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UniProtKB - P21802 (FGFR2_HUMAN)

Entry version 259 (07 Apr 2021)
Sequence version 1 (01 May 1991)
Previous versions | rss
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Protein

Fibroblast growth factor receptor 2

Gene

FGFR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.13 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by ARQ 523 and ARQ 069; these compounds maintain the kinase in an inactive conformation and inhibit autophosphorylation.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei517ATPPROSITE-ProRule annotation1 Publication1
Binding sitei571ATPPROSITE-ProRule annotation1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei626Proton acceptorPROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi487 – 495ATPPROSITE-ProRule annotation1 Publication9
Nucleotide bindingi565 – 567ATPPROSITE-ProRule annotation1 Publication3

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHeparin-binding, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processApoptosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.10.1, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P21802

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-109704, PI3K Cascade
R-HSA-1257604, PIP3 activates AKT signaling
R-HSA-190375, FGFR2c ligand binding and activation
R-HSA-190377, FGFR2b ligand binding and activation
R-HSA-2023837, Signaling by FGFR2 amplification mutants
R-HSA-2033519, Activated point mutants of FGFR2
R-HSA-2219530, Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654221, Phospholipase C-mediated cascade, FGFR2
R-HSA-5654695, PI-3K cascade:FGFR2
R-HSA-5654699, SHC-mediated cascade:FGFR2
R-HSA-5654700, FRS-mediated FGFR2 signaling
R-HSA-5654727, Negative regulation of FGFR2 signaling
R-HSA-5655253, Signaling by FGFR2 in disease
R-HSA-5673001, RAF/MAP kinase cascade
R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8851708, Signaling by FGFR2 IIIa TM
R-HSA-8853333, Signaling by FGFR2 fusions

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P21802

SIGNOR Signaling Network Open Resource

More...SIGNORi		P21802

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Fibroblast growth factor receptor 2 (EC:2.7.10.14 Publications)
Short name:
FGFR-2
Alternative name(s):
K-sam
Short name:
KGFR
Keratinocyte growth factor receptor
CD_antigen: CD332
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:FGFR2
Synonyms:BEK, KGFR, KSAM
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 10

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:3689, FGFR2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		176943, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P21802

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000066468.20

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini22 – 377ExtracellularSequence analysisAdd BLAST356
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei378 – 398HelicalSequence analysisAdd BLAST21
Topological domaini399 – 821CytoplasmicSequence analysisAdd BLAST423

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Crouzon syndrome (CS)17 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_004112105Y → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs1434545235EnsemblClinVar.1
Natural variantiVAR_017261263P → L in CS. 1 PublicationCorresponds to variant dbSNP:rs779326224Ensembl.1
Natural variantiVAR_004118267S → P in CS. 1 PublicationCorresponds to variant dbSNP:rs121918505EnsemblClinVar.1
Natural variantiVAR_004119268T → TG in CS. 1 Publication1
Natural variantiVAR_004120276F → V in CS. 3 PublicationsCorresponds to variant dbSNP:rs1057519036EnsemblClinVar.1
Natural variantiVAR_004121278C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant dbSNP:rs776587763EnsemblClinVar.1
Natural variantiVAR_017263278C → Y in CS. 1 PublicationCorresponds to variant dbSNP:rs776587763EnsemblClinVar.1
Natural variantiVAR_017264281Y → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs1057519038EnsemblClinVar.1
Natural variantiVAR_004122287 – 289Missing in CS. 3
Natural variantiVAR_017265288I → S in CS. 1 Publication1
Natural variantiVAR_004123289Q → P in CS and JWS. 5 PublicationsCorresponds to variant dbSNP:rs121918497EnsemblClinVar.1
Natural variantiVAR_017266290W → G in CS. 1 PublicationCorresponds to variant dbSNP:rs121918501EnsemblClinVar.1
Natural variantiVAR_004125290W → R in CS. Corresponds to variant dbSNP:rs121918501EnsemblClinVar.1
Natural variantiVAR_004126292K → E in CS. 1 PublicationCorresponds to variant dbSNP:rs121918500EnsemblClinVar.1
Natural variantiVAR_004127301Y → C in CS. 1 PublicationCorresponds to variant dbSNP:rs1554930684EnsemblClinVar.1
Natural variantiVAR_004130328Y → C in CS. 1 PublicationCorresponds to variant dbSNP:rs121918493EnsemblClinVar.1
Natural variantiVAR_004131331N → I in CS. 1 Publication1
Natural variantiVAR_004132337A → ANA in CS. 1
Natural variantiVAR_017268337A → P in CS. 1 PublicationCorresponds to variant dbSNP:rs387906676EnsemblClinVar.1
Natural variantiVAR_004133338G → E in CS. 1 PublicationCorresponds to variant dbSNP:rs1057519044EnsemblClinVar.1
Natural variantiVAR_015011338G → R in CS. 3 PublicationsCorresponds to variant dbSNP:rs1057519043EnsemblClinVar.1
Natural variantiVAR_004134340Y → H in CS. 2 PublicationsCorresponds to variant dbSNP:rs121918489EnsemblClinVar.1
Natural variantiVAR_004135341T → P in PS and CS. 3 PublicationsCorresponds to variant dbSNP:rs121918495EnsemblClinVar.1
Natural variantiVAR_004136342C → F in CS. 3 PublicationsCorresponds to variant dbSNP:rs121918487EnsemblClinVar.1
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_017271342C → W in CS. 3 PublicationsCorresponds to variant dbSNP:rs121918496EnsemblClinVar.1
Natural variantiVAR_004139342C → Y in CS and PS. 8 PublicationsCorresponds to variant dbSNP:rs121918487EnsemblClinVar.1
Natural variantiVAR_004140344A → G in CS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121918492EnsemblClinVar.1
Natural variantiVAR_004141344A → P in CS and PS. 1 Publication1
Natural variantiVAR_004142347S → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs121918494EnsemblClinVar.1
Natural variantiVAR_004143351S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant dbSNP:rs121918502EnsemblClinVar.1
Natural variantiVAR_004144354S → C in CS. 5 PublicationsCorresponds to variant dbSNP:rs121918490EnsemblClinVar.1
Natural variantiVAR_017272354S → Y in CS. 1 Publication1
Natural variantiVAR_004145356 – 358Missing in CS. 1 Publication3
Natural variantiVAR_004146359V → F in CS and PS. 2 Publications1
Natural variantiVAR_017273362A → S in CS. 1 Publication1
Natural variantiVAR_004147384G → R in CS. 1 PublicationCorresponds to variant dbSNP:rs1554927408EnsemblClinVar.1
Natural variantiVAR_017276549N → H in CS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057519045EnsemblClinVar.1
Natural variantiVAR_017281678R → G in CS. 1 Publication1
Jackson-Weiss syndrome (JWS)5 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004123289Q → P in CS and JWS. 5 PublicationsCorresponds to variant dbSNP:rs121918497EnsemblClinVar.1
Natural variantiVAR_004140344A → G in CS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121918492EnsemblClinVar.1
Apert syndrome (APRS)8 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004114252S → F in APRS; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121918498EnsemblClinVar.1
Natural variantiVAR_004115252S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant dbSNP:rs79184941EnsemblClinVar.1
Natural variantiVAR_004117253P → R in APRS; common mutation. 5 PublicationsCorresponds to variant dbSNP:rs77543610EnsemblClinVar.1
Pfeiffer syndrome (PS)13 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017259172A → F in PS; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_004116252 – 253SP → FS in PS. Corresponds to variant dbSNP:rs281865420Ensembl.2
Natural variantiVAR_004115252S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant dbSNP:rs79184941EnsemblClinVar.1
Natural variantiVAR_017262273Missing in PS; type 2. 1 PublicationCorresponds to variant dbSNP:rs121918503Ensembl.1
Natural variantiVAR_004121278C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant dbSNP:rs776587763EnsemblClinVar.1
Natural variantiVAR_004124290W → C in PS; severe; also in a lung squamous cell carcinoma sample; somatic mutation. 3 PublicationsCorresponds to variant dbSNP:rs121918499EnsemblClinVar.1
Natural variantiVAR_004129321D → A in PS. 1 PublicationCorresponds to variant dbSNP:rs121918510EnsemblClinVar.1
Natural variantiVAR_017269340Y → C in PS. 2 PublicationsCorresponds to variant dbSNP:rs1554928884EnsemblClinVar.1
Natural variantiVAR_004135341T → P in PS and CS. 3 PublicationsCorresponds to variant dbSNP:rs121918495EnsemblClinVar.1
Natural variantiVAR_017270342C → G in PS. 1 PublicationCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_004139342C → Y in CS and PS. 8 PublicationsCorresponds to variant dbSNP:rs121918487EnsemblClinVar.1
Natural variantiVAR_004141344A → P in CS and PS. 1 Publication1
Natural variantiVAR_004146359V → F in CS and PS. 2 Publications1
Natural variantiVAR_017275375Y → C in PS and BSTVS. 3 PublicationsCorresponds to variant dbSNP:rs121913478EnsemblClinVar.1
Natural variantiVAR_017277565E → G in PS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918506EnsemblClinVar.1
Natural variantiVAR_017278641K → R in PS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057519047EnsemblClinVar.1
Natural variantiVAR_017280663G → E in PS. 1 Publication1
Beare-Stevenson cutis gyrata syndrome (BSTVS)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease characterized by craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017274372S → C in BSTVS. 1 PublicationCorresponds to variant dbSNP:rs121913477EnsemblClinVar.1
Natural variantiVAR_017275375Y → C in PS and BSTVS. 3 PublicationsCorresponds to variant dbSNP:rs121913478EnsemblClinVar.1
Familial scaphocephaly syndrome (FSPC)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023788526K → E in FSPC; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918507EnsemblClinVar.1
Lacrimo-auriculo-dento-digital syndrome (LADDS)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Lacrimo-auriculo-dento-digital syndrome is characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029884628A → T in LADDS; strongly reduced kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121918509EnsemblClinVar.1
Natural variantiVAR_029885648A → T in LADDS. 1 PublicationCorresponds to variant dbSNP:rs121918508EnsemblClinVar.1
Natural variantiVAR_029886649 – 650RD → S in LADDS. 1 Publication2
Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004137342C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_004138342C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant dbSNP:rs121918488EnsemblClinVar.1
Natural variantiVAR_004143351S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant dbSNP:rs121918502EnsemblClinVar.1
Bent bone dysplasia syndrome (BBDS)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067977381Y → D in BBDS. 1 PublicationCorresponds to variant dbSNP:rs387906678EnsemblClinVar.1
Natural variantiVAR_067978391M → R in BBDS; the mutation selectively reduces plasma-membrane levels of the protein and markedly diminishes the receptor's responsiveness to extracellular FGF. 1 PublicationCorresponds to variant dbSNP:rs387906677EnsemblClinVar.1
Saethre-Chotzen syndrome (SCS)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075856269 – 270Missing in SCS. 1 Publication2

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi265N → Q: Reduced N-glycosylation. Reduced expression at the cell surface. 1 Publication1
Mutagenesisi549N → T: Constitutive kinase activity. 1 Publication1
Mutagenesisi565E → A: Constitutive kinase activity. 1 Publication1
Mutagenesisi656 – 657Missing : Loss of kinase activity. 1 Publication2
Mutagenesisi769Y → F: Increases fibroblast proliferation. Decreases phosphorylation of PLCG1 and FRS2. Decreases activation of MAP kinases. 2 Publications1

Keywords - Diseasei

Craniosynostosis, Disease variant, Ectodermal dysplasia, Lacrimo-auriculo-dento-digital syndrome, Mental retardation, Proto-oncogene

Organism-specific databases

DisGeNET

More...DisGeNETi		2263

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		FGFR2

MalaCards human disease database

More...MalaCardsi		FGFR2
MIMi101200, phenotype
101400, phenotype
101600, phenotype
123150, phenotype
123500, phenotype
123790, phenotype
149730, phenotype
207410, phenotype
609579, phenotype
614592, phenotype

Open Targets

More...OpenTargetsi		ENSG00000066468

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		83, Antley-Bixler syndrome
87, Apert syndrome
207, Crouzon disease
1555, Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
168624, Familial scaphocephaly syndrome, McGillivray type
313855, FGFR2-related bent bone dysplasia
1540, Jackson-Weiss syndrome
2363, Lacrimoauriculodentodigital syndrome
93258, Pfeiffer syndrome type 1
93259, Pfeiffer syndrome type 2
93260, Pfeiffer syndrome type 3
794, Saethre-Chotzen syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA28128

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P21802, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4142

Drug and drug target database

More...DrugBanki		DB02058, 3-[4-(1-formylpiperazin-4-yl)-benzylidenyl]-2-indolinone
DB02491, 4-[4-(1-Amino-1-Methylethyl)Phenyl]-5-Chloro-N-[4-(2-Morpholin-4-Ylethyl)Phenyl]Pyrimidin-2-Amine
DB12147, Erdafitinib
DB10770, Foreskin fibroblast (neonatal)
DB10772, Foreskin keratinocyte (neonatal)
DB12010, Fostamatinib
DB01109, Heparin
DB09078, Lenvatinib
DB09079, Nintedanib
DB00039, Palifermin
DB15102, Pemigatinib
DB08901, Ponatinib
DB15822, Pralsetinib
DB08896, Regorafenib
DB15685, Selpercatinib
DB01901, Sucrosofate
DB01041, Thalidomide

DrugCentral

More...DrugCentrali		P21802

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1809

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		FGFR2

Domain mapping of disease mutations (DMDM)

More...DMDMi		120049

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 21Sequence analysisAdd BLAST21
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001678322 – 821Fibroblast growth factor receptor 2Add BLAST800

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi62 ↔ 107PROSITE-ProRule annotation
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi83N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi123N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi179 ↔ 231PROSITE-ProRule annotation1 Publication
Glycosylationi228N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi265N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi278 ↔ 342PROSITE-ProRule annotation1 Publication
Glycosylationi297N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi318N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi331N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei466Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei586Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei588Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei656Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei657Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei769Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei780PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on several tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-769 is essential for interaction with PLCG1.2 Publications
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.2 Publications
Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P21802

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P21802

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P21802

PeptideAtlas

More...PeptideAtlasi		P21802

PRoteomics IDEntifications database

More...PRIDEi		P21802

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		53905 [P21802-1]
53910 [P21802-14]
53911 [P21802-15]
53912 [P21802-16]
53913 [P21802-17]
53914 [P21802-18]
53915 [P21802-19]
53916 [P21802-2]
53917 [P21802-20]
53918 [P21802-21]
53919 [P21802-22]
53920 [P21802-23]
53921 [P21802-3]
53922 [P21802-4]
53923 [P21802-5]
53924 [P21802-6]
53926 [P21802-8]

Consortium for Top Down Proteomics

More...TopDownProteomicsi		P21802-8 [P21802-8]

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		1997, 1 N-Linked glycan (1 site)

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P21802, 9 sites, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P21802

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P21802

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000066468, Expressed in C1 segment of cervical spinal cord and 235 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P21802, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P21802, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000066468, Tissue enhanced (brain)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer. Homodimer after ligand binding.

Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21.

Interacts with PLCG1, GRB2 and PAK4.

Interacts with FLRT2 (By similarity).

By similarity21 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

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GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		108554, 104 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P21802

Database of interacting proteins

More...DIPi		DIP-3788N

Protein interaction database and analysis system

More...IntActi		P21802, 89 interactors

Molecular INTeraction database

More...MINTi		P21802

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000410294

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P21802

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P21802, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1821
Legend: HelixTurnBeta strandPDB Structure known for this area
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