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PR01834

Identifier
VEGFRECEPTR2  [View Relations]  [View Alignment]  
Accession
PR01834
No. of Motifs
7
Creation Date
17-FEB-2003
Title
Vascular endothelial growth factor receptor type 2 signature
Database References
PRINTS; PR01832 VEGFRECEPTOR
PDB; 1VR2
SCOP; 1VR2
CATH; 1VR2
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. WALTENBERGER, J., CLAESSON-WELSH, L., SIEGBAHN, A., SHIBUYA, M. AND
HELDIN, C.-H.
Different signal transduction properties of KDR and Flt1, two receptors for
vascular endothelial growth factor.
J.BIOL.CHEM. 269 26988-26995 (1994).

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.
 
The tyrosine kinase domain of VEGFR-2 tranduces signals for endothelial
cells with a greater efficacy than VEGFR-1. VEGFR-2 expression in adult
endothelial cells appears to account for most of the mitogenic and
chemotactic effects of VEGF [4]. At the post-receptor level, activation of
endothelial cells by VEGF leads to the autophosphorylation of VEGFR-2 and
the subsequent tyrosine phosphorylation of numerous downstream targets.
 
VEGFRECEPTR2 is a 7-element fingerprint that provides a signature for the
type 2 vascular endothelial growth factor receptors. The fingerprint was
derived from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the VEGFR2 subtypes, but distinguish them 
from the rest of the VEGFR family - motifs 1-4 lie in the extracellular
domain, motif 1 residing in the 2nd Ig domain and motif 3 in the 5th Ig
domain; and motifs 5-7 lie in the C-terminal cytoplasmic domain. 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
O08775        Q8VCD0        VGR2_COTJA    VGR2_HUMAN    
VGR2_MOUSE
Sequence Titles
O08775      VEGF RECEPTOR-2/FLK-1 - RATTUS NORVEGICUS (RAT). 
Q8VCD0 KINASE INSERT DOMAIN PROTEIN RECEPTOR - Mus musculus (Mouse).
VGR2_COTJA Vascular endothelial growth factor receptor 2 precursor (EC 2.7.1.112) (VEGFR-2) (Endothelial kinase receptor EK1) (Quek 1) (Quek1) - Coturnix coturnix japonica (Japanese quail).
VGR2_HUMAN Vascular endothelial growth factor receptor 2 precursor (EC 2.7.1.112) (VEGFR-2) (Kinase insert domain receptor) (Protein-tyrosine kinase receptor Flk-1) - Homo sapiens (Human).
VGR2_MOUSE Vascular endothelial growth factor receptor 2 precursor (EC 2.7.1.112) (VEGFR-2) (Protein-tyrosine kinase receptor flk-1) (Fetal liver kinase 1) (Kinase NYK) - Mus musculus (Mouse).
Scan History
SPTR40_20f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
TLPSYMISYAGMVF VGR2_MOUSE 188 188 -
TIPSYMISYAGMVF O08775 186 186 -
TIPSYMISYAGMVF VGR2_HUMAN 186 186 -
TIPSHLINYAGMVF VGR2_COTJA 181 181 -

Motif 2 width=22
Element Seqn Id St Int Rpt
KINDETYQSIMYIVVVVGYRIY VGR2_MOUSE 205 3 -
KINDETYQSIMYIVLVVGYRIY O08775 203 3 -
KINDESYQSIMYIVVVVGYRIY VGR2_HUMAN 203 3 -
KIDNESYQSVIYIVAVVGYRIY VGR2_COTJA 198 3 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ANPPLHHIQWYWQLEE VGR2_MOUSE 451 224 -
ANPPLHHIQWYWQLEE O08775 449 224 -
AIPPPHHIHWYWQLEE VGR2_HUMAN 449 224 -
AVPPPAAVLWYWQLEE VGR2_COTJA 440 220 -

Motif 4 width=19
Element Seqn Id St Int Rpt
QDKKTKKRHCLVKQLIILE VGR2_MOUSE 643 176 -
QDKKTKKRHCLVKQLVILE O08775 641 176 -
QDRKTKKRHCVVRQLTVLE VGR2_HUMAN 645 180 -
QDKKAKTQHCLVKHLTVQE VGR2_COTJA 636 180 -

Motif 5 width=18
Element Seqn Id St Int Rpt
SETLSMEEDSGLSLPTSP VGR2_MOUSE 1179 517 -
SETLSMEEDSGLSLPTSP O08775 1177 517 -
SETLSMEEDSGLSLPTSP VGR2_HUMAN 1181 517 -
SVSLNMEEDSGLSLPTSP VGR2_COTJA 1174 519 -

Motif 6 width=20
Element Seqn Id St Int Rpt
SCMEEEEVCDPKFHYDNTAG VGR2_MOUSE 1198 1 -
SCMEEEEVCDPKFHYDNTAG O08775 1196 1 -
SCMEEEEVCDPKFHYDNTAG VGR2_HUMAN 1200 1 -
SCKEEEEVCDPKFHYDNTAG VGR2_COTJA 1193 1 -

Motif 7 width=15
Element Seqn Id St Int Rpt
SHYLQNSKRKSRPVS VGR2_MOUSE 1219 1 -
SHYLQNSKRKSRPVS O08775 1217 1 -
SQYLQNSKRKSRPVS VGR2_HUMAN 1221 1 -
SQYRQGSKRKSRPVS VGR2_COTJA 1214 1 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
TLPSYMISYAGMVF Q8VCD0 188 188 -
TLPSYMISYAGMVF VGR2_MOUSE 188 188 -
TIPSYMISYAGMVF O08775 186 186 -
TIPSYMISYAGMVF VGR2_HUMAN 186 186 -
TIPSHLINYAGMVF VGR2_COTJA 181 181 -

Motif 2 width=22
Element Seqn Id St Int Rpt
KINDETYQSIMYIVVVVGYRIY Q8VCD0 205 3 -
KINDETYQSIMYIVVVVGYRIY VGR2_MOUSE 205 3 -
KINDETYQSIMYIVLVVGYRIY O08775 203 3 -
KINDESYQSIMYIVVVVGYRIY VGR2_HUMAN 203 3 -
KIDNESYQSVIYIVAVVGYRIY VGR2_COTJA 198 3 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ANPPLHHIQWYWQLEE Q8VCD0 451 224 -
ANPPLHHIQWYWQLEE VGR2_MOUSE 451 224 -
ANPPLHHIQWYWQLEE O08775 449 224 -
AIPPPHHIHWYWQLEE VGR2_HUMAN 449 224 -
AVPPPAAVLWYWQLEE VGR2_COTJA 440 220 -

Motif 4 width=19
Element Seqn Id St Int Rpt
QDKKTKKRHCLVKQLIILE Q8VCD0 643 176 -
QDKKTKKRHCLVKQLIILE VGR2_MOUSE 643 176 -
QDKKTKKRHCLVKQLVILE O08775 641 176 -
QDRKTKKRHCVVRQLTVLE VGR2_HUMAN 645 180 -
QDKKAKTQHCLVKHLTVQE VGR2_COTJA 636 180 -

Motif 5 width=18
Element Seqn Id St Int Rpt
SETLSMEEDSGLSLPTSP Q8VCD0 1179 517 -
SETLSMEEDSGLSLPTSP VGR2_MOUSE 1179 517 -
SETLSMEEDSGLSLPTSP O08775 1177 517 -
SETLSMEEDSGLSLPTSP VGR2_HUMAN 1181 517 -
SVSLNMEEDSGLSLPTSP VGR2_COTJA 1174 519 -

Motif 6 width=20
Element Seqn Id St Int Rpt
SCMEEEEVCDPKFHYDNTAG Q8VCD0 1198 1 -
SCMEEEEVCDPKFHYDNTAG VGR2_MOUSE 1198 1 -
SCMEEEEVCDPKFHYDNTAG O08775 1196 1 -
SCMEEEEVCDPKFHYDNTAG VGR2_HUMAN 1200 1 -
SCKEEEEVCDPKFHYDNTAG VGR2_COTJA 1193 1 -

Motif 7 width=15
Element Seqn Id St Int Rpt
SHYLQNSKRKSRPVS Q8VCD0 1219 1 -
SHYLQNSKRKSRPVS VGR2_MOUSE 1219 1 -
SHYLQNSKRKSRPVS O08775 1217 1 -
SQYLQNSKRKSRPVS VGR2_HUMAN 1221 1 -
SQYRQGSKRKSRPVS VGR2_COTJA 1214 1 -