AiPD: Autoinhibited Protein Database

P21804

Gene name	FGFR1 (CEK1)
Protein name	Fibroblast growth factor receptor 1
Names	FGFR-1 , bFGF-R-1 , EC 2.7.10.1 , Basic fibroblast growth factor receptor 1 , Tyrosine kinase receptor CEK1
Species	Gallus gallus (Chicken)
KEGG Pathway	gga:396516
EC number	2.7.10.1: Protein-tyrosine kinases
Protein Class

Descriptions

Fibroblast growth factor receptor 1 (FGFR1) is one of the members of FGFR family belonging to the receptor tyrosine kinases (RTK) in cell proliferation, differentiation, migration, and maintenance of cellular homeostasis. FGFR1 consists of the ligand-binding region (immunoglobulin (Ig) domain 1-like domains) designated D1, D2, and D3, and a kinase domain. The D1 domain and the acid box (AB)-containing linker between D1 and D2 are involved in autoinhibition. Loss of D1 or the linker enhances the affinity of FGFR for FGF and HS and increases the signaling capacity of FGFR. Specifically, the AB region blocks the heparan sulfate (HS)-binding site on the D2 domain in cis to suppress HS-binding affinity of EGFR. D1 is dispensable for autoinhibition but plays a minor role in autoinhibition.

Autoinhibitory domains (AIDs)

464-466 (Helix αN) SS

Target domain	476-763 (Protein kinase domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

464-466 (Helix αN)

Target domain

476-763 (Protein kinase domain)

Relief mechanism

Ligand binding (Binding of the glial cell line-derived neurotrophic factor (GDNF) family ligand), PTM (Phosphorylation at Tyr-905)

Assay

517-521 (Autoinhibitory segment) SS

Target domain	476-763 (Protein kinase domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

517-521 (Autoinhibitory segment)

Target domain

476-763 (Protein kinase domain)

Relief mechanism

Ligand binding (Binding of the glial cell line-derived neurotrophic factor (GDNF) family ligand), PTM (Phosphorylation at Tyr-905)

Assay

Accessory elements

638-663 (Activation loop from InterPro)

Target domain	462-763 (Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1)
Relief mechanism
Assay

638-663 (Activation loop from InterPro)

Target domain	462-765 (Protein kinase domain)
Relief mechanism
Assay

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100

Lew ED et al. (2007) "Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation", Proceedings of the National Academy of Sciences of the United States of America, 104, 19802-7

Kalinina J et al. (2012) "The alternatively spliced acid box region plays a key role in FGF receptor autoinhibition", Structure (London, England : 1993), 20, 77-88

Uchikawa E et al. (2019) "Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex", eLife, 8,

Nielsen J et al. (2022) "Structural Investigations of Full-Length Insulin Receptor Dynamics and Signalling", Journal of molecular biology, 434, 167458

Chen YS et al. (2021) "Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone-receptor activation", Proceedings of the National Academy of Sciences of the United States of America, 118,

Craddock BP et al. (2007) "Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region", FEBS letters, 581, 3235-40

Klein T et al. (2015) "Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase", Nature communications, 6, 7877

Knowles PP et al. (2006) "Structure and chemical inhibition of the RET tyrosine kinase domain", The Journal of biological chemistry, 281, 33577-87

Huang X et al. (2009) "Structural insights into the inhibited states of the Mer receptor tyrosine kinase", Journal of structural biology, 165, 88-96

Autoinhibited structure

Activated structure

1 structures for P21804

Entry ID	Method	Resolution	Chain	Position	Source
AF-P21804-F1	Predicted				AlphaFoldDB

No variants for P21804

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for P21804

No associated diseases with P21804

18 regional properties for P21804

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	476 - 765	IPR000719
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	478 - 752	IPR001245
domain	Immunoglobulin subtype 2	45 - 107	IPR003598-1
domain	Immunoglobulin subtype 2	167 - 235	IPR003598-2
domain	Immunoglobulin subtype 2	266 - 346	IPR003598-3
domain	Immunoglobulin subtype	39 - 118	IPR003599-1
domain	Immunoglobulin subtype	161 - 246	IPR003599-2
domain	Immunoglobulin subtype	260 - 357	IPR003599-3
domain	Immunoglobulin-like domain	33 - 118	IPR007110-1
domain	Immunoglobulin-like domain	145 - 244	IPR007110-2
domain	Immunoglobulin-like domain	253 - 355	IPR007110-3
active_site	Tyrosine-protein kinase, active site	617 - 629	IPR008266
domain	Immunoglobulin I-set	166 - 245	IPR013098-1
domain	Immunoglobulin I-set	260 - 356	IPR013098-2
domain	Immunoglobulin-like beta-sandwich domain	41 - 112	IPR013151
binding_site	Protein kinase, ATP binding site	482 - 512	IPR017441
domain	Tyrosine-protein kinase, catalytic domain	476 - 752	IPR020635
domain	Fibroblast growth factor receptor 1, catalytic domain	462 - 763	IPR028174

Functions

		Description
EC Number	2.7.10.1	Protein-tyrosine kinases
Subcellular Localization	Cell membrane ; Single-pass type I membrane protein Nucleus Cytoplasm, cytosol Cytoplasmic vesicle	After ligand binding, both receptor and ligand are rapidly internalized Can translocate to the nucleus after internalization, or by translocation from the endoplasmic reticulum or Golgi apparatus to the cytosol, and from there to the nucleus (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

5 GO annotations of cellular component

Name	Definition
cytoplasmic vesicle	A vesicle found in the cytoplasm of a cell.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
receptor complex	Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

4 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
fibroblast growth factor binding	Binding to a fibroblast growth factor.
fibroblast growth factor receptor activity	Combining with a fibroblast growth factor receptor ligand and transmitting the signal across the plasma membrane to initiate a change in cell activity.
heparin binding	Binding to heparin, a member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells and which consist predominantly of alternating alpha-(1->4)-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues.

7 GO annotations of biological process

Name	Definition
epicardial cell to mesenchymal cell transition	A transition where an epicardial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell. The epicardium is a part of the pericardium.
peptidyl-tyrosine phosphorylation	The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
positive regulation of cell differentiation	Any process that activates or increases the frequency, rate or extent of cell differentiation.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of DNA-templated transcription	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of MAP kinase activity	Any process that activates or increases the frequency, rate or extent of MAP kinase activity.
positive regulation of phospholipase C activity	Any process that increases the rate of phospholipase C activity.

76 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P43481	KIT	Mast/stem cell growth factor receptor Kit	Bos taurus (Bovine)	SS
Q06805	TIE1	Tyrosine-protein kinase receptor Tie-1	Bos taurus (Bovine)	PR
Q06807	TEK	Angiopoietin-1 receptor	Bos taurus (Bovine)	SS
Q28889	KIT	Mast/stem cell growth factor receptor Kit	Felis catus (Cat) (Felis silvestris catus)	SS
P13369	CSF1R	Macrophage colony-stimulating factor 1 receptor	Felis catus (Cat) (Felis silvestris catus)	SS
P18460	FGFR3	Fibroblast growth factor receptor 3	Gallus gallus (Chicken)	SS
P18461	FGFR2	Fibroblast growth factor receptor 2	Gallus gallus (Chicken)	SS
Q08156	KIT	Mast/stem cell growth factor receptor Kit	Gallus gallus (Chicken)	SS
Q8AXY6	MUSK	Muscle, skeletal receptor tyrosine protein kinase	Gallus gallus (Chicken)	SS
Q5F3X2	DDR1	receptor protein-tyrosine kinase	Gallus gallus (Chicken)	SS
Q91987	NTRK2	BDNF/NT-3 growth factors receptor	Gallus gallus (Chicken)	SS
Q91044	NTRK3	NT-3 growth factor receptor	Gallus gallus (Chicken)	SS
Q8QHL3	FLT1	Vascular endothelial growth factor receptor 1	Gallus gallus (Chicken)	SS
Q98949	TYRO3	Tyrosine-protein kinase receptor TYRO3	Gallus gallus (Chicken)	PR
Q9PUF6	PDGFRA	Platelet-derived growth factor receptor alpha	Gallus gallus (Chicken)	SS
Q91009	NTRK1	High affinity nerve growth factor receptor	Gallus gallus (Chicken)	SS
Q07494	EPHB1	Ephrin type-B receptor 1	Gallus gallus (Chicken)	SS
Q07407	htl	Fibroblast growth factor receptor homolog 1	Drosophila melanogaster (Fruit fly)	PR
Q6J9G0	STYK1	Tyrosine-protein kinase STYK1	Homo sapiens (Human)	PR
P36888	FLT3	Receptor-type tyrosine-protein kinase FLT3	Homo sapiens (Human)	EV
P16234	PDGFRA	Platelet-derived growth factor receptor alpha	Homo sapiens (Human)	EV
P09619	PDGFRB	Platelet-derived growth factor receptor beta	Homo sapiens (Human)	EV
P35916	FLT4	Vascular endothelial growth factor receptor 3	Homo sapiens (Human)	SS
P35968	KDR	Vascular endothelial growth factor receptor 2	Homo sapiens (Human)	EV
P17948	FLT1	Vascular endothelial growth factor receptor 1	Homo sapiens (Human)	SS
P07333	CSF1R	Macrophage colony-stimulating factor 1 receptor	Homo sapiens (Human)	SS
P10721	KIT	Mast/stem cell growth factor receptor Kit	Homo sapiens (Human)	EV
P22455	FGFR4	Fibroblast growth factor receptor 4	Homo sapiens (Human)	SS
P22607	FGFR3	Fibroblast growth factor receptor 3	Homo sapiens (Human)	EV
P07949	RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Homo sapiens (Human)	EV
P35590	TIE1	Tyrosine-protein kinase receptor Tie-1	Homo sapiens (Human)	PR
Q02763	TEK	Angiopoietin-1 receptor	Homo sapiens (Human)	SS
P21802	FGFR2	Fibroblast growth factor receptor 2	Homo sapiens (Human)	EV
P11362	FGFR1	Fibroblast growth factor receptor 1	Homo sapiens (Human)	EV
Q03142	Fgfr4	Fibroblast growth factor receptor 4	Mus musculus (Mouse)	PR
P05532	Kit	Mast/stem cell growth factor receptor Kit	Mus musculus (Mouse)	PR
Q91V87	Fgfrl1	Fibroblast growth factor receptor-like 1	Mus musculus (Mouse)	PR
P35917	Flt4	Vascular endothelial growth factor receptor 3	Mus musculus (Mouse)	SS
P05622	Pdgfrb	Platelet-derived growth factor receptor beta	Mus musculus (Mouse)	SS
P09581	Csf1r	Macrophage colony-stimulating factor 1 receptor	Mus musculus (Mouse)	SS
P35969	Flt1	Vascular endothelial growth factor receptor 1	Mus musculus (Mouse)	SS
P35546	Ret	Proto-oncogene tyrosine-protein kinase receptor Ret	Mus musculus (Mouse)	SS
Q06806	Tie1	Tyrosine-protein kinase receptor Tie-1	Mus musculus (Mouse)	SS
Q00342	Flt3	Receptor-type tyrosine-protein kinase FLT3	Mus musculus (Mouse)	SS
Q6J9G1	Styk1	Tyrosine-protein kinase STYK1	Mus musculus (Mouse)	PR
Q61851	Fgfr3	Fibroblast growth factor receptor 3	Mus musculus (Mouse)	PR
Q02858	Tek	Angiopoietin-1 receptor	Mus musculus (Mouse)	SS
P35918	Kdr	Vascular endothelial growth factor receptor 2	Mus musculus (Mouse)	PR
P21803	Fgfr2	Fibroblast growth factor receptor 2	Mus musculus (Mouse)	SS
P26618	Pdgfra	Platelet-derived growth factor receptor alpha	Mus musculus (Mouse)	SS
P16092	Fgfr1	Fibroblast growth factor receptor 1	Mus musculus (Mouse)	SS
Q2HWD6	KIT	Mast/stem cell growth factor receptor Kit	Sus scrofa (Pig)	SS
Q7TQM3	Fgfrl1	Fibroblast growth factor receptor-like 1	Rattus norvegicus (Rat)	PR
P53767	Flt1	Vascular endothelial growth factor receptor 1	Rattus norvegicus (Rat)	PR
P20786	Pdgfra	Platelet-derived growth factor receptor alpha	Rattus norvegicus (Rat)	SS
Q91ZT1	Flt4	Vascular endothelial growth factor receptor 3	Rattus norvegicus (Rat)	SS
G3V9H8	Ret	Proto-oncogene tyrosine-protein kinase receptor Ret	Rattus norvegicus (Rat)	SS
Q498D6	Fgfr4	Fibroblast growth factor receptor 4	Rattus norvegicus (Rat)	PR
Q05030	Pdgfrb	Platelet-derived growth factor receptor beta	Rattus norvegicus (Rat)	SS
O08775	Kdr	Vascular endothelial growth factor receptor 2	Rattus norvegicus (Rat)	SS
Q04589	Fgfr1	Fibroblast growth factor receptor 1	Rattus norvegicus (Rat)	SS
Q17833	old-1	Tyrosine-protein kinase receptor old-1	Caenorhabditis elegans	PR
Q19238	F09A5.2	Putative tyrosine-protein kinase F09A5.2	Caenorhabditis elegans	SS
P34892	kin-16	Receptor-like tyrosine-protein kinase kin-16	Caenorhabditis elegans	PR
G5ED65	ver-1	Protein ver-1	Caenorhabditis elegans	PR
Q10656	egl-15	Myoblast growth factor receptor egl-15	Caenorhabditis elegans	PR
Q8AXB3	kdrl	Vascular endothelial growth factor receptor kdr-like	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q5GIT4	kdr	Vascular endothelial growth factor receptor 2	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
O73791	tek	Angiopoietin-1 receptor	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q8JG38	fgfr2	Fibroblast growth factor receptor 2	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q9I8N6	csf1r	Macrophage colony-stimulating factor 1 receptor	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q90413	fgfr4	Fibroblast growth factor receptor 4	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q9DE49	pdgfra	Platelet-derived growth factor receptor alpha	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q8JFR5	kita	Mast/stem cell growth factor receptor kita	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q5MD89	flt4	Vascular endothelial growth factor receptor 3	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q90Z00	fgfr1a	Fibroblast growth factor receptor 1-A	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MFTWRCLILW	AVLVTATLSA	ARPAPTLPDQ	ALPKANIEVE	SHSAHPGDLL	QLRCRLRDDV
70	80	90	100	110	120
QSINWVRDGV	QLPENNRTRI	TGEEVEVRDA	VPEDSGLYAC	MTNSPSGSET	TYFSVNVSDA
130	140	150	160	170	180
LPSAEDDDDE	DDSSSEEKEA	DNTKPNQAVA	PYWTYPEKME	KKLHAVPAAK	TVKFKCPSGG
190	200	210	220	230	240
TPNPTLRWLK	NGKEFKPDHR	IGGYKVRYAT	WSIIMDSVVP	SDKGNYTCIV	ENKYGSINHT
250	260	270	280	290	300
YQLDVVERSP	HRPILQAGLP	ANKTVALGSN	VEFVCKVYSD	PQPHIQWLKH	IEVNGSKIGP
310	320	330	340	350	360
DNLPYVQILK	TAGVNTTDKE	MEVLHLRNVS	FEDAGEYTCL	AGNSIGISHH	SAWLTVLEAT
370	380	390	400	410	420
EQSPAMMTSP	LYLEIIIYCT	GAFLISCMVV	TVIIYKMKST	TKKTDFNSQL	AVHKLAKSIP
430	440	450	460	470	480
LRRQVTVSAD	SSSSMNSGVM	LVRPSRLSSS	GTPMLAGVSE	YELPEDPRWE	LPRDRLILGK
490	500	510	520	530	540
PLGEGCFGQV	VLAEAIGLDK	DKPNRVTKVA	VKMLKSDATE	KDLSDLISEM	EMMKMIGKHK
550	560	570	580	590	600
NIINLLGACT	QDGPLYVIVE	YASKGNLREY	LQARRPPGME	YCYNPTRIPE	EQLSFKDLVS
610	620	630	640	650	660
CAYQVARGME	YLASKKCIHR	DLAARNVLVT	EDNVMKIADF	GLARDIHHID	YYKKTTNGRL
670	680	690	700	710	720
PVKWMAPEAL	FDRIYTHQSD	VWSFGVLLWE	IFTLGGSPYP	GVPVEELFKL	LKEGHRMDKP
730	740	750	760	770	780
SNCTNELYMM	MRDCWHAVPS	QRPTFKQLVE	DLDRIVAMTS	NQEYLDLSVP	LDQYSPGFPA
790	800	810
TRSSTCSSGE	DSVFSHDPLP	DEPCLPRCPP	HSHGALKRH

Descriptions

Annotation based on sequence homology with P11362

Autoinhibitory domains (AIDs)

Accessory elements

638-663 (Activation loop from InterPro)

638-663 (Activation loop from InterPro)

References

Autoinhibited structure

Activated structure

1 structures for P21804

No variants for P21804

No associated diseases with P21804

18 regional properties for P21804

Functions

5 GO annotations of cellular component

4 GO annotations of molecular function

7 GO annotations of biological process

76 homologous proteins in AiPD