Reviewed, UniProtKB/Swiss-Prot P11362 (FGFR1_HUMAN)

Names and origin

Protein names

Recommended name:
    Basic fibroblast growth factor receptor 1
      Short name=FGFR-1
      Short name=bFGF-R
    EC=2.7.10.1
Alternative name(s):
    Fms-like tyrosine kinase 2
    c-fgr
    CD_antigen=CD331

Gene names

Name:	FGFR1
Synonyms:	FGFBR, FLG, FLT2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	822 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for basic fibroblast growth factor. A shorter form of the receptor could be a receptor for FGF1 (aFGF).
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with SHB. Interacts with KLB By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Binding of FGF1 and heparin promotes autophosphorylation on tyrosine residues and activation of the receptor.
Involvement in disease	Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly. Defects in FGFR1 are a cause of isolated hypogonadotropic hypogonadism (IHH) [MIM:146110]. Hypogonadism is a condition characterized by abnormally decreased gonadal function, with retardation of growth and sexual development. Hypogonadotropic hypogonadism is due to inadequate secretion of gonadotropins. It results from failure to release sufficient gonadotropin-releasing hormone. Defects in FGFR1 are the cause of Kallmann syndrome type 2 (KAL2) [MIM:147950]; also known as hypogonadotropic hypogonadism and anosmia. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In some cases, midline cranial anomalies (cleft lip/palate and imperfect fusion) are present and anosmia may be absent or inconspicuous. Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:166250]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant. Defects in FGFR1 are the cause of non-syndromic trigonocephaly [MIM:190440]; also known as metopic craniosynostosis. The term trigonocephaly describes the typical keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome. A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow. A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Craniosynostosis Disease mutation Dwarfism Kallmann syndrome
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Heparin-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	MAPKKK cascade Traceable author statement. Source: ProtInc cell growth Non-traceable author statement. Source: UniProtKB fibroblast growth factor receptor signaling pathway Ref.1 Non-traceable author statement. Source: UniProtKB protein amino acid phosphorylation Ref.1 Ref.4 Non-traceable author statement. Source: UniProtKB skeletal system development Ref.31 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB fibroblast growth factor receptor activity Ref.1 Ref.4 Ref.7 Traceable author statement. Source: UniProtKB heparin binding Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDH1	P12830	1	EBI-1028277,EBI-727477
CTNNB1	P35222	1	EBI-1028277,EBI-491549

Alternative products

This entry describes 18 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11362-1)

Also known as: Alpha A1; IV;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P11362-8)

Also known as: Alpha A2;

The sequence of this isoform differs from the canonical sequence as follows:
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Isoform 3 (identifier: P11362-17)

Also known as: Alpha A3;

The sequence of this isoform differs from the canonical sequence as follows:
     32-61: QPWGAPVEVESFLVHPGDLLQLRCRLRDDV → CPDLQEAKSCSASFHSITPLPFGLGTRLSD
     62-822: Missing.

Isoform 4 (identifier: P11362-2)

Also known as: Alpha B1;

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

Isoform 5 (identifier: P11362-9)

Also known as: Alpha B2;

The sequence of this isoform differs from the canonical sequence as follows:
     428-429: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Isoform 6 (identifier: P11362-3)

Also known as: Beta A1; II; H2;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.

Isoform 7 (identifier: P11362-10)

Also known as: Beta A2;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Isoform 8 (identifier: P11362-4)

Also known as: Beta B1;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     428-429: Missing.

Isoform 9 (identifier: P11362-11)

Also known as: Beta B2;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     428-429: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Isoform 10 (identifier: P11362-5)

Also known as: Gamma A1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.

Isoform 11 (identifier: P11362-12)

Also known as: Gamma A2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Isoform 12 (identifier: P11362-6)

Also known as: Gamma B1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     428-429: Missing.

Isoform 13 (identifier: P11362-13)

Also known as: Gamma B2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     428-429: Missing.
     619-662: CIHRDLAARN...YYKKTTNGRL → VWNLKAPLVH...RTGHSPHRLL
     663-822: Missing.

Isoform 14 (identifier: P11362-7)

Also known as: A; III;

The sequence of this isoform differs from the canonical sequence as follows:
     148-149: Missing.

Isoform 15 (identifier: P11362-14)

Also known as: I; H3;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     148-149: Missing.

Isoform 16 (identifier: P11362-15)

Also known as: V;

The sequence of this isoform differs from the canonical sequence as follows:
     120-150: DALPSSEDDDDDDDSSSEEKETDNTKPNRMP → ACPDLQEAKWCSASFHSITPLPFGLGTRLSD
     151-822: Missing.

Isoform 17 (identifier: P11362-16)

Also known as: H4;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     313-391: TAGVNTTDKE...TGAFLISCMV → VIMAPVFVGQ...RAAGMGGAGL
     392-822: Missing.

Isoform 18 (identifier: P11362-18)

Also known as: H5;

The sequence of this isoform differs from the canonical sequence as follows:
     31-119: Missing.
     148-149: Missing.
     313-391: TAGVNTTDKE...TGAFLISCMV → VIMAPVFVGQ...RAAGMGGAGL
     392-822: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 822	801	Basic fibroblast growth factor receptor 1		PRO_0000016780
Regions
	Topological domain	22 – 376	355	Extracellular Potential
	Transmembrane	377 – 397	21	Potential
	Topological domain	398 – 822	425	Cytoplasmic Potential
	Domain	25 – 119	95	Ig-like C2-type 1
	Domain	158 – 246	89	Ig-like C2-type 2
	Domain	255 – 357	103	Ig-like C2-type 3
	Domain	478 – 767	290	Protein kinase
	Nucleotide binding	484 – 492	9	ATP By similarity
	Region	160 – 177	18	Heparin-binding
Sites
	Active site	623	1	Proton acceptor By similarity
	Binding site	514	1	ATP By similarity
	Site	428 – 429	2	Breakpoint for translocation to form CEP110-FGFR1 OR FGFR1-CEP110 fusion proteins
	Site	428 – 429	2	Breakpoint for translocation to form FGFR1OP-FGFR1 or FGFR1-FGFR1OP fusion proteins
	Site	428 – 429	2	Breakpoint for translocation to form FGFR1OP2-FGFR1
	Site	766	1	Mediates interaction with PLC-gamma and SHB
Amino acid modifications
	Modified residue	653	1	Phosphotyrosine
	Modified residue	654	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	766	1	Phosphotyrosine; by autocatalysis
	Glycosylation	77	1	N-linked (GlcNAc...) Potential
	Glycosylation	117	1	N-linked (GlcNAc...) Potential
	Glycosylation	227	1	N-linked (GlcNAc...) Potential
	Glycosylation	240	1	N-linked (GlcNAc...) Potential
	Glycosylation	264	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...)
	Glycosylation	317	1	N-linked (GlcNAc...) Potential
	Glycosylation	330	1	N-linked (GlcNAc...) Potential
	Disulfide bond	55 ↔ 101		Potential
	Disulfide bond	178 ↔ 230		Potential
	Disulfide bond	277 ↔ 341		Potential
Natural variations
	Alternative sequence	1 – 160	160	Missing in isoform 10, isoform 11, isoform 12 and isoform 13.		VSP_002957
	Alternative sequence	31 – 119	89	Missing in isoform 6, isoform 7, isoform 8, isoform 9, isoform 15, isoform 17 and isoform 18.		VSP_002958
	Alternative sequence	32 – 61	30	QPWGA…LRDDV → CPDLQEAKSCSASFHSITPL PFGLGTRLSD in isoform 3.		VSP_009836
	Alternative sequence	62 – 822	761	Missing in isoform 3.		VSP_009837
	Alternative sequence	120 – 150	31	DALPS…PNRMP → ACPDLQEAKWCSASFHSITP LPFGLGTRLSD in isoform 16.		VSP_009838
	Alternative sequence	148 – 149	2	Missing in isoform 14, isoform 15 and isoform 18.		VSP_002959
	Alternative sequence	151 – 822	672	Missing in isoform 16.		VSP_009839
	Alternative sequence	313 – 391	79	TAGVN…ISCMV → VIMAPVFVGQSTGKETTVSG AQVPVGRLSCPRMGSFLTLQ AHTLHLSRDLATSPRTSNRG HKVEVSWEQRAAGMGGAGL in isoform 17 and isoform 18.		VSP_009840
	Alternative sequence	392 – 822	431	Missing in isoform 17 and isoform 18.		VSP_009841
	Alternative sequence	428 – 429	2	Missing in isoform 4, isoform 5, isoform 8, isoform 9, isoform 12 and isoform 13.		VSP_002960
	Alternative sequence	619 – 662	44	CIHRD…TNGRL → VWNLKAPLVHTPRPGSQECP GDRGQCDEDSRLWPRTGHSP HRLL in isoform 2, isoform 5, isoform 7, isoform 9, isoform 11 and isoform 13.		VSP_009842
	Alternative sequence	663 – 822	160	Missing in isoform 2, isoform 5, isoform 7, isoform 9, isoform 11 and isoform 13.		VSP_009843
	Natural variant	22	1	R → S: dbSNP rs17175750.		VAR_019290
	Natural variant	48	1	G → S in IHH.		VAR_030968
	Natural variant	77	1	N → K		VAR_030969
	Natural variant	78	1	R → C in KAL2.		VAR_030970
	Natural variant	97	1	G → D in KAL2.		VAR_017885
	Natural variant	99	1	Y → C in KAL2.		VAR_017886
	Natural variant	101	1	C → F in KAL2.		VAR_030971
	Natural variant	102	1	V → I in KAL2.		VAR_030972
	Natural variant	125	1	S → L in a breast infiltrating ductal carcinoma sample; somatic mutation.		VAR_042201
	Natural variant	129	1	D → A in KAL2.		VAR_030973
	Natural variant	167	1	A → S in KAL2; with cleft palate, corpus callosum agenesis, unilateral deafness and fusion of fourth and fifth metacarpal bones.		VAR_017887
	Natural variant	178	1	C → S in KAL2; with severe ear anomalies.		VAR_030974
	Natural variant	213	1	W → G: dbSNP rs17851623.		VAR_030975
	Natural variant	224	1	D → H in KAL2.		VAR_030976
	Natural variant	237	1	G → D in KAL2.		VAR_030977
	Natural variant	237	1	G → S in IHH/KAL2; also found in a family member with isolated anosmia; may impair proper folding.		VAR_030978
	Natural variant	245	1	L → P in KAL2.		VAR_030979
	Natural variant	250	1	R → W in KAL2.		VAR_030980
	Natural variant	252	1	P → R in PS; seems to be a gain of function.		VAR_004111
	Natural variant	252	1	P → T in a lung bronchoalveolar carcinoma sample; somatic mutation.		VAR_042202
	Natural variant	254	1	R → Q in KAL2.		VAR_030981
	Natural variant	270	1	G → D in KAL2.		VAR_030982
	Natural variant	273	1	V → M in KAL2.		VAR_030983
	Natural variant	274	1	E → G in KAL2; also found in a family member with isolated anosmia.		VAR_030984
	Natural variant	277	1	C → Y in KAL2.		VAR_017888
	Natural variant	283	1	P → R in KAL2.