Reviewed, UniProtKB/Swiss-Prot P05230 (FGF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Heparin-binding growth factor 1
      Short name=HBGF-1
Alternative name(s):
    Acidic fibroblast growth factor
      Short name=aFGF
    Beta-endothelial cell growth factor
    ECGF-beta

Gene names

Name:	FGF1
Synonyms:	FGFA

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	155 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	The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.
Subunit structure	Monomer. Binds FGFR2. Forms a ternary complex containing 2 molecules each of FGFR2 and FGF1 for 1 heparin molecule. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP1.
Miscellaneous	This protein binds heparin, although less strongly than does bFGF.
Sequence similarities	Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Coding sequence diversity	Polymorphism
Ligand	Heparin-binding
Molecular function	Developmental protein Growth factor Mitogen
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	anatomical structure morphogenesis Ref.4 Traceable author statement. Source: ProtInc fibroblast growth factor receptor signaling pathway Inferred from Experiment. Source: Reactome multicellular organismal development Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from Experiment. Source: Reactome
Molecular function	growth factor activity Ref.4 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FGFR2	P21802	1	EBI-698068,EBI-1028658
FGFR3	P22607	2	EBI-698068,EBI-348399

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Propeptide

1 – 15

15

Chain

16 – 155

140

Heparin-binding growth factor 1

Regions

Region

127 – 143

17

Heparin-binding

Sites

Binding site

33

1

Heparin

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Natural variations

Natural variant

21

1

G → E

Secondary structure

1

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155

Helix Strand Turn

Details...

Turn

11 – 13

3

Beta strand

23 – 25

3

Beta strand

27 – 31

5

Turn

32 – 35

4

Beta strand

36 – 40

5

Beta strand

46 – 49

4

Beta strand

59 – 65

7

Beta strand

68 – 73

6

Turn

74 – 76

3

Beta strand

79 – 82

4

Beta strand

88 – 93

6

Helix

96 – 98

3

Beta strand

100 – 105

6

Turn

106 – 108

3

Beta strand

109 – 115

7

Helix

118 – 120

3

Helix

135 – 137

3

Beta strand

147 – 151

5

Sequences

	Sequence		Length	Mass (Da)
	P05230-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: F586E8BFB09F1580	FASTA	155	17,460
	10 20 30 40 50 60 MAEGEITTFT ALTEKFNLPP GNYKKPKLLY CSNGGHFLRI LPDGTVDGTR DRSDQHIQLQ 70 80 90 100 110 120 LSAESVGEVY IKSTETGQYL AMDTDGLLYG SQTPNEECLF LERLEENHYN TYISKKHAEK 130 140 150 NWFVGLKKNG SCKRGPRTHY GQKAILFLPL PVSSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization." Jaye M., Howk R., Burgess W., Ricca G.A., Chiu I.-M., Ravera M.W., O'Brien S.J., Modi W.S., Maciag T., Drohan W.N. Science 233:541-545(1986) [PubMed: 3523756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain stem.
[2]	"Structural analysis of the gene for human acidic fibroblast growth factor." Mergia A., Tischer E., Graves D., Tumolo A., Miller J., Gospodarowicz D., Abraham J.A., Shipley G.D., Fiddes J.C. Biochem. Biophys. Res. Commun. 164:1121-1129(1989) [PubMed: 2590193] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of the gene coding for human class 1 heparin-binding growth factor and its expression in fetal tissues." Wang W.P., Lehtoma K., Varban M.L., Krishnan I., Chiu I.M. Mol. Cell. Biol. 9:2387-2395(1989) [PubMed: 2474753] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Brain stem.
[4]	"Alternative splicing generates two forms of mRNA coding for human heparin-binding growth factor 1." Chiu I.M., Wang W.P., Lehtoma K. Oncogene 5:755-762(1990) [PubMed: 1693186] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain stem.
[5]	"Cloning and sequence analysis of the human acidic fibroblast growth factor gene and its preservation in leukemia patients." Wang W.P., Quick D., Balcerzak S.P., Needleman S.W., Chiu I.M. Oncogene 6:1521-1529(1991) [PubMed: 1717925] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"An acidic fibroblast growth factor protein generated by alternate splicing acts like an antagonist." Li Y.L., Kha H., Golden J.A., Migchielsen A.A.J., Goetzl E.J., Turck E.J. J. Exp. Med. 175:1073-1080(1992) [PubMed: 1372643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"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., Chambers S.W., 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], VARIANT GLU-21.
[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]. Tissue: Liver.
[9]	"The expression of acidic fibroblast growth factor (heparin-binding growth factor-1) and cytokine genes in human cardiac allografts and T cells." Zhao X.M., Yeoh T.K., Hiebert M., Frist W.H., Miller G.G. Transplantation 56:1177-1182(1993) [PubMed: 7504343] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-154.
[10]	"The gene for human acidic fibroblast growth factor encodes two upstream exons alternatively spliced to the first coding exon." Crumley G., Dionne C.A., Jaye M. Biochem. Biophys. Res. Commun. 171:7-13(1990) [PubMed: 2393407] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-40.
[11]	"Human class 1 heparin-binding growth factor: structure and homology to bovine acidic brain fibroblast growth factor." Harper J.W., Strydom D.J., Lobb R.R. Biochemistry 25:4097-4103(1986) [PubMed: 2427112] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-155.
[12]	"The complete amino acid sequence of human brain-derived acidic fibroblast growth factor." Gimenez-Gallego G., Conn G., Hatcher V.B., Thomas K.A. Biochem. Biophys. Res. Commun. 138:611-617(1986) [PubMed: 3527167] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-155.
[13]	"Amino acid sequence of human acidic fibroblast growth factor." Gautschi-Sova P., Mueller T., Boehlen P. Biochem. Biophys. Res. Commun. 140:874-880(1986) [PubMed: 3778488] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-155.
[14]	"Human brain-derived acidic and basic fibroblast growth factors: amino terminal sequences and specific mitogenic activities." Gimenez-Gallego G., Conn G., Hatcher V.B., Thomas K.A. Biochem. Biophys. Res. Commun. 135:541-548(1986) [PubMed: 3964259] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-47.
[15]	"Partial molecular characterization of endothelial cell mitogens from human brain: acidic and basic fibroblast growth factors." Gautschi P., Frater-Schroeder M., Boehlen P. FEBS Lett. 204:203-207(1986) [PubMed: 3732516] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-49.
[16]	"Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors." Wu D.Q., Kan M.K., Sato G.H., Okamoto T., Sato J.D. J. Biol. Chem. 266:16778-16785(1991) [PubMed: 1885605] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH FGFBP1 AND FGF2, INTERACTION WITH FGFBP1.
[17]	"Three-dimensional structures of acidic and basic fibroblast growth factors." Zhu X., Komiya H., Chirino A., Faham S., Fox G.M., Arakawa T., Hsu B.T., Rees D.C. Science 251:90-93(1991) [PubMed: 1702556] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 16-155.
[18]	"X-ray crystal structure of human acidic fibroblast growth factor." Blaber M., Disalvo J., Thomas K.A. Biochemistry 35:2086-2094(1996) [PubMed: 8652550] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-155.
[19]	"Structure of a heparin-linked biologically active dimer of fibroblast growth factor." DiGabriele A.D., Lax I., Chen D.I., Svahn C.M., Jaye M., Schlessinger J., Hendrickson W.A. Nature 393:812-817(1998) [PubMed: 9655399] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 21-155 IN COMPLEX WITH HEPARIN.
[20]	"Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity." Plotnikov A.N., Hubbard S.R., Schlessinger J., Mohammadi M. Cell 101:413-424(2000) [PubMed: 10830168] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 22-155 IN COMPLEX WITH FGFR1.
[21]	"Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin." Pellegrini L., Burke D.F., von Delft F., Mulloy B., Blundell T.L. Nature 407:1029-1034(2000) [PubMed: 11069186] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 16-155 IN COMPLEX WITH FGFR2 AND HEPARIN.
[22]	"Structural interactions of fibroblast growth factor receptor with its ligands." Stauber D.J., DiGabriele A.D., Hendrickson W.A. Proc. Natl. Acad. Sci. U.S.A. 97:49-54(2000) [PubMed: 10618369] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 21-155 IN COMPLEX WITH FGFR2.
[23]	"Alternative type I and I' turn conformations in the beta8/beta9 beta-hairpin of human acidic fibroblast growth factor." Kim J., Blaber S.I., Blaber M. Protein Sci. 11:459-466(2002) [PubMed: 11847269] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 16-155.
[24]	"Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity." Olsen S.K., Ibrahimi O.A., Raucci A., Zhang F., Eliseenkova A.V., Yayon A., Basilico C., Linhardt R.J., Schlessinger J., Mohammadi M. Proc. Natl. Acad. Sci. U.S.A. 101:935-940(2004) [PubMed: 14732692] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH FGFR3.
[25]	"1H-NMR assignment and solution structure of human acidic fibroblast growth factor activated by inositol hexasulfate." Pineda-Lucena A., Jimenez M.A., Nieto J.L., Santoro J., Rico M., Gimenez-Gallego G. J. Mol. Biol. 242:81-98(1994) [PubMed: 7521397] [Abstract] Cited for: STRUCTURE BY NMR OF 24-155 IN COMPLEX WITH INOSITOL HEXASULFATE, PROTEIN SEQUENCE OF 24-27.
[26]	"Three-dimensional structure of acidic fibroblast growth factor in solution: effects of binding to a heparin functional analog." Pineda-Lucena A., Jimenez M.A., Lozano R.M., Nieto J.L., Santoro J., Rico M., Gimenez-Gallego G. J. Mol. Biol. 264:162-178(1996) [PubMed: 8950275] [Abstract] Cited for: STRUCTURE BY NMR OF 24-155.
[27]	"Solution structure of acidic fibroblast growth factor bound to 1,3, 6-naphthalenetrisulfonate: a minimal model for the anti-tumoral action of suramins and suradistas." Lozano R.M., Jimenez M., Santoro J., Rico M., Gimenez-Gallego G. J. Mol. Biol. 281:899-915(1998) [PubMed: 9719643] [Abstract] Cited for: STRUCTURE BY NMR OF 24-155.
+	Additional computationally mapped references.

Cross-references

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Sequence databases

EMBLGenBankDDBJ

M13361 mRNA. Translation: AAA79245.1.
M30492, M30490, M30491 Genomic DNA. Translation: AAA52446.1.
M23087, M23086 Genomic DNA. Translation: AAA52638.1.
X51943 mRNA. Translation: CAA36206.1.
X65778 mRNA. Translation: CAA46661.1.
AY601819 Genomic DNA. Translation: AAS99352.1.
BC032697 mRNA. Translation: AAH32697.1.
S67291 mRNA. Translation: AAB29057.2.
M60515 mRNA. Translation: AAA51672.1.
M60516 mRNA. Translation: AAA51673.1.

PIR

A33665.

RefSeq

NP_000791.1.
NP_149127.1.
NP_149128.1.

UniGene

Hs.483635

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AXM	X-ray	3.00	A/B/C/D/E/F	21-155	[»]
1DJS	X-ray	2.40	B	21-155	[»]
1DZC	NMR	-	A	28-155	[»]
1DZD	NMR	-	A	29-155	[»]
1E0O	X-ray	2.80	A/C	16-155	[»]
1EVT	X-ray	2.80	A/B	22-155	[»]
1HKN	X-ray	2.00	A/B/C/D/E/F	17-155	[»]
1JQZ	X-ray	1.65	A/B	16-155	[»]
1JT3	X-ray	1.95	A/B	16-155	[»]
1JT4	X-ray	1.78	A/B	16-155	[»]
1JT5	X-ray	1.85	A/B	16-155	[»]
1JT7	X-ray	1.70	A/B/C/D	16-155	[»]
1JTC	X-ray	1.70	A/B/C/D	16-155	[»]
1JY0	X-ray	1.70	A/B	16-155	[»]
1K5U	X-ray	2.00	A/B/C	16-155	[»]
1K5V	X-ray	2.10	A/B	16-155	[»]
1M16	X-ray	1.70	A/B	16-155	[»]
1NZK	X-ray	1.95	A/B/C/D	16-152	[»]
1P63	X-ray	1.60	A/B	16-155	[»]
1PZZ	X-ray	2.00	A/B	16-155	[»]
1Q03	X-ray	2.05	A/B	16-155	[»]
1Q04	X-ray	1.80	A/B	16-155	[»]
1QCT	model	-	A/D	24-153	[»]
1RG8	X-ray	1.10	A/B	16-155	[»]
1RML	NMR	-	A	1-155	[»]
1RY7	X-ray	3.20	A	1-155	[»]
1YTO	X-ray	2.10	A/B/C/D	16-155	[»]
1Z2V	X-ray	1.90	A/B	16-155	[»]
1Z4S	X-ray	2.60	A/B/C/D	16-155	[»]
2AFG	X-ray	2.00	A/B/C/D	16-155	[»]
2AQZ	X-ray	1.85	A/B	16-155	[»]
2AXM	X-ray	3.00	A/B	21-155	[»]
2ERM	NMR	-	B	17-155	[»]
2HW9	X-ray	1.60	A/B	16-155	[»]
2HWA	X-ray	1.65	A/B	16-155	[»]
2HWM	X-ray	1.60	A/B	16-155	[»]
2HZ9	X-ray	1.70	A/B	16-155	[»]
2NTD	X-ray	2.52	A/B/C/D	16-155	[»]
2Q9X	X-ray	1.70	A	16-155	[»]
3B9U	X-ray	1.55	A	16-155	[»]
3BA4	X-ray	1.80	A/B	16-155	[»]
3BA5	X-ray	1.75	A/B	16-155	[»]
3BA7	X-ray	1.60	A/B	16-155	[»]
3BAD	X-ray	2.00	A/B	16-155	[»]
3BAG	X-ray	1.75	A/B	16-155	[»]
3BAH	X-ray	1.65	A/B	16-155	[»]
3BAO	X-ray	1.55	A/B	16-155	[»]
3BAQ	X-ray	1.80	A/B	16-155	[»]
3BAU	X-ray	1.60	A/B	16-155	[»]
3BAV	X-ray	1.62	A/B	16-155	[»]
3BB2	X-ray	1.50	A/B	16-155	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:3787N.

IntAct

P05230.