMID: 10741750.
Osborne J, Moore PS, Chang Y, KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways, Hum Immunol 1999 Oct;60(10):921-7,
PMID: 10566591.
Nicholas J, Ruvolo VR, Burns WH, Sandford G, Wan X, Ciufo D, Hendrickson SB, Guo HG, Hayward GS, Reitz MS, Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6, Nat Med 1997 Mar;3(3):287-92,
PMID: 9055855.
Molden J, Chang Y, You Y, Moore PS, Goldsmith MA, A Kaposi's sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6)
activates signaling through the shared gp130 receptor subunit, J Biol Chem 1997 Aug 1;272(31):19625-31,
PMID: 9235971.
Neipel,F., Albrecht,J.C. and Fleckenstein,B. Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? J. Virol. 71 (6), 4187-4192 (1997),
Medline: 97296220.
Moore PS, Boshoff C, Weiss RA, Chang Y, Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV, Science 1996 Dec 6;274(5293):1739-44,
PMID: 8939871.
Comment:
The following description was provided by Patrick S. Moore, Departments of Pathology & Epidemiology, Columbia University.
Expression pattern: Lytic and constitutive expression in B cells. Not expressed in the majority of KS tumors (Nicholas et al. 1997, Moore et al. 1996).
Description: vIL-6 is a secreted cytokine functionally similar to cellular IL-6. Crystallographic studies show that it can bind directly to and activate the gp130 receptor-transducer in the absence of the high-affinity IL-6 receptor gp80 (IL-6Ra) although gp80 binding may result in more efficient signal transduction (Chow et al. 2001, Molden et al. 1997, Li, Wang, Nicholas 2001). Activation of gp130 by vIL-6 results in similar downstream signal pathway activation as occurs with cellular IL-6 (Osborne et al. 1999). vIL-6 expression is likely to be responsible for B cell hyperplasia in multicentric Castleman's disease and it is an autocrine growth factor, along with IL-10, for primary effusion lymphoma cell lines.
Blast Summary: PSI-Blast Search
K2 shows significant similarity to interleukin-6 proteins from several mammals, but no similarity is found to any herpesvirus or other viral proteins. Significant interleukin-6 similarities using gapped BLAST include residues 37-191 are 26% similar to Aotus lemurinus IL-6 (6648940|gb|AAF21298.1|AF097323_1), residues 28-191 are 28% similar to Cercocebus torquatus IL-6 (1170539|sp|P46650|IL6_CERTO) and residues 28-191 are 25% similar to human IL-6 (3319067|pdb|1ALU).
Top Blast Hits: Updated monthly
Click here to view the entire PsiBlast results.
COGS Summary: COGS Search
No hits to the COGs database.
Blocks Summary: Blocks Search
***** IPB003573 (Interleukin-6/G-CSF/MGF family) with a combined E-value of 1e-10.
IPB003573B 70-113
IPB003573C 162-192
ProDom Summary: Protein Domain Search
Residues 28-191 are identical to a (FACTOR GRO TH INTERLEUKIN-6) protein domain (PD004356 which is seen in O40918_KSHV.
Paralogs: Local Blast Search
No paralogs found in Human Herpesvirus 8.
Pfam Summary: Pfam Search
Pfam Result(s) Predicted Using Pfam 6.0:
Residues 72 to 192 (P_SCORE 1.4e-015) place KSHV009 in the IL6 family (PF00489) which is described as Interleukin-6/G-CSF/MGF family.
Pfam Result(s) Predicted Using Pfam-Pro 1.0:
No significant hits to the Pfam-Pro database.
Top PDB Hits:
pdb|1ALU| Human Interleukin-6 75 8e-015
pdb|1IL6| Human Interleukin-6, Nmr, Minimized Average Struct... 75 8e-015
Gene Protein Sequence:
MCWFKLWSLLLVGSLLVSGTRGKLPDAPEFEKDLLIQRLNWMLWVIDECF
RDLCYRTGICKGILEPAAIFHLKLPAINDTDHCGLIGFNETSCLKKLADG
FFEFEVLFKFLTTEFGKSVINVDVMELLTKTLGWDIQEELNKLTKTHYSP
PKFDRGLLGRLQGLKYWVRHFASFYVLSAMEKFAGQAVRVLDSIPDVTPD
VHDK$
Gene Nucleotide Sequence: Sequence Viewer
ATGTGCTGGTTCAAGTTGTGGTCTCTCTTGCTGGTCGGTTCACTGCTGGT
ATCTGGAACGCGGGGCAAGTTGCCGGACGCCCCCGAGTTTGAAAAGGATC
TTCTCATTCAGAGACTCAATTGGATGCTATGGGTGATCGATGAATGCTTC
CGCGACCTCTGTTACCGTACCGGCATCTGCAAGGGTATTCTAGAGCCCGC
TGCTATTTTTCATCTGAAACTACCAGCCATCAACGATACTGATCACTGCG
GGTTAATAGGATTTAATGAGACTAGCTGCCTTAAAAAGCTCGCCGATGGC
TTTTTTGAATTCGAGGTGTTGTTTAAGTTTTTAACGACGGAGTTTGGAAA
ATCAGTGATAAACGTGGACGTCATGGAGCTTCTGACGAAGACCTTAGGAT
GGGACATACAGGAAGAGCTCAATAAGCTGACTAAGACGCACTACAGTCCA
CCCAAATTTGACCGCGGTCTATTAGGGAGGCTTCAGGGACTTAAGTATTG
GGTGAGACACTTTGCTTCGTTTTATGTTCTGAGTGCAATGGAAAAGTTTG
CAGGTCAAGCGGTGCGTGTTTTGGACTCTATCCCAGACGTGACTCCTGAC
GTCCACGATAAGTAA