P35916 (VGFR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vascular endothelial growth factor receptor 3
Short name=VEGFR-3
EC=2.7.10.1

Alternative name(s):
Fms-like tyrosine kinase 4
Short name=FLT-4
Tyrosine-protein kinase receptor FLT4

Gene names

Name:	FLT4
Synonyms:	VEGFR3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1363 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. Ref.5 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.13 Ref.17
Enzyme regulation	Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51. Ref.19 Ref.24 Ref.27
Subunit structure	Interacts with VEGFC and VEGFD. Monomer in the absence of bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the interaction is enhanced by stimulation with VEGFC. Interacts with CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP-2. Identified in a complex with SRC and ITGB1. Ref.5 Ref.6 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.25 Ref.26 Ref.27 Ref.28
Subcellular location	Cell membrane; Single-pass type I membrane protein Ref.6 Ref.13 Ref.22 Ref.29. Cytoplasm Ref.6 Ref.13 Ref.22 Ref.29. Nucleus. Note: Ligand-mediated autophosphorylation leads to rapid internalization. Ref.6 Ref.13 Ref.22 Ref.29 Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.6 Ref.13 Ref.22 Ref.29. Note: Ligand-mediated autophosphorylation leads to rapid internalization. Ref.6 Ref.13 Ref.22 Ref.29 Isoform 2: Cell membrane; Single-pass type I membrane protein Ref.6 Ref.13 Ref.22 Ref.29. Isoform 3: Secreted. Cytoplasm Ref.6 Ref.13 Ref.22 Ref.29.
Tissue specificity	Detected in endothelial cells (at protein level). Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney. Ref.1 Ref.14 Ref.28
Domain	The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding.
Post-translational modification	Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation in response to H2O2 is mediated by a process that requires SRC and PRKCD activity. Phosphorylation at Tyr-1068 is required for autophosphorylation at additional tyrosine residues. Phosphorylation at Tyr-1063 and Tyr-1337 is important for interaction with CRK and subsequent activation of MAPK8. Phosphorylation at Tyr-1230, Tyr-1231 and Tyr-1337 is important for interaction with GRB2 and subsequent activation of the AKT1 and MAPK1/ERK2 and/or MAPK3/ERK1 signaling pathways. In response to endothelial cell adhesion onto collagen, can also be phosphorylated in the absence of FLT4 kinase activity by SRC at Tyr-830, Tyr-833, Tyr-853, Tyr-1063, Tyr-1333, and Tyr-1337. Ref.5 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.24 Ref.27
Involvement in disease	Lymphedema, hereditary, 1A (LMPH1A) [MIM:153100]: A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.19 Ref.35 Ref.36 Ref.37 Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.38 Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 7 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.
Sequence caution	The sequence CAA48290.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Angiogenesis
Cellular component	Cell membrane Cytoplasm Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	lymphangiogenesis Inferred from mutant phenotype Ref.24. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype Ref.16. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype Ref.16. Source: UniProtKB positive regulation of JNK cascade Inferred from mutant phenotype Ref.20. Source: UniProtKB positive regulation of endothelial cell migration Inferred from mutant phenotype Ref.16. Source: UniProtKB positive regulation of endothelial cell proliferation Inferred from mutant phenotype Ref.16. Source: UniProtKB positive regulation of protein kinase C signaling cascade Inferred from mutant phenotype Ref.16. Source: UniProtKB positive regulation of protein phosphorylation Inferred from mutant phenotype Ref.16Ref.24. Source: UniProtKB positive regulation vascular endothelial growth factor production Inferred from mutant phenotype Ref.24. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.14Ref.15. Source: UniProtKB regulation of blood vessel remodeling Inferred from sequence or structural similarity. Source: UniProtKB sprouting angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB vascular endothelial growth factor receptor signaling pathway Inferred from mutant phenotype Ref.16Ref.24. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.4. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW vascular endothelial growth factor-activated receptor activity Inferred from mutant phenotype Ref.16Ref.24. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSP90AB1	P08238	2	EBI-1005467,EBI-352572
KDR	P35968	3	EBI-1005467,EBI-1005487
VEGFC	P49767	2	EBI-1005467,EBI-3405539

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35916-2)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P35916-1)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1298-1363: SCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY → R

Isoform 3 (identifier: P35916-3)

Also known as: sVegfr3;

The sequence of this isoform differs from the canonical sequence as follows:
     724-765: VDLADSNQKL...CVNSSASVAV → REGGPGEGQV...ESTWRTPTRS
     766-1298: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Ref.12
	Chain	25 – 1363	1339	Vascular endothelial growth factor receptor 3		PRO_0000016776
Regions
	Topological domain	25 – 775	751	Extracellular Potential
	Transmembrane	776 – 796	21	Helical; Potential
	Topological domain	797 – 1363	567	Cytoplasmic Potential
	Domain	30 – 127	98	Ig-like C2-type 1
	Domain	151 – 213	63	Ig-like C2-type 2
	Domain	219 – 326	108	Ig-like C2-type 3
	Domain	331 – 415	85	Ig-like C2-type 4
	Domain	422 – 552	131	Ig-like C2-type 5
	Domain	555 – 671	117	Ig-like C2-type 6
	Domain	678 – 764	87	Ig-like C2-type 7
	Domain	845 – 1173	329	Protein kinase
	Nucleotide binding	851 – 859	9	ATP By similarity
Sites
	Active site	1037	1	Proton acceptor By similarity
	Binding site	879	1	ATP Probable
Amino acid modifications
	Modified residue	830	1	Phosphotyrosine; by SRC Ref.27
	Modified residue	833	1	Phosphotyrosine; by SRC Ref.27
	Modified residue	853	1	Phosphotyrosine; by SRC Ref.27
	Modified residue	1063	1	Phosphotyrosine; by autocatalysis and SRC Ref.20 Ref.27
	Modified residue	1068	1	Phosphotyrosine; by autocatalysis Ref.20 Ref.27
	Modified residue	1230	1	Phosphotyrosine; by autocatalysis Ref.17 Ref.20
	Modified residue	1231	1	Phosphotyrosine; by autocatalysis Ref.17 Ref.20
	Modified residue	1265	1	Phosphotyrosine; by autocatalysis Ref.17
	Modified residue	1333	1	Phosphotyrosine; by autocatalysis and SRC Ref.17 Ref.27
	Modified residue	1337	1	Phosphotyrosine; by autocatalysis and SRC Ref.17 Ref.20 Ref.27
	Modified residue	1363	1	Phosphotyrosine; by autocatalysis Ref.17
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
	Glycosylation	251	1	N-linked (GlcNAc...) Potential
	Glycosylation	299	1	N-linked (GlcNAc...) Potential
	Glycosylation	411	1	N-linked (GlcNAc...) Potential
	Glycosylation	515	1	N-linked (GlcNAc...) Potential
	Glycosylation	527	1	N-linked (GlcNAc...) Ref.21
	Glycosylation	594	1	N-linked (GlcNAc...) Potential
	Glycosylation	683	1	N-linked (GlcNAc...) Potential
	Glycosylation	690	1	N-linked (GlcNAc...) Potential
	Glycosylation	758	1	N-linked (GlcNAc...) Potential
	Disulfide bond	51 ↔ 111		By similarity
	Disulfide bond	158 ↔ 206		By similarity
	Disulfide bond	252 ↔ 310		By similarity
	Disulfide bond	445 ↔ 534		By similarity
	Disulfide bond	578 ↔ 653		By similarity
	Disulfide bond	699 ↔ 751		By similarity
Natural variations
	Alternative sequence	724 – 765	42	VDLAD…ASVAV → REGGPGEGQVRRPARPTIPN PGGPAPPPHPLQESTWRTPT RS in isoform 3.		VSP_041993
	Alternative sequence	766 – 1298	533	Missing in isoform 3.		VSP_041994
	Alternative sequence	1298 – 1363	66	SCKGP…TDNSY → R in isoform 2.		VSP_041995
	Natural variant	149	1	N → D. Ref.39 Corresponds to variant rs34221241 [ dbSNP | Ensembl ].		VAR_042062
	Natural variant	378	1	R → C in a renal clear cell carcinoma sample; somatic mutation. Ref.39		VAR_042063
	Natural variant	494	1	T → A. Ref.38 Ref.39 Corresponds to variant rs307826 [ dbSNP | Ensembl ].		VAR_018407
	Natural variant	527	1	N → S. Ref.39 Corresponds to variant rs35874891 [ dbSNP | Ensembl ].		VAR_034379
	Natural variant	641	1	P → S. Ref.37 Ref.39 Corresponds to variant rs55667289 [ dbSNP | Ensembl ].		VAR_018408
	Natural variant	857	1	G → R in LMPH1A; loss of kinase activity. Ref.19 Ref.37		VAR_018409
	Natural variant	868	1	H → Y. Ref.39 Corresponds to variant rs35171798 [ dbSNP | Ensembl ].		VAR_042064
	Natural variant	890	1	H → Q. Ref.4 Ref.7 Ref.8 Ref.38 Corresponds to variant rs448012 [ dbSNP | Ensembl ].		VAR_018410
	Natural variant	954	1	P → S in HCI. Ref.38 Corresponds to variant rs34255532 [ dbSNP | Ensembl ].		VAR_018411
	Natural variant	1010	1	T → I in a metastatic melanoma sample; somatic mutation. Ref.39		VAR_042065
	Natural variant	1031	1	R → Q. Ref.39 Corresponds to variant rs56082504 [ dbSNP | Ensembl ].		VAR_042066
	Natural variant	1035	1	H → R in LMPH1A; loss of kinase activity. Ref.36		VAR_018412
	Natural variant	1041	1	R → P in LMPH1A; loss of kinase activity. Ref.17 Ref.37		VAR_018413
	Natural variant	1044	1	L → P in LMPH1A; loss of kinase activity. Ref.37		VAR_018414
	Natural variant	1049	1	D → N. Ref.39 Corresponds to variant rs56310180 [ dbSNP | Ensembl ].		VAR_042067
	Natural variant	1075	1	R → Q. Ref.39		VAR_042068
	Natural variant	1114	1	P → L in LMPH1A; loss of kinase activity. Ref.35 Ref.37		VAR_018415
	Natural variant	1137	1	P → S in HCI. Ref.38		VAR_018416
	Natural variant	1146	1	R → H. Ref.4 Ref.7 Ref.38 Ref.39 Corresponds to variant rs1130379 [ dbSNP | Ensembl ].		VAR_018417
Experimental info
	Mutagenesis	879	1	K → G: Abolishes enzyme activity. Ref.17
	Mutagenesis	1063	1	Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. Ref.20 Ref.27
	Mutagenesis	1068	1	Y → F: Global loss of autophosphorylation. Abolishes stimulation of cell proliferation and cell migration. Ref.20 Ref.27
	Mutagenesis	1230	1	Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. Ref.17 Ref.20
	Mutagenesis	1231	1	Y → F: Loss of phosphorylation site. Strongly reduces stimulation of cell proliferation and cell migration. Ref.17 Ref.20
	Mutagenesis	1265	1	Y → F: Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration. Ref.17
	Mutagenesis	1333	1	Y → F: Loss of phosphorylation site. Reduced autophosphorylation. Ref.14 Ref.17
	Mutagenesis	1337	1	Y → F: Reduced autophosphorylation. Strongly reduces stimulation of cell proliferation and cell migration. Ref.14 Ref.17 Ref.27
	Mutagenesis	1363	1	Y → F: Loss of phosphorylation site. Slighly reduced autophosphorylation. Ref.14 Ref.17
	Sequence conflict	24	1	G → D in CAA49505. Ref.3
	Sequence conflict	24	1	G → D in AAO89504. Ref.7
	Sequence conflict	24	1	G → D in AAO89505. Ref.7
	Sequence conflict	538	1	N → D in BAF84368. Ref.8
	Sequence conflict	745	1	R → P in CAA49505. Ref.3
	Sequence conflict	745	1	R → P in AAO89504. Ref.7
	Sequence conflict	745	1	R → P in AAO89505. Ref.7
	Sequence conflict	752 – 753	2	NA → RP in CAA49505. Ref.3
	Sequence conflict	752 – 753	2	NA → RP in AAO89504. Ref.7
	Sequence conflict	752 – 753	2	NA → RP in AAO89505. Ref.7
	Sequence conflict	1128	1	L → V in CAA49505. Ref.3
	Sequence conflict	1128	1	L → V in AAO89504. Ref.7
	Sequence conflict	1128	1	L → V in AAO89505. Ref.7
	Sequence conflict	1164	1	E → D in CAA49505. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified November 16, 2011. Version 3. Checksum: B1473AAAC95E7E93	FASTA	1,363	152,757
	10 20 30 40 50 60 MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS CRGQHPLEWA 70 80 90 100 110 120 WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE VHANDTGSYV CYYKYIKARI 130 140 150 160 170 180 EGTTAASSYV FVRDFEQPFI NKPDTLLVNR KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG 190 200 210 220 230 240 QEVVWDDRRG MLVSTPLLHD ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL 250 260 270 280 290 300 ELLVGEKLVL NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV 310 320 330 340 350 360 SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE LVKLPVKLAA 370 380 390 400 410 420 YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA LWNSAAGLRR NISLELVVNV 430 440 450 460 470 480 PPQIHEKEAS SPSIYSRHSR QALTCTAYGV PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ 490 500 510 520 530 540 DLMPQCRDWR AVTTQDAVNP IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV 550 560 570 580 590 600 GQDERLIYFY VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD 610 620 630 640 650 660 AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH YVCEVQDRRS 670 680 690 700 710 720 HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL VAGAHAPSIV WYKDERLLEE 730 740 750 760 770 780 KSGVDLADSN QKLSIQRVRE EDAGRYLCSV CNAKGCVNSS ASVAVEGSED KGSMEIVILV 790 800 810 820 830 840 GTGVIAVFFW VLLLLIFCNM RRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDASQWEF 850 860 870 880 890 900 PRERLHLGRV LGYGAFGKVV EASAFGIHKG SSCDTVAVKM LKEGATASEH RALMSELKIL 910 920 930 940 950 960 IHIGNHLNVV NLLGACTKPQ GPLMVIVEFC KYGNLSNFLR AKRDAFSPCA EKSPEQRGRF 970 980 990 1000 1010 1020 RAMVELARLD RRRPGSSDRV LFARFSKTEG GARRASPDQE AEDLWLSPLT MEDLVCYSFQ 1030 1040 1050 1060 1070 1080 VARGMEFLAS RKCIHRDLAA RNILLSESDV VKICDFGLAR DIYKDPDYVR KGSARLPLKW 1090 1100 1110 1120 1130 1140 MAPESIFDKV YTTQSDVWSF GVLLWEIFSL GASPYPGVQI NEEFCQRLRD GTRMRAPELA 1150 1160 1170 1180 1190 1200 TPAIRRIMLN CWSGDPKARP AFSELVEILG DLLQGRGLQE EEEVCMAPRS SQSSEEGSFS 1210 1220 1230 1240 1250 1260 QVSTMALHIA QADAEDSPPS LQRHSLAARY YNWVSFPGCL ARGAETRGSS RMKTFEEFPM 1270 1280 1290 1300 1310 1320 TPTTYKGSVD NQTDSGMVLA SEEFEQIESR HRQESGFSCK GPGQNVAVTR AHPDSQGRRR 1330 1340 1350 1360 RPERGARGGQ VFYNSEYGEL SEPSEEDHCS PSARVTFFTD NSY
	Isoform 2 (Short) [UniParc]. Checksum: 3DC469ED3CB8B3B1	FASTA	1,298	145,599
	10 20 30 40 50 60 MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS CRGQHPLEWA 70 80 90 100 110 120 WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE VHANDTGSYV CYYKYIKARI 130 140 150 160 170 180 EGTTAASSYV FVRDFEQPFI NKPDTLLVNR KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG 190 200 210 220 230 240 QEVVWDDRRG MLVSTPLLHD ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL 250 260 270 280 290 300 ELLVGEKLVL NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV 310 320 330 340 350 360 SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE LVKLPVKLAA 370 380 390 400 410 420 YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA LWNSAAGLRR NISLELVVNV 430 440 450 460 470 480 PPQIHEKEAS SPSIYSRHSR QALTCTAYGV PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ 490 500 510 520 530 540 DLMPQCRDWR AVTTQDAVNP IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV 550 560 570 580 590 600 GQDERLIYFY VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD 610 620 630 640 650 660 AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH YVCEVQDRRS 670 680 690 700 710 720 HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL VAGAHAPSIV WYKDERLLEE 730 740 750 760 770 780 KSGVDLADSN QKLSIQRVRE EDAGRYLCSV CNAKGCVNSS ASVAVEGSED KGSMEIVILV 790 800 810 820 830 840 GTGVIAVFFW VLLLLIFCNM RRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDASQWEF 850 860 870 880 890 900 PRERLHLGRV LGYGAFGKVV EASAFGIHKG SSCDTVAVKM LKEGATASEH RALMSELKIL 910 920 930 940 950 960 IHIGNHLNVV NLLGACTKPQ GPLMVIVEFC KYGNLSNFLR AKRDAFSPCA EKSPEQRGRF 970 980 990 1000 1010 1020 RAMVELARLD RRRPGSSDRV LFARFSKTEG GARRASPDQE AEDLWLSPLT MEDLVCYSFQ 1030 1040 1050 1060 1070 1080 VARGMEFLAS RKCIHRDLAA RNILLSESDV VKICDFGLAR DIYKDPDYVR KGSARLPLKW 1090 1100 1110 1120 1130 1140 MAPESIFDKV YTTQSDVWSF GVLLWEIFSL GASPYPGVQI NEEFCQRLRD GTRMRAPELA 1150 1160 1170 1180 1190 1200 TPAIRRIMLN CWSGDPKARP AFSELVEILG DLLQGRGLQE EEEVCMAPRS SQSSEEGSFS 1210 1220 1230 1240 1250 1260 QVSTMALHIA QADAEDSPPS LQRHSLAARY YNWVSFPGCL ARGAETRGSS RMKTFEEFPM 1270 1280 1290 TPTTYKGSVD NQTDSGMVLA SEEFEQIESR HRQESGFR
	Isoform 3 (sVegfr3) [UniParc]. Checksum: 873CB1459C93C49A	FASTA	830	93,174
	10 20 30 40 50 60 MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS CRGQHPLEWA 70 80 90 100 110 120 WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE VHANDTGSYV CYYKYIKARI 130 140 150 160 170 180 EGTTAASSYV FVRDFEQPFI NKPDTLLVNR KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG 190 200 210 220 230 240 QEVVWDDRRG MLVSTPLLHD ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL 250 260 270 280 290 300 ELLVGEKLVL NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV 310 320 330 340 350 360 SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE LVKLPVKLAA 370 380 390 400 410 420 YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA LWNSAAGLRR NISLELVVNV 430 440 450 460 470 480 PPQIHEKEAS SPSIYSRHSR QALTCTAYGV PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ 490 500 510 520 530 540 DLMPQCRDWR AVTTQDAVNP IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV 550 560 570 580 590 600 GQDERLIYFY VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD 610 620 630 640 650 660 AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH YVCEVQDRRS 670 680 690 700 710 720 HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL VAGAHAPSIV WYKDERLLEE 730 740 750 760 770 780 KSGREGGPGE GQVRRPARPT IPNPGGPAPP PHPLQESTWR TPTRSCKGPG QNVAVTRAHP 790 800 810 820 830 DSQGRRRRPE RGARGGQVFY NSEYGELSEP SEEDHCSPSA RVTFFTDNSY

References

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[1]	"FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines." Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L., Alitalo R., Alitalo K. Cancer Res. 52:5738-5743(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[2]	Erratum Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L., Alitalo R., Alitalo K. Cancer Res. 53:3845-3845(1993)
[3]	"Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene." Galland F., Karamysheva A., Mattei M.-G., Rosnet O., Marchetto S., Birnbaum D. Genomics 13:475-478(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor." Galland F., Karamysheva A., Pebusque M.-J., Borg J.-P., Rottapel R., Dubreuil P., Rosnet O., Birnbaum D. Oncogene 8:1233-1240(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS GLN-890 AND HIS-1146. Tissue: Placenta.
[5]	"Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4." Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I. Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH VEGFC, PHOSPHORYLATION, FUNCTION IN CELL PROLIFERATION.
[6]	"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis." Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M. Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH VEGFD, SUBCELLULAR LOCATION.
[7]	Lian Z., Feitelson M. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS GLN-890 AND HIS-1146.
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-890. Tissue: Placenta.
[9]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter." Aprelikova O., Pajusola K., Partanen J., Armstrong E., Alitalo R., Bailey S.K., McMahon J., Wasmuth J., Huebner K., Alitalo K. Cancer Res. 52:746-748(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 761-1190.
[11]	"Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts." Pajusola K., Aprelikova O., Armstrong E., Morris S., Alitalo K. Oncogene 8:2931-2937(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1293-1363 (ISOFORM 1), ALTERNATIVE SPLICING.
[12]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-39.
[13]	"Biochemical characterization of two isoforms of FLT4, a VEGF receptor-related tyrosine kinase." Borg J.P., deLapeyriere O., Noguchi T., Rottapel R., Dubreuil P., Birnbaum D. Oncogene 10:973-984(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, GLYCOSYLATION, SUBCELLULAR LOCATION.
[14]	"Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor." Fournier E., Dubreuil P., Birnbaum D., Borg J.P. Oncogene 11:921-931(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF SHC1, CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH SHC1 AND GRB2, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1333; TYR-1337 AND TYR-1363, TISSUE SPECIFICITY.
[15]	"Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)." Achen M.G., Jeltsch M., Kukk E., Maekinen T., Vitali A., Wilks A.F., Alitalo K., Stacker S.A. Proc. Natl. Acad. Sci. U.S.A. 95:548-553(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VEGFD, FUNCTION AS VEGFD RECEPTOR, AUTOPHOSPHORYLATION.
[16]	"Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3." Makinen T., Veikkola T., Mustjoki S., Karpanen T., Catimel B., Nice E.C., Wise L., Mercer A., Kowalski H., Kerjaschki D., Stacker S.A., Achen M.G., Alitalo K. EMBO J. 20:4762-4773(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR VEGFC AND VEGFD IN CELL SURVIVAL; PROLIFERATION AND MIGRATION, FUNCTION IN ACTIVATION OF PROTEIN KINASE C; AKT1; PIK3R1; MAPK1/ERK2 AND MAPK3/ERK1.
[17]	"Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites." Dixelius J., Makinen T., Wirzenius M., Karkkainen M.J., Wernstedt C., Alitalo K., Claesson-Welsh L. J. Biol. Chem. 278:40973-40979(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KDR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANT LMPH1A PRO-1041, MUTAGENESIS OF LYS-879; TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363, PHOSPHORYLATION AT TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363.
[18]	"Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity." Alam A., Herault J.P., Barron P., Favier B., Fons P., Delesque-Touchard N., Senegas I., Laboudie P., Bonnin J., Cassan C., Savi P., Ruggeri B., Carmeliet P., Bono F., Herbert J.M. Biochem. Biophys. Res. Commun. 324:909-915(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN KDR SIGNALING AND IN ANGIOGENESIS, INTERACTION WITH KDR, PHOSPHORYLATION.
[19]	"Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress." Wang J.F., Zhang X., Groopman J.E. J. Biol. Chem. 279:27088-27097(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL SURVIVAL, PHOSPHORYLATION IN RESPONSE TO OXIDATIVE STRESS, INTERACTION WITH PIK3R1; SHC1; GRB2, PTPN11/SHP-2 AND PLCG1, ENZYME REGULATION BY MAZ51, CHARACTERIZATION OF VARIANT LMPH1A ARG-857.
[20]	"Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation, migration, and survival of endothelial cells through the activation of ERK, AKT, and JNK pathways." Salameh A., Galvagni F., Bardelli M., Bussolino F., Oliviero S. Blood 106:3423-3431(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF AKT1; MAPK1/ERK2; MAPK3/ERK1 AND MAPK8, FUNCTION IN PROMOTING CELL SURVIVAL; PROLIFERATION AND MIGRATION, CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH CRK AND GRB2, PHOSPHORYLATION AT TYR-1063; TYR-1068; TYR-1230; TYR-1231 AND TYR-1337, MUTAGENESIS OF TYR-1063; TYR-1068; TYR-1230 AND TYR-1231.
[21]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-527, MASS SPECTROMETRY. Tissue: Plasma.
[22]	"Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells." Garces C.A., Kurenova E.V., Golubovskaya V.M., Cance W.G. Cancer Res. 66:1446-1454(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PROMOTING CELL SURVIVAL, INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION.
[23]	"Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis." Goldman J., Rutkowski J.M., Shields J.D., Pasquier M.C., Cui Y., Schmokel H.G., Willey S., Hicklin D.J., Pytowski B., Swartz M.A. FASEB J. 21:1003-1012(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LYMPHANGIOGENESIS.
[24]	"Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells." Matsuura M., Onimaru M., Yonemitsu Y., Suzuki H., Nakano T., Ishibashi H., Shirasuna K., Sueishi K. Am. J. Pathol. 175:1709-1721(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN CANCER, FUNCTION AS VEGFC RECEPTOR IN TUMOR LYMPHANGIOGENESIS; CELL PROLIFERATION; CELL SURVIVAL; IN ACTIVATION OF PIK3R1; AKT1 AND MAP KINASES AND IN UP-REGULATION OF VEGFA AND VEGFC EXPRESSION, ENZYME REGULATION, AUTOPHOSPHORYLATION.
[25]	"Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo." Kurenova E.V., Hunt D.L., He D., Magis A.T., Ostrov D.A., Cance W.G. J. Med. Chem. 52:4716-4724(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN CANCER, INTERACTION WITH PTK2/FAK1.
[26]	"Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans." Au A.C., Hernandez P.A., Lieber E., Nadroo A.M., Shen Y.M., Kelley K.A., Gelb B.D., Diaz G.A. Am. J. Hum. Genet. 87:436-444(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPN14.
[27]	"Endothelial cell adhesion to the extracellular matrix induces c-Src-dependent VEGFR-3 phosphorylation without the activation of the receptor intrinsic kinase activity." Galvagni F., Pennacchini S., Salameh A., Rocchigiani M., Neri F., Orlandini M., Petraglia F., Gotta S., Sardone G.L., Matteucci G., Terstappen G.C., Oliviero S. Circ. Res. 106:1839-1848(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-830; TYR-833; TYR-853; TYR-1063; TYR-1068; TYR-1333 AND TYR-1337, IDENTIFICATION IN A COMPLEX WITH SRC AND ITGB1, MUTAGENESIS OF TYR-1063; TYR-1068 AND TYR-1337, ENZYME REGULATION BY MAZ51, INTERACTION WITH ITGB1; CRK AND SHC1, FUNCTION IN ACTIVATION OF MAPK8 AND IN REGULATION OF ANGIOGENIC SPROUTING, MASS SPECTROMETRY.
[28]	"VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts." Nilsson I., Bahram F., Li X., Gualandi L., Koch S., Jarvius M., Soderberg O., Anisimov A., Kholova I., Pytowski B., Baldwin M., Yla-Herttuala S., Alitalo K., Kreuger J., Claesson-Welsh L. EMBO J. 29:1377-1388(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KDR, FUNCTION IN MODULATING KDR SIGNALING AND IN ANGIOGENESIS, TISSUE SPECIFICITY.
[29]	"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis." Wang Y., Nakayama M., Pitulescu M.E., Schmidt T.S., Bochenek M.L., Sakakibara A., Adams S., Davy A., Deutsch U., Luthi U., Barberis A., Benjamin L.E., Makinen T., Nobes C.D., Adams R.H. Nature 465:483-486(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS, SUBCELLULAR LOCATION.
[30]	"Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages." Yuen D., Pytowski B., Chen L. Invest. Ophthalmol. Vis. Sci. 52:2593-2597(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LYMPHANGIOGENESIS.
[31]	"VEGF receptor protein-tyrosine kinases: structure and regulation." Roskoski R. Jr. Biochem. Biophys. Res. Commun. 375:287-291(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON STRUCTURE AND FUNCTION.
[32]	"VEGFs and receptors involved in angiogenesis versus lymphangiogenesis." Lohela M., Bry M., Tammela T., Alitalo K. Curr. Opin. Cell Biol. 21:154-165(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN LYMPHANGIOGENESIS AND CANCER.
[33]	"Signal transduction by vascular endothelial growth factor receptors." Koch S., Tugues S., Li X., Gualandi L., Claesson-Welsh L. Biochem. J. 437:169-183(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND SIGNALING.
[34]	"Lymphangiogenesis and cancer metastasis." Al-Rawi M.A., Jiang W.G. Front. Biosci. 16:723-739(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN LYMPHANGIOGENESIS AND ROLE IN CANCER.
[35]	"Hereditary lymphedema: evidence for linkage and genetic heterogeneity." Ferrell R.E., Levinson K.L., Esman J.H., Kimak M.A., Lawrence E.C., Barmada M.M., Finegold D.N. Hum. Mol. Genet. 7:2073-2078(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LMPH1A LEU-1114.
[36]	"Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase." Irrthum A., Karkkainen M.J., Devriendt K., Alitalo K., Vikkula M. Am. J. Hum. Genet. 67:295-301(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LMPH1A, CHARACTERIZATION OF VARIANT LMPH1A ARG-1035.
[37]	"Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema." Karkkainen M.J., Ferrell R.E., Lawrence E.C., Kimak M.A., Levinson K.L., McTigue M.A., Alitalo K., Finegold D.N. Nat. Genet. 25:153-159(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LMPH1A ARG-857; PRO-1041; PRO-1044 AND LEU-1114, VARIANT SER-641, CHARACTERIZATION OF VARIANTS.
[38]	"Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma." Walter J.W., North P.E., Waner M., Mizeracki A., Blei F., Walker J.W.T., Reinisch J.F., Marchuk D.A. Genes Chromosomes Cancer 33:295-303(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HCI SER-954 AND SER-1137, VARIANTS ALA-494; GLN-890 AND HIS-1146.
[39]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-149; CYS-378; ALA-494; SER-527; SER-641; TYR-868; ILE-1010; GLN-1031; ASN-1049; GLN-1075 AND HIS-1146.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

FLT4 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	X69878 mRNA. Translation: CAA49505.1. U43143 mRNA. Translation: AAA85215.1. EU826564 mRNA. Translation: ACF47600.1. AY233382 mRNA. Translation: AAO89504.1. AY233383 mRNA. Translation: AAO89505.1. AK291679 mRNA. Translation: BAF84368.1. AC122714 Genomic DNA. No translation available. X68203 mRNA. Translation: CAA48290.1. Different initiation. S66407 mRNA. Translation: AAB28539.1.
IPI	IPI00293565. IPI00337568.
PIR	A48999.
RefSeq	NP_002011.2. NM_002020.4. NP_891555.2. NM_182925.4.
UniGene	Hs.646917.
3D structure databases
ProteinModelPortal	P35916.
SMR	P35916. Positions 28-462, 632-765, 822-1180.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5739N.
IntAct	P35916. 4 interactions.
MINT	MINT-1182429.
STRING	9606.ENSP00000261937.
PTM databases
PhosphoSite	P35916.
Polymorphism databases
DMDM	1718189.
Proteomic databases
PaxDb	P35916.
PRIDE	P35916.
Protocols and materials databases
DNASU	2324.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261937; ENSP00000261937; ENSG00000037280. ENST00000393347; ENSP00000377016; ENSG00000037280.
GeneID	2324.
KEGG	hsa:2324.
UCSC	uc003mlz.4. human. uc003mma.4. human.
Organism-specific databases
CTD	2324.
GeneCards	GC05M180028.
HGNC	HGNC:3767. FLT4.
MIM	136352. gene. 153100. phenotype. 602089. phenotype.
neXtProt	NX_P35916.
Orphanet	79452. Milroy disease.
PharmGKB	PA28183.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000037949.
HOVERGEN	HBG053432.
KO	K05097.
OMA	QINEEFC.
OrthoDB	EOG49W2DJ.
PhylomeDB	P35916.
Enzyme and pathway databases
BRENDA	2.7.10.1. 2681.
Pathway_Interaction_DB	vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2. lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P35916.
Bgee	P35916.
CleanEx	HS_FLT4.
Genevestigator	P35916.
GermOnline	ENSG00000037280. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 9 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR003598. Ig_sub2. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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. IPR009137. Tyr_kinase_VEGFR3_rcpt_N. IPR009134. Tyr_kinase_VEGFR_rcpt_N. [Graphical view]
Pfam	PF07679. I-set. 2 hits. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR01832. VEGFRECEPTOR. PR01835. VEGFRECEPTR3.
SMART	SM00409. IG. 4 hits. SM00408. IGc2. 2 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50835. 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]
ProtoNet	Search...
Other
BindingDB	P35916.
ChEMBL	CHEMBL1955.
ChiTaRS	FLT4. human.
DrugBank	DB00398. Sorafenib. DB01268. Sunitinib.
GenomeRNAi	2324.
NextBio	9433.
SOURCE	Search...

Entry information

Entry name

VGFR3_HUMAN

Accession

Primary (citable) accession number: P35916
Secondary accession number(s): A8K6L4 , B5A926, Q16067, Q86W07, Q86W08

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 16, 2011
Last modified:	May 1, 2013
This is version 153 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.