ID FGFR2_HUMAN Reviewed; 821 AA.
AC P21802; B4DFC2; E7EVR6; E9PCR0; P18443; Q01742; Q12922; Q14300;
AC Q14301; Q14302; Q14303; Q14304; Q14305; Q14672; Q14718; Q14719;
AC Q1KHY5; Q86YI4; Q8IXC7; Q96KL9; Q96KM0; Q96KM1; Q96KM2; Q9NZU2;
AC Q9NZU3; Q9UD01; Q9UD02; Q9UIH3; Q9UIH4; Q9UIH5; Q9UIH6; Q9UIH7;
AC Q9UIH8; Q9UM87; Q9UMC6; Q9UNS7; Q9UQH7; Q9UQH8; Q9UQH9; Q9UQI0;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 01-MAY-2013, entry version 181.
DE RecName: Full=Fibroblast growth factor receptor 2;
DE Short=FGFR-2;
DE EC=2.7.10.1;
DE AltName: Full=K-sam;
DE Short=KGFR;
DE AltName: Full=Keratinocyte growth factor receptor;
DE AltName: CD_antigen=CD332;
DE Flags: Precursor;
GN Name=FGFR2; Synonyms=BEK, KGFR, KSAM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Neonatal brain stem;
RX PubMed=1697263;
RA Dionne C.A., Crumley G.R., Bellot F., Kaplow J.M., Searfoss G.,
RA Ruta M., Burgess W.H., Jaye M., Schlessinger J.;
RT "Cloning and expression of two distinct high-affinity receptors cross-
RT reacting with acidic and basic fibroblast growth factors.";
RL EMBO J. 9:2685-2692(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 16).
RX PubMed=2172978; DOI=10.1073/pnas.87.20.8180;
RA Houssaint E., Blanquet P.R., Champion-Arnaud P., Gesnel M.-C.,
RA Torriglia A., Courtois Y., Breathnach R.;
RT "Related fibroblast growth factor receptor genes exist in the human
RT genome.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8180-8184(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 17).
RX PubMed=1647213; DOI=10.1016/0167-4781(91)90015-E;
RA Seno M., Sasada R., Watanabe T., Ishimaru K., Igarashi K.;
RT "Two cDNAs encoding novel human FGF receptor.";
RL Biochim. Biophys. Acta 1089:244-246(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Stomach cancer;
RX PubMed=2377625; DOI=10.1073/pnas.87.15.5983;
RA Hattori Y., Odagiri H., Nakatani H., Miyagawa K., Naito K.,
RA Sakamoto H., Katoh O., Yoshida T., Sugimura T., Terada M.;
RT "K-sam, an amplified gene in stomach cancer, is a member of the
RT heparin-binding growth factor receptor genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5983-5987(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 14 AND 15).
RX PubMed=1313574; DOI=10.1073/pnas.89.7.2960;
RA Katoh M., Hattori Y., Sasaki H., Tanaka M., Sugano K., Yazaki Y.,
RA Sugimura T., Terada M.;
RT "K-sam gene encodes secreted as well as transmembrane receptor
RT tyrosine kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2960-2964(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), DOMAIN, AND SUBUNIT.
RC TISSUE=Placenta;
RX PubMed=1400433;
RA Dell K.R., Williams L.T.;
RT "A novel form of fibroblast growth factor receptor 2. Alternative
RT splicing of the third immunoglobulin-like domain confers ligand
RT binding specificity.";
RL J. Biol. Chem. 267:21225-21229(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 19), SUBUNIT, DOMAIN, AND
RP VARIANT ARG-613.
RC TISSUE=Mammary gland;
RX PubMed=1309608; DOI=10.1073/pnas.89.1.246;
RA Miki T., Bottaro D.P., Fleming T.P., Smith C.L., Burgess W.H.,
RA Chan A.M.-L., Aaronson S.A.;
RT "Determination of ligand-binding specificity by alternative splicing:
RT two distinct growth factor receptors encoded by a single gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:246-250(1992).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 19).
RC TISSUE=Cornea, and Mammary gland;
RX PubMed=7866434;
RA Wilson S.E., Weng J., Chwang E.L., Gollahon L., Leitch A.M.,
RA Shay J.W.;
RT "Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and
RT their receptors in human breast cells and tissues: alternative
RT receptors.";
RL Cell. Mol. Biol. Res. 40:337-350(1994).
RN [9]
RP ERRATUM.
RA Wilson S.E., Weng J., Chwang E.L., Gollahon L., Leitch A.M.,
RA Shay J.W.;
RL Cell. Mol. Biol. Res. 40:707-707(1994).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CS SER-342.
RC TISSUE=Blood;
RA Steinberger D., Mueller U.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7; 9; 10; 11; 12 AND 13), AND
RP VARIANT ARG-613.
RX PubMed=10626794;
RA Ueda T., Sasaki H., Kuwahara Y., Nezu M., Shibuya T., Sakamoto H.,
RA Ishii H., Yanagihara K., Mafune K., Makuuchi M., Terada M.;
RT "Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short
RT homology-mediated recombination, generating preferential expression of
RT specific messenger RNAs.";
RL Cancer Res. 59:6080-6086(1999).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 5; 6; 8; 14 AND 18).
RX PubMed=11856867;
RA Ingersoll R.G., Paznekas W.A., Tran A.K., Scott A.F., Jiang G.,
RA Jabs E.W.;
RT "Fibroblast growth factor receptor 2 (FGFR2): genomic sequence and
RT variations.";
RL Cytogenet. Cell Genet. 94:121-126(2001).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
RA Lind D.L., Cox D.R.;
RT "Sequence and polymorphisms in fibroblast growth factor receptor 2
RT (FGFR2) gene in humans.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 23).
RA Jang J.;
RT "Identification of a novel variant of FGFR2.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-6 AND THR-186.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 21).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [17]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [18]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 20).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [19]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 314-427.
RX PubMed=10712195; DOI=10.1086/302831;
RA Glaser R.L., Jiang W., Boyadjiev S.A., Tran A.K., Zachary A.A.,
RA Van Maldergem L., Johnson D., Walsh S., Oldridge M., Wall S.A.,
RA Wilkie A.O.M., Jabs E.W.;
RT "Paternal origin of FGFR2 mutations in sporadic cases of Crouzon
RT syndrome and Pfeiffer syndrome.";
RL Am. J. Hum. Genet. 66:768-777(2000).
RN [20]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-209; 212-767 AND 771-821
RP (ISOFORMS 5; 14 AND 18).
RX PubMed=10196476; DOI=10.1016/S0378-1119(99)00047-5;
RA Zhang Y., Gorry M.C., Post J.C., Ehrlich G.D.;
RT "Genomic organization of the human fibroblast growth factor receptor 2
RT (FGFR2) gene and comparative analysis of the human FGFR gene family.";
RL Gene 230:69-79(1999).
RN [21]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 249-313, AND VARIANTS APRS
RP TRP-252 AND ARG-253.
RX PubMed=7668257;
RA Park W.-J., Theda C., Maestri N.E., Meyers G.A., Fryburg J.S.,
RA Dufresne C., Cohen M.M. Jr., Jabs E.W.;
RT "Analysis of phenotypic features and FGFR2 mutations in Apert
RT syndrome.";
RL Am. J. Hum. Genet. 57:321-328(1995).
RN [22]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 251-259.
RX PubMed=8676562;
RA Wada C., Ishigaki M., Toyo-oka Y., Yamabe H., Ohnuki Y., Takada F.,
RA Yamazaki Y., Ohtani H.;
RT "Nucleotide sequences at intron 6 and exon 7 junction of fibroblast
RT growth factor receptor 2 and rapid mutational analysis in Apert
RT syndrome.";
RL Rinsho Byori 44:435-438(1996).
RN [23]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 251-318.
RX PubMed=8673103; DOI=10.1038/ng0596-48;
RA Moloney D.M., Slaney S.F., Oldridge M., Wall S.A., Sahlin P.,
RA Stenman G., Wilkie A.O.M.;
RT "Exclusive paternal origin of new mutations in Apert syndrome.";
RL Nat. Genet. 13:48-53(1996).
RN [24]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 263-361, AND VARIANTS CS PRO-289;
RP ARG-338; SER-342; TYR-342; GLY-344 AND CYS-354.
RX PubMed=7581378; DOI=10.1093/hmg/4.8.1387;
RA Gorry M.C., Preston R.A., White G.J., Zhang Y., Singhal V.K.,
RA Losken H.W., Parker M.G., Nwokoro N.A., Post J.C., Ehrlich G.D.;
RT "Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common
RT point mutation shared with Jackson-Weiss syndrome.";
RL Hum. Mol. Genet. 4:1387-1390(1995).
RN [25]
RP FUNCTION (ISOFORM 3), SUBUNIT, AND DOMAIN.
RX PubMed=8961926; DOI=10.1021/bi961942c;
RA Gray T.E., Eisenstein M., Yayon A., Givol D.;
RT "Asparagine-344 is a key residue for ligand binding in keratinocyte
RT growth factor receptor.";
RL Biochemistry 35:15640-15645(1996).
RN [26]
RP INTERACTION WITH FGF1; FGF2; FGF3; FGF4; FGF6; FGF7 AND FGF9, AND
RP FUNCTION IN CELL PROLIFERATION.
RX PubMed=8663044; DOI=10.1074/jbc.271.25.15292;
RA Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A.,
RA Coulier F., Gao G., Goldfarb M.;
RT "Receptor specificity of the fibroblast growth factor family.";
RL J. Biol. Chem. 271:15292-15297(1996).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF PAK4; REGULATION OF CELL PROLIFERATION
RP AND APOPTOSIS, AND INTERACTION WITH GRB2 AND PAK4.
RX PubMed=12529371; DOI=10.1074/jbc.M205875200;
RA Lu Y., Pan Z.-Z., Devaux Y., Ray P.;
RT "p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte
RT growth factor receptor and participates in keratinocyte growth factor-
RT mediated inhibition of oxidant-induced cell death.";
RL J. Biol. Chem. 278:10374-10380(2003).
RN [28]
RP FUNCTION IN OSTEOBLAST DIFFERENTIATION AND IN PHOSPHORYLATION OF CBL,
RP INTERACTION WITH CBL, UBIQUITINATION, AND CHARACTERIZATION OF VARIANT
RP APRS TRP-252.
RX PubMed=15190072; DOI=10.1074/jbc.M402469200;
RA Kaabeche K., Lemonnier J., Le Mee S., Caverzasio J., Marie P.J.;
RT "Cbl-mediated degradation of Lyn and Fyn induced by constitutive
RT fibroblast growth factor receptor-2 activation supports osteoblast
RT differentiation.";
RL J. Biol. Chem. 279:36259-36267(2004).
RN [29]
RP FUNCTION IN CELL PROLIFERATION AND ACTIVATION OF SIGNALING PATHWAYS,
RP MUTAGENESIS OF TYR-769, PHOSPHORYLATION AT TYR-769, AND INTERACTION
RP WITH PLCG1.
RX PubMed=15629145; DOI=10.1016/j.bbrc.2004.12.031;
RA Ceridono M., Belleudi F., Ceccarelli S., Torrisi M.R.;
RT "Tyrosine 769 of the keratinocyte growth factor receptor is required
RT for receptor signaling but not endocytosis.";
RL Biochem. Biophys. Res. Commun. 327:523-532(2005).
RN [30]
RP INTERACTION WITH FGF1; FGF7; FGF8; FGF9; FGF10; FGF19; FGF21; FGF22
RP AND FGF23, AND FUNCTION IN STIMULATION OF CELL PROLIFERATION.
RX PubMed=16597617; DOI=10.1074/jbc.M601252200;
RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M.,
RA Ornitz D.M.;
RT "Receptor specificity of the fibroblast growth factor family. The
RT complete mammalian FGF family.";
RL J. Biol. Chem. 281:15694-15700(2006).
RN [31]
RP FUNCTION IN PHOSPHORYLATION OF PLCG1 (ISOFORM 1), CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, GLYCOSYLATION, INTERACTION WITH PLCG1,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-265 AND 656-TYR-TYR-657,
RP UBIQUITINATION, AND CHARACTERIZATION OF VARIANT PS PHE-278.
RX PubMed=16844695; DOI=10.1074/jbc.M600448200;
RA Hatch N.E., Hudson M., Seto M.L., Cunningham M.L., Bothwell M.;
RT "Intracellular retention, degradation, and signaling of glycosylation-
RT deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F.";
RL J. Biol. Chem. 281:27292-27305(2006).
RN [32]
RP INTERACTION WITH FGF19; FGF21 AND KLB, AND FUNCTION IN PHOSPHORYLATION
RP OF FRS2 AND ACTIVATION OF MAP KINASES.
RX PubMed=17623664; DOI=10.1074/jbc.M704165200;
RA Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R.,
RA Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A.,
RA Kuro-o M.;
RT "Tissue-specific expression of betaKlotho and fibroblast growth factor
RT (FGF) receptor isoforms determines metabolic activity of FGF19 and
RT FGF21.";
RL J. Biol. Chem. 282:26687-26695(2007).
RN [33]
RP FUNCTION IN STAT1 PHOSPHORYLATION, GLYCOSYLATION, SUBCELLULAR
RP LOCATION, AND PHOSPHORYLATION.
RX PubMed=17311277; DOI=10.1002/jcp.21014;
RA Citores L., Bai L., Sorensen V., Olsnes S.;
RT "Fibroblast growth factor receptor-induced phosphorylation of STAT1 at
RT the Golgi apparatus without translocation to the nucleus.";
RL J. Cell. Physiol. 212:148-156(2007).
RN [34]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18374639; DOI=10.1016/j.bone.2008.02.009;
RA Dufour C., Guenou H., Kaabeche K., Bouvard D., Sanjay A., Marie P.J.;
RT "FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt
RT signaling and osteoblast survival.";
RL Bone 42:1032-1039(2008).
RN [35]
RP FUNCTION AS FGF7 RECEPTOR AND IN PHOSPHORYLATION OF PLCG1 AND FRS2,
RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-466; TYR-586; TYR-588;
RP TYR-656 AND TYR-657, AND MASS SPECTROMETRY.
RX PubMed=19410646; DOI=10.1016/j.cellsig.2009.04.004;
RA Luo Y., Yang C., Jin C., Xie R., Wang F., McKeehan W.L.;
RT "Novel phosphotyrosine targets of FGFR2IIIb signaling.";
RL Cell. Signal. 21:1370-1378(2009).
RN [36]
RP FUNCTION IN FIBROBLAST PROLIFERATION; ACTIVATION OF MAP KINASES AND
RP PHOSPHORYLATION OF PLCG1 AND FRS2, INTERACTION WITH PLCG1 AND FRS2,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-769.
RX PubMed=19103595; DOI=10.1074/jbc.M803998200;
RA Cha J.Y., Maddileti S., Mitin N., Harden T.K., Der C.J.;
RT "Aberrant receptor internalization and enhanced FRS2-dependent
RT signaling contribute to the transforming activity of the fibroblast
RT growth factor receptor 2 IIIb C3 isoform.";
RL J. Biol. Chem. 284:6227-6240(2009).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [38]
RP FUNCTION, AND UBIQUITINATION.
RX PubMed=21596750; DOI=10.1074/jbc.M110.197525;
RA Severe N., Miraoui H., Marie P.J.;
RT "The Casitas B lineage lymphoma (Cbl) mutant G306E enhances osteogenic
RT differentiation in human mesenchymal stromal cells in part by
RT decreased Cbl-mediated platelet-derived growth factor receptor alpha
RT and fibroblast growth factor receptor 2 ubiquitination.";
RL J. Biol. Chem. 286:24443-24450(2011).
RN [39]
RP REVIEW ON LIGAND SPECIFICITY, ALTERNATIVE SPLICING, AND SIGNALING.
RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001;
RA Eswarakumar V.P., Lax I., Schlessinger J.;
RT "Cellular signaling by fibroblast growth factor receptors.";
RL Cytokine Growth Factor Rev. 16:139-149(2005).
RN [40]
RP REVIEW ON LIGAND SPECIFICITY, ALTERNATIVE SPLICING, SIGNALING, AND
RP ROLE IN DISEASE.
RX PubMed=19387476; DOI=10.1038/jid.2009.97;
RA Katoh M.;
RT "FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer
RT pathologies.";
RL J. Invest. Dermatol. 129:1861-1867(2009).
RN [41]
RP REVIEW ON FUNCTION IN FGF SIGNALING.
RX PubMed=20094046; DOI=10.1038/nrc2780;
RA Turner N., Grose R.;
RT "Fibroblast growth factor signalling: from development to cancer.";
RL Nat. Rev. Cancer 10:116-129(2010).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 147-366 IN COMPLEX WITH FGF2.
RX PubMed=10830168; DOI=10.1016/S0092-8674(00)80851-X;
RA Plotnikov A.N., Hubbard S.R., Schlessinger J., Mohammadi M.;
RT "Crystal structures of two FGF-FGFR complexes reveal the determinants
RT of ligand-receptor specificity.";
RL Cell 101:413-424(2000).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 148-366 IN COMPLEX WITH FGF1
RP AND HEPARIN, AND INTERACTION WITH FGF1 AND HEPARIN.
RX PubMed=11069186; DOI=10.1038/35039551;
RA Pellegrini L., Burke D.F., von Delft F., Mulloy B., Blundell T.L.;
RT "Crystal structure of fibroblast growth factor receptor ectodomain
RT bound to ligand and heparin.";
RL Nature 407:1029-1034(2000).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 147-362 IN COMPLEX WITH FGF1.
RX PubMed=10618369; DOI=10.1073/pnas.97.1.49;
RA Stauber D.J., DiGabriele A.D., Hendrickson W.A.;
RT "Structural interactions of fibroblast growth factor receptor with its
RT ligands.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:49-54(2000).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 147-366 OF VARIANTS APRS
RP TRP-252 AND ARG-253 IN COMPLEX WITH FGF2.
RX PubMed=11390973; DOI=10.1073/pnas.121183798;
RA Ibrahimi O.A., Eliseenkova A.V., Plotnikov A.N., Yu K., Ornitz D.M.,
RA Mohammadi M.;
RT "Structural basis for fibroblast growth factor receptor 2 activation
RT in Apert syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7182-7187(2001).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 140-371 IN COMPLEX WITH
RP FGF10.
RX PubMed=12591959; DOI=10.1073/pnas.0436500100;
RA Yeh B.K., Igarashi M., Eliseenkova A.V., Plotnikov A.N., Sher I.,
RA Ron D., Aaronson S.A., Mohammadi M.;
RT "Structural basis by which alternative splicing confers specificity in
RT fibroblast growth factor receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2266-2271(2003).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 149-368 IN COMPLEX WITH
RP FGF8, FUNCTION AS FGF8 RECEPTOR, INTERACTION WITH FGF8, AND DISULFIDE
RP BONDS.
RX PubMed=16384934; DOI=10.1101/gad.1365406;
RA Olsen S.K., Li J.Y.H., Bromleigh C., Eliseenkova A.V., Ibrahimi O.A.,
RA Lao Z., Zhang F., Linhardt R.J., Joyner A.L., Mohammadi M.;
RT "Structural basis by which alternative splicing modulates the
RT organizer activity of FGF8 in the brain.";
RL Genes Dev. 20:185-198(2006).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 458-778 IN COMPLEX WITH ATP
RP ANALOG; PEPTIDE SUBSTRATE AND MAGNESIUM, ENZYME REGULATION,
RP PHOSPHORYLATION AT TYR-586; TYR-656 AND TYR-657, MUTAGENESIS OF
RP ASN-549 AND GLU-565, CHARACTERIZATION OF VARIANT FSPC GLU-526,
RP CHARACTERIZATION OF VARIANT CS HIS-549, CHARACTERIZATION OF VARIANTS
RP PS GLY-565 AND ARG-641, AND CHARACTERIZATION OF VARIANT
RP CRANIOSYNOSTOSIS ASN-659.
RX PubMed=17803937; DOI=10.1016/j.molcel.2007.06.028;
RA Chen H., Ma J., Li W., Eliseenkova A.V., Xu C., Neubert T.A.,
RA Miller W.T., Mohammadi M.;
RT "A molecular brake in the kinase hinge region regulates the activity
RT of receptor tyrosine kinases.";
RL Mol. Cell 27:717-730(2007).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 458-766 OF VARIANT LADDS
RP THR-628 IN COMPLEX WITH ATP ANALOG, CATALYTIC ACTIVITY, SUBUNIT, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=18056630; DOI=10.1073/pnas.0709905104;
RA Lew E.D., Bae J.H., Rohmann E., Wollnik B., Schlessinger J.;
RT "Structural basis for reduced FGFR2 activity in LADD syndrome:
RT Implications for FGFR autoinhibition and activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:19802-19807(2007).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 458-778 IN COMPLEX WITH ATP,
RP ACTIVE SITE, MASS SPECTROMETRY, AUTOPHOSPHORYLATION, AND
RP PHOSPHORYLATION AT TYR-466; TYR-586; TYR-588; TYR-656; TYR-657 AND
RP TYR-769.
RX PubMed=19060208; DOI=10.1073/pnas.0807752105;
RA Chen H., Xu C.F., Ma J., Eliseenkova A.V., Li W., Pollock P.M.,
RA Pitteloud N., Miller W.T., Neubert T.A., Mohammadi M.;
RT "A crystallographic snapshot of tyrosine trans-phosphorylation in
RT action.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:19660-19665(2008).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 458-768 IN COMPLEX WITH
RP INHIBITOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND ENZYME
RP REGULATION.
RX PubMed=21454610; DOI=10.1074/jbc.M110.213736;
RA Eathiraj S., Palma R., Hirschi M., Volckova E., Nakuci E., Castro J.,
RA Chen C.R., Chan T.C., France D.S., Ashwell M.A.;
RT "A novel mode of protein kinase inhibition exploiting hydrophobic
RT motifs of autoinhibited kinases: discovery of ATP-independent
RT inhibitors of fibroblast growth factor receptor.";
RL J. Biol. Chem. 286:20677-20687(2011).
RN [52]
RP VARIANTS CS HIS-340; ARG-342; SER-342; TYR-342 AND CYS-354.
RX PubMed=7987400; DOI=10.1038/ng0994-98;
RA Reardon W., Winter R.M., Rutland P., Pulleyn L.J., Jones B.M.,
RA Malcolm S.;
RT "Mutations in the fibroblast growth factor receptor 2 gene cause
RT Crouzon syndrome.";
RL Nat. Genet. 8:98-103(1994).
RN [53]
RP VARIANTS CS CYS-328 AND CYS-347, AND VARIANT JWS GLY-344.
RX PubMed=7874170; DOI=10.1038/ng1194-275;
RA Jabs E.W., Li X., Scott A.F., Meyers G.A., Chen W., Eccles M., Mao J.,
RA Charnas L.R., Jackson C.E., Jaye M.;
RT "Jackson-Weiss and Crouzon syndromes are allelic with mutations in
RT fibroblast growth factor receptor 2.";
RL Nat. Genet. 8:275-279(1994).
RN [54]
RP VARIANTS CS.
RX PubMed=7655462; DOI=10.1093/hmg/4.6.1077;
RA Oldridge M., Wilkie A.O.M., Slaney S.F., Poole M.D., Pulleyn L.J.,
RA Rutland P., Hockley A.D., Wake M.J.C., Goldin J.H., Winter R.M.,
RA Reardon W., Malcolm S.;
RT "Mutations in the third immunoglobulin domain of the fibroblast growth
RT factor receptor-2 gene in Crouzon syndrome.";
RL Hum. Mol. Genet. 4:1077-1082(1995).
RN [55]
RP VARIANTS CS GLY-290; TRP-342 AND CYS-354, AND VARIANT JWS ARG-342.
RX PubMed=8528214; DOI=10.1093/hmg/4.7.1229;
RA Park W.-J., Meyers G.A., Li X., Theda C., Day D., Orlow S.J.,
RA Jones M.C., Jabs E.W.;
RT "Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show
RT allelic heterogeneity and phenotypic variability.";
RL Hum. Mol. Genet. 4:1229-1233(1995).
RN [56]
RP VARIANT PS ALA-321.
RX PubMed=7719333; DOI=10.1038/ng0295-108;
RA Lajeunie E., Wei M.H., Bonaventure J., Munnich A., le Merrer M.,
RA Renier D.;
RT "FGFR2 mutations in Pfeiffer syndrome.";
RL Nat. Genet. 9:108-108(1995).
RN [57]
RP VARIANTS APRS TRP-252 AND ARG-253.
RX PubMed=7719344; DOI=10.1038/ng0295-165;
RA Wilkie A.O.M., Slaney S.F., Oldridge M., Poole M.D., Ashworth G.J.,
RA Hockley A.D., Hayward R.D., David D.J., Pulleyn L.J., Rutland P.,
RA Malcolm S., Winter R.M., Reardon W.;
RT "Apert syndrome results from localized mutations of FGFR2 and is
RT allelic with Crouzon syndrome.";
RL Nat. Genet. 9:165-172(1995).
RN [58]
RP VARIANTS PS PRO-341; ARG-342 AND TYR-342.
RX PubMed=7719345; DOI=10.1038/ng0295-173;
RA Rutland P., Pulleyn L.J., Reardon W., Baraister M., Hayward R.,
RA Jones B.M., Malcolm S., Winter R.M., Oldridge M., Slaney S.F.,
RA Poole M.D., Wilkie A.O.M.;
RT "Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon
RT syndrome phenotypes.";
RL Nat. Genet. 9:173-176(1995).
RN [59]
RP VARIANTS CS GLY-268 INS; PHE-342 AND TYR-342, VARIANTS PS PHE-278;
RP ARG-342; SER-342; PRO-344 AND PHE-359, AND VARIANT JWS PRO-289.
RX PubMed=8644708;
RA Meyers G.A., Day D., Goldberg R., Daentl D.L., Przylepa K.A.,
RA Abrams L.J., Graham J.M. Jr., Feingold M., Moeschler J.B.,
RA Rawnsley E., Scott A.F., Jabs E.W.;
RT "FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and
RT Pfeiffer syndromes: evidence for missense changes, insertions, and a
RT deletion due to alternative RNA splicing.";
RL Am. J. Hum. Genet. 58:491-498(1996).
RN [60]
RP VARIANTS CS CYS-105; GLU-338; CYS-351 AND ARG-384.
RX PubMed=8946174;
RA Pulleyn L.J., Reardon W., Wilkes D., Rutland P., Jones B.M.,
RA Hayward R., Hall C.M., Brueton L., Chun N., Lammer E., Malcolm S.,
RA Winter R.M.;
RT "Spectrum of craniosynostosis phenotypes associated with novel
RT mutations at the fibroblast growth factor receptor 2 locus.";
RL Eur. J. Hum. Genet. 4:283-291(1996).
RN [61]
RP VARIANTS CS ILE-331; ASN-ALA-337 INS AND 356-TRP--THR-358 DEL.
RX PubMed=8956050;
RX DOI=10.1002/(SICI)1098-1004(1996)8:4<386::AID-HUMU18>3.3.CO;2-A;
RA Steinberger D., Mulliken J.B., Mueller U.;
RT "Crouzon syndrome: previously unrecognized deletion, duplication, and
RT point mutation within FGFR2 gene.";
RL Hum. Mutat. 8:386-390(1996).
RN [62]
RP VARIANTS BSTVS CYS-372 AND CYS-375.
RX PubMed=8696350; DOI=10.1038/ng0896-492;
RA Przylepa K.A., Paznekas W.A., Zhang M., Golabi M., Bias W.,
RA Bamshad M.J., Carey J.C., Hall B.D., Stevenson R., Orlow S.J.,
RA Cohen M.M. Jr., Jabs E.W.;
RT "Fibroblast growth factor receptor 2 mutations in Beare-Stevenson
RT cutis gyrata syndrome.";
RL Nat. Genet. 13:492-494(1996).
RN [63]
RP VARIANT PS CYS-290.
RX PubMed=9150725; DOI=10.1007/s004390050413;
RA Tartaglia M., Valeri S., Velardi F., di Rocco C., Battaglia P.A.;
RT "Trp290Cys mutation in exon IIIa of the fibroblast growth factor
RT receptor 2 (FGFR2) gene is associated with Pfeiffer syndrome.";
RL Hum. Genet. 99:602-606(1997).
RN [64]
RP VARIANT JWS SER-342.
RX PubMed=9385368; DOI=10.1007/s004390050584;
RA Tartaglia M., Di Rocco C., Lajeunie E., Valeri S., Velardi F.,
RA Battaglia P.A.;
RT "Jackson-Weiss syndrome: identification of two novel FGFR2 missense
RT mutations shared with Crouzon and Pfeiffer craniosynostotic
RT disorders.";
RL Hum. Genet. 101:47-50(1997).
RN [65]
RP VARIANT CS LEU-252, VARIANT APRS PHE-252, AND VARIANT PS
RP 252-PHE-SER-253.
RX PubMed=9002682; DOI=10.1093/hmg/6.1.137;
RA Oldridge M., Lunt P.W., Zackai E.H., McDonald-Mcginn D.M., Muenke M.,
RA Moloney D.M., Twigg S.R.F., Heath J.K., Howard T.D., Hoganson G.,
RA Gagnon D.M., Jabs E.W., Wilkie A.O.M.;
RT "Genotype-phenotype correlation for nucleotide substitutions in the
RT IgII-IgIII linker of FGFR2.";
RL Hum. Mol. Genet. 6:137-143(1997).
RN [66]
RP VARIANT CS GLU-292.
RX PubMed=9152842;
RA Steinberger D., Collmann H., Schmalenberger B., Mueller U.;
RT "A novel mutation (a886g) in exon 5 of FGFR2 in members of a family
RT with Crouzon phenotype and plagiocephaly.";
RL J. Med. Genet. 34:420-422(1997).
RN [67]
RP VARIANTS CS PHE-278; PRO-337; ARG-338; ARG-342; PHE-342 AND TYR-342,
RP VARIANTS APRS TRP-252 AND ARG-253, AND VARIANT JWS PHE-278.
RX PubMed=9677057;
RX DOI=10.1002/(SICI)1096-8628(19980707)78:3<237::AID-AJMG5>3.3.CO;2-5;
RA Passos-Bueno M.R., Sertie A.L., Richieri-Costa A., Alonso L.G.,
RA Zatz M., Alonso N., Brunoni D., Ribeiro S.F.M.;
RT "Description of a new mutation and characterization of FGFR1, FGFR2,
RT and FGFR3 mutations among Brazilian patients with syndromic
RT craniosynostoses.";
RL Am. J. Med. Genet. 78:237-241(1998).
RN [68]
RP VARIANTS CS VAL-276 AND CYS-301, AND VARIANT CRANIOSYNOSTOSIS SER-314.
RX PubMed=9521581; DOI=10.1007/s004390050668;
RA Steinberger D., Vriend G., Mulliken J.B., Mueller U.;
RT "The mutations in FGFR2-associated craniosynostoses are clustered in
RT five structural elements of immunoglobulin-like domain III of the
RT receptor.";
RL Hum. Genet. 102:145-150(1998).
RN [69]
RP VARIANTS APRS TRP-252 AND ARG-253.
RX PubMed=9452027;
RA Tsai F.-J., Hwu W.-L., Lin S.-P., Chang J.-G., Wang T.-R., Tsai C.-H.;
RT "Two common mutations 934C to G and 937C to G of fibroblast growth
RT factor receptor 2 (FGFR2) gene in Chinese patients with Apert
RT syndrome.";
RL Hum. Mutat. Suppl. 1:S18-S19(1998).
RN [70]
RP VARIANT PS CYS-351.
RX PubMed=9693549;
RA Mathijssen I.M., Vaandrager J.M., Hoogeboom A.J.,
RA Hesseling-Janssen A.L.W., van den Ouweland A.M.W.;
RT "Pfeiffer's syndrome resulting from an S351C mutation in the
RT fibroblast growth factor receptor-2 gene.";
RL J. Craniofac. Surg. 9:207-209(1998).
RN [71]
RP VARIANT PS TRP-252.
RX PubMed=9719378;
RA Passos-Bueno M.R., Richieri-Costa A., Sertie A.L., Kneppers A.;
RT "Presence of the Apert canonical S252W FGFR2 mutation in a patient
RT without severe syndactyly.";
RL J. Med. Genet. 35:677-679(1998).
RN [72]
RP VARIANT CS SER-362.
RX PubMed=10574673;
RA Everett E.T., Britto D.A., Ward R.E., Hartsfield J.K. Jr.;
RT "A novel FGFR2 gene mutation in Crouzon syndrome associated with
RT apparent nonpenetrance.";
RL Cleft Palate Craniofac. J. 36:533-541(1999).
RN [73]
RP VARIANTS PS CYS-340 AND GLY-342.
RX PubMed=10394936; DOI=10.1007/s004390050979;
RA Cornejo-Roldan L.R., Roessler E., Muenke M.;
RT "Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer
RT syndrome.";
RL Hum. Genet. 104:425-431(1999).
RN [74]
RP VARIANT PS ASP-273 DEL.
RX PubMed=10945669; DOI=10.1034/j.1399-0004.2000.580116.x;
RA Priolo M., Lerone M., Baffico M., Baldi M., Ravazzolo R., Cama A.,
RA Capra V., Silengo M.;
RT "Pfeiffer syndrome type 2 associated with a single amino acid deletion
RT in the FGFR2 gene.";
RL Clin. Genet. 58:81-83(2000).
RN [75]
RP VARIANTS CS/PS ARG-342 AND TYR-342, VARIANTS CS LEU-263; VAL-276;
RP PHE-278; TYR-278; SER-288; PRO-289; PRO-341; TRP-342; CYS-354; TYR-354
RP AND PHE-359, AND VARIANT PS SER-342.
RX PubMed=11173845;
RA Kress W., Collmann H., Buesse M., Halliger-Keller B., Mueller C.R.;
RT "Clustering of FGFR2 gene mutations in patients with Pfeiffer and
RT Crouzon syndromes (FGFR2-associated craniosynostoses).";
RL Cytogenet. Cell Genet. 91:134-137(2000).
RN [76]
RP VARIANT SER-315.
RX PubMed=10951518; DOI=10.1038/sj.ejhg.5200499;
RA Johnson D., Wall S.A., Mann S., Wilkie A.O.M.;
RT "A novel mutation, Ala315Ser, in FGFR2: a gene-environment interaction
RT leading to craniosynostosis?";
RL Eur. J. Hum. Genet. 8:571-577(2000).
RN [77]
RP VARIANTS ABS2 ARG-342; SER-342 AND CYS-351.
RX PubMed=10633130; DOI=10.1136/jmg.37.1.26;
RA Reardon W., Smith A., Honour J.W., Hindmarsh P., Das D., Rumsby G.,
RA Nelson I., Malcolm S., Ades L., Sillence D., Kumar D.,
RA DeLozier-Blanchet C., McKee S., Kelly T., McKeehan W.L., Baraitser M.,
RA Winter R.M.;
RT "Evidence for digenic inheritance in some cases of Antley-Bixler
RT syndrome?";
RL J. Med. Genet. 37:26-32(2000).
RN [78]
RP VARIANTS CS CYS-281; PRO-289; ARG-342 AND TYR-342.
RX PubMed=11380921; DOI=10.1046/j.1442-200x.2001.01392.x;
RA Tsai F.-J., Yang C.-F., Wu J.-Y., Tsai C.-H., Lee C.-C.;
RT "Mutation analysis of Crouzon syndrome and identification of one novel
RT mutation in Taiwanese patients.";
RL Pediatr. Int. 43:263-266(2001).
RN [79]
RP VARIANTS CS CYS-105; PRO-267; VAL-276; CYS-281; PRO-289; ARG-338;
RP HIS-340; PHE-342; TRP-342; CYS-347; CYS-354; HIS-549 AND GLY-678,
RP VARIANTS PS PHE-172; 252-PHE-SER-253; CYS-290; CYS-340; PRO-341;
RP ARG-342; SER-342; CYS-375; GLY-565; ARG-641 AND GLU-663, VARIANTS APRS
RP TRP-252 AND ARG-253, VARIANTS CS/PS PHE-278 AND TYR-342, VARIANT
RP CRANIOSYNOSTOSIS ASN-659, AND VARIANTS THR-186 AND SER-315.
RX PubMed=11781872; DOI=10.1086/338758;
RA Kan S.-H., Elanko N., Johnson D., Cornejo-Roldan L.R., Cook J.,
RA Reich E.W., Tomkins S., Verloes A., Twigg S.R.F., Rannan-Eliya S.,
RA McDonald-McGinn D.M., Zackai E.H., Wall S.A., Muenke M.,
RA Wilkie A.O.M.;
RT "Genomic screening of fibroblast growth-factor receptor 2 reveals a
RT wide spectrum of mutations in patients with syndromic
RT craniosynostosis.";
RL Am. J. Hum. Genet. 70:472-486(2002).
RN [80]
RP VARIANT BSTVS CYS-375.
RX PubMed=12000365; DOI=10.1034/j.1399-0004.2002.610309.x;
RA Wang T.-J., Huang C.-B., Tsai F.-J., Wu J.-Y., Lai R.-B., Hsiao M.;
RT "Mutation in the FGFR2 gene in a Taiwanese patient with Beare-
RT Stevenson cutis gyrata syndrome.";
RL Clin. Genet. 61:218-221(2002).
RN [81]
RP VARIANT FSPC GLU-526.
RX PubMed=16061565; DOI=10.1136/jmg.2004.027888;
RA McGillivray G., Savarirayan R., Cox T.C., Stojkoski C., McNeil R.,
RA Bankier A., Bateman J.F., Roscioli T., Gardner R.J.M., Lamande S.R.;
RT "Familial scaphocephaly syndrome caused by a novel mutation in the
RT FGFR2 tyrosine kinase domain.";
RL J. Med. Genet. 42:656-662(2005).
RN [82]
RP VARIANTS LADDS THR-628; THR-648 AND 649-ARG-ASP-650 DELINS SER.
RX PubMed=16501574; DOI=10.1038/ng1757;
RA Rohmann E., Brunner H.G., Kayserili H., Uyguner O., Nuernberg G.,
RA Lew E.D., Dobbie A., Eswarakumar V.P., Uzumcu A., Ulubil-Emeroglu M.,
RA Leroy J.G., Li Y., Becker C., Lehnerdt K., Cremers C.W.R.J.,
RA Yueksel-Apak M., Nuernberg P., Kubisch C., Schlessinger J.,
RA van Bokhoven H., Wollnik B.;
RT "Mutations in different components of FGF signaling in LADD
RT syndrome.";
RL Nat. Genet. 38:414-417(2006).
RN [83]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-203.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [84]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-57; THR-186; CYS-203; VAL-272;
RP ASN-283; CYS-290 AND THR-612.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [85]
RP VARIANTS BBDS ASP-381 AND ARG-391, AND CHARACTERIZATION OF VARIANT
RP BBDS ARG-391.
RX PubMed=22387015; DOI=10.1016/j.ajhg.2012.02.005;
RA Merrill A.E., Sarukhanov A., Krejci P., Idoni B., Camacho N.,
RA Estrada K.D., Lyons K.M., Deixler H., Robinson H., Chitayat D.,
RA Curry C.J., Lachman R.S., Wilcox W.R., Krakow D.;
RT "Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has
RT deficient canonical FGF signaling.";
RL Am. J. Hum. Genet. 90:550-557(2012).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface
CC receptor for fibroblast growth factors and plays an essential role
CC in the regulation of cell proliferation, differentiation,
CC migration and apoptosis, and in the regulation of embryonic
CC development. Required for normal embryonic patterning, trophoblast
CC function, limb bud development, lung morphogenesis, osteogenesis
CC and skin development. Plays an essential role in the regulation of
CC osteoblast differentiation, proliferation and apoptosis, and is
CC required for normal skeleton development. Promotes cell
CC proliferation in keratinocytes and immature osteoblasts, but
CC promotes apoptosis in differentiated osteoblasts. Phosphorylates
CC PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of
CC several signaling cascades. Activation of PLCG1 leads to the
CC production of the cellular signaling molecules diacylglycerol and
CC inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers
CC recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates
CC activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase
CC signaling pathway, as well as of the AKT1 signaling pathway. FGFR2
CC signaling is down-regulated by ubiquitination, internalization and
CC degradation. Mutations that lead to constitutive kinase activation
CC or impair normal FGFR2 maturation, internalization and degradation
CC lead to aberrant signaling. Over-expressed FGFR2 promotes
CC activation of STAT1.
CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC [protein]-L-tyrosine phosphate.
CC -!- ENZYME REGULATION: Present in an inactive conformation in the
CC absence of bound ligand. Ligand binding leads to dimerization and
CC activation by autophosphorylation on tyrosine residues. Inhibited
CC by ARQ 523 and ARQ 069; these compounds maintain the kinase in an
CC inactive conformation and inhibit autophosphorylation.
CC -!- SUBUNIT: Monomer. Homodimer after ligand binding. Interacts
CC predominantly with FGF1 and FGF2, but can also interact with FGF3,
CC FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in
CC vitro). Ligand specificity is determined by tissue-specific
CC expression of isoforms, and differences in the third Ig-like
CC domain are crucial for ligand specificity. Isoform 1 has high
CC affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3
CC has high affinity for FGF1 and FGF7, and has much higher affinity
CC for FGF7 than isoform 1 (in vitro). Affinity for fibroblast growth
CC factors (FGFs) is increased by heparan sulfate glycosaminoglycans
CC that function as coreceptors. Likewise, KLB increases the affinity
CC for FGF19 and FGF21. Interacts with PLCG1, GRB2 and PAK4.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-1028658, EBI-1028658;
CC P03968:FGF1 (xeno); NbExp=2; IntAct=EBI-1028658, EBI-6358090;
CC P05230:FGF1; NbExp=2; IntAct=EBI-1028658, EBI-698068;
CC P09038:FGF2; NbExp=3; IntAct=EBI-1028658, EBI-977447;
CC P21781:FGF7; NbExp=2; IntAct=EBI-6354683, EBI-3937699;
CC P62993:GRB2; NbExp=5; IntAct=EBI-1028658, EBI-401755;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Golgi apparatus. Cytoplasmic vesicle. Note=Detected on
CC osteoblast plasma membrane lipid rafts. After ligand binding, the
CC activated receptor is rapidly internalized and degraded.
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I
CC membrane protein. Note=After ligand binding, the activated
CC receptor is rapidly internalized and degraded.
CC -!- SUBCELLULAR LOCATION: Isoform 3: Cell membrane; Single-pass type I
CC membrane protein. Note=After ligand binding, the activated
CC receptor is rapidly internalized and degraded.
CC -!- SUBCELLULAR LOCATION: Isoform 14: Secreted.
CC -!- SUBCELLULAR LOCATION: Isoform 19: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=23;
CC Name=1; Synonyms=BEK, FGFR2IIIc;
CC IsoId=P21802-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P21802-2; Sequence=VSP_002978;
CC Name=3; Synonyms=BFR-1, FGFR2IIIb, KGFR;
CC IsoId=P21802-3; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972;
CC Name=4; Synonyms=K-sam;
CC IsoId=P21802-4; Sequence=VSP_002964, VSP_002969, VSP_002970,
CC VSP_002971, VSP_002972, VSP_002975,
CC VSP_002976;
CC Name=5; Synonyms=K-sam-I, BEK, IgIIIc;
CC IsoId=P21802-5; Sequence=VSP_002975;
CC Name=6; Synonyms=K-sam-IIC2;
CC IsoId=P21802-6; Sequence=VSP_002975, VSP_002984;
CC Name=7; Synonyms=K-sam-IIO2;
CC IsoId=P21802-7; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002979;
CC Name=8; Synonyms=K-sam-IIC3;
CC IsoId=P21802-8; Sequence=VSP_002975, VSP_002978;
CC Name=9; Synonyms=K-sam-IIH1;
CC IsoId=P21802-9; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002980;
CC Name=10; Synonyms=K-sam-IIH2;
CC IsoId=P21802-10; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002981;
CC Name=11; Synonyms=K-sam-IIH3, K-sam-IIO4;
CC IsoId=P21802-11; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002982;
CC Name=12; Synonyms=K-sam-IIO1;
CC IsoId=P21802-12; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002983;
CC Name=13; Synonyms=K-sam-IIO3;
CC IsoId=P21802-13; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002977;
CC Name=14; Synonyms=K-sam-IV, Soluble KGFR;
CC IsoId=P21802-14; Sequence=VSP_002965, VSP_002966;
CC Name=15; Synonyms=K-sam-III;
CC IsoId=P21802-15; Sequence=VSP_002968;
CC Name=16; Synonyms=TK14;
CC IsoId=P21802-16; Sequence=VSP_002967, VSP_002975;
CC Note=Ref.2 (AAA61188) sequence is in conflict in position:
CC 315:T->L;
CC Name=17;
CC IsoId=P21802-17; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002978;
CC Name=18; Synonyms=K-sam-IIC1, KGFR, IgIIIb;
CC IsoId=P21802-18; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002975;
CC Name=19; Synonyms=Soluble KGFR;
CC IsoId=P21802-19; Sequence=VSP_002969, VSP_002970, VSP_002971,
CC VSP_002972, VSP_002973, VSP_002974;
CC Name=20;
CC IsoId=P21802-20; Sequence=VSP_019608, VSP_019609;
CC Name=21;
CC IsoId=P21802-21; Sequence=VSP_002964, VSP_041915;
CC Name=22;
CC IsoId=P21802-22; Sequence=VSP_002964, VSP_002969, VSP_002970,
CC VSP_002971, VSP_002972, VSP_002978;
CC Name=23;
CC IsoId=P21802-23; Sequence=VSP_041914;
CC -!- DOMAIN: The second and third Ig-like domains directly interact
CC with fibroblast growth factors (FGF) and heparan sulfate
CC proteoglycans. Alternative splicing events affecting the third Ig-
CC like domain are crucial for ligand selectivity.
CC -!- PTM: Autophosphorylated. Binding of FGF family members together
CC with heparan sulfate proteoglycan or heparin promotes receptor
CC dimerization and autophosphorylation on several tyrosine residues.
CC Autophosphorylation occurs in trans between the two FGFR molecules
CC present in the dimer. Phosphorylation at Tyr-769 is essential for
CC interaction with PLCG1.
CC -!- PTM: N-glycosylated in the endoplasmic reticulum. The N-glycan
CC chains undergo further maturation to an Endo H-resistant form in
CC the Golgi apparatus.
CC -!- PTM: Ubiquitinated. FGFR2 is rapidly ubiquitinated after
CC autophosphorylation, leading to internalization and degradation.
CC Subject to degradation both in lysosomes and by the proteasome.
CC -!- DISEASE: Crouzon syndrome (CS) [MIM:123500]: An autosomal dominant
CC syndrome characterized by craniosynostosis, hypertelorism,
CC exophthalmos and external strabismus, parrot-beaked nose, short
CC upper lip, hypoplastic maxilla, and a relative mandibular
CC prognathism. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- DISEASE: Jackson-Weiss syndrome (JWS) [MIM:123150]: An autosomal
CC dominant craniosynostosis syndrome characterized by craniofacial
CC abnormalities and abnormality of the feet: broad great toes with
CC medial deviation and tarsal-metatarsal coalescence. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Apert syndrome (APRS) [MIM:101200]: A syndrome
CC characterized by facio-cranio-synostosis, osseous and membranous
CC syndactyly of the four extremities, and midface hypoplasia. The
CC craniosynostosis is bicoronal and results in acrocephaly of
CC brachysphenocephalic type. Syndactyly of the fingers and toes may
CC be total (mitten hands and sock feet) or partial affecting the
CC second, third, and fourth digits. Intellectual deficit is frequent
CC and often severe, usually being associated with cerebral
CC malformations. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- DISEASE: Pfeiffer syndrome (PS) [MIM:101600]: A syndrome
CC characterized by the association of craniosynostosis, broad and
CC deviated thumbs and big toes, and partial syndactyly of the
CC fingers and toes. Three subtypes are known: mild autosomal
CC dominant form (type 1); cloverleaf skull, elbow ankylosis, early
CC death, sporadic (type 2); craniosynostosis, early demise, sporadic
CC (type 3). Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- DISEASE: Beare-Stevenson cutis gyrata syndrome (BSTVS)
CC [MIM:123790]: An autosomal dominant disease characterized by
CC craniofacial anomalies, particularly craniosynostosis, and ear
CC defects, cutis gyrata, acanthosis nigricans, anogenital anomalies,
CC skin tags, and prominent umbilical stump. The skin furrows have a
CC corrugated appearance and are widespread. Cutis gyrata variably
CC affects the scalp, forehead, face, preauricular area, neck, trunk,
CC hands, and feet. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- DISEASE: Familial scaphocephaly syndrome (FSPC) [MIM:609579]: An
CC autosomal dominant craniosynostosis syndrome characterized by
CC scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion,
CC and mild intellectual disability. Scaphocephaly is the most common
CC of the craniosynostosis conditions and is characterized by a long,
CC narrow head. It is due to premature fusion of the sagittal suture
CC or from external deformation. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Lacrimo-auriculo-dento-digital syndrome (LADDS)
CC [MIM:149730]: An autosomal dominant ectodermal dysplasia, a
CC heterogeneous group of disorders due to abnormal development of
CC two or more ectodermal structures. Lacrimo-auriculo-dento-digital
CC syndrome is characterized by aplastic/hypoplastic lacrimal and
CC salivary glands and ducts, cup-shaped ears, hearing loss,
CC hypodontia and enamel hypoplasia, and distal limb segments
CC anomalies. In addition to these cardinal features, facial
CC dysmorphism, malformations of the kidney and respiratory system
CC and abnormal genitalia have been reported. Craniosynostosis and
CC severe syndactyly are not observed. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Antley-Bixler syndrome, without genital anomalies or
CC disordered steroidogenesis (ABS2) [MIM:207410]: A rare syndrome
CC characterized by craniosynostosis, radiohumeral synostosis present
CC from the perinatal period, midface hypoplasia, choanal stenosis or
CC atresia, femoral bowing and multiple joint contractures.
CC Arachnodactyly and/or camptodactyly have also been reported.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- DISEASE: Bent bone dysplasia syndrome (BBDS) [MIM:614592]: A
CC perinatal lethal skeletal dysplasia characterized by poor
CC mineralization of the calvarium, craniosynostosis, dysmorphic
CC facial features, prenatal teeth, hypoplastic pubis and clavicles,
CC osteopenia, and bent long bones. Dysmorphic facial features
CC included low-set ears, hypertelorism, midface hypoplasia,
CC prematurely erupted fetal teeth, and micrognathia. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fibroblast growth factor receptor subfamily.
CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG57383.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FGFR2ID40570ch10q26.html";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FGFR2";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgfr2/";
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DR EMBL; X52832; CAA37014.1; -; mRNA.
DR EMBL; M55614; AAA61188.1; -; mRNA.
DR EMBL; X56191; CAA39654.1; -; mRNA.
DR EMBL; M35718; AAA36152.1; -; mRNA.
DR EMBL; M87770; AAA59470.1; -; mRNA.
DR EMBL; M87771; AAA59471.1; -; mRNA.
DR EMBL; M87772; AAA59472.1; -; mRNA.
DR EMBL; M97193; AAA52449.1; -; mRNA.
DR EMBL; U11814; AAA68514.1; -; mRNA.
DR EMBL; M80634; AAA36147.1; -; mRNA.
DR EMBL; Z71929; CAA96492.1; -; mRNA.
DR EMBL; AB030073; BAA89296.1; -; mRNA.
DR EMBL; AB030074; BAA89297.1; -; mRNA.
DR EMBL; AB030075; BAA89298.1; -; mRNA.
DR EMBL; AB030076; BAA89299.1; -; mRNA.
DR EMBL; AB030077; BAA89300.1; -; mRNA.
DR EMBL; AB030078; BAA89301.1; -; mRNA.
DR EMBL; AF360695; AAK94205.1; -; Genomic_DNA.
DR EMBL; AF410480; AAK94205.1; JOINED; Genomic_DNA.
DR EMBL; AF360695; AAK94206.1; -; Genomic_DNA.
DR EMBL; AF410480; AAK94206.1; JOINED; Genomic_DNA.
DR EMBL; AF360695; AAK94207.1; -; Genomic_DNA.
DR EMBL; AF410480; AAK94207.1; JOINED; Genomic_DNA.
DR EMBL; AF360695; AAK94208.1; -; Genomic_DNA.
DR EMBL; AF410480; AAK94208.1; JOINED; Genomic_DNA.
DR EMBL; AF360695; AAK94209.1; -; Genomic_DNA.
DR EMBL; AF410480; AAK94209.1; JOINED; Genomic_DNA.
DR EMBL; AF487553; AAM74056.1; -; Genomic_DNA.
DR EMBL; AB084153; BAC45037.1; -; mRNA.
DR EMBL; DQ493927; ABE96832.1; -; Genomic_DNA.
DR EMBL; AK294026; BAG57383.1; ALT_INIT; mRNA.
DR EMBL; AC009988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039243; AAH39243.2; -; mRNA.
DR EMBL; AF169399; AAF43273.1; -; Genomic_DNA.
DR EMBL; AF169399; AAF43274.1; -; Genomic_DNA.
DR EMBL; AF097353; AAD31560.1; -; Genomic_DNA.
DR EMBL; AF097341; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097342; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097343; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097345; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097346; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097347; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097348; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097349; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097350; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097351; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097352; AAD31560.1; JOINED; Genomic_DNA.
DR EMBL; AF097353; AAD31561.1; -; Genomic_DNA.
DR EMBL; AF097341; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097342; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097344; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097345; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097346; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097347; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097348; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097349; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097350; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097351; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097352; AAD31561.1; JOINED; Genomic_DNA.
DR EMBL; AF097340; AAD31562.1; -; Genomic_DNA.
DR EMBL; AF097337; AAD31562.1; JOINED; Genomic_DNA.
DR EMBL; AF097338; AAD31562.1; JOINED; Genomic_DNA.
DR EMBL; AF097339; AAD31562.1; JOINED; Genomic_DNA.
DR EMBL; AF097354; AAD31565.1; -; Genomic_DNA.
DR EMBL; AF097341; AAD31567.1; -; Genomic_DNA.
DR EMBL; S82438; AAD14392.1; -; Genomic_DNA.
DR EMBL; Y17131; CAA76643.1; -; Genomic_DNA.
DR EMBL; L49237; AAC41933.1; -; Genomic_DNA.
DR EMBL; L49242; AAC41934.1; -; Genomic_DNA.
DR EMBL; L49238; AAC41935.1; -; Genomic_DNA.
DR EMBL; L49239; AAC41936.1; -; Genomic_DNA.
DR EMBL; L49240; AAC41937.1; -; Genomic_DNA.
DR EMBL; L49241; AAC41938.1; -; Genomic_DNA.
DR IPI; IPI00216602; -.
DR IPI; IPI00216603; -.
DR IPI; IPI00216604; -.
DR IPI; IPI00216605; -.
DR IPI; IPI00218416; -.
DR IPI; IPI00218417; -.
DR IPI; IPI00218418; -.
DR IPI; IPI00218419; -.
DR IPI; IPI00218420; -.
DR IPI; IPI00218421; -.
DR IPI; IPI00218422; -.
DR IPI; IPI00218423; -.
DR IPI; IPI00218424; -.
DR IPI; IPI00218425; -.
DR IPI; IPI00384713; -.
DR IPI; IPI00386650; -.
DR IPI; IPI00647907; -.
DR IPI; IPI00759837; -.
DR IPI; IPI00873362; -.
DR IPI; IPI00942110; -.
DR PIR; A35969; A35969.
DR PIR; A42691; TVHUF2.
DR PIR; A45081; A45081.
DR PIR; C42691; C42691.
DR PIR; S16236; S16236.
DR RefSeq; NP_000132.3; NM_000141.4.
DR RefSeq; NP_001138385.1; NM_001144913.1.
DR RefSeq; NP_001138386.1; NM_001144914.1.
DR RefSeq; NP_001138387.1; NM_001144915.1.
DR RefSeq; NP_001138388.1; NM_001144916.1.
DR RefSeq; NP_001138389.1; NM_001144917.1.
DR RefSeq; NP_001138390.1; NM_001144918.1.
DR RefSeq; NP_001138391.1; NM_001144919.1.
DR RefSeq; NP_075259.4; NM_022970.3.
DR RefSeq; NP_075418.1; NM_023029.2.
DR UniGene; Hs.533683; -.
DR PDB; 1DJS; X-ray; 2.40 A; A=153-362.
DR PDB; 1E0O; X-ray; 2.80 A; B/D=148-366.
DR PDB; 1EV2; X-ray; 2.20 A; E/F/G/H=147-366.
DR PDB; 1GJO; X-ray; 2.40 A; A=456-768.
DR PDB; 1II4; X-ray; 2.70 A; E/F/G/H=147-366.
DR PDB; 1IIL; X-ray; 2.30 A; E/F/G/H=147-366.
DR PDB; 1NUN; X-ray; 2.90 A; B=140-361.
DR PDB; 1OEC; X-ray; 2.40 A; A=456-768.
DR PDB; 1WVZ; NMR; -; A=147-249.
DR PDB; 2FDB; X-ray; 2.28 A; P/R=149-368.
DR PDB; 2PSQ; X-ray; 2.40 A; A/B=413-768.
DR PDB; 2PVF; X-ray; 1.80 A; A=458-778, B=764-778.
DR PDB; 2PVY; X-ray; 2.20 A; A/B/C/D=458-768.
DR PDB; 2PWL; X-ray; 2.40 A; A/B=458-768.
DR PDB; 2PY3; X-ray; 2.30 A; A/B=458-768.
DR PDB; 2PZ5; X-ray; 2.40 A; A/B=458-768.
DR PDB; 2PZP; X-ray; 2.40 A; A/B=458-768.
DR PDB; 2PZR; X-ray; 3.00 A; A/B=458-768.
DR PDB; 2Q0B; X-ray; 2.90 A; A/B=458-768.
DR PDB; 3B2T; X-ray; 1.80 A; A/B=458-766.
DR PDB; 3CAF; X-ray; 1.96 A; A=150-249.
DR PDB; 3CLY; X-ray; 2.00 A; A=458-778.
DR PDB; 3CU1; X-ray; 2.60 A; A/C=150-249.
DR PDB; 3DAR; X-ray; 2.20 A; A/B=146-249.
DR PDB; 3EUU; X-ray; 2.34 A; A/B=150-249.
DR PDB; 3OJ2; X-ray; 2.20 A; C/D=140-361.
DR PDB; 3OJM; X-ray; 2.10 A; B=140-361.
DR PDB; 3RI1; X-ray; 2.10 A; A/B=458-768.
DR PDBsum; 1DJS; -.
DR PDBsum; 1E0O; -.
DR PDBsum; 1EV2; -.
DR PDBsum; 1GJO; -.
DR PDBsum; 1II4; -.
DR PDBsum; 1IIL; -.
DR PDBsum; 1NUN; -.
DR PDBsum; 1OEC; -.
DR PDBsum; 1WVZ; -.
DR PDBsum; 2FDB; -.
DR PDBsum; 2PSQ; -.
DR PDBsum; 2PVF; -.
DR PDBsum; 2PVY; -.
DR PDBsum; 2PWL; -.
DR PDBsum; 2PY3; -.
DR PDBsum; 2PZ5; -.
DR PDBsum; 2PZP; -.
DR PDBsum; 2PZR; -.
DR PDBsum; 2Q0B; -.
DR PDBsum; 3B2T; -.
DR PDBsum; 3CAF; -.
DR PDBsum; 3CLY; -.
DR PDBsum; 3CU1; -.
DR PDBsum; 3DAR; -.
DR PDBsum; 3EUU; -.
DR PDBsum; 3OJ2; -.
DR PDBsum; 3OJM; -.
DR PDBsum; 3RI1; -.
DR ProteinModelPortal; P21802; -.
DR DIP; DIP-3788N; -.
DR IntAct; P21802; 8.
DR MINT; MINT-118359; -.
DR MEROPS; I43.001; -.
DR PhosphoSite; P21802; -.
DR DMDM; 120049; -.
DR PaxDb; P21802; -.
DR PRIDE; P21802; -.
DR Ensembl; ENST00000346997; ENSP00000263451; ENSG00000066468.
DR Ensembl; ENST00000351936; ENSP00000309878; ENSG00000066468.
DR Ensembl; ENST00000356226; ENSP00000348559; ENSG00000066468.
DR Ensembl; ENST00000357555; ENSP00000350166; ENSG00000066468.
DR Ensembl; ENST00000358487; ENSP00000351276; ENSG00000066468.
DR Ensembl; ENST00000359354; ENSP00000352309; ENSG00000066468.
DR Ensembl; ENST00000360144; ENSP00000353262; ENSG00000066468.
DR Ensembl; ENST00000369056; ENSP00000358052; ENSG00000066468.
DR Ensembl; ENST00000369058; ENSP00000358054; ENSG00000066468.
DR Ensembl; ENST00000369060; ENSP00000358056; ENSG00000066468.
DR Ensembl; ENST00000369061; ENSP00000358057; ENSG00000066468.
DR Ensembl; ENST00000457416; ENSP00000410294; ENSG00000066468.
DR GeneID; 2263; -.
DR KEGG; hsa:2263; -.
DR UCSC; uc001lfg.4; human.
DR UCSC; uc010qtl.2; human.
DR UCSC; uc021pzw.1; human.
DR UCSC; uc021pzy.1; human.
DR UCSC; uc021qaa.1; human.
DR CTD; 2263; -.
DR GeneCards; GC10M123223; -.
DR HGNC; HGNC:3689; FGFR2.
DR HPA; CAB010886; -.
DR HPA; HPA035305; -.
DR MIM; 101200; phenotype.
DR MIM; 101600; phenotype.
DR MIM; 123150; phenotype.
DR MIM; 123500; phenotype.
DR MIM; 123790; phenotype.
DR MIM; 149730; phenotype.
DR MIM; 176943; gene.
DR MIM; 207410; phenotype.
DR MIM; 609579; phenotype.
DR MIM; 614592; phenotype.
DR neXtProt; NX_P21802; -.
DR Orphanet; 263476; Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis.
DR Orphanet; 87; Apert syndrome.
DR Orphanet; 207; Crouzon disease.
DR Orphanet; 1555; Cutis gyrata - acanthosis nigricans - craniosynostosis.
DR Orphanet; 168624; Familial scaphocephaly syndrome, McGillivray type.
DR Orphanet; 1540; Jackson-Weiss syndrome.
DR Orphanet; 2363; Lacrimo-auriculo-dento-digital syndrome.
DR Orphanet; 93258; Pfeiffer syndrome type 1.
DR Orphanet; 93259; Pfeiffer syndrome type 2.
DR Orphanet; 93260; Pfeiffer syndrome type 3.
DR Orphanet; 794; Saethre-Chotzen syndrome.
DR PharmGKB; PA28128; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000263410; -.
DR HOVERGEN; HBG000345; -.
DR KO; K05093; -.
DR OMA; YEPCLPK; -.
DR OrthoDB; EOG4640BC; -.
DR BRENDA; 2.7.10.1; 2681.
DR Pathway_Interaction_DB; fgf_pathway; FGF signaling pathway.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR BindingDB; P21802; -.
DR ChEMBL; CHEMBL4142; -.
DR DrugBank; DB00039; Palifermin.
DR EvolutionaryTrace; P21802; -.
DR GenomeRNAi; 2263; -.
DR NextBio; 9189; -.
DR ArrayExpress; P21802; -.
DR Bgee; P21802; -.
DR Genevestigator; P21802; -.
DR GermOnline; ENSG00000066468; Homo sapiens.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0060076; C:excitatory synapse; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017134; F:fibroblast growth factor binding; IDA:UniProtKB.
DR GO; GO:0005007; F:fibroblast growth factor-activated receptor activity; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0060667; P:branch elongation involved in salivary gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; ISS:UniProtKB.
DR GO; GO:0048755; P:branching morphogenesis of a nerve; ISS:UniProtKB.
DR GO; GO:0060449; P:bud elongation involved in lung branching; ISS:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
DR GO; GO:0060365; P:coronal suture morphogenesis; IEA:Compara.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
DR GO; GO:0061031; P:endodermal digestive tract morphogenesis; IEA:Compara.
DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0035603; P:fibroblast growth factor receptor signaling pathway involved in hemopoiesis; ISS:UniProtKB.
DR GO; GO:0060595; P:fibroblast growth factor receptor signaling pathway involved in mammary gland specification; ISS:UniProtKB.
DR GO; GO:0035602; P:fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow; ISS:UniProtKB.
DR GO; GO:0035607; P:fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development; ISS:UniProtKB.
DR GO; GO:0035604; P:fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow; ISS:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0032808; P:lacrimal gland development; ISS:UniProtKB.
DR GO; GO:0060601; P:lateral sprouting from an epithelium; ISS:UniProtKB.
DR GO; GO:0070307; P:lens fiber cell development; IEA:Compara.
DR GO; GO:0060174; P:limb bud formation; ISS:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; ISS:UniProtKB.
DR GO; GO:0060463; P:lung lobe morphogenesis; ISS:UniProtKB.
DR GO; GO:0060484; P:lung-associated mesenchyme development; ISS:UniProtKB.
DR GO; GO:0060615; P:mammary gland bud formation; ISS:UniProtKB.
DR GO; GO:0003149; P:membranous septum morphogenesis; ISS:UniProtKB.
DR GO; GO:0060915; P:mesenchymal cell differentiation involved in lung development; ISS:UniProtKB.
DR GO; GO:0060916; P:mesenchymal cell proliferation involved in lung development; ISS:UniProtKB.
DR GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Compara.
DR GO; GO:0045839; P:negative regulation of mitosis; IEA:Compara.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; IEA:Compara.
DR GO; GO:0042476; P:odontogenesis; ISS:UniProtKB.
DR GO; GO:0035265; P:organ growth; ISS:UniProtKB.
DR GO; GO:0030916; P:otic vesicle formation; ISS:UniProtKB.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB.
DR GO; GO:0010518; P:positive regulation of phospholipase activity; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; ISS:UniProtKB.
DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; ISS:UniProtKB.
DR GO; GO:0060523; P:prostate epithelial cord elongation; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0021860; P:pyramidal neuron development; ISS:UniProtKB.
DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0010453; P:regulation of cell fate commitment; ISS:UniProtKB.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; TAS:UniProtKB.
DR GO; GO:0033688; P:regulation of osteoblast proliferation; TAS:UniProtKB.
DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0060529; P:squamous basal epithelial stem cell differentiation involved in prostate gland acinus development; ISS:UniProtKB.
DR GO; GO:0048489; P:synaptic vesicle transport; IEA:Compara.
DR GO; GO:0001657; P:ureteric bud development; ISS:UniProtKB.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:UniProtKB.
DR GO; GO:0021847; P:ventricular zone neuroblast division; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_cat_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016248; Tyr_kinase_fibroblast_GF_rcpt.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR PIRSF; PIRSF000628; FGFR; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; Kinase_like; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding;
KW Cell membrane; Complete proteome; Craniosynostosis;
KW Cytoplasmic vesicle; Disease mutation; Disulfide bond;
KW Ectodermal dysplasia; Glycoprotein; Golgi apparatus; Heparin-binding;
KW Immunoglobulin domain; Kinase;
KW Lacrimo-auriculo-dento-digital syndrome; Membrane; Mental retardation;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene;
KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1 21 Potential.
FT CHAIN 22 821 Fibroblast growth factor receptor 2.
FT /FTId=PRO_0000016783.
FT TOPO_DOM 22 377 Extracellular (Potential).
FT TRANSMEM 378 398 Helical; (Potential).
FT TOPO_DOM 399 821 Cytoplasmic (Potential).
FT DOMAIN 25 125 Ig-like C2-type 1.
FT DOMAIN 154 247 Ig-like C2-type 2.
FT DOMAIN 256 358 Ig-like C2-type 3.
FT DOMAIN 481 770 Protein kinase.
FT NP_BIND 487 495 ATP.
FT NP_BIND 565 567 ATP.
FT REGION 161 178 Heparin-binding.
FT ACT_SITE 626 626 Proton acceptor.
FT BINDING 517 517 ATP.
FT BINDING 571 571 ATP.
FT MOD_RES 466 466 Phosphotyrosine; by autocatalysis.
FT MOD_RES 586 586 Phosphotyrosine; by autocatalysis.
FT MOD_RES 588 588 Phosphotyrosine; by autocatalysis.
FT MOD_RES 656 656 Phosphotyrosine; by autocatalysis.
FT MOD_RES 657 657 Phosphotyrosine; by autocatalysis.
FT MOD_RES 769 769 Phosphotyrosine; by autocatalysis.
FT CARBOHYD 83 83 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 123 123 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 228 228 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 241 241 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 265 265 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 297 297 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 318 318 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 331 331 N-linked (GlcNAc...) (Potential).
FT DISULFID 62 107 By similarity.
FT DISULFID 179 231
FT DISULFID 278 342
FT VAR_SEQ 37 152 EPPTKYQISQPEVYVAAPGESLEVRCLLKDAAVISWTKDGV
FT HLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETW
FT YFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKR -> G
FT (in isoform 20).
FT /FTId=VSP_019608.
FT VAR_SEQ 37 125 Missing (in isoform 4, isoform 21 and
FT isoform 22).
FT /FTId=VSP_002964.
FT VAR_SEQ 250 361 Missing (in isoform 23).
FT /FTId=VSP_041914.
FT VAR_SEQ 250 254 ERSPH -> GSQGL (in isoform 14).
FT /FTId=VSP_002965.
FT VAR_SEQ 255 821 Missing (in isoform 14).
FT /FTId=VSP_002966.
FT VAR_SEQ 313 313 K -> KVTK (in isoform 16).
FT /FTId=VSP_002967.
FT VAR_SEQ 314 429 Missing (in isoform 15).
FT /FTId=VSP_002968.
FT VAR_SEQ 314 330 AAGVNTTDKEIEVLYIR -> HSGINSSNAEVLALF (in
FT isoform 3, isoform 4, isoform 7, isoform
FT 9, isoform 10, isoform 11, isoform 12,
FT isoform 13, isoform 17, isoform 18,
FT isoform 19 and isoform 22).
FT /FTId=VSP_002969.
FT VAR_SEQ 334 335 FE -> EA (in isoform 3, isoform 4,
FT isoform 7, isoform 9, isoform 10, isoform
FT 11, isoform 12, isoform 13, isoform 17,
FT isoform 18, isoform 19 and isoform 22).
FT /FTId=VSP_002970.
FT VAR_SEQ 341 353 TCLAGNSIGISFH -> ICKVSNYIGQANQ (in
FT isoform 3, isoform 4, isoform 7, isoform
FT 9, isoform 10, isoform 11, isoform 12,
FT isoform 13, isoform 17, isoform 18,
FT isoform 19 and isoform 22).
FT /FTId=VSP_002971.
FT VAR_SEQ 361 361 P -> PKQQ (in isoform 3, isoform 4,
FT isoform 7, isoform 9, isoform 10, isoform
FT 11, isoform 12, isoform 13, isoform 17,
FT isoform 18, isoform 19 and isoform 22).
FT /FTId=VSP_002972.
FT VAR_SEQ 362 365 APGR -> GRRC (in isoform 19).
FT /FTId=VSP_002973.
FT VAR_SEQ 366 821 Missing (in isoform 19).
FT /FTId=VSP_002974.
FT VAR_SEQ 428 429 Missing (in isoform 4, isoform 5, isoform
FT 6, isoform 8, isoform 16 and isoform 18).
FT /FTId=VSP_002975.
FT VAR_SEQ 429 430 Missing (in isoform 20).
FT /FTId=VSP_019609.
FT VAR_SEQ 761 821 LTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPD
FT PMPYEPCLPQYPHINGSVKT -> PPNPSLMSIFRK (in
FT isoform 4).
FT /FTId=VSP_002976.
FT VAR_SEQ 768 821 EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPC
FT LPQYPHINGSVKT -> SFQSSLKSSSTGIPGWPPGSEVFS
FT EVAFRGILNYDIERPILCAGSKKIYDI (in isoform
FT 10).
FT /FTId=VSP_002981.
FT VAR_SEQ 768 821 EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPC
FT LPQYPHINGSVKT -> GRLPAWASQEKENSQTSLFAISHV
FT TLSSISKTRSSAKRDEKPGSSPHLALVRSQGLPQSVVP
FT (in isoform 11).
FT /FTId=VSP_002982.
FT VAR_SEQ 768 821 EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPC
FT LPQYPHINGSVKT -> PLS (in isoform 12).
FT /FTId=VSP_002983.
FT VAR_SEQ 768 821 Missing (in isoform 13).
FT /FTId=VSP_002977.
FT VAR_SEQ 768 821 EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPC
FT LPQYPHINGSVKT -> I (in isoform 2, isoform
FT 8, isoform 17 and isoform 22).
FT /FTId=VSP_002978.
FT VAR_SEQ 768 821 EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPC
FT LPQYPHINGSVKT -> RYKLLPCPDKHNKRCKPEERGDLT
FT EAGAAGSSRCVDSRKRVRQEKISTG (in isoform 7).
FT /FTId=VSP_002979.
FT VAR_SEQ 768 821 EYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPC
FT LPQYPHINGSVKT -> RILTLTTNENFQSTSGREGTEIHA
FT LQCLRSEVTPAISCESPLADTGSKVPN (in isoform
FT 9).
FT /FTId=VSP_002980.
FT VAR_SEQ 769 821 YLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCL
FT PQYPHINGSVKT -> EKKVSGAVDCHKPPCNPSHLPCVLA
FT VDQ (in isoform 21).
FT /FTId=VSP_041915.
FT VAR_SEQ 778 821 QYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGS
FT VKT -> PYSPCYPDPR (in isoform 6).
FT /FTId=VSP_002984.
FT VARIANT 6 6 R -> P (in dbSNP:rs3750819).
FT /FTId=VAR_017258.
FT VARIANT 57 57 S -> L (in dbSNP:rs56226109).
FT /FTId=VAR_042204.
FT VARIANT 105 105 Y -> C (in CS).
FT /FTId=VAR_004112.
FT VARIANT 172 172 A -> F (in PS; requires 2 nucleotide
FT substitutions).
FT /FTId=VAR_017259.
FT VARIANT 186 186 M -> T (in dbSNP:rs755793).
FT /FTId=VAR_017260.
FT VARIANT 203 203 R -> C (in breast cancer samples;
FT infiltrating ductal carcinoma; somatic
FT mutation).
FT /FTId=VAR_036380.
FT VARIANT 252 253 SP -> FS (in PS).
FT /FTId=VAR_004116.
FT VARIANT 252 252 S -> F (in APRS; requires 2 nucleotide
FT substitutions).
FT /FTId=VAR_004114.
FT VARIANT 252 252 S -> L (in CS).
FT /FTId=VAR_004113.
FT VARIANT 252 252 S -> W (in APRS and PS; common mutation).
FT /FTId=VAR_004115.
FT VARIANT 253 253 P -> R (in APRS; common mutation).
FT /FTId=VAR_004117.
FT VARIANT 263 263 P -> L (in CS).
FT /FTId=VAR_017261.
FT VARIANT 267 267 S -> P (in CS).
FT /FTId=VAR_004118.
FT VARIANT 268 268 T -> TG (in CS).
FT /FTId=VAR_004119.
FT VARIANT 272 272 G -> V (in an ovarian serous carcinoma
FT sample; somatic mutation).
FT /FTId=VAR_042205.
FT VARIANT 273 273 Missing (in PS; type 2).
FT /FTId=VAR_017262.
FT VARIANT 276 276 F -> V (in CS).
FT /FTId=VAR_004120.
FT VARIANT 278 278 C -> F (in CS, JWS and PS; forms
FT disulfide-linked dimers with constitutive
FT kinase activity, is retained in an
FT intracellular compartment and not
FT detected at the cell surface).
FT /FTId=VAR_004121.
FT VARIANT 278 278 C -> Y (in CS).
FT /FTId=VAR_017263.
FT VARIANT 281 281 Y -> C (in CS).
FT /FTId=VAR_017264.
FT VARIANT 283 283 D -> N (in a lung squamous cell carcinoma
FT sample; somatic mutation).
FT /FTId=VAR_042206.
FT VARIANT 287 289 Missing (in CS).
FT /FTId=VAR_004122.
FT VARIANT 288 288 I -> S (in CS).
FT /FTId=VAR_017265.
FT VARIANT 289 289 Q -> P (in CS and JWS).
FT /FTId=VAR_004123.
FT VARIANT 290 290 W -> C (in PS; severe; also in a lung
FT squamous cell carcinoma sample; somatic
FT mutation).
FT /FTId=VAR_004124.
FT VARIANT 290 290 W -> G (in CS).
FT /FTId=VAR_017266.
FT VARIANT 290 290 W -> R (in CS).
FT /FTId=VAR_004125.
FT VARIANT 292 292 K -> E (in CS).
FT /FTId=VAR_004126.
FT VARIANT 301 301 Y -> C (in CS).
FT /FTId=VAR_004127.
FT VARIANT 314 314 A -> S (in craniosynostosis).
FT /FTId=VAR_004128.
FT VARIANT 315 315 A -> S (in a non-syndromic
FT craniosynostosis patient with abnormal
FT intrauterine history; confers
FT predisposition to craniosynostosis).
FT /FTId=VAR_017267.
FT VARIANT 321 321 D -> A (in PS).
FT /FTId=VAR_004129.
FT VARIANT 328 328 Y -> C (in CS).
FT /FTId=VAR_004130.
FT VARIANT 331 331 N -> I (in CS).
FT /FTId=VAR_004131.
FT VARIANT 337 337 A -> ANA (in CS).
FT /FTId=VAR_004132.
FT VARIANT 337 337 A -> P (in CS).
FT /FTId=VAR_017268.
FT VARIANT 338 338 G -> E (in CS).
FT /FTId=VAR_004133.
FT VARIANT 338 338 G -> R (in CS).
FT /FTId=VAR_015011.
FT VARIANT 340 340 Y -> C (in PS).
FT /FTId=VAR_017269.
FT VARIANT 340 340 Y -> H (in CS).
FT /FTId=VAR_004134.
FT VARIANT 341 341 T -> P (in PS and CS).
FT /FTId=VAR_004135.
FT VARIANT 342 342 C -> F (in CS).
FT /FTId=VAR_004136.
FT VARIANT 342 342 C -> G (in PS).
FT /FTId=VAR_017270.
FT VARIANT 342 342 C -> R (in CS, JWS, PS and ABS2).
FT /FTId=VAR_004137.
FT VARIANT 342 342 C -> S (in CS, JWS, PS and ABS2).
FT /FTId=VAR_004138.
FT VARIANT 342 342 C -> W (in CS).
FT /FTId=VAR_017271.
FT VARIANT 342 342 C -> Y (in CS and PS).
FT /FTId=VAR_004139.
FT VARIANT 344 344 A -> G (in CS and JWS).
FT /FTId=VAR_004140.
FT VARIANT 344 344 A -> P (in CS and PS).
FT /FTId=VAR_004141.
FT VARIANT 347 347 S -> C (in CS).
FT /FTId=VAR_004142.
FT VARIANT 351 351 S -> C (in CS, PS and ABS2).
FT /FTId=VAR_004143.
FT VARIANT 354 354 S -> C (in CS).
FT /FTId=VAR_004144.
FT VARIANT 354 354 S -> Y (in CS).
FT /FTId=VAR_017272.
FT VARIANT 356 358 Missing (in CS).
FT /FTId=VAR_004145.
FT VARIANT 359 359 V -> F (in CS and PS).
FT /FTId=VAR_004146.
FT VARIANT 362 362 A -> S (in CS).
FT /FTId=VAR_017273.
FT VARIANT 372 372 S -> C (in BSTVS).
FT /FTId=VAR_017274.
FT VARIANT 375 375 Y -> C (in PS and BSTVS).
FT /FTId=VAR_017275.
FT VARIANT 381 381 Y -> D (in BBDS).
FT /FTId=VAR_067977.
FT VARIANT 384 384 G -> R (in CS).
FT /FTId=VAR_004147.
FT VARIANT 391 391 M -> R (in BBDS; the mutation selectively
FT reduces plasma-membrane levels of the
FT protein and markedly diminishes the
FT receptor's responsiveness to
FT extracellular FGF).
FT /FTId=VAR_067978.
FT VARIANT 526 526 K -> E (in FSPC; constitutive kinase
FT activity).
FT /FTId=VAR_023788.
FT VARIANT 549 549 N -> H (in CS; constitutive kinase
FT activity).
FT /FTId=VAR_017276.
FT VARIANT 565 565 E -> G (in PS; constitutive kinase
FT activity).
FT /FTId=VAR_017277.
FT VARIANT 612 612 R -> T (in a lung adenocarcinoma sample;
FT somatic mutation).
FT /FTId=VAR_046071.
FT VARIANT 613 613 G -> R.
FT /FTId=VAR_015012.
FT VARIANT 628 628 A -> T (in LADDS; strongly reduced kinase
FT activity).
FT /FTId=VAR_029884.
FT VARIANT 641 641 K -> R (in PS; constitutive kinase
FT activity).
FT /FTId=VAR_017278.
FT VARIANT 648 648 A -> T (in LADDS).
FT /FTId=VAR_029885.
FT VARIANT 649 650 RD -> S (in LADDS).
FT /FTId=VAR_029886.
FT VARIANT 659 659 K -> N (in craniosynostosis; constitutive
FT kinase activity).
FT /FTId=VAR_017279.
FT VARIANT 663 663 G -> E (in PS).
FT /FTId=VAR_017280.
FT VARIANT 678 678 R -> G (in CS).
FT /FTId=VAR_017281.
FT MUTAGEN 265 265 N->Q: Reduced N-glycosylation. Reduced
FT expression at the cell surface.
FT MUTAGEN 549 549 N->T: Constitutive kinase activity.
FT MUTAGEN 565 565 E->A: Constitutive kinase activity.
FT MUTAGEN 656 657 Missing: Loss of kinase activity.
FT MUTAGEN 769 769 Y->F: Increases fibroblast proliferation.
FT Decreases phosphorylation of PLCG1 and
FT FRS2. Decreases activation of MAP
FT kinases.
FT CONFLICT 246 246 L -> P (in Ref. 16; BAG57383).
FT CONFLICT 310 310 K -> N (in Ref. 16; BAG57383).
FT STRAND 152 157
FT TURN 159 162
FT STRAND 166 170
FT STRAND 175 178
FT STRAND 181 185
FT STRAND 188 193
FT HELIX 200 202
FT STRAND 208 210
FT HELIX 211 213
FT STRAND 215 218
FT HELIX 223 225
FT STRAND 227 235
FT STRAND 238 249
FT STRAND 266 269
FT STRAND 274 277
FT STRAND 287 293
FT STRAND 296 298
FT STRAND 299 301
FT STRAND 309 313
FT STRAND 315 319
FT TURN 321 325
FT STRAND 326 329
FT HELIX 334 336
FT STRAND 338 346
FT STRAND 349 360
FT HELIX 472 474
FT HELIX 478 480
FT STRAND 481 489
FT STRAND 494 501
FT STRAND 504 506
FT STRAND 511 518
FT HELIX 525 541
FT STRAND 550 554
FT STRAND 556 558
FT STRAND 561 565
FT STRAND 568 571
FT HELIX 572 577
FT HELIX 594 596
FT HELIX 600 619
FT HELIX 629 631
FT STRAND 632 634
FT TURN 636 638
FT STRAND 640 642
FT TURN 652 654
FT TURN 657 659
FT STRAND 664 666
FT HELIX 667 669
FT HELIX 672 676
FT HELIX 682 697
FT HELIX 709 717
FT STRAND 726 728
FT HELIX 730 739
FT HELIX 744 746
FT HELIX 750 764
SQ SEQUENCE 821 AA; 92025 MW; 6CD5001C960ED82F CRC64;
MVSWGRFICL VVVTMATLSL ARPSFSLVED TTLEPEEPPT KYQISQPEVY VAAPGESLEV
RCLLKDAAVI SWTKDGVHLG PNNRTVLIGE YLQIKGATPR DSGLYACTAS RTVDSETWYF
MVNVTDAISS GDDEDDTDGA EDFVSENSNN KRAPYWTNTE KMEKRLHAVP AANTVKFRCP
AGGNPMPTMR WLKNGKEFKQ EHRIGGYKVR NQHWSLIMES VVPSDKGNYT CVVENEYGSI
NHTYHLDVVE RSPHRPILQA GLPANASTVV GGDVEFVCKV YSDAQPHIQW IKHVEKNGSK
YGPDGLPYLK VLKAAGVNTT DKEIEVLYIR NVTFEDAGEY TCLAGNSIGI SFHSAWLTVL
PAPGREKEIT ASPDYLEIAI YCIGVFLIAC MVVTVILCRM KNTTKKPDFS SQPAVHKLTK
RIPLRRQVTV SAESSSSMNS NTPLVRITTR LSSTADTPML AGVSEYELPE DPKWEFPRDK
LTLGKPLGEG CFGQVVMAEA VGIDKDKPKE AVTVAVKMLK DDATEKDLSD LVSEMEMMKM
IGKHKNIINL LGACTQDGPL YVIVEYASKG NLREYLRARR PPGMEYSYDI NRVPEEQMTF
KDLVSCTYQL ARGMEYLASQ KCIHRDLAAR NVLVTENNVM KIADFGLARD INNIDYYKKT
TNGRLPVKWM APEALFDRVY THQSDVWSFG VLMWEIFTLG GSPYPGIPVE ELFKLLKEGH
RMDKPANCTN ELYMMMRDCW HAVPSQRPTF KQLVEDLDRI LTLTTNEEYL DLSQPLEQYS
PSYPDTRSSC SSGDDSVFSP DPMPYEPCLP QYPHINGSVK T
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