Reviewed, UniProtKB/Swiss-Prot P55075 (FGF8_HUMAN)

Names and origin

Protein names

Recommended name:
    Fibroblast growth factor 8
      Short name=FGF-8
Alternative name(s):
    Heparin-binding growth factor 8
      Short name=HBGF-8
    Androgen-induced growth factor
      Short name=AIGF

Gene names

Name:	FGF8
Synonyms:	AIGF

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	233 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	Stimulates growth of the cells in an autocrine manner. Mediates hormonal action on the growth of cancer cells.
Subcellular location	Secreted.
Developmental stage	In adults expression is restricted to the gonads.
Involvement in disease	Defects in FGF8 are the cause of Kallmann syndrome type 6 (KAL6) [MIM:612702]. Kallmann syndrome is a disorder that associates 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 patients other developmental anomalies can be present, which include renal agenesis, cleft lip and/or palate, selective tooth agenesis, and bimanual synkinesis. In some cases anosmia may be absent or inconspicuous. Ref.9 Defects in FGF8 are a cause of idiopathic hypogonadotropic hypogonadism (IHH) [MIM:146110]. IHH is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. Ref.9
Sequence similarities	Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Hypogonadotropic hypogonadism Kallmann syndrome
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	bone development Ref.9 Inferred from mutant phenotype. Source: UniProtKB cell proliferation Non-traceable author statement. Source: UniProtKB fibroblast growth factor receptor signaling pathway Inferred from genetic interaction. Source: MGI gastrulation Ref.4 Traceable author statement. Source: ProtInc gonad development Ref.9 Inferred from mutant phenotype. Source: UniProtKB mesonephros development Inferred from expression pattern. Source: UniProtKB metanephros development Inferred from expression pattern. Source: UniProtKB positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from Experiment. Source: Reactome
Molecular function	growth factor activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform FGF-8E (identifier: P55075-1)

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 FGF-8A (identifier: P55075-2)

The sequence of this isoform differs from the canonical sequence as follows:
     24-52: Missing.

Isoform FGF-8B (identifier: P55075-3)

The sequence of this isoform differs from the canonical sequence as follows:
     24-51: EGPGRGPALGRELASLFRAGREPQGVSQ → VTVQSSPNFT

Isoform FGF-8F (identifier: P55075-4)

The sequence of this isoform differs from the canonical sequence as follows:
     52-52: Q → QVTVQSSPNFTQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 233

211

Fibroblast growth factor 8

PRO_0000008970

Amino acid modifications

Glycosylation

155

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

24 – 52

29

Missing in isoform FGF-8A.

VSP_001525

Alternative sequence

24 – 51

28

EGPGR…QGVSQ → VTVQSSPNFT in isoform FGF-8B.

VSP_001524

Alternative sequence

52

1

Q → QVTVQSSPNFTQ in isoform FGF-8F.

VSP_001526

Natural variant

14

1

H → N in IHH. Ref.9

VAR_057962

Natural variant

26

1

P → L in KAL6. Ref.9

VAR_057963

Natural variant

40

1

F → L in IHH. Ref.9

VAR_057964

Natural variant

89

1

K → E in IHH. Ref.9

VAR_057965

Natural variant

116

1

R → G in KAL6. Ref.9

VAR_057966

Natural variant

218

1

T → M in IHH. Ref.9

VAR_057967

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

233

Helix Strand Turn

Details...

Helix

52 – 57

6

Beta strand

63 – 65

3

Beta strand

69 – 76

8

Turn

77 – 79

3

Beta strand

80 – 85

6

Beta strand

91 – 95

5

Helix

100 – 102

3

Beta strand

104 – 110

7

Turn

111 – 113

3

Beta strand

114 – 119

6

Turn

120 – 122

3

Beta strand

125 – 128

4

Beta strand

134 – 138

5

Helix

143 – 145

3

Beta strand

146 – 151

6

Beta strand

157 – 164

8

Helix

180 – 182

3

Helix

188 – 190

3

Beta strand

192 – 195

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform FGF-8E [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 4C1EAF932A3A211D	FASTA	233	26,525
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQEGPGRGP ALGRELASLF RAGREPQGVS QQHVREQSLV 70 80 90 100 110 120 TDQLSRRLIR TYQLYSRTSG KHVQVLANKR INAMAEDGDP FAKLIVETDT FGSRVRVRGA 130 140 150 160 170 180 ETGLYICMNK KGKLIAKSNG KGKDCVFTEI VLENNYTALQ NAKYEGWYMA FTRKGRPRKG 190 200 210 220 230 SKTRQHQREV HFMKRLPRGH HTTEQSLRFE FLNYPPFTRS LRGSQRTWAP EPR
	Isoform FGF-8A. Checksum: 9A4CAB7686A2B190	FASTA	204	23,522
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQHVREQSL VTDQLSRRLI RTYQLYSRTS GKHVQVLANK 70 80 90 100 110 120 RINAMAEDGD PFAKLIVETD TFGSRVRVRG AETGLYICMN KKGKLIAKSN GKGKDCVFTE 130 140 150 160 170 180 IVLENNYTAL QNAKYEGWYM AFTRKGRPRK GSKTRQHQRE VHFMKRLPRG HHTTEQSLRF 190 200 EFLNYPPFTR SLRGSQRTWA PEPR
	Isoform FGF-8B. Checksum: A39424271EF7CBFF	FASTA	215	24,711
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQVTVQSSP NFTQHVREQS LVTDQLSRRL IRTYQLYSRT 70 80 90 100 110 120 SGKHVQVLAN KRINAMAEDG DPFAKLIVET DTFGSRVRVR GAETGLYICM NKKGKLIAKS 130 140 150 160 170 180 NGKGKDCVFT EIVLENNYTA LQNAKYEGWY MAFTRKGRPR KGSKTRQHQR EVHFMKRLPR 190 200 210 GHHTTEQSLR FEFLNYPPFT RSLRGSQRTW APEPR
	Isoform FGF-8F. Checksum: 73DA5874CA918E6A	FASTA	244	27,715
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQEGPGRGP ALGRELASLF RAGREPQGVS QQVTVQSSPN 70 80 90 100 110 120 FTQHVREQSL VTDQLSRRLI RTYQLYSRTS GKHVQVLANK RINAMAEDGD PFAKLIVETD 130 140 150 160 170 180 TFGSRVRVRG AETGLYICMN KKGKLIAKSN GKGKDCVFTE IVLENNYTAL QNAKYEGWYM 190 200 210 220 230 240 AFTRKGRPRK GSKTRQHQRE VHFMKRLPRG HHTTEQSLRF EFLNYPPFTR SLRGSQRTWA PEPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human androgen-induced growth factor in prostate and breast cancer cells: its molecular cloning and growth properties." Tanaka A., Miyamoto K., Matsuo H., Matsumoto K., Yoshida H. FEBS Lett. 363:226-230(1995) [PubMed: 7737407] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM FGF-8A).
[2]	"Molecular cloning and characterization of human FGF8 alternative messenger RNA forms." Ghosh A.K., Shankar D.B., Shackleford G.M., Wu K., T'Ang A., Miller G.J., Zheng J., Roy-Burman P. Cell Growth Differ. 7:1425-1434(1996) [PubMed: 8891346] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS FGF-8A; FGF-8B AND FGF-8E). Tissue: Prostate.
[3]	"Structure and sequence of human FGF8." Gemel J., Gorry M., Ehrlich G.D., Macarthur C.A. Genomics 35:253-257(1996) [PubMed: 8661131] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS FGF-8B; FGF-8E AND FGF-8F). Tissue: Placenta.
[4]	"The human FGF-8 gene localizes on chromosome 10q24 and is subjected to induction by androgen in breast cancer cells." Payson R.A., Wu J., Liu Y., Chiu I.-M. Oncogene 13:47-53(1996) [PubMed: 8700553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS FGF-8A AND FGF-8F).
[5]	"A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma." Tanaka S., Ueo H., Mafune K., Mori M., Wands J.R., Sugimachi K. Dig. Dis. Sci. 46:1016-1021(2001) [PubMed: 11341643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FGF-8F). Tissue: Oesophageal carcinoma.
[6]	NIEHS SNPs program Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM FGF-8F).
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] (ISOFORM FGF-8A).
[9]	"Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice." Falardeau J., Chung W.C.J., Beenken A., Raivio T., Plummer L., Sidis Y., Jacobson-Dickman E.E., Eliseenkova A.V., Ma J., Dwyer A., Quinton R., Na S., Hall J.E., Huot C., Alois N., Pearce S.H., Cole L.W., Hughes V. , Mohammadi M., Tsai P., Pitteloud N. J. Clin. Invest. 118:2822-2831(2008) [PubMed: 18596921] [Abstract] Cited for: VARIANTS KAL6 LEU-26 AND GLY-116, VARIANTS IHH ASN-14; LEU-40; GLU-89 AND MET-218.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S78466 , S78462, S78463, S78464, S78465 Genomic DNA. Translation: AAB34255.1.
D38752 Genomic DNA. Translation: BAA22527.1.
U46213 mRNA. Translation: AAB40955.1.
U46212 mRNA. Translation: AAB40954.1.
U46211 mRNA. Translation: AAB40953.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50784.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50785.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50782.1.
U36223 mRNA. Translation: AAB17893.1.
U36228 , U36225, U36226, U36227 Genomic DNA. Translation: AAB17894.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50783.1.
U56978 mRNA. Translation: AAB03787.1.
AB014615 mRNA. Translation: BAA28605.1.
AF520763 Genomic DNA. Translation: AAM55238.1.
CH471066 Genomic DNA. Translation: EAW49746.1.
BC128235 mRNA. Translation: AAI28236.1.

IPI

IPI00183471.
IPI00218332.
IPI00218333.
IPI00219933.

RefSeq

NP_006110.1.
NP_149353.1.
NP_149354.1.
NP_149355.1.

UniGene

Hs.57710

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FDB	X-ray	2.28	M/N	52-204	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P55075.

Proteomic databases

PRIDE

P55075.

Genome annotation databases

Ensembl

ENST00000344255; ENSP00000340039; ENSG00000107831; Homo sapiens. [Genome view]

GeneID

2253.

KEGG

hsa:2253.

UCSC

uc001ktp.1. human.
uc001ktq.1. human.
uc001ktr.1. human.
uc001kts.1. human.

Organism-specific databases

CTD

2253.

GeneCards

GC10M103519.

H-InvDB

HIX0035300.

HGNC

HGNC:3686. FGF8.

MIM

146110. phenotype.
600483. gene.
612702. phenotype.

Orphanet

478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.

PharmGKB

PA28125.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P55075.

OMA

NYPFNRR.

Enzyme and pathway databases

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.

Reactome

REACT_9470. Signaling by FGFR.

Gene expression databases

ArrayExpress

P55075.

Bgee

P55075.

CleanEx

HS_FGF8.

Genevestigator

P55075.

GermOnline

ENSG00000107831. Homo sapiens.

Family and domain databases

InterPro

IPR008996. Cytokine_IL1-like.
IPR002348. IL1_HBGF.
[Graphical view]

PANTHER

PTHR11486. IL1_HBGF. 1 hit.

Pfam

PF00167. FGF. 1 hit.
[Graphical view]

PRINTS

PR00262. IL1HBGF.

SMART

SM00442. FGF. 1 hit.
[Graphical view]

PROSITE

PS00247. HBGF_FGF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

9121.

SOURCE

Search...

Entry information

Entry name

FGF8_HUMAN

Accession

Primary (citable) accession number: P55075
Secondary accession number(s): A1A514, Q14915, Q15766

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	February 9, 2010
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.