Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Fibroblast growth factor receptor 1  

UniProtKB / Swiss-Prot ID :  FGFR1_HUMAN

Gene Name (Synonyms) : 
FGFR1, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cell membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm, cytosol. Cytoplasmic vesicle. Note=After ligand binding, both receptor and ligand are rapidly internalized. Can translocate to the nucleus after internalization, or by translocation  

Protein Function :  Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. 

Transmembrane Topology (topPTM) : FGFR1_HUMAN 

Protein Sequence MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDG...
Predicted Secondary Structure CCCHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCEEEEECCCCEEEEEEECCCCCEEEEEECC...
Protein Variant
LocationDescription
22R -> S (in dbSNP:rs17175750). VAR_019290
48G -> S (in IHH). VAR_030968
77N -> K. VAR_030969
78R -> C (in KAL2). VAR_030970
97G -> D (in KAL2). VAR_017885
99Y -> C (in KAL2). VAR_017886
101C -> F (in KAL2). VAR_030971
102V -> I (in KAL2; dbSNP:rs55642501). VAR_030972
125S -> L (in a breast infiltrating ductalcarcinoma sample; somatic mutation).
129D -> A (in KAL2). VAR_030973
167A -> S (in KAL2; with cleft palate,corpus callosum agenesis, unilateral
178C -> S (in KAL2; with severe earanomalies).
213W -> G (in dbSNP:rs17851623). VAR_030975
224D -> H (in KAL2). VAR_030976
237G -> D (in KAL2). VAR_030977
237G -> S (in IHH/KAL2; also found in afamily member with isolated anosmia; may
245L -> P (in KAL2). VAR_030979
250R -> W (in KAL2). VAR_030980
252P -> R (in PS; seems to be a gain offunction).
252P -> T (in a lung bronchoalveolarcarcinoma sample; somatic mutation).
254R -> Q (in KAL2). VAR_030981
270G -> D (in KAL2). VAR_030982
273V -> M (in KAL2). VAR_030983
274E -> G (in KAL2; also found in a familymember with isolated anosmia).
277C -> Y (in KAL2). VAR_017888
283P -> R (in KAL2). VAR_030985
300I -> T (in TRIGNO1). VAR_030986
330N -> I (in OGD). VAR_030987
332S -> C (in KAL2). VAR_030988
339Y -> C (in KAL2). VAR_030989
343A -> V (in KAL2). VAR_030990
346S -> C (in KAL2; also found in a familymember with isolated anosmia).
366P -> L (in IHH/KAL2). VAR_030992
374Y -> C (in OGD; elevated basal activityand increased FGF2-mediated activity).
381C -> R (in OGD). VAR_030994
520A -> T (in KAL2). VAR_030995
538I -> V (in KAL2). VAR_030996
607V -> M (in KAL2; with bimanualsynkinesis).
621H -> R (in KAL2). VAR_030997
622R -> G (in KAL2; with severe earanomalies).
622R -> Q (in KAL2). VAR_030999
664V -> L (in a lung large cell carcinomasample; somatic mutation).
666W -> R (in KAL2; with cleft palate). VAR_017890
685S -> F (in KAL2). VAR_031000
687G -> R (in KAL2). VAR_031001
693I -> F (in KAL2). VAR_031002
703G -> R (in KAL2). VAR_031003
703G -> S (in KAL2). VAR_031004
719M -> R (in KAL2). VAR_017891
722P -> H (in IHH; associated with K-724;also found in a family member with
722P -> S (in KAL2). VAR_031006
724N -> K (in IHH; associated with H-722;also found in a family member with
745P -> S (in KAL2). VAR_031008
769L -> V (in dbSNP:rs2956723). VAR_031009
772P -> S (in KAL2; with cleft palate,unilateral absence of nasal cartilage,
795V -> I (in KAL2; also found in a familymember with isolated anosmia).
818G -> R (in dbSNP:rs17182456). VAR_019291
822R -> C (in dbSNP:rs17182463). VAR_019292
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
154PhosphotyrosinePVAPYWTSP
EECCEECCC
16.16Phosphositeplus
Link-
154Phosphotyrosine (FGFR1)PVAPYWTSP
EECCEECCC
16.16PhosphoELM
Link-
164N6-acetyllysineKMEKKLHAV
CCCCCEEEE
32.00Phosphositeplus
Link-
172N6-acetyllysineVPAAKTVKF
EECCCCEEE
56.83Phosphositeplus
Link-
279noneFMCKVYSDP
EEEEEEECC
4.75HPRD
Link-
280PhosphotyrosineMCKVYSDPQ
EEEEEECCC
7.89Phosphositeplus
Link-
280Phosphotyrosine (FGFR1)MCKVYSDPQ
EEEEEECCC
7.89PhosphoELM
Link-
296N-linked (GlcNAc...).HIEVNGSKI
ECCCCCCEE
35.91UniProtKB
Link-
307PhosphotyrosineDNLPYVQIL
CCCCEEEEE
14.25Phosphositeplus
Link-
307Phosphotyrosine (FGFR1)DNLPYVQIL
CCCCEEEEE
14.25PhosphoELM
Link-
368noneERPAVMTSP
CCCCCCCCC
4.82HPRD
Link-
428PhosphothreonineRRQVTVSAD
ECCCCCCCC
10.62Phosphositeplus
Link-
447PhosphoserineLVRPSRLSS
EEECCCCCC
34.98Phosphositeplus
Link-
450PhosphoserinePSRLSSSGT
CCCCCCCCC
22.73Phosphositeplus
Link-
451PhosphoserineSRLSSSGTP
CCCCCCCCC
37.06Phosphositeplus
Link-
452PhosphoserineRLSSSGTPM
CCCCCCCCC
43.22Phosphositeplus
Link-
463PhosphotyrosineGVSEYELPE
CCCHHHCCC
18.43Phosphositeplus
Link
463Phosphotyrosine (FGFR1)GVSEYELPE
CCCHHHCCC
18.43PhosphoELM
Link
463Phosphotyrosine; by autocatalysis.GVSEYELPE
CCCHHHCCC
18.43UniProtKB
Link
583PhosphotyrosinePGLEYCYNP
CCCCCCCCC
12.79Phosphositeplus
Link-
583Phosphotyrosine (FGFR1)PGLEYCYNP
CCCCCCCCC
12.79PhosphoELM
Link-
583Phosphotyrosine; by autocatalysis.PGLEYCYNP
CCCCCCCCC
12.79UniProtKB
Link-
585PhosphotyrosineLEYCYNPSH
CCCCCCCCC
29.25Phosphositeplus
Link-
585Phosphotyrosine (FGFR1)LEYCYNPSH
CCCCCCCCC
29.25PhosphoELM
Link-
585Phosphotyrosine; by autocatalysis.LEYCYNPSH
CCCCCCCCC
29.25UniProtKB
Link-
605PhosphotyrosineVSCAYQVAR
HHHHHHHHH
14.09Phosphositeplus
Link
605Phosphotyrosine (FGFR1)VSCAYQVAR
HHHHHHHHH
14.09PhosphoELM
Link
653PhosphotyrosineHHIDYYKKT
CCCCCEEEE
19.31HPRD
Link
653PhosphotyrosineHHIDYYKKT
CCCCCEEEE
19.31Phosphositeplus
Link
653Phosphotyrosine (FGFR1)HHIDYYKKT
CCCCCEEEE
19.31PhosphoELM
Link
653Phosphotyrosine; by autocatalysis.HHIDYYKKT
CCCCCEEEE
19.31UniProtKB
Link
654PhosphotyrosineHIDYYKKTT
CCCCEEEEE
11.40Phosphositeplus
Link
654Phosphotyrosine (FGFR1)HIDYYKKTT
CCCCEEEEE
11.40PhosphoELM
Link
654Phosphotyrosine; by autocatalysis.HIDYYKKTT
CCCCEEEEE
11.40UniProtKB
Link
677PhosphotyrosineFDRIYTHQS
CCCCCCCHH
10.08HPRD
Link
677PhosphotyrosineFDRIYTHQS
CCCCCCCHH
10.08Phosphositeplus
Link
677Phosphotyrosine (SHB)FDRIYTHQS
CCCCCCCHH
10.08HPRD
Link
701PhosphotyrosineGGSPYPGVP
CCCCCCCCC
17.83HPRD
Link
730PhosphotyrosineTNELYMMMR
CHHHHHHHH
4.10Phosphositeplus
Link
730Phosphotyrosine (FGFR1)TNELYMMMR
CHHHHHHHH
4.10PhosphoELM
Link
730Phosphotyrosine; by autocatalysis.TNELYMMMR
CHHHHHHHH
4.10UniProtKB
Link
766PhosphotyrosineSNQEYLDLS
CCCHHHHHH
8.85Phosphositeplus
Link-
766Phosphotyrosine (FGFR1)SNQEYLDLS
CCCHHHHHH
8.85PhosphoELM
Link-
766Phosphotyrosine; by autocatalysis.SNQEYLDLS
CCCHHHHHH
8.85UniProtKB
Link-
777PhosphoserineLDQYSPSFP
CCCCCCCCC
14.40Phosphositeplus
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
FGF5_HUMANphysical interactionDIP:10932EDIP8386828
CADH1_HUMANphysical interaction
physical interaction
EBI-1381427
EBI-1381454
intact11401320
11401320
CTNB1_HUMANphysical interactionEBI-1381449
intact11401320
GRB2_HUMANin vivoHPRD:00634HPRD9480847
NCA11_HUMANin vivoHPRD:00634HPRD12121226
FGF1_HUMANin vitro
in vivo
HPRD:00634HPRD11032250
10336501
FPPS_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:00634HPRD12020352
FGFR1_HUMANin vitro
in vivo
HPRD:00634HPRD8752212
8622701
7516330
12181353
12601080
PLCG1_HUMANin vitro
in vivo
HPRD:00634HPRD12601080
1689310
FRS2_HUMANin vitro
in vivo
HPRD:00634HPRD11877385
11090629
9632781
I17RD_HUMANin vivoHPRD:00634HPRD12604616
FGF2_HUMANin vitro
in vivo
HPRD:00634HPRD10950949
11030354
FGF7_HUMANin vitroHPRD:00634HPRD8663044
CRK_HUMANin vitroHPRD:00634HPRD10464310
FGF3_HUMANin vitroHPRD:00634HPRD8663044
FGF4_HUMANin vitroHPRD:00634HPRD11486033
P85A_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
CBP_HUMANin vitro
in vivo
HPRD:00634HPRD15929978
FGF8_HUMANin vitro
in vivo
HPRD:00634HPRD10574949
FGF9_HUMANin vitro
in vivo
HPRD:00634HPRD10574949
SLAP1_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
KS6A1_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
NRP1_HUMANin vitroHPRD:00634HPRD15695515
3BP2_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
P85B_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
FGF17_HUMANin vitroHPRD:00634HPRD10751172
FGF18_HUMANin vitroHPRD:00634HPRD10751172
NCK2_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
RTN3_HUMANin vitro
in vivo
HPRD:00634HPRD15117958
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Disease Reference
Kegg disease
H00255 Hypogonadotropic hypogonadism, including: Kallmann syndrome (KAL); Fertile eunuch syndrome (FEUNS)
H00443 Osteoglophonic dysplasia (OD); Osteoglophonic dwarfism (OGD)
H00458 Craniosynostosis, including: Pfeiffer syndrome; Apert syndrome; Crouzon syndrome; Jackson-Weiss synd
H00516 Isolated orofacial clefts, including: Cleft lip with or without cleft palate; Cleft palate
H01207 Trigonocephaly
OMIM disease
101600Pfeiffer syndrome (PS)
147950Hypogonadotropic hypogonadism 2 with or without anosmia (HH2)
166250Osteoglophonic dysplasia (OGD)
615465Hartsfield syndrome (HRTFDS)
190440Trigonocephaly 1 (TRIGNO1)
Drug Reference
Kegg drug
D08878 Brivanib alaninate (JAN/USAN/INN)
D08907 Dovitinib lactate (USAN)
D09589 Brivanib (USAN)
D09919 Lenvatinib (USAN/INN)
D09920 Lenvatinib mesilate (JAN); Lenvatinib mesylate (USAN)
D10137 Regorafenib hydrate (JAN); Stivarga (TN)
D10138 Regorafenib (USAN/INN)
D10396 Nintedanib esylate (USAN)
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
N-linked Glycosylation
ReferencePubMed
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry.";
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.;
J. Proteome Res. 4:2070-2080(2005).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296, AND MASSSPECTROMETRY.
Phosphorylation
ReferencePubMed
"Identification of six novel autophosphorylation sites on fibroblastgrowth factor receptor 1 and elucidation of their importance inreceptor activation and signal transduction.";
Mohammadi M., Dikic I., Sorokin A., Burgess W.H., Jaye M.,Schlessinger J.;
Mol. Cell. Biol. 16:977-989(1996).
Cited for: PHOSPHORYLATION AT TYR-463; TYR-583; TYR-585; TYR-653; TYR-654 ANDTYR-730, CATALYTIC ACTIVITY, ENZYME REGULATION, FUNCTION INPHOSPHORYLATION OF PLCG1 AND SHC1; ACTIVATION OF MAP KINASES ANDREGULATION OF CELL PROLIFERATION AND DIFFERENTIATION, AND MUTAGENESISOF TYR-653 AND TYR-654.
"Autophosphorylation of FGFR1 kinase is mediated by a sequential andprecisely ordered reaction.";
Furdui C.M., Lew E.D., Schlessinger J., Anderson K.S.;
Mol. Cell 21:711-717(2006).
Cited for: PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583 AND TYR-585, ANDMASS SPECTROMETRY.
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-653, AND MASSSPECTROMETRY.
"The precise sequence of FGF receptor autophosphorylation iskinetically driven and is disrupted by oncogenic mutations.";
Lew E.D., Furdui C.M., Anderson K.S., Schlessinger J.;
Sci. Signal. 2:RA6-RA6(2009).
Cited for: FUNCTION AS PROTO-ONCOGENE, ACTIVE SITE, MUTAGENESIS OF ASN-546 ANDASP-623, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-463; TYR-653;TYR-654; TYR-583; TYR-585 AND TYR-730, MASS SPECTROMETRY, AND ENZYMEREGULATION.
"The selectivity of receptor tyrosine kinase signaling is controlledby a secondary SH2 domain binding site.";
Bae J.H., Lew E.D., Yuzawa S., Tome F., Lax I., Schlessinger J.;
Cell 138:514-524(2009).
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 458-774 IN COMPLEX WITH PLCG1AND ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,AUTOPHOSPHORYLATION, AND PHOSPHORYLATION AT TYR-653; TYR-654 ANDTYR-766.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures