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PR00434

Identifier
INTERLEUKIN6  [View Relations]  [View Alignment]  
Accession
PR00434
No. of Motifs
4
Creation Date
29-NOV-1995  (UPDATE 07-JUN-1999)
Title
Interleukin-6 signature
Database References
PRINTS; PR00433 IL6GCSFMGF
INTERPRO; IPR001716
PDB; 1BGC
SCOP; 1BGC
Literature References
1. HIRANO, T., YASUKAWA, K., HARADA, H., TAGA, T., WATANABE, Y., MATSUDA,
T., KASHIWAMURA, S., NAKAJIMA, K., KOYAMA, K., IWAMATSU, A., TSUNASAWA, S.,
SAKIYAMA, F., MATSUI, H., TAKAHARA, Y., TANIGUCHI, T. AND KISHIMOTO, T.
Complementary DNA for a novel human interleukin (BSF-2) that induces B
lymphocytes to produce immunoglobulins.
NATURE 324 73-76 (1986).
 
2. LUETTICKEN, C., KRUETTGEN, A., MOELLER, C., HEINRICH, P.C. AND
ROSE-JOHN, S.
Evidence for the importance of a positive charge and an alpha-helical 
structure of the C-terminus for biological activity of human IL-6.
FEBS LETT. 282 265-267 (1991).
 
3. CLOGSTON, C.L., BOONE, T.C., CRANDALL, B.C., MENDIAZ, E.A. AND LU, H.S.
Disulfide structures of human interleukin-6 are similar to those of human
granulocyte colony stimulating factor.
ARCH.BIOCHEM.BIOPHYS. 272 144-151 (1989).
 
4. WALTER, M.R., COOK, W.J., ZHAO, B.G., CAMERON, R.P., EALICK. S.E., 
WALTER, R.L., REICHERT, P., NAGABHUSHAN, T.L., TROTTA, P.P. AND BUGG, C.E.
Crystal structure of recombinant human interleukin-4.
J.BIOL.CHEM. 267 20371-20376 (1992).

Documentation
Interleukin-6 (IL6), also refered to as B-cell differentiation factor-2
(BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of
biological functions [1]: it induces the final maturation of B-cells into
immunoglobulin-producing cells [1]; and it induces nerve cell
differentiation, and myeloma and plasmacytoma growth [1,2].
 
IL6 has a compact, globular fold (similar to other cytokines), stablised by
2 disulphide bonds [3]. One half of the structure is dominated by a 4 alpha-
helix bundle with a left-handed twist [4]; the helices are anti-parallel,
with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-
sheet. The fourth alpha-helix is important to the biological activity of 
the molecule [2].
 
INTERLEUKIN6 is a 4-element fingerprint that provides a signature for the
interleukin-6 cytokines. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length - motif 1 encodes the first
alpha helix; motif 2 encodes part of the first beta strand; motif 3 spans
part of the first beta strand and the second helix, and corresponds to
the region encoded by PROSITE pattern INTERLEUKIN_6 (PS00254), the 2 Cys
residues of which form a disulphide bond; and motif 4 spans the fourth
helix. Two iterations on OWL26.3 were required to reach convergence, at
which point a true set comprising 14 sequences was identified. A single
partial match (MGF_CHICK) was also found, a myelomonocytic growth factor
that matches motifs 3 and 4.
 
An update on SPTR37_9f identified a true set of 15 sequences.
Summary Information
15 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
415151515
30000
20000
1234
True Positives
IL6_BOVIN     IL6_CANFA     IL6_CAPHI     IL6_CERTO     
IL6_FELCA IL6_HORSE IL6_HUMAN IL6_MACFA
IL6_MACMU IL6_MOUSE IL6_PIG IL6_RAT
IL6_SHEEP O35736 O46568
Sequence Titles
IL6_BOVIN   INTERLEUKIN-6 PRECURSOR (IL-6) - BOS TAURUS (BOVINE). 
IL6_CANFA INTERLEUKIN-6 PRECURSOR (IL-6) - CANIS FAMILIARIS (DOG).
IL6_CAPHI INTERLEUKIN-6 PRECURSOR (IL-6) - CAPRA HIRCUS (GOAT).
IL6_CERTO INTERLEUKIN-6 PRECURSOR (IL-6) - CERCOCEBUS TORQUATUS ATYS (RED-CROWNED MANGABEY) (SOOTY MANGABEY).
IL6_FELCA INTERLEUKIN-6 PRECURSOR (IL-6) - FELIS SILVESTRIS CATUS (CAT).
IL6_HORSE INTERLEUKIN-6 PRECURSOR (IL-6) - EQUUS CABALLUS (HORSE).
IL6_HUMAN INTERLEUKIN-6 PRECURSOR (IL-6) (B-CELL STIMULATORY FACTOR 2) (BSF-2) (INTERFERON BETA-2) (HYBRIDOMA GROWTH FACTOR) - HOMO SAPIENS (HUMAN).
IL6_MACFA INTERLEUKIN-6 PRECURSOR (IL-6) - MACACA FASCICULARIS (CRAB EATING MACAQUE) (CYNOMOLGUS MONKEY).
IL6_MACMU INTERLEUKIN-6 PRECURSOR (IL-6) - MACACA MULATTA (RHESUS MACAQUE).
IL6_MOUSE INTERLEUKIN-6 PRECURSOR (IL-6) (INTERLEUKIN HP-1) (B-CELL HYBRIDOMA GROWTH FACTOR) - MUS MUSCULUS (MOUSE).
IL6_PIG INTERLEUKIN-6 PRECURSOR (IL-6) - SUS SCROFA (PIG).
IL6_RAT INTERLEUKIN-6 PRECURSOR (IL-6) - RATTUS NORVEGICUS (RAT).
IL6_SHEEP INTERLEUKIN-6 PRECURSOR (IL-6) - OVIS ARIES (SHEEP).
O35736 INTERLEUKIN-6 PRECURSOR (IL-6) - MARMOTA MONAX (WOODCHUCK).
O46568 INTERLEUKIN-6 PRECURSOR (IL-6) - EQUUS CABALLUS (HORSE).
Scan History
OWL26_3    2  100  NSINGLE    
SPTR37_9f 2 16 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
LIKYILGKISALRKEMC IL6_CANFA 51 51 -
QIRYILDGISALRKETC IL6_HUMAN 56 56 -
LIKHIVDKISAIRKEIC IL6_SHEEP 56 56 -
LIKRMVDKISAMRKEIC IL6_BOVIN 56 56 -
LITHVLWEIVEMRKELC IL6_MOUSE 54 54 -

Motif 2 width=23
Element Seqn Id St Int Rpt
CEDSKEALAENNLHLPKLEGKDG IL6_CANFA 73 5 -
CESSKEALAENNLNLPKMAEKDG IL6_HUMAN 78 5 -
CENSKETLAENKLKLPKMEEKDG IL6_SHEEP 78 5 -
CESSKETLAENKLNLPKMEEKDG IL6_BOVIN 78 5 -
CMNNDDALAENNLKLPEIQRNDG IL6_MOUSE 76 5 -

Motif 3 width=22
Element Seqn Id St Int Rpt
CFQSGFNQETCLTRITTGLVEF IL6_CANFA 96 0 -
CFQSGFNEETCLVKIITGLLEF IL6_HUMAN 101 0 -
CFQSGFNQAICLIKTTAGLLEY IL6_SHEEP 101 0 -
CFQSGFNQAICLIRTTAGLLEY IL6_BOVIN 101 0 -
CYQTGYNQEICLLKISSGLLEY IL6_MOUSE 99 0 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LILRSLEDFLQFSLRAVR IL6_CANFA 188 70 -
LILRSFKEFLQSSLRALR IL6_HUMAN 193 70 -
IILRSLENFLQFSLRAIR IL6_SHEEP 189 66 -
LILRNLENFLQFSLRAIR IL6_BOVIN 189 66 -
FILKSLEEFLKVTLRSTR IL6_MOUSE 192 71 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
LIKYILGKISAMRKEMC IL6_PIG 56 56 -
HIKYILGKISALKNEMC O46568 53 53 -
HIKYILGKISALKNEMC IL6_HORSE 53 53 -
LIKYILGKISALRKEMC IL6_CANFA 51 51 -
HIRYILDGISALRKETC IL6_MACFA 56 56 -
QIRYILDGISALRKETC IL6_HUMAN 56 56 -
HIRYILDGISALRKETC IL6_MACMU 56 56 -
LIKYILGKISALKKEMC IL6_FELCA 52 52 -
HIRYILDGISALRKETC IL6_CERTO 56 56 -
LIKHIVDKISAIRKEIC IL6_CAPHI 56 56 -
LIKHIVDKISAIRKEIC IL6_SHEEP 56 56 -
LIKRMVDKISAMRKEIC IL6_BOVIN 56 56 -
QISYLIKEVFEMRKELC O35736 49 49 -
LITYVLREILEMRKELC IL6_RAT 54 54 -
LITHVLWEIVEMRKELC IL6_MOUSE 54 54 -

Motif 2 width=23
Element Seqn Id St Int Rpt
CENSKEVLAENNLNLPKMAEKDG IL6_PIG 78 5 -
CENSKEVLAENNLNLPKMAEKDG O46568 75 5 -
CENSKEVLAENNLNLPKMAEKDG IL6_HORSE 75 5 -
CEDSKEALAENNLHLPKLEGKDG IL6_CANFA 73 5 -
CESSKEALAENNLNLPKMAEKDG IL6_MACFA 78 5 -
CESSKEALAENNLNLPKMAEKDG IL6_HUMAN 78 5 -
CESSKEALAENNLNLPKMAEKDG IL6_MACMU 78 5 -
CEDSKEALAENNLNLPKLAEKDG IL6_FELCA 74 5 -
CDSTKEALAENNLNLPKMAEKDG IL6_CERTO 78 5 -
CENSKETLAENKLKLPKMEEKDG IL6_CAPHI 78 5 -
CENSKETLAENKLKLPKMEEKDG IL6_SHEEP 78 5 -
CESSKETLAENKLNLPKMEEKDG IL6_BOVIN 78 5 -
CIKSHVAVSENNLNLPKMTEKDG O35736 71 5 -
CMNSDDALSENNLKLPEIQRNDG IL6_RAT 76 5 -
CMNNDDALAENNLKLPEIQRNDG IL6_MOUSE 76 5 -

Motif 3 width=22
Element Seqn Id St Int Rpt
CFQSGFNQETCLMRITTGLVEF IL6_PIG 101 0 -
CFQSGFNQETCLMKITTGLSEF O46568 98 0 -
CFQSGFNQETCLMKITTGLSEF IL6_HORSE 98 0 -
CFQSGFNQETCLTRITTGLVEF IL6_CANFA 96 0 -
CFQSGFNEDTCLVKIITGLLEF IL6_MACFA 101 0 -
CFQSGFNEETCLVKIITGLLEF IL6_HUMAN 101 0 -
CFQSGFNEDTCLVKIITGLLEF IL6_MACMU 101 0 -
CFQSGFNQETCLTRITTGLQEF IL6_FELCA 97 0 -
CFQSGFNEDTCLVKIITGLLEF IL6_CERTO 101 0 -
CFQSGFNQAICLIKTTAGLLEY IL6_CAPHI 101 0 -
CFQSGFNQAICLIKTTAGLLEY IL6_SHEEP 101 0 -
CFQSGFNQAICLIRTTAGLLEY IL6_BOVIN 101 0 -
CFQTGYNRDDCLVRITSGLLEF O35736 94 0 -
CFQTGYNQEICLLKICSGLLEF IL6_RAT 99 0 -
CYQTGYNQEICLLKISSGLLEY IL6_MOUSE 99 0 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LILRSLEDFLQFSLRAIR IL6_PIG 193 70 -
LILRSLEDFLQFSLRAIR O46568 189 69 -
LILRSLEDFLQFSLRAVR IL6_HORSE 189 69 -
LILRSLEDFLQFSLRAVR IL6_CANFA 188 70 -
LILRSFKEFLQSSLRALR IL6_MACFA 193 70 -
LILRSFKEFLQSSLRALR IL6_HUMAN 193 70 -
LILRSFKEFLQSNLRALR IL6_MACMU 193 70 -
LTLRRLEDFLQFSLRAVR IL6_FELCA 189 70 -
LILRSFKEFLQSSLRALR IL6_CERTO 193 70 -
IILRSLENFLQFSLRAIR IL6_CAPHI 189 66 -
IILRSLENFLQFSLRAIR IL6_SHEEP 189 66 -
LILRNLENFLQFSLRAIR IL6_BOVIN 189 66 -
LILSNFEDFLQFTLRAVR O35736 188 72 -
LILKALEEFLKVTMRSTR IL6_RAT 192 71 -
FILKSLEEFLKVTLRSTR IL6_MOUSE 192 71 -