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Reviewed, UniProtKB/Swiss-Prot P11362 (FGFR1_HUMAN)

Last modified November 4, 2008. Version 130. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length822 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Binary interactions

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 822801Basic fibroblast growth factor receptor 1
PRO_0000016780

Regions

Topological domain22 – 376355Extracellular Potential
Transmembrane377 – 39721 Potential
Topological domain398 – 822425Cytoplasmic Potential
Domain25 – 11995Ig-like C2-type 1
Domain158 – 24689Ig-like C2-type 2
Domain255 – 357103Ig-like C2-type 3
Domain478 – 767290Protein kinase
Nucleotide binding484 – 4929ATP By similarity
Region160 – 17718Heparin-binding

Sites

Active site6231Proton acceptor By similarity
Binding site5141ATP By similarity
Site428 – 4292Breakpoint for translocation to form CEP110-FGFR1 OR FGFR1-CEP110 fusion proteins
Site428 – 4292Breakpoint for translocation to form FGFR1OP-FGFR1 or FGFR1-FGFR1OP fusion proteins
Site428 – 4292Breakpoint for translocation to form FGFR1OP2-FGFR1
Site7661Mediates interaction with PLC-gamma and SHB

Amino acid modifications

Modified residue6531Phosphotyrosine
Modified residue6541Phosphotyrosine; by autocatalysis By similarity
Modified residue7661Phosphotyrosine; by autocatalysis
Glycosylation771N-linked (GlcNAc...) Potential
Glycosylation1171N-linked (GlcNAc...) Potential
Glycosylation2271N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Glycosylation2641N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...)
Glycosylation3171N-linked (GlcNAc...) Potential
Glycosylation3301N-linked (GlcNAc...) Potential
Disulfide bond55 ↔ 101 Potential
Disulfide bond178 ↔ 230 Potential
Disulfide bond277 ↔ 341 Potential

Natural variations

Alternative sequence1 – 160160Missing in isoform 10, isoform 11, isoform 12 and isoform 13.
VSP_002957
Alternative sequence31 – 11989Missing in isoform 6, isoform 7, isoform 8, isoform 9, isoform 15, isoform 17 and isoform 18.
VSP_002958
Alternative sequence32 – 6130QPWGA…LRDDV → CPDLQEAKSCSASFHSITPL PFGLGTRLSD in isoform 3.
VSP_009836
Alternative sequence62 – 822761Missing in isoform 3.
VSP_009837
Alternative sequence120 – 15031DALPS…PNRMP → ACPDLQEAKWCSASFHSITP LPFGLGTRLSD in isoform 16.
VSP_009838
Alternative sequence148 – 1492Missing in isoform 14, isoform 15 and isoform 18.
VSP_002959
Alternative sequence151 – 822672Missing in isoform 16.
VSP_009839
Alternative sequence313 – 39179TAGVN…ISCMV → VIMAPVFVGQSTGKETTVSG AQVPVGRLSCPRMGSFLTLQ AHTLHLSRDLATSPRTSNRG HKVEVSWEQRAAGMGGAGL in isoform 17 and isoform 18.
VSP_009840
Alternative sequence392 – 822431Missing in isoform 17 and isoform 18.
VSP_009841
Alternative sequence428 – 4292Missing in isoform 4, isoform 5, isoform 8, isoform 9, isoform 12 and isoform 13.
VSP_002960
Alternative sequence619 – 66244CIHRD…TNGRL → VWNLKAPLVHTPRPGSQECP GDRGQCDEDSRLWPRTGHSP HRLL in isoform 2, isoform 5, isoform 7, isoform 9, isoform 11 and isoform 13.
VSP_009842
Alternative sequence663 – 822160Missing in isoform 2, isoform 5, isoform 7, isoform 9, isoform 11 and isoform 13.
VSP_009843
Natural variant221R → S: dbSNP rs17175750.
VAR_019290
Natural variant481G → S in IHH.
VAR_030968
Natural variant771N → K
VAR_030969
Natural variant781R → C in KAL2.
VAR_030970
Natural variant971G → D in KAL2.
VAR_017885
Natural variant991Y → C in KAL2.
VAR_017886
Natural variant1011C → F in KAL2.
VAR_030971
Natural variant1021V → I in KAL2.
VAR_030972
Natural variant1251S → L in a breast infiltrating ductal carcinoma sample; somatic mutation.
VAR_042201
Natural variant1291D → A in KAL2.
VAR_030973
Natural variant1671A → S in KAL2; with cleft palate, corpus callosum agenesis, unilateral deafness and fusion of fourth and fifth metacarpal bones.
VAR_017887
Natural variant1781C → S in KAL2; with severe ear anomalies.
VAR_030974
Natural variant2131W → G: dbSNP rs17851623.
VAR_030975
Natural variant2241D → H in KAL2.
VAR_030976
Natural variant2371G → D in KAL2.
VAR_030977
Natural variant2371G → S in IHH/KAL2; also found in a family member with isolated anosmia; may impair proper folding.
VAR_030978
Natural variant2451L → P in KAL2.
VAR_030979
Natural variant2501R → W in KAL2.
VAR_030980
Natural variant2521P → R in PS; seems to be a gain of function.
VAR_004111
Natural variant2521P → T in a lung bronchoalveolar carcinoma sample; somatic mutation.
VAR_042202
Natural variant2541R → Q in KAL2.
VAR_030981
Natural variant2701G → D in KAL2.
VAR_030982
Natural variant2731V → M in KAL2.
VAR_030983
Natural variant2741E → G in KAL2; also found in a family member with isolated anosmia.
VAR_030984
Natural variant2771C → Y in KAL2.
VAR_017888
Natural variant2831P → R in KAL2.