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Protein

Vascular endothelial growth factor receptor kdr-like

Gene

kdrl

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for VEGF or VEGFC. Has a tyrosine-protein kinase activity. Combinations of multiple VEGF receptors are required for development of different blood vessel types in the embryo. Involved in angiogenesis, specifically in VEGF-induced sprouting of new blood vessels. Particularly involved in artery formation. Does not appear to be required for hematopoiesis.3 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei843ATPPROSITE-ProRule annotationBy similarity1
Active sitei1003Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi815 – 823ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • artery morphogenesis Source: ZFIN
  • blood vessel development Source: ZFIN
  • cell differentiation Source: UniProtKB-KW
  • embryonic heart tube development Source: ZFIN
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • sprouting angiogenesis Source: ZFIN
  • thyroid gland development Source: ZFIN
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis, Differentiation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Vascular endothelial growth factor receptor kdr-like (EC:2.7.10.1)
Alternative name(s):
Fetal liver kinase 1
Short name:
FLK-1
Kinase insert domain receptor-A
Kinase insert domain receptor-like
Protein-tyrosine kinase receptor flk-1
Vascular endothelial growth factor receptor 4
Short name:
VEGFR-4
Gene namesi
Name:kdrl
Synonyms:flkImported, flk-1, flk11 Publication, flka, kdr, kdra, vegfr2, vegfr4, vegr2
ORF Names:si:ch211-276g21.4
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)Imported
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Unplaced

Organism-specific databases

ZFINiZDB-GENE-000705-1. kdrl.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 740ExtracellularSequence analysisAdd BLAST712
Transmembranei741 – 761HelicalSequence analysisAdd BLAST21
Topological domaini762 – 1302CytoplasmicSequence analysisAdd BLAST541

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi845L → R in y17; abolishes kinase activity and causes specific defects in artery development. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000001677529 – 1302Vascular endothelial growth factor receptor kdr-likeAdd BLAST1274

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi55 ↔ 104PROSITE-ProRule annotation
Glycosylationi69N-linked (GlcNAc...)Curated1
Glycosylationi97N-linked (GlcNAc...)Curated1
Disulfide bondi150 ↔ 199PROSITE-ProRule annotationBy similarity
Glycosylationi242N-linked (GlcNAc...)Curated1
Disulfide bondi243 ↔ 302PROSITE-ProRule annotation
Glycosylationi265N-linked (GlcNAc...)Curated1
Glycosylationi291N-linked (GlcNAc...)Curated1
Glycosylationi326N-linked (GlcNAc...)Curated1
Glycosylationi370N-linked (GlcNAc...)Curated1
Glycosylationi380N-linked (GlcNAc...)Curated1
Glycosylationi408N-linked (GlcNAc...)Curated1
Disulfide bondi444 ↔ 524PROSITE-ProRule annotation
Glycosylationi453N-linked (GlcNAc...)Curated1
Glycosylationi466N-linked (GlcNAc...)Curated1
Glycosylationi505N-linked (GlcNAc...)Curated1
Glycosylationi517N-linked (GlcNAc...)Curated1
Glycosylationi532N-linked (GlcNAc...)Curated1
Disulfide bondi565 ↔ 618PROSITE-ProRule annotation
Glycosylationi607N-linked (GlcNAc...)Curated1
Glycosylationi611N-linked (GlcNAc...)Curated1
Glycosylationi630N-linked (GlcNAc...)Curated1
Glycosylationi648N-linked (GlcNAc...)Curated1
Glycosylationi655N-linked (GlcNAc...)Curated1
Disulfide bondi664 ↔ 712PROSITE-ProRule annotation
Modified residuei1029Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1034Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1150Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylated and activated by vegfaa and vegfab.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8AXB3.
PRIDEiQ8AXB3.

Expressioni

Tissue specificityi

First expressed in embryos between 5- and 7-somites. At 7 somites, expressed in discrete bilateral stripes both anteriorly and posteriorly, and in a transverse ectodermal stripe in the hindbrain. From 7-somites, expression seems to extend caudally from the head, and in both directions in the trunk region, until by 20-somites, expression is detected as a continuous band from the anterior head region to the tailbud. Concurrently, cells expressing kdrl in the mid- and posterior trunk regions converge medially. By 24 hours post-fertilization (hpf), expressed in all the endothelial cells lining the vasculature.5 Publications

Interactioni

Subunit structurei

Interacts with isoform VEGF165 of vegfaa and isoform VEGF171 of vegfab.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
bcanA4JYN22EBI-2267980,EBI-2268253
bocQ8UVD62EBI-2267980,EBI-2268159
epycA8BBB92EBI-2267980,EBI-2268109
fgfr2A4JYI82EBI-2267980,EBI-2268196
fgfr3A4JYQ22EBI-2267980,EBI-2268403
igfbp7Q6NW922EBI-2267980,EBI-1579483
igsf8Q6NZ262EBI-2267980,EBI-2268334
lrrtm1A8BBG32EBI-2267980,EBI-2263357
lrrtm4l1A8BB402EBI-2267980,EBI-2263384
optcA8BBE62EBI-2267980,EBI-2268084
pdgfrlQ6P5M12EBI-2267980,EBI-2268346
robo3Q90Z694EBI-2267980,EBI-2267985
vstm4bA4JYE72EBI-2267980,EBI-2268137

Protein-protein interaction databases

IntActiQ8AXB3. 16 interactors.
STRINGi7955.ENSDARP00000007209.

Structurei

3D structure databases

ProteinModelPortaliQ8AXB3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 115Ig-like C2-type 1CuratedAdd BLAST82
Domaini143 – 206Ig-like C2-type 2CuratedAdd BLAST64
Domaini222 – 318Ig-like C2-type 3CuratedAdd BLAST97
Domaini326 – 412Ig-like C2-type 4CuratedAdd BLAST87
Domaini419 – 542Ig-like C2-type 5CuratedAdd BLAST124
Domaini545 – 636Ig-like C2-type 6CuratedAdd BLAST92
Domaini643 – 728Ig-like C2-type 7CuratedAdd BLAST86
Domaini809 – 1139Protein kinasePROSITE-ProRule annotationCuratedAdd BLAST331

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOVERGENiHBG053432.
InParanoidiQ8AXB3.
KOiK05096.
PhylomeDBiQ8AXB3.

Family and domain databases

Gene3Di2.60.40.10. 7 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PfamiPF07679. I-set. 2 hits.
PF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 6 hits.
SM00408. IGc2. 6 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 6 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 6 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8AXB3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPLKTSVKA FFTLHVLFSC ISHGLVEGSR LPDPQLLPDG DTHLQHVGGT
60 70 80 90 100
LTLICRGSTA LHWRLASRNV SSVRIESCEE RLHKHCSKLV IHNLRHNDTG
110 120 130 140 150
IYSCSHKKSS DHEVSTYVFV KDPHHPFVEA YSLPHPLFAY RNDPYFVVPC
160 170 180 190 200
RTTYPNQNVI LETQMNPMAD DVKRGVQWDP KKGFTVPLKP YDSYHLITCL
210 220 230 240 250
TRVDNAEFSS VYLLKRLTME IKNLAIEPER PRVLVGDTLI LNCSAETTYN
260 270 280 290 300
GRIHFEWEFH KERINRTHHF STTPVQLAQI MVMSKALIVP NVTMEDKGTY
310 320 330 340 350
TCTGSIEFKK LQMSTKVIVY EHPFLNVTHN KRKFTSTVEG RRVQFEPRVN
360 370 380 390 400
AVPAPDRVLW YKDGVAISEN STCYETAGYN LTIKQVRQKD AGIFTIALSN
410 420 430 440 450
QERGLYRNIS YKLEVRVKPK IFEEDVAPAG PQTFRYDQRH KLTCTAFGIP
460 470 480 490 500
MPNITWFWQP CDPSANLTEC KLYTDPLPIE NVDDHFPQNP IKDVNSKVGL
510 520 530 540 550
LKSKNRTIST LVVKTANVSG VYSCTARNEL GNRTMRIPFY VDDHPQPFEI
560 570 580 590 600
EPSTAVAGDD ITLTCRGTRY LYDRLTWYDP LGHKVPKDET TLRIEPYTIS
610 620 630 640 650
LSIKLPNVSR NHTLGYECQA LKINTNKVVN VTSALTIDER QGPWLMQNLT
660 670 680 690 700
NQDVNSSSTL TLACLAYGVP APFITWYKDK TPVTEGPGIT LKDDGTLIIE
710 720 730 740 750
RVKKDDEGIY ECRASNDGGE AKTSAVITVV GEDGKPNIEV IILVSTGAAA
760 770 780 790 800
TFLWIMLILF IRKLRKPSSA DLKTGYLSII MDPEQMPLDE QCDRLPYDSN
810 820 830 840 850
KWEFPQDRLR LGKTLGHGAF GKVVEASAFG IDKISTCKTV AVKMLKVGAT
860 870 880 890 900
NNEWRALMSE LKILIHIGHH LNVVNLLGAC TKRGGPLMII VEFCKYGNLS
910 920 930 940 950
NYLRSKRGDF VVYKSQDGKA VRSSSGCDLS ELIKRRLESV ASTGSSASSG
960 970 980 990 1000
FIEDKSYCDS EEEEEEQEDL YKKVLTLEDL ICYSFQVAKG MEFLASRKCI
1010 1020 1030 1040 1050
HRDLAARNIL LSENNVVKIC DFGLARDVYK DPDYVRKGDA RLPLKWMAPE
1060 1070 1080 1090 1100
AIFDKIYTTQ SDVWSFGVLM WEIFSLGASP YPGLHIDEEF CCRLKEGTRM
1110 1120 1130 1140 1150
KAPEYSSSEI YQTMLDCWHG EPSQRPTFTE LVERLGDLLQ ASVQQEGKHY
1160 1170 1180 1190 1200
IPINTALLTK ADPSNQSPTE ETSTRPVSLR DSGTAWNIKI RPESVKTFDE
1210 1220 1230 1240 1250
VILENGTNKI HEGGQSDSGI GLSSDDLKTL KRLESLARPR SFMSRAMKRK
1260 1270 1280 1290 1300
SKESVLLEGE MDKYPPLVPS LSLEDSSLDS EMECHSPPPD YNYVVRYSTP

PV
Length:1,302
Mass (Da):146,950
Last modified:March 1, 2003 - v1
Checksum:iEB18BDCCB6F5430B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10A → G in CAM73177 (PubMed:18296487).Curated1
Sequence conflicti49G → E in AAL16381 (PubMed:12086862).Curated1
Sequence conflicti240 – 243ILNC → HPSTA in AAF03237 (PubMed:9630750).Curated4
Sequence conflicti252R → W in AAF03237 (PubMed:9630750).Curated1
Sequence conflicti267T → P in AAL16381 (PubMed:12086862).Curated1
Sequence conflicti485Missing in AAL16381 (PubMed:12086862).Curated1
Sequence conflicti583H → Y in AAL16381 (PubMed:12086862).Curated1
Sequence conflicti622K → N in AAL16381 (PubMed:12086862).Curated1
Sequence conflicti622K → N in CAM73177 (PubMed:18296487).Curated1
Sequence conflicti622K → N in AAI29159 (Ref. 5) Curated1
Sequence conflicti622K → N in AAF03237 (PubMed:9630750).Curated1
Sequence conflicti1203L → R in AAB18415 (PubMed:9053314).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY056466 mRNA. Translation: AAL16381.1.
AF487829 mRNA. Translation: AAN47136.1.
CU458916 mRNA. Translation: CAM73177.1.
AL935131 Genomic DNA. Translation: CAQ13438.1.
BC129158 mRNA. Translation: AAI29159.1.
AF180354 mRNA. Translation: AAF03237.1.
U89515 mRNA. Translation: AAB62405.1.
U82383 mRNA. Translation: AAB41042.1.
U75995 mRNA. Translation: AAB18415.1.
RefSeqiNP_571547.1. NM_131472.1.
UniGeneiDr.75094.

Genome annotation databases

GeneIDi796537.
KEGGidre:796537.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY056466 mRNA. Translation: AAL16381.1.
AF487829 mRNA. Translation: AAN47136.1.
CU458916 mRNA. Translation: CAM73177.1.
AL935131 Genomic DNA. Translation: CAQ13438.1.
BC129158 mRNA. Translation: AAI29159.1.
AF180354 mRNA. Translation: AAF03237.1.
U89515 mRNA. Translation: AAB62405.1.
U82383 mRNA. Translation: AAB41042.1.
U75995 mRNA. Translation: AAB18415.1.
RefSeqiNP_571547.1. NM_131472.1.
UniGeneiDr.75094.

3D structure databases

ProteinModelPortaliQ8AXB3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8AXB3. 16 interactors.
STRINGi7955.ENSDARP00000007209.

Proteomic databases

PaxDbiQ8AXB3.
PRIDEiQ8AXB3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi796537.
KEGGidre:796537.

Organism-specific databases

CTDi796537.
ZFINiZDB-GENE-000705-1. kdrl.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOVERGENiHBG053432.
InParanoidiQ8AXB3.
KOiK05096.
PhylomeDBiQ8AXB3.

Miscellaneous databases

PROiQ8AXB3.

Family and domain databases

Gene3Di2.60.40.10. 7 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PfamiPF07679. I-set. 2 hits.
PF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 6 hits.
SM00408. IGc2. 6 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 6 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 6 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVGFR4_DANRE
AccessioniPrimary (citable) accession number: Q8AXB3
Secondary accession number(s): A1L1P1
, B0R127, O42377, P79743, Q8UUW9, Q98891, Q9PTL0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be an ortholog of KDR, but PubMed:18516225 has shown that it represents a fourth vertebrate vascular endothelial growth factor receptor (VEGFR) that is not present in eutherian mammals (marsupials and placental mammals).Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.