FLT4

Protein identityUniProt · HPA

UniProt accession

P35916

Gene

FLT4

Ensembl

ENSG00000037280

Chromosome

5

Canonical length

1363 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, RAS pathway related proteins, Transporters

Subcellular location

Microtubules,Cytokinetic bridge,Primary cilium,Calyx,Connecting piece,Mid piece,Principal piece

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1363 residues, UniProt reviewed canonical sequence.

>P35916|FLT4
     1  MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS CRGQHPLEWA
    61  WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE VHANDTGSYV CYYKYIKARI
   121  EGTTAASSYV FVRDFEQPFI NKPDTLLVNR KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG
   181  QEVVWDDRRG MLVSTPLLHD ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL
   241  ELLVGEKLVL NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV
   301  SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE LVKLPVKLAA
   361  YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA LWNSAAGLRR NISLELVVNV
   421  PPQIHEKEAS SPSIYSRHSR QALTCTAYGV PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ
   481  DLMPQCRDWR AVTTQDAVNP IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV
   541  GQDERLIYFY VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD
   601  AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH YVCEVQDRRS
   661  HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL VAGAHAPSIV WYKDERLLEE
   721  KSGVDLADSN QKLSIQRVRE EDAGRYLCSV CNAKGCVNSS ASVAVEGSED KGSMEIVILV
   781  GTGVIAVFFW VLLLLIFCNM RRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDASQWEF
   841  PRERLHLGRV LGYGAFGKVV EASAFGIHKG SSCDTVAVKM LKEGATASEH RALMSELKIL
   901  IHIGNHLNVV NLLGACTKPQ GPLMVIVEFC KYGNLSNFLR AKRDAFSPCA EKSPEQRGRF
   961  RAMVELARLD RRRPGSSDRV LFARFSKTEG GARRASPDQE AEDLWLSPLT MEDLVCYSFQ
  1021  VARGMEFLAS RKCIHRDLAA RNILLSESDV VKICDFGLAR DIYKDPDYVR KGSARLPLKW
  1081  MAPESIFDKV YTTQSDVWSF GVLLWEIFSL GASPYPGVQI NEEFCQRLRD GTRMRAPELA
  1141  TPAIRRIMLN CWSGDPKARP AFSELVEILG DLLQGRGLQE EEEVCMAPRS SQSSEEGSFS
  1201  QVSTMALHIA QADAEDSPPS LQRHSLAARY YNWVSFPGCL ARGAETRGSS RMKTFEEFPM
  1261  TPTTYKGSVD NQTDSGMVLA SEEFEQIESR HRQESGFSCK GPGQNVAVTR AHPDSQGRRR
  1321  RPERGARGGQ VFYNSEYGEL SEPSEEDHCS PSARVTFFTD NSY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FLT4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

25 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FLT4.

Disease | AllUniProt

Conditions FLT4 is implicated in, by any mechanism.

• Lymphatic malformation 1 (LMPHM1) MIM:153100
• Hemangioma, capillary infantile (HCI) MIM:602089
• Congenital heart defects, multiple types, 7 (CHTD7) MIM:618780

Disease | GeneticClinVar

67 pathogenic / likely-pathogenic of 607 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary lymphedema type I
• Congenital heart defects, multiple types, 7
• FLT4-related disorder
• Inborn genetic diseases
• Non-immune hydrops fetalis

ReferencesPubMed · IEDB

Publications for FLT4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.15

gnomAD pLI

1

gnomAD missense Z

2.83

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood vessel morphogenesis
• cell migration
• cell surface receptor protein tyrosine kinase signaling pathway
• cellular response to vascular endothelial growth factor stimulus
• lung alveolus development
• lymph vessel development
• lymphangiogenesis
• negative regulation of apoptotic process
• peptidyl-tyrosine phosphorylation
• positive regulation of cell migration
• positive regulation of cell population proliferation
• positive regulation of endothelial cell migration
• positive regulation of endothelial cell proliferation
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of JNK cascade
• positive regulation of MAPK cascade
• positive regulation of protein phosphorylation
• positive regulation of vascular endothelial growth factor production
• protein autophosphorylation
• regulation of blood vessel remodeling
• respiratory system process
• sprouting angiogenesis
• vascular endothelial growth factor receptor signaling pathway
• vascular endothelial growth factor signaling pathway
• vasculature development

Molecular functions

• ATP binding
• growth factor binding
• protein homodimerization activity
• protein phosphatase binding
• transmembrane receptor protein tyrosine kinase activity
• vascular endothelial growth factor receptor activity

Cellular components

• cytoplasm
• extracellular region
• nucleus
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, receptor class III, conserved site
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Protein kinase, ATP binding site
• Tyrosine-protein kinase, catalytic domain
• Immunoglobulin-like domain superfamily
• VEGFR-2, transmembrane domain
• Receptor Tyrosine Kinase
• VEGFR1-3, fifth immunoglobulin-like domain
• VEGFR1-3-like, N-terminal Ig-like domain
• Immunoglobulin I-set domain
• Protein tyrosine and serine/threonine kinase
• Immunoglobulin domain
• VEGFR-2 Transmembrane domain
• Vascular endothelial growth factor receptor 1-like, Ig-like domain
• VEGFR1-3, N-terminal Ig-like domain
• VEGFR-1-like, immunoglobulin-like domain

KeywordsUniProt

• Angiogenesis
• ATP-binding
• Cell membrane
• Cytoplasm
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Kinase
• Membrane
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of FLT4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CRK
• GRB2
• PIK3R1
• PTPN14
• SHC1
• VEGFC
• VEGFD
• PLCG1
• PTK2