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PR01835

Identifier
VEGFRECEPTR3  [View Relations]  [View Alignment]  
Accession
PR01835
No. of Motifs
7
Creation Date
21-FEB-2003
Title
Vascular endothelial growth factor receptor type 3 signature
Database References
PRINTS; PR01832 VEGFRECEPTOR
Literature References
1. CONNOLLY, D.T., HEUVELMAN, D.M., NELSON, R., OLANDER, J.V., EPPLEY, B.L.,
DELFINO, J.J., SIEGEL, N.R., LEIMGRUBER, R.M. AND FEDER, J.
Tumor vascular permeability factor stimulates endothelial cell growth and
angiogenesis.
J.CLIN.INVEST. 84 1470-1478 (1989).
 
2. AIELLO, L.P., AVERY, R.L., ARRIGG, P.G., KEYT, B.A., JAMPEL, H.D.,
SHAH, S.T., PASQUALE, L.R.,THIEME, H., IWAMOTO, M.A. AND  PARK, J.E.
Vascular endothelial growth factor in ocular fluid of patients with diabetic
retinopathy and other retinal disorders.
N.ENGL.J.MED. 331 1480-1487 (1994).
 
3. MUSTONEN, T. AND ALITALO, K.
Endothelial receptor tyrosine kinases involved in angiogenesis.
J.CELL.BIOL. 129 895-898 (1995).
 
4. IRRTHUM, A., KARKKAINEN, M.J., DEVRIENDT, K., ALITALO, K. AND VIKKULA, M.
Congenital hereditary lymphedema caused by a mutation that inactivates
VEGFR3 tyrosine kinase.
AM.J.HUM.GENET. 67 295-301 (2000).

Documentation
Vascular endothelial growth factor (VEGF) is a potent and specific
endothelial cell mitogen [1]. Through binding with its receptor, VEGFR, VEGF
has critical roles in the growth and maintenance of vascular endothelial
cells and in the development of new blood- and lymphatic-vessels in
physiological and pathological states [2]. The vessel systems are important 
for the supply of oxygen and nutrients to all tissues of the body, as well
as for the drainage of excess fluids with waste metabolites from peripheral
tissues. VEGF receptors have a characteristic structure, with 7 Ig-like
domains in the extracellular domain and a cytoplasmic tyrosine kinase domain
with a long kinase insert region.
 
The VEGF receptor family consists of three members, VEGFR-1 (Flt-1), VEGFR-2
(KDR/Flk-1) and VEGFR-3 (Flt-4), all of which belong to the receptor type
tyrosine kinase superfamily [3]. Among these receptors, VEGFR-1 binds
strongest to VEGF, VEGF-2 binds more weakly, and VEGFR-3 shows essentially
no binding, although it does bind to other members of the VEGF family.
 
In humans, an A to G transition corresponding to a histidine to arginine
substitution in the catalytic loop of VEGFR3 has been linked to congenital
hereditary lymphedema. In vitro expression studies show that this amino acid
substitution causes loss of VEGFR3 tyrosine kinase acivity. Thus, defective
VEGFR3 signalling is responsible for 5q34-q35-linked congenital hereditary
lymphedema [4].
 
VEGFRECEPTR3 is a 7-element fingerprint that provides a signature for the
type 3 vascular endothelial growth factor receptors. The fingerprint was
derived from an initial alignment of 3 sequences: the motifs were drawn from
conserved regions spanning the N-terminal half of the extracellular domain,
focusing on those sections that characterise the VEGFR3 subtypes, but 
distinguish them from the rest of the VEGFR family - motif 1 lies in the
N-terminal signalling region; and motifs 4, 6 and 7 reside within Ig domains
2, 3 and 5 respectively. Two iterations on SPTR40_20f were required to reach
convergence, at which point a true set comprising 5 sequences was identified.
Summary Information
5 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
75555555
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
P79701        Q91ZT0        Q91ZT1        VGR3_HUMAN    
VGR3_MOUSE
Sequence Titles
P79701      VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR - Coturnix coturnix (common quail). 
Q91ZT0 RECEPTOR TYROSINE KINASE VEGFR-3KT - Rattus norvegicus (Rat).
Q91ZT1 RECEPTOR TYROSINE KINASE VEGFR-3 - Rattus norvegicus (Rat).
VGR3_HUMAN Vascular endothelial growth factor receptor 3 precursor (EC 2.7.1.112) (VEGFR-3) (Tyrosine-protein kinase receptor FLT4) - Homo sapiens (Human).
VGR3_MOUSE Vascular endothelial growth factor receptor 3 precursor (EC 2.7.1.112) (VEGFR-3) (Tyrosine-protein kinase receptor FLT4) - Mus musculus (Mouse).
Scan History
SPTR40_20f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
QPGAALNRRLWLCLGLLQGLANGYSMTP Q91ZT1 2 2 -
QPGAALNLRLWLCLGLLQGLANGYSMTP VGR3_MOUSE 2 2 -
QRGAALCLRLWLCLGLLDGLVSGYSMTP VGR3_HUMAN 2 2 -

Motif 2 width=18
Element Seqn Id St Int Rpt
TLNITEDSYVIDTGDSLS Q91ZT1 31 1 -
TLNITEDSYVIDTGDSLS VGR3_MOUSE 31 1 -
TLNITEESHVIDTGDSLS VGR3_HUMAN 31 1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
YYKYIKARIEGTTAAST Q91ZT1 112 63 -
YYKYIKARIEGTTAAST VGR3_MOUSE 112 63 -
YYKYIKARIEGTTAASS VGR3_HUMAN 112 63 -

Motif 4 width=19
Element Seqn Id St Int Rpt
LVSIPGLNITLRSQSSVLH Q91ZT1 159 30 -
LVSIPGLNITLRSQSSALH VGR3_MOUSE 159 30 -
LVSIPGLNVTLRSQSSVLW VGR3_HUMAN 159 30 -

Motif 5 width=30
Element Seqn Id St Int Rpt
RDALYLQCETTWGDQDFLSNPFLVHITGNE Q91ZT1 199 21 -
RDALYLQCETTWGDQNFLSNLFVVHITGNE VGR3_MOUSE 199 21 -
HDALYLQCETTWGDQDFLSNPFLVHITGNE VGR3_HUMAN 199 21 -

Motif 6 width=23
Element Seqn Id St Int Rpt
GKQAERAKWVPERRSQQTHTELS Q91ZT1 270 41 -
GKQAERAKWVPERRSQQTHTELS VGR3_MOUSE 270 41 -
GKQAERGKWVPERRSQQTHTELS VGR3_HUMAN 270 41 -

Motif 7 width=29
Element Seqn Id St Int Rpt
YGVPQPLSVQWHWRPWTPCKTFAQRSLRR Q91ZT1 448 155 -
YGVPQPLSVQWHWRPWTPCKTFAQRSLRR VGR3_MOUSE 448 155 -
YGVPLPLSIQWHWRPWTPCKMFAQRSLRR VGR3_HUMAN 448 155 -
Final Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
QPGAALNRRLWLCLGLLQGLANGYSMTP Q91ZT0 2 2 -
QPGAALNRRLWLCLGLLQGLANGYSMTP Q91ZT1 2 2 -
QPGAALNLRLWLCLGLLQGLANGYSMTP VGR3_MOUSE 2 2 -
QRGAALCLRLWLCLGLLDGLVSGYSMTP VGR3_HUMAN 2 2 -
KRVCTLPLWLWLGIVSEADLVSSYSMTP P79701 2 2 -

Motif 2 width=18
Element Seqn Id St Int Rpt
TLNITEDSYVIDTGDSLS Q91ZT0 31 1 -
TLNITEDSYVIDTGDSLS Q91ZT1 31 1 -
TLNITEDSYVIDTGDSLS VGR3_MOUSE 31 1 -
TLNITEESHVIDTGDSLS VGR3_HUMAN 31 1 -
TLSITEEEHIINAKDTLT P79701 31 1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
YYKYIKARIEGTTAAST Q91ZT0 112 63 -
YYKYIKARIEGTTAAST Q91ZT1 112 63 -
YYKYIKARIEGTTAAST VGR3_MOUSE 112 63 -
YYKYIKARIEGTTAASS VGR3_HUMAN 112 63 -
YYKYIDAKIEGTTAVSA P79701 121 72 -

Motif 4 width=19
Element Seqn Id St Int Rpt
LVSIPGLNITLRSQSSVLH Q91ZT0 159 30 -
LVSIPGLNITLRSQSSVLH Q91ZT1 159 30 -
LVSIPGLNITLRSQSSALH VGR3_MOUSE 159 30 -
LVSIPGLNVTLRSQSSVLW VGR3_HUMAN 159 30 -
LVSIPDLNVTLISQNSLIH P79701 168 30 -

Motif 5 width=30
Element Seqn Id St Int Rpt
RDALYLQCETTWGDQDFLSNPFLVHITGNE Q91ZT0 199 21 -
RDALYLQCETTWGDQDFLSNPFLVHITGNE Q91ZT1 199 21 -
RDALYLQCETTWGDQNFLSNLFVVHITGNE VGR3_MOUSE 199 21 -
HDALYLQCETTWGDQDFLSNPFLVHITGNE VGR3_HUMAN 199 21 -
RDSLFVQCETVIDNKVFKSNFFIIHIAGIE P79701 208 21 -

Motif 6 width=23
Element Seqn Id St Int Rpt
GKQAERAKWVPERRSQQTHTELS Q91ZT0 270 41 -
GKQAERAKWVPERRSQQTHTELS Q91ZT1 270 41 -
GKQAERAKWVPERRSQQTHTELS VGR3_MOUSE 270 41 -
GKQAERGKWVPERRSQQTHTELS VGR3_HUMAN 270 41 -
GKQMQRAVIESERRSLQTHTELS P79701 279 41 -

Motif 7 width=29
Element Seqn Id St Int Rpt
YGVPQPLSVQWHWRPWTPCKTFAQRSLRR Q91ZT0 448 155 -
YGVPQPLSVQWHWRPWTPCKTFAQRSLRR Q91ZT1 448 155 -
YGVPQPLSVQWHWRPWTPCKTFAQRSLRR VGR3_MOUSE 448 155 -
YGVPLPLSIQWHWRPWTPCKMFAQRSLRR VGR3_HUMAN 448 155 -
YGIPAPEVIQWQWRPWMPCRMFSRRSLNS P79701 456 154 -