O15520 (FGF10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor 10
Short name=FGF-10

Alternative name(s):
Keratinocyte growth factor 2

Gene names

Name:

FGF10

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	208 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	Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. May play a role in wound healing. Ref.8
Subunit structure	Interacts with FGFR1 and FGFR2. Interacts with FGFBP1. Ref.7 Ref.8
Subcellular location	Secreted Potential.
Involvement in disease	Aplasia of lacrimal and salivary glands (ALSG) [MIM:180920]: A rare condition characterized by dry conjunctival mucosae, irritable eyes, epiphora (constant tearing), and xerostomia (dryness of the mouth), which increases risk of dental erosion, dental caries, periodontal disease, and oral infections. ALSG has variable expressivity, and affected individuals may have aplasia or hypoplasia of the lacrimal, parotid, submandibular, and sublingual glands and absence of the lacrimal puncta. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]: An autosomal dominant ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Lacrimo-auriculo-dento-digital syndrome is characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13
Sequence similarities	Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
Cellular component	Secreted
Disease	Disease mutation Ectodermal dysplasia Lacrimo-auriculo-dento-digital syndrome
Domain	Signal
Molecular function	Growth factor
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ERK1 and ERK2 cascade Inferred from direct assay PubMed 17959718. Source: UniProtKB Harderian gland development Inferred from electronic annotation. Source: Compara Type II pneumocyte differentiation Inferred from electronic annotation. Source: Compara actin cytoskeleton reorganization Inferred from direct assay PubMed 17449030. Source: UniProtKB activation of MAPK activity Inferred from direct assay PubMed 14975937. Source: UniProtKB angiogenesis Inferred from electronic annotation. Source: Compara blood vessel remodeling Inferred from electronic annotation. Source: Compara branch elongation involved in salivary gland morphogenesis Inferred from electronic annotation. Source: Compara bronchiole morphogenesis Inferred from electronic annotation. Source: Compara bud outgrowth involved in lung branching Inferred from direct assay PubMed 9740653. Source: MGI determination of left/right symmetry Inferred from electronic annotation. Source: Compara embryonic camera-type eye development Inferred from electronic annotation. Source: Compara embryonic digestive tract morphogenesis Inferred from electronic annotation. Source: Compara embryonic genitalia morphogenesis Inferred from electronic annotation. Source: Compara embryonic pattern specification Inferred from electronic annotation. Source: Compara epithelial cell migration Inferred from electronic annotation. Source: Compara epithelial cell proliferation involved in salivary gland morphogenesis Inferred from electronic annotation. Source: Compara female genitalia morphogenesis Inferred from electronic annotation. Source: Compara fibroblast growth factor receptor signaling pathway involved in mammary gland specification Inferred from direct assay PubMed 11923311. Source: MGI hair follicle morphogenesis Inferred from electronic annotation. Source: Compara induction of positive chemotaxis Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Traceable author statement. Source: Reactome keratinocyte proliferation Inferred from electronic annotation. Source: Compara lacrimal gland development Inferred from mutant phenotype PubMed 17213838. Source: UniProtKB limb bud formation Inferred from electronic annotation. Source: Compara lung epithelium development Inferred from direct assay PubMed 9740653. Source: MGI lung proximal/distal axis specification Inferred from electronic annotation. Source: Compara lung saccule development Inferred from mutant phenotype PubMed 17071719. Source: UniProtKB male genitalia morphogenesis Inferred from electronic annotation. Source: Compara mammary gland bud formation Inferred from electronic annotation. Source: Compara mesenchymal cell differentiation involved in lung development Inferred from electronic annotation. Source: Compara mesenchymal-epithelial cell signaling involved in lung development Inferred from electronic annotation. Source: Compara mesonephros development Inferred from expression pattern PubMed 18437684. Source: UniProtKB metanephros development Inferred from expression pattern PubMed 18437684. Source: UniProtKB metanephros morphogenesis Inferred from electronic annotation. Source: Compara muscle cell fate commitment Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cell cycle arrest Inferred from direct assay PubMed 17188682. Source: UniProtKB negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara organ induction Inferred from electronic annotation. Source: Compara otic vesicle formation Inferred from electronic annotation. Source: Compara pancreas development Inferred from electronic annotation. Source: Compara pituitary gland development Inferred from electronic annotation. Source: Compara positive regulation of ATPase activity Inferred from direct assay PubMed 12804770. Source: UniProtKB positive regulation of DNA repair Inferred from direct assay PubMed 14975937. Source: UniProtKB positive regulation of DNA replication Inferred from mutant phenotype PubMed 17471512. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 14975937. Source: UniProtKB positive regulation of Notch signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of Ras protein signal transduction Inferred from direct assay PubMed 12804770. Source: UniProtKB positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S Inferred from direct assay PubMed 17188682. Source: UniProtKB positive regulation of epithelial cell migration Inferred from direct assay PubMed 17500053. Source: UniProtKB positive regulation of epithelial cell proliferation involved in wound healing Non-traceable author statement PubMed 19152659. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of hair follicle cell proliferation Inferred from direct assay PubMed 16086254. Source: UniProtKB positive regulation of keratinocyte migration Inferred from direct assay PubMed 17449030PubMed 19152659. Source: UniProtKB positive regulation of keratinocyte proliferation Inferred from direct assay PubMed 17449030. Source: UniProtKB positive regulation of lymphocyte proliferation Inferred from direct assay PubMed 19152659. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 17449030. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 17500053. Source: UniProtKB positive regulation of urothelial cell proliferation Inferred from direct assay PubMed 11923311. Source: UniProtKB positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of white fat cell proliferation Inferred from electronic annotation. Source: Compara protein localization to cell surface Inferred from direct assay PubMed 17449030. Source: UniProtKB radial glial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of activin receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Inferred from electronic annotation. Source: Compara regulation of prostatic bud formation Inferred from electronic annotation. Source: Compara regulation of saliva secretion Inferred from mutant phenotype PubMed 19102732. Source: UniProtKB regulation of smoothened signaling pathway Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara salivary gland development Inferred from mutant phenotype PubMed 17213838. Source: UniProtKB secretion by lung epithelial cell involved in lung growth Inferred from direct assay PubMed 10541313. Source: UniProtKB semicircular canal fusion Inferred from electronic annotation. Source: Compara smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara somatic stem cell maintenance Inferred from electronic annotation. Source: Compara spleen development Inferred from electronic annotation. Source: Compara submandibular salivary gland formation Inferred from electronic annotation. Source: Compara tear secretion Inferred from mutant phenotype PubMed 19102732. Source: UniProtKB thymus development Inferred from direct assay PubMed 17969154. Source: UniProtKB thyroid gland development Inferred from electronic annotation. Source: Compara tissue regeneration Inferred from electronic annotation. Source: Compara urothelial cell proliferation Inferred from direct assay PubMed 11923311. Source: UniProtKB white fat cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from direct assay PubMed 16597614. Source: UniProtKB extracellular space Inferred from direct assay PubMed 16597614. Source: UniProtKB nucleus Inferred from direct assay PubMed 11923311PubMed 16597614PubMed 17471512. Source: UniProtKB plasma membrane Inferred from direct assay PubMed 16597614. Source: UniProtKB
Molecular_function	chemoattractant activity Inferred from direct assay PubMed 17449030. Source: UniProtKB fibroblast growth factor receptor binding Inferred from direct assay PubMed 11923311. Source: UniProtKB growth factor activity Inferred from direct assay PubMed 11923311PubMed 15690149. Source: UniProtKB heparin binding Inferred from direct assay PubMed 11923311. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 37

37

Potential

Chain

38 – 208

171

Fibroblast growth factor 10

PRO_0000008981

Regions

Compositional bias

52 – 62

11

Poly-Ser

Amino acid modifications

Glycosylation

51

1

N-linked (GlcNAc...) Potential

Glycosylation

196

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

106

1

C → F in LADDS. Ref.13

VAR_029888

Natural variant

156

1

I → R in LADDS. Ref.12

VAR_029889

Experimental info

Sequence conflict

120

1

V → A in AAL05875. Ref.3

Sequence conflict

134

1

M → R in AAL05875. Ref.3

Secondary structure

1

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208

Helix Strand Turn

Details...

Helix

70 – 73

4

Beta strand

76 – 84

9

Beta strand

89 – 92

4

Beta strand

98 – 101

4

Beta strand

111 – 117

7

Beta strand

120 – 125

6

Turn

126 – 129

4

Beta strand

130 – 134

5

Beta strand

138 – 145

8

Beta strand

150 – 156

7

Beta strand

162 – 171

10

Beta strand

174 – 177

4

Helix

189 – 191

3

Helix

197 – 199

3

Beta strand

201 – 205

5

Sequences

	Sequence		Length	Mass (Da)
	O15520 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: C0A0705C108680B3	FASTA	208	23,436
	10 20 30 40 50 60 MWKWILTHCA SAFPHLPGCC CCCFLLLFLV SSVPVTCQAL GQDMVSPEAT NSSSSSFSSP 70 80 90 100 110 120 SSAGRHVRSY NHLQGDVRWR KLFSFTKYFL KIEKNGKVSG TKKENCPYSI LEITSVEIGV 130 140 150 160 170 180 VAVKAINSNY YLAMNKKGKL YGSKEFNNDC KLKERIEENG YNTYASFNWQ HNGRQMYVAL 190 200 NGKGAPRRGQ KTRRKNTSAH FLPMVVHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and expression of human fibroblast growth factor-10." Emoto H., Tagashira S., Mattei M.-G., Yamasaki M., Hashimoto G., Katsumata T., Negoro T., Nakatsuka M., Birnbaum D., Coulier F., Itoh N. J. Biol. Chem. 272:23191-23194(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Cutaneous wound healing by keratinocyte growth factor 2." Jimenez P.A., Gruber J.R., Liu B., Feng P., Florence C., Blunt A., Huddleston K.A., Teliska M., Alfonso P., Coleman T.A., Ornitz D.M., Dillon P.A., Duan R.D. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[3]	Zhang Y., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"The fibroblast growth factor binding protein is a novel interaction partner of FGF-7, FGF-10 and FGF-22 and regulates FGF activity: implications for epithelial repair." Beer H.-D., Bittner M., Niklaus G., Munding C., Max N., Goppelt A., Werner S. Oncogene 24:5269-5277(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGFBP1.
[8]	"Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family." Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M. J. Biol. Chem. 281:15694-15700(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGFR1 AND FGFR2, FUNCTION IN STIMULATION OF CELL PROLIFERATION.
[9]	"Fibroblast growth factor signalling: from development to cancer." Turner N., Grose R. Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors." Yeh B.K., Igarashi M., Eliseenkova A.V., Plotnikov A.N., Sher I., Ron D., Aaronson S.A., Mohammadi M. Proc. Natl. Acad. Sci. U.S.A. 100:2266-2271(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 69-208 IN COMPLEX WITH FGFR2.
[11]	"Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands." Entesarian M., Matsson H., Klar J., Bergendal B., Olson L., Arakaki R., Hayashi Y., Ohuchi H., Falahat B., Bolstad A.I., Jonsson R., Wahren-Herlenius M., Dahl N. Nat. Genet. 37:125-127(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ALSG.
[12]	"LADD syndrome is caused by FGF10 mutations." Milunsky J.M., Zhao G., Maher T.A., Colby R., Everman D.B. Clin. Genet. 69:349-354(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LADDS ARG-156.
[13]	"Mutations in different components of FGF signaling in LADD syndrome." Rohmann E., Brunner H.G., Kayserili H., Uyguner O., Nuernberg G., Lew E.D., Dobbie A., Eswarakumar V.P., Uzumcu A., Ulubil-Emeroglu M., Leroy J.G., Li Y., Becker C., Lehnerdt K., Cremers C.W.R.J., Yueksel-Apak M., Nuernberg P., Kubisch C. , Schlessinger J., van Bokhoven H., Wollnik B. Nat. Genet. 38:414-417(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LADDS PHE-106.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB002097 mRNA. Translation: BAA22331.1.
U67918 mRNA. Translation: AAB61991.1.
AF411527 mRNA. Translation: AAL05875.1.
CR541665 mRNA. Translation: CAG46466.1.
AY604046 Genomic DNA. Translation: AAS99733.1.
BC069561 mRNA. Translation: AAH69561.1.
BC105021 mRNA. Translation: AAI05022.1.
BC105023 mRNA. Translation: AAI05024.1.

IPI

IPI00007307.

RefSeq

NP_004456.1. NM_004465.1.

UniGene

Hs.664499.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NUN	X-ray	2.90	A	64-208	[»]

ProteinModelPortal

O15520.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6037N.

IntAct

O15520. 1 interaction.

MINT

MINT-257957.

STRING

9606.ENSP00000264664.

PTM databases

PhosphoSite

O15520.

Proteomic databases

PaxDb

O15520.

PRIDE

O15520.

Protocols and materials databases

DNASU

2255.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264664; ENSP00000264664; ENSG00000070193.

GeneID

2255.

KEGG

hsa:2255.

UCSC

uc003jog.1. human.

Organism-specific databases

CTD

2255.

GeneCards

GC05M044340.

HGNC

HGNC:3666. FGF10.

HPA

CAB010315.

MIM

149730. phenotype.
180920. phenotype.
602115. gene.

neXtProt

NX_O15520.

Orphanet

86815. Aplasia of lacrimal and salivary glands.
2363. Lacrimo-auriculo-dento-digital syndrome.

PharmGKB

PA28106.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG327524.

HOGENOM

HOG000236341.

HOVERGEN

HBG007580.

InParanoid

O15520.

KO

K04358.

OMA

GSKEFNT.

OrthoDB

EOG4DZ1WH.

PhylomeDB

O15520.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O15520.

Bgee

O15520.

CleanEx

HS_FGF10.

Genevestigator

O15520.

GermOnline

ENSG00000070193. Homo sapiens.

Family and domain databases

InterPro

IPR008996. Cytokine_IL1-like.
IPR002209. GF_heparin-bd.
IPR002348. IL1_HBGF.
[Graphical view]

PANTHER

PTHR11486. PTHR11486. 1 hit.

Pfam

PF00167. FGF. 1 hit.
[Graphical view]

PRINTS

PR00263. HBGFFGF.
PR00262. IL1HBGF.

SMART

SM00442. FGF. 1 hit.
[Graphical view]

SUPFAM

SSF50353. Cytok_IL1_like. 1 hit.

PROSITE

PS00247. HBGF_FGF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O15520.

GenomeRNAi

2255.

NextBio

9135.

SOURCE

Search...

Entry information

Entry name

FGF10_HUMAN

Accession

Primary (citable) accession number: O15520
Secondary accession number(s): Q6FHT6, Q96P59

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.