Reviewed, UniProtKB/Swiss-Prot O15520 (FGF10_HUMAN)

Names and origin

Protein names

Recommended name:
    Fibroblast growth factor 10
      Short name(s)=FGF-10
Alternative name(s):
    Keratinocyte growth factor 2

Gene names

Name:

FGF10

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	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	Could be a growth factor active in the process of wound healing. Acts as a mitogen in the lung. May act in a manner similar to FGF-7.
Subunit structure	Interacts with FGFBP1.
Subcellular location	SecretedPotential.
Involvement in disease	Defects in FGF10 are the cause of autosomal dominant aplasia of lacrimal and salivary glands (ALSG) [MIM:180920]. 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. The disorder is characterized by irritable eyes, recurrent eye infections, epiphora (constant tearing) and xerostomia (dryness of the mouth), which increases the risk of dental erosion, dental caries, periodontal disease and oral infections. Defects in FGF10 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome 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.
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
Gene Ontology (GO)
Biological process	fibroblast growth factor receptor signaling pathway Non-traceable author statement. Source: UniProtKB organ morphogenesis Traceable author statement. Source: ProtInc positive regulation of receptor-mediated endocytosis Non-traceable author statement. Source: UniProtKB positive regulation of urothelial cell proliferation Inferred from direct assay. Source: UniProtKB protein import into nucleus, translocation Non-traceable author statement. Source: UniProtKB regulation of transcription Non-traceable author statement. Source: UniProtKB response to stress Non-traceable author statement. Source: UniProtKB
Cellular component	cell surface Non-traceable author statement. Source: UniProtKB extracellular space Ref.1 Traceable author statement. Source: ProtInc nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	fibroblast growth factor receptor binding Inferred from direct assay. Source: UniProtKB growth factor activity Inferred from direct assay. Source: UniProtKB heparin binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FGFR2	P21802	1	EBI-1035684,EBI-1028658

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 37

37

Potential

Chain

38 – 208

171

Fibroblast growth factor 10

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.

Natural variant

156

1

I → R in LADDS.

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)
	O15520-1 [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: 9287324] [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, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A. 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: 15489334] [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: 15806171] [Abstract] Cited for: INTERACTION WITH FGFBP1.
[8]	"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: 12591959] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 69-208 IN COMPLEX WITH FGFR2.
[9]	"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: 15654336] [Abstract] Cited for: INVOLVEMENT IN ALSG.
[10]	"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: 16630169] [Abstract] Cited for: VARIANT LADDS ARG-156.
[11]	"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: 16501574] [Abstract] Cited for: VARIANT LADDS PHE-106.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

RefSeq

NP_004456.1.

UniGene

Hs.664499

3D structure databases

PDBMSD

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

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6037N.

IntAct

O15520.

PTM databases

PhosphoSite

O15520.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000070193. Homo sapiens. [Contig view]

GeneID

2255.

KEGG

hsa:2255.

Organism-specific databases

H-InvDB

HIX0031935.

HGNC

HGNC:3666. FGF10.

HPA

CAB010315.

MIM

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

Orphanet

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

PharmGKB

PA28106.

GenAtlas

Search...

GeneCards

Search...

GeneLynx

Search...

Phylogenomic databases

HOGENOM

O15520.

HOVERGEN

O15520.

Enzyme and pathway databases

Reactome

REACT_9470. Signaling by FGFR.

Gene expression databases

ArrayExpress

O15520.

CleanEx

HS_FGF10.

GermOnline

ENSG00000070193. Homo sapiens.

Family and domain databases

InterPro

IPR002209. GF_heparin_bd.
IPR002348. IL1_HBGF.
[Graphical view]

PANTHER

PTHR11486. IL1_HBGF. 1 hit.

Pfam

PF00167. FGF. 1 hit.
[Graphical view]

PRINTS

PR00263. HBGFFGF.
PR00262. IL1HBGF.

ProDom

PD000831. IL1_HBGF. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00442. FGF. 1 hit.
[Graphical view]

PROSITE

PS00247. HBGF_FGF. 1 hit.
[Graphical view]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

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:	July 22, 2008
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)