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PR01883

Identifier
LEUKAEMIAIF  [View Relations]  [View Alignment]  
Accession
PR01883
No. of Motifs
9
Creation Date
26-JUL-2004
Title
Leukaemia inhibitory factor signature
Database References

PROSITE; PS00590 LIF_OSM
PFAM; PF01291 LIF_OSM
PRODOM; PD011266
INTERPRO; IPR003624; IPR001581
PDB; 1LKI
SCOP; 1LKI
CATH; 1LKI
Literature References
1. ROBINSON, R.C., GREY, L.M., STAUNTON, D., VANKELECOM, H.,
VERNALLIS, A.B., MOREAU, J.F., STUART, D.I., HEATH, J.K.
AND JONES, E.Y.
The crystal structure and biological function of leukemia inhibitory
factor: implications for receptor binding. 
CELL 77 1101-1116 (1994).
 
2. HINDS, M.G., MAURER, T., ZHANG, J.G., NICOLA, N.A. AND NORTON, R.S.
Solution structure of leukemia inhibitory factor.
J.BIOL.CHEM. 273 13738-13745 (1998).

Documentation
Leukaemia inhibitory factor (LIF) is a secreted protein that has the
capacity to induce terminal differentiation in leukaemic cells. Its
activities include induction of hematopoietic differentiation in normal
and myeloid leukaemia cells, induction of neuronal cell differentiation,
and stimulation of acute-phase protein synthesis in hepatocytes. LIF
belongs to a family of proteins that includes oncostatin M (OSM) and
ciliary neurotrophic factor (CNF).
 
The structure of murine LIF has been determined to 2.0A resolution
using X-ray crystallography [1]. The protein core comprises 4 alpha-
helices arranged in the up-up-down-down orientation typical of other
4-helix bundle cytokines. Sequence alignments of the related molecules,
OSM and CNF, when mapped to the LIF structure, indicate regions of
conserved surface character [1]. Analysis of the biological function
and receptor specificity of a series of human-mouse LIF chimeras
implicate two regions of receptor interaction within the fourth helix
and the preceding loop. 
 
The solution structure of a murine-human chimera of LIF has been 
determined using multidimensional heteronuclear NMR spectroscopy [2]. The 
overall topology resembles that of the crystal structure of murine LIF: 
some small differences between the structures are evident in the N-terminal
region; the main difference occurs at the C-terminal end of the CD
loop. This loop is close to a receptor-binding site on LIF that makes
a major contribution to high affinity binding to the LIF receptor 
alpha-chain, and hence these differences may have implications for
derived structural models of LIF receptor interactions [2].
 
LEUKAEMIAIF is a 9-element fingerprint that provides a signature for
leukaemia inhibitory factor. The fingerprint was derived from an initial 
alignment of 8 sequences: the motifs were drawn from conserved regions 
spanning the full alignment length - motif 1 encodes the C-terminus of the 
signal peptide; motif 2 spans helix 1; motif 3 includes the beta-turn 
following helix 1; motif 4 spans helix 2 and the following beta-turn; 
motifs 5 and 6 span helix 3; motif 7 encodes helix 4; motif 8 lies N-
terminal to the C-terminal helix; and motif 9 spans this helix. A single
iteration on SPTR41_24f was required to reach convergence, no further 
sequences being identified beyond the starting set.
Summary Information
8 codes involving  9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
9888888888
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
LIF_BOVIN     LIF_HUMAN     LIF_MOUSE     LIF_MUSVI     
LIF_RAT O88211 Q64015 Q9GKZ8
Sequence Titles
LIF_BOVIN   Leukemia inhibitory factor precursor (LIF) - Bos taurus (Bovine). 
LIF_HUMAN Leukemia inhibitory factor precursor (LIF) (Differentiation- stimulating factor) (D factor) (Melanoma-derived LPL inhibitor) (MLPLI) - Homo sapiens (Human).
LIF_MOUSE Leukemia inhibitory factor precursor (LIF) (Differentiation- stimulating factor) (D factor) - Mus musculus (Mouse).
LIF_MUSVI Leukemia inhibitory factor precursor (LIF) - Mustela vison (American mink).
LIF_RAT Leukemia inhibitory factor precursor (LIF) (Cholinergic neuronal differentiation factor) - Rattus norvegicus (Rat).
O88211 Leukemia inhibitory factor precursor - Rattus norvegicus (Rat).
Q64015 LIF - Mus sp.
Q9GKZ8 Leukemia inhibitory factor - Sus scrofa (Pig).
Scan History
SPTR41_24f 1  140  NSINGLE    
Initial Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
LLLILHWKHGAGSPLPITPVNATCA O88211 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA LIF_MOUSE 12 12 -
LLLILHWKHGAGSPLPITPVNATCA LIF_RAT 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA Q64015 15 15 -
LLLVLHWKHGAGTPLPITPVNATCA LIF_MUSVI 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA LIF_HUMAN 11 11 -
LLLVLHWKHGAGSPLSITPVNATCA Q9GKZ8 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA LIF_BOVIN 11 11 -

Motif 2 width=22
Element Seqn Id St Int Rpt
NLMNQIKSQLAQLNGSANALFI O88211 43 7 -
NLMNQIKNQLAQLNGSANALFI LIF_MOUSE 44 7 -
NLMNQIKSQLAQLNGSANALFI LIF_RAT 43 7 -
NLMNQIKNQLAQLNGSANALFI Q64015 47 7 -
NLMNQIRNQLAHVNGSANALFI LIF_MUSVI 43 7 -
NLMNQIRSQLAQLNGSANALFI LIF_HUMAN 43 7 -
NLMNQIKNQLAQLNSSANALFI Q9GKZ8 43 7 -
NLMNQIRNQLGQLNSSANSLFI LIF_BOVIN 43 7 -

Motif 3 width=11
Element Seqn Id St Int Rpt
YYTAQGEPFPN O88211 66 1 -
YYTAQGEPFPN LIF_MOUSE 67 1 -
YYTAQGEPFPN LIF_RAT 66 1 -
SYTAQGEPFPN Q64015 69 0 -
YYTAQGEPFPN LIF_MUSVI 66 1 -
YYTAQGEPFPN LIF_HUMAN 66 1 -
YYTAQGEPFPN Q9GKZ8 66 1 -
YYTAQGEPFPN LIF_BOVIN 66 1 -

Motif 4 width=17
Element Seqn Id St Int Rpt
NVDKLCAPNMTDFPPFH O88211 77 0 -
NVEKLCAPNMTDFPSFH LIF_MOUSE 78 0 -
NVDKLCAPNMTDFPPFH LIF_RAT 77 0 -
NVEKLCAPNMTDFPSFH Q64015 79 -1 -
NLDKLCGPNVTDFPPFH LIF_MUSVI 77 0 -
NLDKLCGPNVTDFPPFH LIF_HUMAN 77 0 -
NLDKLCGPNVTNFPPFH Q9GKZ8 77 0 -
NLDKLCSPNVTDFPPFH LIF_BOVIN 77 0 -

Motif 5 width=22
Element Seqn Id St Int Rpt
NGTEKTKLVELYRMVAYLGASL O88211 95 1 -
NGTEKTKLVELYRMVAYLSASL LIF_MOUSE 96 1 -
NGTEKTKLVELYRMVTYLGASL LIF_RAT 95 1 -
NGTEKTKLVELYRMVAYLSASL Q64015 97 1 -
NGTEKTRLVELYRIIAYLGASL LIF_MUSVI 95 1 -
NGTEKAKLVELYRIVVYLGTSL LIF_HUMAN 95 1 -
NGTEKARLVELYRIIAYLGASL Q9GKZ8 95 1 -
NGTEKARLVELYRIIAYLGASL LIF_BOVIN 95 1 -

Motif 6 width=16
Element Seqn Id St Int Rpt
NITWDQKNLNPTAVSL O88211 118 1 -
NITRDQKVLNPTAVSL LIF_MOUSE 119 1 -
NITWDQKNLNPTAVSL LIF_RAT 118 1 -
NITRDQKVLNPTAVSL Q64015 120 1 -
NITRDQKVLNPNALSL LIF_MUSVI 118 1 -
NITRDQKILNPSALSL LIF_HUMAN 118 1 -
NITRDQRSLNPGAVNL Q9GKZ8 118 1 -
NITRDQKVLNPYAHGL LIF_BOVIN 118 1 -

Motif 7 width=21
Element Seqn Id St Int Rpt
KLNATTDVMRGLLSNVLCRLC O88211 136 2 -
KLNATIDVMRGLLSNVLCRLC LIF_MOUSE 137 2 -
KLNATTDVMRGLLSSVLCRLC LIF_RAT 136 2 -
KLNATIDVMRGLLSNVLCRLC Q64015 138 2 -
KLKATADILRGLLSNVLCRLC LIF_MUSVI 136 2 -
KLNATADILRGLLSNVLCRLC LIF_HUMAN 136 2 -
KLNATADSMRGLLSNVLCRLC Q9GKZ8 136 2 -
KLSTTADVLRGLLSNVLCRLC LIF_BOVIN 136 2 -

Motif 8 width=16
Element Seqn Id St Int Rpt
CNKYHVGHVDVPCVPD O88211 156 -1 -
CNKYRVGHVDVPPVPD LIF_MOUSE 157 -1 -
CNKYHVGHVDVPCVPD LIF_RAT 156 -1 -
CNKYRVGHVDVPPVPD Q64015 158 -1 -
CNKYHVAHVDVAYGPD LIF_MUSVI 156 -1 -
CSKYHVGHVDVTYGPD LIF_HUMAN 156 -1 -
CNKYHVAHVDVAYGPD Q9GKZ8 156 -1 -
CSKYHVSHVDVTYGPD LIF_BOVIN 156 -1 -

Motif 9 width=21
Element Seqn Id St Int Rpt
KEAFQRKKLGCQLLGTYKQVI O88211 175 3 -
KEAFQRKKLGCQLLGTYKQVI LIF_MOUSE 176 3 -
KEAFQRKKLGCQLLGTYKQVI LIF_RAT 175 3 -
KEAFQRKKLGCQLLGTYKQVI Q64015 177 3 -
KDVFQKKKLGCQLLGKYKQVI LIF_MUSVI 175 3 -
KDVFQKKKLGCQLLGKYKQII LIF_HUMAN 175 3 -
KDVFQKKKLGCQLLGKYKQVI Q9GKZ8 175 3 -
KDVFQKKKLGCQLLGKYKQVI LIF_BOVIN 175 3 -
Final Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
LLLILHWKHGAGSPLPITPVNATCA O88211 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA LIF_MOUSE 12 12 -
LLLILHWKHGAGSPLPITPVNATCA LIF_RAT 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA Q64015 15 15 -
LLLVLHWKHGAGTPLPITPVNATCA LIF_MUSVI 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA LIF_HUMAN 11 11 -
LLLVLHWKHGAGSPLSITPVNATCA Q9GKZ8 11 11 -
LLLVLHWKHGAGSPLPITPVNATCA LIF_BOVIN 11 11 -

Motif 2 width=22
Element Seqn Id St Int Rpt
NLMNQIKSQLAQLNGSANALFI O88211 43 7 -
NLMNQIKNQLAQLNGSANALFI LIF_MOUSE 44 7 -
NLMNQIKSQLAQLNGSANALFI LIF_RAT 43 7 -
NLMNQIKNQLAQLNGSANALFI Q64015 47 7 -
NLMNQIRNQLAHVNGSANALFI LIF_MUSVI 43 7 -
NLMNQIRSQLAQLNGSANALFI LIF_HUMAN 43 7 -
NLMNQIKNQLAQLNSSANALFI Q9GKZ8 43 7 -
NLMNQIRNQLGQLNSSANSLFI LIF_BOVIN 43 7 -

Motif 3 width=11
Element Seqn Id St Int Rpt
YYTAQGEPFPN O88211 66 1 -
YYTAQGEPFPN LIF_MOUSE 67 1 -
YYTAQGEPFPN LIF_RAT 66 1 -
SYTAQGEPFPN Q64015 69 0 -
YYTAQGEPFPN LIF_MUSVI 66 1 -
YYTAQGEPFPN LIF_HUMAN 66 1 -
YYTAQGEPFPN Q9GKZ8 66 1 -
YYTAQGEPFPN LIF_BOVIN 66 1 -

Motif 4 width=17
Element Seqn Id St Int Rpt
NVDKLCAPNMTDFPPFH O88211 77 0 -
NVEKLCAPNMTDFPSFH LIF_MOUSE 78 0 -
NVDKLCAPNMTDFPPFH LIF_RAT 77 0 -
NVEKLCAPNMTDFPSFH Q64015 79 -1 -
NLDKLCGPNVTDFPPFH LIF_MUSVI 77 0 -
NLDKLCGPNVTDFPPFH LIF_HUMAN 77 0 -
NLDKLCGPNVTNFPPFH Q9GKZ8 77 0 -
NLDKLCSPNVTDFPPFH LIF_BOVIN 77 0 -

Motif 5 width=22
Element Seqn Id St Int Rpt
NGTEKTKLVELYRMVAYLGASL O88211 95 1 -
NGTEKTKLVELYRMVAYLSASL LIF_MOUSE 96 1 -
NGTEKTKLVELYRMVTYLGASL LIF_RAT 95 1 -
NGTEKTKLVELYRMVAYLSASL Q64015 97 1 -
NGTEKTRLVELYRIIAYLGASL LIF_MUSVI 95 1 -
NGTEKAKLVELYRIVVYLGTSL LIF_HUMAN 95 1 -
NGTEKARLVELYRIIAYLGASL Q9GKZ8 95 1 -
NGTEKARLVELYRIIAYLGASL LIF_BOVIN 95 1 -

Motif 6 width=16
Element Seqn Id St Int Rpt
NITWDQKNLNPTAVSL O88211 118 1 -
NITRDQKVLNPTAVSL LIF_MOUSE 119 1 -
NITWDQKNLNPTAVSL LIF_RAT 118 1 -
NITRDQKVLNPTAVSL Q64015 120 1 -
NITRDQKVLNPNALSL LIF_MUSVI 118 1 -
NITRDQKILNPSALSL LIF_HUMAN 118 1 -
NITRDQRSLNPGAVNL Q9GKZ8 118 1 -
NITRDQKVLNPYAHGL LIF_BOVIN 118 1 -

Motif 7 width=21
Element Seqn Id St Int Rpt
KLNATTDVMRGLLSNVLCRLC O88211 136 2 -
KLNATIDVMRGLLSNVLCRLC LIF_MOUSE 137 2 -
KLNATTDVMRGLLSSVLCRLC LIF_RAT 136 2 -
KLNATIDVMRGLLSNVLCRLC Q64015 138 2 -
KLKATADILRGLLSNVLCRLC LIF_MUSVI 136 2 -
KLNATADILRGLLSNVLCRLC LIF_HUMAN 136 2 -
KLNATADSMRGLLSNVLCRLC Q9GKZ8 136 2 -
KLSTTADVLRGLLSNVLCRLC LIF_BOVIN 136 2 -

Motif 8 width=16
Element Seqn Id St Int Rpt
CNKYHVGHVDVPCVPD O88211 156 -1 -
CNKYRVGHVDVPPVPD LIF_MOUSE 157 -1 -
CNKYHVGHVDVPCVPD LIF_RAT 156 -1 -
CNKYRVGHVDVPPVPD Q64015 158 -1 -
CNKYHVAHVDVAYGPD LIF_MUSVI 156 -1 -
CSKYHVGHVDVTYGPD LIF_HUMAN 156 -1 -
CNKYHVAHVDVAYGPD Q9GKZ8 156 -1 -
CSKYHVSHVDVTYGPD LIF_BOVIN 156 -1 -

Motif 9 width=21
Element Seqn Id St Int Rpt
KEAFQRKKLGCQLLGTYKQVI O88211 175 3 -
KEAFQRKKLGCQLLGTYKQVI LIF_MOUSE 176 3 -
KEAFQRKKLGCQLLGTYKQVI LIF_RAT 175 3 -
KEAFQRKKLGCQLLGTYKQVI Q64015 177 3 -
KDVFQKKKLGCQLLGKYKQVI LIF_MUSVI 175 3 -
KDVFQKKKLGCQLLGKYKQII LIF_HUMAN 175 3 -
KDVFQKKKLGCQLLGKYKQVI Q9GKZ8 175 3 -
KDVFQKKKLGCQLLGKYKQVI LIF_BOVIN 175 3 -