Reviewed, UniProtKB/Swiss-Prot P21802 (FGFR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Fibroblast growth factor receptor 2
      Short name=FGFR-2
    EC=2.7.10.1
Alternative name(s):
    Keratinocyte growth factor receptor 2
    CD_antigen=CD332

Gene names

Name:	FGFR2
Synonyms:	BEK, KGFR, KSAM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	821 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	Receptor for acidic and basic fibroblast growth factors.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Isoform 14: Secreted. Isoform 19: Secreted.
Involvement in disease	Defects in FGFR2 are a cause of Crouzon syndrome (CS) [MIM:123500]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism. Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:123150]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence. Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:101200]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a 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. Defects in FGFR2 are a cause of Pfeiffer syndrome (PS) [MIM:101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3). Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:123790]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:609579]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an 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. Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome 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. Defects in FGFR2 are the cause of Antley-Bixler syndrome (ABS) [MIM:207410]. ABS is a multiple congenital anomaly syndrome characterized by craniosynostosis, radiohumeral synostosis, midface hypoplasia, malformed ears, arachnodactyly and multiple joint contractures. ABS is a heterogeneous disorder and occurs with and without abnormal genitalia in both sexes.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Craniosynostosis Disease mutation Ectodermal dysplasia Lacrimo-auriculo-dento-digital syndrome
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Heparin-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell growth Ref.18 Non-traceable author statement. Source: UniProtKB fibroblast growth factor receptor signaling pathway Inferred from Experiment. Source: Reactome protein amino acid phosphorylation Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Ref.1 Non-traceable author statement. Source: UniProtKB plasma membrane Ref.1 Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro fibroblast growth factor receptor activity Ref.1 Ref.6 Ref.18 Non-traceable author statement. Source: UniProtKB heparin binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.23 Ref.25 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FGF1	P05230	1	EBI-1028658,EBI-698068
FGF10	O15520	1	EBI-1028658,EBI-1035684
FGF2	P09038	1	EBI-1028732,EBI-977447

Alternative products

This entry describes 20 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P21802-1)

Also known as: BEK;

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: P21802-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Isoform 3 (identifier: P21802-3)

Also known as: BFR-1;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ

Isoform 4 (identifier: P21802-4)

Also known as: K-sam;

The sequence of this isoform differs from the canonical sequence as follows:
     37-125: Missing.
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     428-429: Missing.
     761-821: LTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → PPNPSLMSIFRK

Isoform 5 (identifier: P21802-5)

Also known as: K-sam-I; BEK; IgIIIc;

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.

Isoform 6 (identifier: P21802-6)

Also known as: K-sam-IIC2;

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.
     778-821: QYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → PYSPCYPDPR

Isoform 7 (identifier: P21802-7)

Also known as: K-sam-IIO2;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → RYKLLPCPDK...RVRQEKISTG

Isoform 8 (identifier: P21802-8)

Also known as: K-sam-IIC3;

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Isoform 9 (identifier: P21802-9)

Also known as: K-sam-IIH1;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → RILTLTTNEN...LADTGSKVPN

Isoform 10 (identifier: P21802-10)

Also known as: K-sam-IIH2;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → SFQSSLKSSS...CAGSKKIYDI

Isoform 11 (identifier: P21802-11)

Also known as: K-sam-IIH3; K-sam-IIO4;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLE...YPHINGSVKT → GRLPAWASQE...SQGLPQSVVP

Isoform 12 (identifier: P21802-12)

Also known as: K-sam-IIO1;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → PLS

Isoform 13 (identifier: P21802-13)

Also known as: K-sam-IIO3;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: Missing.

Isoform 14 (identifier: P21802-14)

Also known as: K-sam-IV; Soluble KGFR;

The sequence of this isoform differs from the canonical sequence as follows:
     250-254: ERSPH → GSQGL
     255-821: Missing.

Isoform 15 (identifier: P21802-15)

Also known as: K-sam-III;

The sequence of this isoform differs from the canonical sequence as follows:
     314-429: Missing.

Isoform 16 (identifier: P21802-16)

Also known as: TK14;

The sequence of this isoform differs from the canonical sequence as follows:
     313-313: K → KVLK
     428-429: Missing.

Isoform 17 (identifier: P21802-17)

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     768-821: EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT → I

Isoform 18 (identifier: P21802-18)

Also known as: K-sam-IIC1; KGFR; IgIIIb;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     428-429: Missing.

Isoform 19 (identifier: P21802-19)

Also known as: Soluble KGFR;

The sequence of this isoform differs from the canonical sequence as follows:
     314-330: AAGVNTTDKEIEVLYIR → HSGINSSNAEVLALF
     334-335: FE → EA
     341-353: TCLAGNSIGISFH → ICKVSNYIGQANQ
     361-361: P → PKQQ
     362-365: APGR → GRRC
     366-821: Missing.

Isoform 20 (identifier: P21802-20)

The sequence of this isoform differs from the canonical sequence as follows:
     37-152: EPPTKYQISQ...FVSENSNNKR → G
     429-430: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 821	800	Fibroblast growth factor receptor 2		PRO_0000016783
Regions
	Topological domain	22 – 377	356	Extracellular Potential
	Transmembrane	378 – 398	21	Potential
	Topological domain	399 – 821	423	Cytoplasmic Potential
	Domain	25 – 125	101	Ig-like C2-type 1
	Domain	154 – 247	94	Ig-like C2-type 2
	Domain	256 – 358	103	Ig-like C2-type 3
	Domain	481 – 770	290	Protein kinase
	Nucleotide binding	487 – 495	9	ATP By similarity
	Region	161 – 178	18	Heparin-binding
Sites
	Active site	626	1	Proton acceptor By similarity
	Binding site	517	1	ATP By similarity
Amino acid modifications
	Modified residue	657	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	83	1	N-linked (GlcNAc...) Potential
	Glycosylation	123	1	N-linked (GlcNAc...) Potential
	Glycosylation	228	1	N-linked (GlcNAc...) Potential
	Glycosylation	241	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	N-linked (GlcNAc...) Potential
	Glycosylation	297	1	N-linked (GlcNAc...) Potential
	Glycosylation	318	1	N-linked (GlcNAc...) Potential
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Disulfide bond	62 ↔ 107		Potential
	Disulfide bond	179 ↔ 231		Potential
	Disulfide bond	278 ↔ 342		Potential
Natural variations
	Alternative sequence	37 – 152	116	EPPTK…SNNKR → G in isoform 20.		VSP_019608
	Alternative sequence	37 – 125	89	Missing in isoform 4.		VSP_002964
	Alternative sequence	250 – 254	5	ERSPH → GSQGL in isoform 14.		VSP_002965
	Alternative sequence	255 – 821	567	Missing in isoform 14.		VSP_002966
	Alternative sequence	313	1	K → KVLK in isoform 16.		VSP_002967
	Alternative sequence	314 – 429	116	Missing in isoform 15.		VSP_002968
	Alternative sequence	314 – 330	17	AAGVN…VLYIR → HSGINSSNAEVLALF in isoform 3, isoform 4, isoform 7, isoform 9, isoform 10, isoform 11, isoform 12, isoform 13, isoform 17, isoform 18 and isoform 19.		VSP_002969
	Alternative sequence	334 – 335	2	FE → EA in isoform 3, isoform 4, isoform 7, isoform 9, isoform 10, isoform 11, isoform 12, isoform 13, isoform 17, isoform 18 and isoform 19.		VSP_002970
	Alternative sequence	341 – 353	13	TCLAG…GISFH → ICKVSNYIGQANQ in isoform 3, isoform 4, isoform 7, isoform 9, isoform 10, isoform 11, isoform 12, isoform 13, isoform 17, isoform 18 and isoform 19.		VSP_002971
	Alternative sequence	361	1	P → PKQQ in isoform 3, isoform 4, isoform 7, isoform 9, isoform 10, isoform 11, isoform 12, isoform 13, isoform 17, isoform 18 and isoform 19.		VSP_002972
	Alternative sequence	362 – 365	4	APGR → GRRC in isoform 19.		VSP_002973
	Alternative sequence	366 – 821	456	Missing in isoform 19.		VSP_002974
	Alternative sequence	428 – 429	2	Missing in isoform 4, isoform 5, isoform 6, isoform 8, isoform 16 and isoform 18.		VSP_002975
	Alternative sequence	429 – 430	2	Missing in isoform 20.		VSP_019609
	Alternative sequence	761 – 821	61	LTLTT…GSVKT → PPNPSLMSIFRK in isoform 4.		VSP_002976
	Alternative sequence	768 – 821	54	EYLDL…GSVKT → SFQSSLKSSSTGIPGWPPGS EVFSEVAFRGILNYDIERPI LCAGSKKIYDI in isoform 10.		VSP_002981
	Alternative sequence	768 – 821	54	EYLDL…GSVKT → GRLPAWASQEKENSQTSLFA ISHVTLSSISKTRSSAKRDE KPGSSPHLALVRSQGLPQSV VP in isoform 11.		VSP_002982
	Alternative sequence	768 – 821	54	EYLDL…GSVKT → PLS in isoform 12.		VSP_002983
	Alternative sequence	768 – 821	54	Missing in isoform 13.		VSP_002977
	Alternative sequence	768 – 821	54	EYLDL…GSVKT → I in isoform 2, isoform 8 and isoform 17.		VSP_002978
	Alternative sequence	768 – 821	54	EYLDL…GSVKT → RYKLLPCPDKHNKRCKPEER GDLTEAGAAGSSRCVDSRKR VRQEKISTG in isoform 7.		VSP_002979
	Alternative sequence	768 – 821	54	EYLDL…GSVKT → RILTLTTNENFQSTSGREGT EIHALQCLRSEVTPAISCES PLADTGSKVPN in isoform 9.		VSP_002980
	Alternative sequence	778 – 821	44	QYSPS…GSVKT → PYSPCYPDPR in isoform 6.		VSP_002984
	Natural variant	6	1	R → P: dbSNP rs3750819.		VAR_017258
	Natural variant	57	1	S → L		VAR_042204
	Natural variant	105	1	Y → C in CS.		VAR_004112
	Natural variant	172	1	A → F in PS; requires 2 nucleotide substitutions.		VAR_017259
	Natural variant	186	1	M → T: dbSNP rs755793.		VAR_017260
	Natural variant	203	1	R → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation.		VAR_036380
	Natural variant	252 – 253	2	SP → FS in PS.		VAR_004116
	Natural variant	252	1	S → F in APRS; requires 2 nucleotide substitutions.		VAR_004114
	Natural variant	252	1	S → L in CS.		VAR_004113
	Natural variant	252	1	S → W in APRS and PS; common mutation.		VAR_004115
	Natural variant	253	1	P → R in APRS; common mutation.		VAR_004117
	Natural variant	263	1	P → L in CS.		VAR_017261