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PR00433

Identifier
IL6GCSFMGF  [View Relations]  [View Alignment]  
Accession
PR00433
No. of Motifs
4
Creation Date
18-DEC-1995  (UPDATE 07-JUN-1999)
Title
Interleukin-6/G-CSF/MGF family signature
Database References
PRINTS; PR00434 INTERLEUKIN6
PROSITE; PS00254 INTERLEUKIN_6
PFAM; PF00489 IL-6
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) is a cytokine involved in a number of biological
functions: e.g., it induces the final maturation of B-cells into immuno-
globulin-producing cells, and induces nerve cell differentiation [1]. A
number of other cytokines may be grouped with IL6 on the basis of sequence
similarity [1-3]: these include granulocyte colony-stimulating factor (GCSF)
and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by
affecting the production, differentiation and function of 2 related white
cell groups in the blood [3]. MGF also acts in hematopoiesis, stimulating
proliferation and colony formation of normal and transformed avian cells
of the myeloid lineage.
 
Proteins belonging to the IL6/GCSF/MGF family have a compact, globular
fold (similar to other interleukins), stabilised 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 [4]. The
fourth helix is important to the biological activity of the molecule [2]. 
 
IL6GCSFMGF is a 4-element fingerprint that provides a signature for the
IL6/GCSF/MGF cytokine family. The fingerprint was derived from an initial
alignment of 8 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length - motif 1 encodes the first 
helix; motif 2 encodes part of the first strand; motif 3 spans part of the
first 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 encodes the fourth helix. Two iterations on
OWL26.3 were required to reach convergence, at which point a true set
comprising 21 sequences was identified. Two partial matches (NRL_1RHGA1 and
NRL_1RHGB1) were also found, both of which are GCSF fragments lacking the
portion of sequence bearing motifs 3 and 4.
 
An update on SPTR37_9f identified a true set of 23 sequences.
Summary Information
23 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
423232323
30000
20000
1234
True Positives
CSF3_BOVIN    CSF3_CANFA    CSF3_HUMAN    CSF3_MOUSE    
CSF3_PIG 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 MGF_CHICK O19180
O35736 O46568 P97712
Sequence Titles
CSF3_BOVIN  GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF) - BOS TAURUS (BOVINE). 
CSF3_CANFA GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF) - CANIS FAMILIARIS (DOG).
CSF3_HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR PRECURSOR (G-CSF) (PLURIPOIETIN) (FILGRASTIM) (LENOGRASTIM) - HOMO SAPIENS (HUMAN).
CSF3_MOUSE GRANULOCYTE COLONY-STIMULATING FACTOR PRECURSOR (G-CSF) - MUS MUSCULUS (MOUSE).
CSF3_PIG GRANULOCYTE COLONY-STIMULATING FACTOR PRECURSOR (G-CSF) - SUS SCROFA (PIG).
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).
MGF_CHICK MYELOMONOCYTIC GROWTH FACTOR PRECURSOR (MGF) - GALLUS GALLUS (CHICKEN).
O19180 GRANULOCYTE-COLONY STIMULATING FACTOR - SUS SCROFA (PIG).
O35736 INTERLEUKIN-6 PRECURSOR (IL-6) - MARMOTA MONAX (WOODCHUCK).
O46568 INTERLEUKIN-6 PRECURSOR (IL-6) - EQUUS CABALLUS (HORSE).
P97712 GRANULOCYTE COLONY STIMULATING FACTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL26_3    2  100  NSINGLE    
SPTR37_9f 2 24 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
LITHVLWEIVEMRKEL IL6_MOUSE 54 54 -
QVRKIQGDGAALQEKL CSF3_HUMAN 50 50 -
QVRKIQGDGAALQEKL NRL_1GNC 21 21 -
FTRKIRGDVAALQRAV MGF_CHICK 45 45 -
QIRYILDGISALRKET IL6_HUMAN 56 56 -
LIKYILGKISALRKEM IL6_CANFA 51 51 -
LIKHIVDKISAIRKEI IL6_SHEEP 56 56 -
LIKRMVDKISAMRKEI IL6_BOVIN 56 56 -

Motif 2 width=24
Element Seqn Id St Int Rpt
CATYKLCHPEELVLLGHSLGIPWA CSF3_HUMAN 69 3 -
CATYKLCHPEELVLLGHSLGIPWA NRL_1GNC 37 0 -
CNKSNMCESSKEALAENNLNLPKM IL6_HUMAN 72 0 -
CDKFNKCEDSKEALAENNLHLPKL IL6_CANFA 67 0 -
CEKNDECENSKETLAENKLKLPKM IL6_SHEEP 72 0 -
CEKNDECESSKETLAENKLNLPKM IL6_BOVIN 72 0 -
CNGNSDCMNNDDALAENNLKLPEI IL6_MOUSE 70 0 -
CDTFQLCTEEELQLVQPDPHLVQA MGF_CHICK 61 0 -

Motif 3 width=26
Element Seqn Id St Int Rpt
CPSQALQLAGCLSQLHSGLFLYQGLL NRL_1GNC 65 4 -
CFQSGFNEETCLVKIITGLLEFEVYL IL6_HUMAN 101 5 -
CFQSGFNQETCLTRITTGLVEFQLHL IL6_CANFA 96 5 -
CFQSGFNQAICLIKTTAGLLEYQIYL IL6_SHEEP 101 5 -
CFQSGFNQAICLIRTTAGLLEYQIYL IL6_BOVIN 101 5 -
CYQTGYNQEICLLKISSGLLEYHSYL IL6_MOUSE 99 5 -
CPSQALQLAGCLSQLHSGLFLYQGLL CSF3_HUMAN 97 4 -
CHKRGFQAEVCFTQIRAGLHAYHDSL MGF_CHICK 89 4 -

Motif 4 width=17
Element Seqn Id St Int Rpt
VASHLQSFLEVSYRVLR CSF3_HUMAN 186 63 -
ILANFQRFLETAYRALR MGF_CHICK 180 65 -
ILRSFKEFLQSSLRALR IL6_HUMAN 194 67 -
VASHLQSFLEVSYRVLR NRL_1GNC 154 63 -
ILRSLEDFLQFSLRAVR IL6_CANFA 189 67 -
ILRSLENFLQFSLRAIR IL6_SHEEP 190 63 -
ILRNLENFLQFSLRAIR IL6_BOVIN 190 63 -
ILKSLEEFLKVTLRSTR IL6_MOUSE 193 68 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
LIKYILGKISAMRKEM IL6_PIG 56 56 -
QIRYILDGISALRKET IL6_HUMAN 56 56 -
HIKYILGKISALKNEM O46568 53 53 -
HIKYILGKISALKNEM IL6_HORSE 53 53 -
LIKYILGKISALRKEM IL6_CANFA 51 51 -
HIRYILDGISALRKET IL6_MACFA 56 56 -
HIRYILDGISALRKET IL6_MACMU 56 56 -
LIKYILGKISALKKEM IL6_FELCA 52 52 -
HIRYILDGISALRKET IL6_CERTO 56 56 -
LIKHIVDKISAIRKEI IL6_CAPHI 56 56 -
LIKHIVDKISAIRKEI IL6_SHEEP 56 56 -
LIKRMVDKISAMRKEI IL6_BOVIN 56 56 -
QISYLIKEVFEMRKEL O35736 49 49 -
LITHVLWEIVEMRKEL IL6_MOUSE 54 54 -
LITYVLREILEMRKEL IL6_RAT 54 54 -
QVRKIQGDGAALQEKL CSF3_HUMAN 50 50 -
QVRKIQADGAELQERL CSF3_PIG 41 41 -
QVRKIQADGAELQERL O19180 41 41 -
QMRKVQADGTALQETL CSF3_CANFA 21 21 -
QVRKIQADGAELQERL CSF3_BOVIN 20 20 -
QVRKIQASGSVLLEQL CSF3_MOUSE 56 56 -
QVRKIQARNTELLEQL P97712 47 47 -
FTRKIRGDVAALQRAV MGF_CHICK 45 45 -

Motif 2 width=24
Element Seqn Id St Int Rpt
CEKYEKCENSKEVLAENNLNLPKM IL6_PIG 72 0 -
CNKSNMCESSKEALAENNLNLPKM IL6_HUMAN 72 0 -
CNNFSKCENSKEVLAENNLNLPKM O46568 69 0 -
CNNFSKCENSKEVLAENNLNLPKM IL6_HORSE 69 0 -
CDKFNKCEDSKEALAENNLHLPKL IL6_CANFA 67 0 -
CNRSNMCESSKEALAENNLNLPKM IL6_MACFA 72 0 -
CNRSNMCESSKEALAENNLNLPKM IL6_MACMU 72 0 -
CDNYNKCEDSKEALAENNLNLPKL IL6_FELCA 68 0 -
CNRSNMCDSTKEALAENNLNLPKM IL6_CERTO 72 0 -
CEKNDECENSKETLAENKLKLPKM IL6_CAPHI 72 0 -
CEKNDECENSKETLAENKLKLPKM IL6_SHEEP 72 0 -
CEKNDECESSKETLAENKLNLPKM IL6_BOVIN 72 0 -
CKNDETCIKSHVAVSENNLNLPKM O35736 65 0 -
CNGNSDCMNNDDALAENNLKLPEI IL6_MOUSE 70 0 -
CNGNSDCMNSDDALSENNLKLPEI IL6_RAT 70 0 -
CATYKLCHPEELVLLGHSLGIPWA CSF3_HUMAN 69 3 -
CATHKLCHPQELVLLGHSLGLPQA CSF3_PIG 57 0 -
CATHKLCHPQELVLLGHSLGLPQA O19180 57 0 -
CATHQLCHPEELVLLGHALGIPQP CSF3_CANFA 37 0 -
CAAHKLCHPEELMLLRHSLGIPQA CSF3_BOVIN 36 0 -
CATYKLCHPEELVLLGHSLGIPKA CSF3_MOUSE 72 0 -
CATYKLCHPEELVLFGHSLGIPKA P97712 63 0 -
CDTFQLCTEEELQLVQPDPHLVQA MGF_CHICK 61 0 -

Motif 3 width=26
Element Seqn Id St Int Rpt
CFQSGFNQETCLMRITTGLVEFQIYL IL6_PIG 101 5 -
CFQSGFNEETCLVKIITGLLEFEVYL IL6_HUMAN 101 5 -
CFQSGFNQETCLMKITTGLSEFQIYL O46568 98 5 -
CFQSGFNQETCLMKITTGLSEFQIYL IL6_HORSE 98 5 -
CFQSGFNQETCLTRITTGLVEFQLHL IL6_CANFA 96 5 -
CFQSGFNEDTCLVKIITGLLEFEVYL IL6_MACFA 101 5 -
CFQSGFNEDTCLVKIITGLLEFEVYL IL6_MACMU 101 5 -
CFQSGFNQETCLTRITTGLQEFQIYL IL6_FELCA 97 5 -
CFQSGFNEDTCLVKIITGLLEFEVYL IL6_CERTO 101 5 -
CFQSGFNQAICLIKTTAGLLEYQIYL IL6_CAPHI 101 5 -
CFQSGFNQAICLIKTTAGLLEYQIYL IL6_SHEEP 101 5 -
CFQSGFNQAICLIRTTAGLLEYQIYL IL6_BOVIN 101 5 -
CFQTGYNRDDCLVRITSGLLEFQVYL O35736 94 5 -
CYQTGYNQEICLLKISSGLLEYHSYL IL6_MOUSE 99 5 -
CFQTGYNQEICLLKICSGLLEFRFYL IL6_RAT 99 5 -
CPSQALQLAGCLSQLHSGLFLYQGLL CSF3_HUMAN 97 4 -
CSSQALQLTGCLNQLHGGLVLYQGLL CSF3_PIG 85 4 -
CSSQALQLTGCLNQLHGGLVLYQGLL O19180 85 4 -
CSSQALQLMGCLRQLHSGLFLYQGLL CSF3_CANFA 65 4 -
CSSQSLQLRGCLNQLHGGLFLYQGLL CSF3_BOVIN 64 4 -
CSSQALQQTQCLSQLHSGLCLYQGLL CSF3_MOUSE 100 4 -
CSSQALQQTKCLSQLHSGLFLYQGLL P97712 91 4 -
CHKRGFQAEVCFTQIRAGLHAYHDSL MGF_CHICK 89 4 -

Motif 4 width=17
Element Seqn Id St Int Rpt
ILRSLEDFLQFSLRAIR IL6_PIG 194 67 -
ILRSFKEFLQSSLRALR IL6_HUMAN 194 67 -
ILRSLEDFLQFSLRAIR O46568 190 66 -
ILRSLEDFLQFSLRAVR IL6_HORSE 190 66 -
ILRSLEDFLQFSLRAVR IL6_CANFA 189 67 -
ILRSFKEFLQSSLRALR IL6_MACFA 194 67 -
ILRSFKEFLQSNLRALR IL6_MACMU 194 67 -
TLRRLEDFLQFSLRAVR IL6_FELCA 190 67 -
ILRSFKEFLQSSLRALR IL6_CERTO 194 67 -
ILRSLENFLQFSLRAIR IL6_CAPHI 190 63 -
ILRSLENFLQFSLRAIR IL6_SHEEP 190 63 -
ILRNLENFLQFSLRAIR IL6_BOVIN 190 63 -
ILSNFEDFLQFTLRAVR O35736 189 69 -
ILKSLEEFLKVTLRSTR IL6_MOUSE 193 68 -
ILKALEEFLKVTMRSTR IL6_RAT 193 68 -
VASHLQSFLEVSYRVLR CSF3_HUMAN 186 63 -
VVSQLQSFLELAYRVLR CSF3_PIG 174 63 -
VVSQLQSFLELAYRVLR O19180 174 63 -
VASNLQSFLELAYRALR CSF3_CANFA 154 63 -
VASQLHRFLELAYRGLR CSF3_BOVIN 153 63 -
AISYLQGFLETARLALH CSF3_MOUSE 189 63 -
VTSYLQSFLETAHHALH P97712 180 63 -
ILANFQRFLETAYRALR MGF_CHICK 180 65 -