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PR00272

Identifier
ERYTHROPTN  [View Relations]  [View Alignment]  
Accession
PR00272
No. of Motifs
6
Creation Date
21-DEC-1993  (UPDATE 07-JUN-1999)
Title
Erythropoietin signature
Database References

PROSITE; PS00817 EPO_TPO
BLOCKS; BL00817
INTERPRO; IPR003013
Literature References
1. SHOEMAKER, C.B. AND MITSOCK, L.D.
Murine erythropoietin gene - Cloning, expression , and human gene homology.
MOL.CELL.BIOL. 6(3) 849-858 (1986).
 
2. TAKEUCHI, M., TAKASAKI, S., MIYAZAKI, H., KATO, T., HOSHI, S., 
KOCHIBE, N. AND KOBATA, A.
Comparative study of the asparagine-linked sugar chains of human
erythropoietins purified from urine and the culture medium of recombinant
chinese hamster ovary cell.
J.BIOL.CHEM. 263(8) 3657-3663 (1988).
 
3. LIN, F.K., LIN, C.H., LAI, P.H., BROWNE, J.K., EGRIE, J.C., SMALLING, R.,
FOX, G.M., CHEN, K.K., CASTRO, M. AND SUGGS, S.
Monkey erythropoietin gene - Cloning, expression and comparison with the
human erythropoietin gene.
GENE 44(2) 201-209 (1986).
 
4. NAGAO, M., SUGA, H., OKANO, M., MASUDA, S., NARITA, H., IKURA, K. AND
SASAKI, R.
Nucleotide sequence of rat erythropoietin.
BIOCHIM.BIOPHYS.ACTA 1171(1) 99-102 (1992).

Documentation
Erythropoietin, a plasma glycoprotein, is the primary physiological
mediator of erythropoiesis [1]. It is involved in the regulation of the
level of peripheral erythrocytes by stimulating the differentiation of 
erythroid progenitor cells, found in the spleen and bone marrow, into mature
erythrocytes [2]. It is primarily produced in adult kidneys and foetal 
liver [3], acting by attachment to specific binding sites on erythroid
progenitor cells, stimulating their differentiation [3]. Severe kidney
dysfunction causes reduction in the plasma levels of erythropoietin,
resulting in chronic anaemia - injection of purified erythropoietin into
the blood stream can help to relieve this type of anaemia [1]. In cases of
severe kidney damage, causing very low erythropoietin levels, the liver
can take over production of the hormone [1].
 
Levels of erythropoietin in plasma fluctuate with varying oxygen tension of
the blood, but androgens and prostaglandins also modulate the levels to some
extent [3]. Erythropoietin glycoprotein sequences are well conserved, a
consequence of which is that the hormones are cross-reactive among mammals,
i.e. that from one species, say human, can stimulate erythropoiesis in
other species, say mouse or rat [4]. The human form has a single O-linked
and 3 N-linked sugar chains, which may affect biological activity, such as
turnover rate, antigenicity, and so on [1].
 
ERYTHROPTN is a 6-element fingerprint that provides a signature for the
erythropoietins. The fingerprint was derived from an initial alignment of 4
sequences: the motifs were drawn from conserved regions spanning the full
alignment length - motif 1 includes the region encoded by PROSITE pattern
EPO (PS00817), the totally conserved Cys of which is involved in disulphide
bond formation; motifs 2 and 4 include conserved Asn residues, all of
which have N-linked sugar chains attached; and motif 5 has 2 conserved Ser
residues, the second of which has an O-linked sugar chain attached. Two
iterations on OWL22.0 were required to reach convergence, at which point a
true set comprising 10 sequences was identified. A single partial match was
also found, an erythropoietin fragment matching just 5 motifs.
 
An update on SPTR37_9f identified a true set of 8 sequences.
Summary Information
8 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
6888888
5000000
4000000
3000000
2000000
123456
True Positives
EPO_BOVIN     EPO_FELCA     EPO_HUMAN     EPO_MACFA     
EPO_MACMU EPO_MOUSE EPO_RAT EPO_SHEEP
Sequence Titles
EPO_BOVIN   ERYTHROPOIETIN PRECURSOR - BOS TAURUS (BOVINE). 
EPO_FELCA ERYTHROPOIETIN PRECURSOR - FELIS SILVESTRIS CATUS (CAT).
EPO_HUMAN ERYTHROPOIETIN PRECURSOR - HOMO SAPIENS (HUMAN).
EPO_MACFA ERYTHROPOIETIN PRECURSOR - MACACA FASCICULARIS (CRAB EATING MACAQUE) (CYNOMOLGUS MONKEY).
EPO_MACMU ERYTHROPOIETIN PRECURSOR - MACACA MULATTA (RHESUS MACAQUE).
EPO_MOUSE ERYTHROPOIETIN PRECURSOR - MUS MUSCULUS (MOUSE).
EPO_RAT ERYTHROPOIETIN PRECURSOR - RATTUS NORVEGICUS (RAT).
EPO_SHEEP ERYTHROPOIETIN PRECURSOR - OVIS ARIES (SHEEP).
Scan History
OWL22_0    2  100  NSINGLE    
OWL26_0 1 100 NSINGLE
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=30
Element Seqn Id St Int Rpt
LLSLVSLPLGLPVPGAPPRLICDSRVLERY EPO_MACFA 13 13 -
LLSLLSLPLGLPVLGAPPRLICDSRVLERY EPO_HUMAN 13 13 -
LLSLLLIPLGLPVLCAPPRLICDSRVLERY EPO_RAT 12 12 -
LLSLLLIPLGLPVLCAPPRLICDSRVLERY EPO_MOUSE 12 12 -

Motif 2 width=30
Element Seqn Id St Int Rpt
LLEAKEAENVTMGCSESCSLNENITVPDTK EPO_MACFA 43 0 -
LLEAKEAENITTGCAEHCSLNENITVPDTK EPO_HUMAN 43 0 -
ILEAKEAENVTMGCAEGPRLSENITVPDTK EPO_RAT 42 0 -
ILEAKEAENVTMGCAEGPRLSENITVPDTK EPO_MOUSE 42 0 -

Motif 3 width=30
Element Seqn Id St Int Rpt
VNFYAWKRMEVGQQAVEVWQGLALLSEAVL EPO_MACFA 73 0 -
VNFYAWKRMEVGQQAVEVWQGLALLSEAVL EPO_HUMAN 73 0 -
VNFYAWKRMKVEEQAVEVWQGLSLLSEAIL EPO_RAT 72 0 -
VNFYAWKRMEVEEQAIEVWQGLSLLSEAIL EPO_MOUSE 72 0 -

Motif 4 width=30
Element Seqn Id St Int Rpt
QAVLANSSQPFEPLQLHMDKAISGLRSITT EPO_MACFA 105 2 -
QALLVNSSQPWEPLQLHVDKAVSGLRSLTT EPO_HUMAN 105 2 -
QALQANSSQPPESLQLHIDKAISGLRSLTS EPO_RAT 104 2 -
QALLANSSQPPETLQLHIDKAISGLRSLTS EPO_MOUSE 104 2 -

Motif 5 width=25
Element Seqn Id St Int Rpt
EAISLPDAASAAPLRTITADTFCKL EPO_MACFA 143 6 -
EAISPPDAASAAPLRTITADTFRKL EPO_HUMAN 144 7 -
ELMSPPDATQAAPLRTLTADTFCKL EPO_RAT 143 7 -
ELMSPPDTTPPAPLRTLTVDTFCKL EPO_MOUSE 143 7 -

Motif 6 width=24
Element Seqn Id St Int Rpt
FRVYSNFLRGKLKLYTGEACRRGD EPO_MACFA 168 0 -
FRVYSNFLRGKLKLYTGEACRTGD EPO_HUMAN 169 0 -
FRVYSNFLRGKLKLYTGEACRRGD EPO_RAT 168 0 -
FRVYANFLRGKLKLYTGEVCRRGD EPO_MOUSE 168 0 -
Final Motifs
Motif 1  width=30
Element Seqn Id St Int Rpt
LLSLVSLPLGLPVPGAPPRLICDSRVLERY EPO_MACFA 13 13 -
LLSLLSLPLGLPVLGAPPRLICDSRVLERY EPO_HUMAN 13 13 -
LLSLVSLPLGLPVPGAPPRLVCDSRVLERY EPO_MACMU 13 13 -
LLSLLLLPLGLPVLGAPPRLICDSRVLERY EPO_FELCA 12 12 -
LLSLLLIPLGLPVLCAPPRLICDSRVLERY EPO_RAT 12 12 -
LLSLLLIPLGLPVLCAPPRLICDSRVLERY EPO_MOUSE 12 12 -
LLSFLLFPLGLPVLGAPPRLICDSRVLERY EPO_SHEEP 13 13 -
MLSFLLFPLGFPVLGAPARLICDSRVLERY EPO_BOVIN 11 11 -

Motif 2 width=30
Element Seqn Id St Int Rpt
LLEAKEAENVTMGCSESCSLNENITVPDTK EPO_MACFA 43 0 -
LLEAKEAENITTGCAEHCSLNENITVPDTK EPO_HUMAN 43 0 -
LLEAKEAENVTMGCSESCSLNENITVPDTK EPO_MACMU 43 0 -
ILGAREAENVTMGCAEGCSFSENITVPDTK EPO_FELCA 42 0 -
ILEAKEAENVTMGCAEGPRLSENITVPDTK EPO_RAT 42 0 -
ILEAKEAENVTMGCAEGPRLSENITVPDTK EPO_MOUSE 42 0 -
ILEAREAENATMGCAEGCSFSENITVPDTK EPO_SHEEP 43 0 -
ILEAREAENATMGCAEGCSFNENITVPDTK EPO_BOVIN 41 0 -

Motif 3 width=30
Element Seqn Id St Int Rpt
VNFYAWKRMEVGQQAVEVWQGLALLSEAVL EPO_MACFA 73 0 -
VNFYAWKRMEVGQQAVEVWQGLALLSEAVL EPO_HUMAN 73 0 -
VNFYAWKRIEVGQQAVEVWQGLALLSEAVL EPO_MACMU 73 0 -
VNFYTWKRMDVGQQAVEVWQGLALLSEAIL EPO_FELCA 72 0 -
VNFYAWKRMKVEEQAVEVWQGLSLLSEAIL EPO_RAT 72 0 -
VNFYAWKRMEVEEQAIEVWQGLSLLSEAIL EPO_MOUSE 72 0 -
VNFYAWKRMEVQQQALEVWQGLALLSEAIF EPO_SHEEP 73 0 -
VNFYAWKRMEVQQQALEVWQGLALLSEAIL EPO_BOVIN 71 0 -

Motif 4 width=30
Element Seqn Id St Int Rpt
QAVLANSSQPFEPLQLHMDKAISGLRSITT EPO_MACFA 105 2 -
QALLVNSSQPWEPLQLHVDKAVSGLRSLTT EPO_HUMAN 105 2 -
QAVLANSSQPFEPLQLHMDKAISGLRSITT EPO_MACMU 105 2 -
QALLANSSQPSETLQLHVDKAVSSLRSLTS EPO_FELCA 104 2 -
QALQANSSQPPESLQLHIDKAISGLRSLTS EPO_RAT 104 2 -
QALLANSSQPPETLQLHIDKAISGLRSLTS EPO_MOUSE 104 2 -
QALLANASQPCEALRLHVDKAVSGLRSLTS EPO_SHEEP 105 2 -
QALLANASQPCEALRLHVDKAVSGLRSLTS EPO_BOVIN 103 2 -

Motif 5 width=25
Element Seqn Id St Int Rpt
EAISLPDAASAAPLRTITADTFCKL EPO_MACFA 143 6 -
EAISPPDAASAAPLRTITADTFRKL EPO_HUMAN 144 7 -
EAISLPDAASAAPLRTITADTFCKL EPO_MACMU 143 6 -
EATSLPEATSAAPLRTFTVDTLCKL EPO_FELCA 143 7 -
ELMSPPDATQAAPLRTLTADTFCKL EPO_RAT 143 7 -
ELMSPPDTTPPAPLRTLTVDTFCKL EPO_MOUSE 143 7 -
AIPLPDATPSAAPLRIFTVDALSKL EPO_SHEEP 145 8 -
AISLPDATPSAAPLRAFTVDALSKL EPO_BOVIN 143 8 -

Motif 6 width=24
Element Seqn Id St Int Rpt
FRVYSNFLRGKLKLYTGEACRRGD EPO_MACFA 168 0 -
FRVYSNFLRGKLKLYTGEACRTGD EPO_HUMAN 169 0 -
FRVYSNFLRGKLKLYTGEACRRGD EPO_MACMU 168 0 -
FRIYSNFLRGKLTLYTGEACRRGD EPO_FELCA 168 0 -
FRVYSNFLRGKLKLYTGEACRRGD EPO_RAT 168 0 -
FRVYANFLRGKLKLYTGEVCRRGD EPO_MOUSE 168 0 -
FRIYSNFLRGKLTLYTGEACRRGD EPO_SHEEP 170 0 -
FRIYSNFLRGKLTLYTGEACRRGD EPO_BOVIN 168 0 -