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PR01485

Identifier
THROMBOPTN  [View Relations]  [View Alignment]  
Accession
PR01485
No. of Motifs
6
Creation Date
15-MAR-2001
Title
Thrombopoietin signature
Database References

PROSITE; PS00817 EPO_TPO
BLOCKS; BL00817
PFAM; PF00758 EPO_TPO
INTERPRO; IPR001323
Literature References
1. KAUSHANSKY, K.
The enigmatic megakaryocyte gradually reveals its secrets.
BIOESSAYS 21 353-360 (1999).
 
2. LOK, S., KAUSHANSKY, K., HOLLY, R.D., KUIJPER, J.L., LOFTON-DAY, C.E.,
OORT, P.J., GRANT, F.J., HEIPEL, M.D., BURKHEAD, S.K., KRAMER, J.M.,
BELL L.A.N., SPRECHER C.A., BLUMBERG H., JOHNSON R., PRUNKARD D.,
CHING, A.F.T., MATHEWES, S.L., BAILEY, M.C., FORSTROM, J.W., BUDDLE, M.M.,
OSBORN, S.G., EVANS, S.J., SHEPPARD, P.O., PRESNELL, S.R., O'HARA, P.J.,
HAGEN, F.S., ROTH, G.J. AND FOSTER, D.C.
Cloning and expression of murine thrombopoietin cDNA and stimulation of
platelet production in vivo.
NATURE 369 565-568 (1994).
 
3. ALEXANDER, W.S.
Thrombopoietin and the c-mpl receptor: insights from gene targeting.
INT.J.BIOCHEM.CELL BIOL. 31 1027-1035 (1999).
 
4. PARK, H., PARK, S.S., JIN, E.H., SONG, J-S., RYU, S-E., YU, M-H.
AND HONG, H.J.
Identification of functionally important residues of human thrombopoietin.
J.BIOL.CHEM. 273 256-261 (1998).

Documentation
Megakaryocytes are large cells found in the bone marrow that, upon
maturation, fragment into platelets. The term thrombopoietin (TPO) was
coined in 1958 to describe a possible humoral entity that stimulates
megakaryocyte development into platelets. The discovery of a novel
haemopoietic cytokine receptor encoded by the proto-oncogene c-mpl raised
speculation that this was the receptor for thrombopoietin, and prompted a
search for the endogenous ligand [1]. The ligand was cloned and in vivo-
administration of the recombinant protein to mice produced a 4-fold increase
in circulating platelets. These results suggested that the c-mpl ligand was
in fact thrombopoietin [2].
 
More recent studies have shown that TPO is expressed in hepatocytes, the
renal proximal tubules, muscle cells and stromal cells in haemopoietic
organs [3]. TPO is a 332-residue protein with a 2-domain structure. The
domain at the N-terminus is 153 amino acids long, shares similarity with
erythropoietin and can itself stimulate megakaryopoiesis in vitro. A four-
alpha-helical structure is predicted, which is typical of many haemopoietic
regulators. The C-terminal domain is 179 amino acids long, is highly 
variable across species and is not required for the binding of c-mpl [4].
 
THROMBOPTN is a 6-element fingerprint that provides a signature for the
thrombopoietins. The fingerprint was derived from an initial alignment of 3
sequences: the motifs were drawn from conserved regions spanning the 
N-terminal domain. Two iterations on SPTR39_15f were required to reach
convergence, at which point a true set comprising 5 sequences was identified.
Summary Information
5 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
6555555
5000000
4000000
3000000
2000000
123456
True Positives
Q9QVR7        TPO_CANFA     TPO_HUMAN     TPO_MOUSE     
TPO_RAT
Sequence Titles
Q9QVR7      TRUNCATED THROMBOPOIETIN - Mus sp.            
TPO_CANFA THROMBOPOIETIN PRECURSOR (MEGAKARYOCYTE COLONY STIMULATING FACTOR) (C-MPL LIGAND) (ML) (MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR) (MGDF) - Canis familiaris (Dog).
TPO_HUMAN THROMBOPOIETIN PRECURSOR (MEGAKARYOCYTE COLONY STIMULATING FACTOR) (MYELOPROLIFERATIVE LEUKEMIA VIRUS ONCOGENE LIGAND) (C-MPL LIGAND) (ML) (MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR) (MGDF) - Homo sapiens (Human).
TPO_MOUSE THROMBOPOIETIN PRECURSOR (MEGAKARYOCYTE COLONY STIMULATING FACTOR) (MYELOPROLIFERATIVE LEUKEMIA VIRUS ONCOGENE LIGAND) (C-MPL LIGAND) (ML) (MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR) (MGDF) - Mus musculus (Mouse).
TPO_RAT THROMBOPOIETIN PRECURSOR - Rattus norvegicus (Rat).
Scan History
SPTR39_15f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
RLTLSSPVAPACDPR Q9QVR7 17 17 -
RLTLSSPVPPACDPR TPO_RAT 17 17 -
RLTLSSPAPPACDLR TPO_HUMAN 17 17 -

Motif 2 width=15
Element Seqn Id St Int Rpt
LLNKLLRDSHLLHSR Q9QVR7 32 0 -
LLNKLLRDSYLLHSR TPO_RAT 32 0 -
VLSKLLRDSHVLHSR TPO_HUMAN 32 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
SQCPDVDPLSIPVLL Q9QVR7 48 1 -
SQCPDVNPLSIPVLL TPO_RAT 48 1 -
SQCPEVHPLPTPVLL TPO_HUMAN 48 1 -

Motif 4 width=13
Element Seqn Id St Int Rpt
PAVDFSLGEWKTQ Q9QVR7 63 0 -
PAVDFSLGEWKTQ TPO_RAT 63 0 -
PAVDFSLGEWKTQ TPO_HUMAN 63 0 -

Motif 5 width=21
Element Seqn Id St Int Rpt
KAQDILGAVSLLLEGVMAARG Q9QVR7 80 4 -
KAQDILGAVSLLLEGVMAARG TPO_RAT 80 4 -
KAQDILGAVTLLLEGVMAARG TPO_HUMAN 80 4 -

Motif 6 width=21
Element Seqn Id St Int Rpt
SCLSSLLGQLSGQVRLLLGAL Q9QVR7 105 4 -
SCLSSLLGQLSGQVRLLLGAL TPO_RAT 105 4 -
TCLSSLLGQLSGQVRLLLGAL TPO_HUMAN 105 4 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
RLTLSSPVAPACDPR Q9QVR7 17 17 -
RLTLSSPVAPACDPR TPO_MOUSE 17 17 -
RLTLSSPVPPACDPR TPO_RAT 17 17 -
RLTLSSPAPPACDLR TPO_HUMAN 17 17 -
RLDPCLPAPPACDPR TPO_CANFA 17 17 -

Motif 2 width=15
Element Seqn Id St Int Rpt
LLNKLLRDSHLLHSR Q9QVR7 32 0 -
LLNKLLRDSHLLHSR TPO_MOUSE 32 0 -
LLNKLLRDSYLLHSR TPO_RAT 32 0 -
VLSKLLRDSHVLHSR TPO_HUMAN 32 0 -
LLNKMLRDSHVLHSR TPO_CANFA 32 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
SQCPDVDPLSIPVLL Q9QVR7 48 1 -
SQCPDVDPLSIPVLL TPO_MOUSE 48 1 -
SQCPDVNPLSIPVLL TPO_RAT 48 1 -
SQCPEVHPLPTPVLL TPO_HUMAN 48 1 -
SQCPDIYPLSTPVLL TPO_CANFA 48 1 -

Motif 4 width=13
Element Seqn Id St Int Rpt
PAVDFSLGEWKTQ Q9QVR7 63 0 -
PAVDFSLGEWKTQ TPO_MOUSE 63 0 -
PAVDFSLGEWKTQ TPO_RAT 63 0 -
PAVDFSLGEWKTQ TPO_HUMAN 63 0 -
PAVDFSLGEWKTQ TPO_CANFA 63 0 -

Motif 5 width=21
Element Seqn Id St Int Rpt
KAQDILGAVSLLLEGVMAARG Q9QVR7 80 4 -
KAQDILGAVSLLLEGVMAARG TPO_MOUSE 80 4 -
KAQDILGAVSLLLEGVMAARG TPO_RAT 80 4 -
KAQDILGAVTLLLEGVMAARG TPO_HUMAN 80 4 -
KAQDVWGAVALLLDGVLAARG TPO_CANFA 80 4 -

Motif 6 width=21
Element Seqn Id St Int Rpt
SCLSSLLGQLSGQVRLLLGAL Q9QVR7 105 4 -
SCLSSLLGQLSGQVRLLLGAL TPO_MOUSE 105 4 -
SCLSSLLGQLSGQVRLLLGAL TPO_RAT 105 4 -
TCLSSLLGQLSGQVRLLLGAL TPO_HUMAN 105 4 -
SCLSSLLGQLSGQVRLLLGAL TPO_CANFA 105 4 -