Reviewed,
UniProtKB/Swiss-Prot P21802 (FGFR2_HUMAN)
Last modified
November 25, 2008.
Version 124.
History...
Clusters with 100%,
90%,
50% identity |
Documents (8) |
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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 |
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| 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
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 | |||||||

Clusters with