Reviewed, UniProtKB/Swiss-Prot P09038 (FGF2_HUMAN)

Names and origin

Protein names

Recommended name:
    Heparin-binding growth factor 2
      Short name=HBGF-2
Alternative name(s):
    Basic fibroblast growth factor
      Short name=BFGF

Gene names

Name:	FGF2
Synonyms:	FGFB

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	210 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. Interacts with CSPG4 and FGFBP1. Found in a complex with FGFBP1, FGF1 and FGF2. Ref.18 Ref.19 Ref.20
Tissue specificity	Expressed in granulosa and cumulus cells.
Post-translational modification	Several N-termini starting at positions 48, 54, 47 and 65 have been identified by direct sequencing.
Miscellaneous	This protein binds heparin more strongly than does aFGF.
Sequence similarities	Belongs to the heparin-binding growth factors family.
Sequence caution	The sequence AAB21432.2 differs from that shown. Reason: Miscellaneous discrepancy. Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Coding sequence diversity	Alternative initiation
Ligand	Heparin-binding
Molecular function	Developmental protein Growth factor Mitogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	Ras protein signal transduction Traceable author statement. Source: ProtInc activation of MAPK activity Traceable author statement. Source: ProtInc angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Inferred from electronic annotation. Source: UniProtKB-KW chemotaxis Traceable author statement. Source: ProtInc fibroblast growth factor receptor signaling pathway Inferred from Experiment. Source: Reactome negative regulation of blood vessel endothelial cell migration Inferred from direct assay. Source: UniProtKB positive regulation of blood vessel endothelial cell migration Inferred from direct assay. Source: UniProtKB positive regulation of cardiac muscle cell proliferation Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Ref.3 Traceable author statement. Source: ProtInc
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW heparin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP1	P29466	1	EBI-977447,EBI-516667
FGFBP1	Q14512	3	EBI-977447,EBI-953742
FGFR2	P21802-5	1	EBI-977447,EBI-1028732

Alternative products

This entry describes 3 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: P09038-1)

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.

Note: Starts at an alternative CUG codon.

Isoform 2 (identifier: P09038-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.

Isoform 3 (identifier: P09038-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     15-15: L → M

Note: Starts at an alternative CUG codon.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 64

64

Or 47, or 53, or 46

PRO_0000008932

Chain

65 – 210

146

Heparin-binding growth factor 2

PRO_0000008933

Regions

Region

183 – 199

17

Heparin-binding By similarity

Motif

101 – 103

3

Cell attachment site; atypical Potential

Motif

143 – 145

3

Cell attachment site; atypical Potential

Sites

Binding site

91

1

Heparin By similarity

Natural variations

Alternative sequence

1 – 55

55

Missing in isoform 2.

VSP_037383

Alternative sequence

1 – 14

14

Missing in isoform 3.

VSP_037384

Alternative sequence

15

1

L → M in isoform 3.

VSP_037385

Secondary structure

1

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210

Helix Strand Turn

Details...

Beta strand

85 – 89

5

Turn

90 – 93

4

Beta strand

94 – 98

5

Beta strand

104 – 107

4

Helix

113 – 115

3

Beta strand

117 – 123

7

Beta strand

126 – 131

6

Turn

132 – 135

4

Beta strand

136 – 140

5

Beta strand

146 – 151

6

Helix

154 – 156

3

Beta strand

158 – 162

5

Beta strand

168 – 175

8

Beta strand

186 – 188

3

Helix

191 – 193

3

Helix

199 – 201

3

Beta strand

203 – 206

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 26, 2009. Version 2. Checksum: A21C7A6E82E4F5BD	FASTA	210	22,623
	10 20 30 40 50 60 MGDRGRGRAL PGGRLGGRGR GRAPERVGGR GRGRGTAAPR AAPAARGSRP GPAGTMAAGS 70 80 90 100 110 120 ITTLPALPED GGSGAFPPGH FKDPKRLYCK NGGFFLRIHP DGRVDGVREK SDPHIKLQLQ 130 140 150 160 170 180 AEERGVVSIK GVCANRYLAM KEDGRLLASK CVTDECFFFE RLESNNYNTY RSRKYTSWYV 190 200 210 ALKRTGQYKL GSKTGPGQKA ILFLPMSAKS
	Isoform 2. Checksum: BE6CE13373007129	FASTA	155	17,254
	10 20 30 40 50 60 MAAGSITTLP ALPEDGGSGA FPPGHFKDPK RLYCKNGGFF LRIHPDGRVD GVREKSDPHI 70 80 90 100 110 120 KLQLQAEERG VVSIKGVCAN RYLAMKEDGR LLASKCVTDE CFFFERLESN NYNTYRSRKY 130 140 150 TSWYVALKRT GQYKLGSKTG PGQKAILFLP MSAKS
	Isoform 3. Checksum: D6B5447137E60343	FASTA	196	21,203
	10 20 30 40 50 60 MGGRGRGRAP ERVGGRGRGR GTAAPRAAPA ARGSRPGPAG TMAAGSITTL PALPEDGGSG 70 80 90 100 110 120 AFPPGHFKDP KRLYCKNGGF FLRIHPDGRV DGVREKSDPH IKLQLQAEER GVVSIKGVCA 130 140 150 160 170 180 NRYLAMKEDG RLLASKCVTD ECFFFERLES NNYNTYRSRK YTSWYVALKR TGQYKLGSKT 190 GPGQKAILFL PMSAKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human basic fibroblast growth factor: nucleotide sequence, genomic organization, and expression in mammalian cells." Abraham J.A., Whang J.L., Tumolo A., Mergia A., Fiddes J.C. Cold Spring Harb. Symp. Quant. Biol. 51:657-668(1986) [PubMed: 3472745] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human basic fibroblast growth factor: nucleotide sequence and genomic organization." Abraham J.A., Whang J.L., Tumolo A., Mergia A., Friedman J., Gospodarowicz D., Fiddes J.C. EMBO J. 5:2523-2528(1986) [PubMed: 3780670] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2).
[3]	"Cloning and expression of cDNA encoding human basic fibroblast growth factor." Kurokawa T., Sasada R., Iwane M., Igarashi K. FEBS Lett. 213:189-194(1987) [PubMed: 2435575] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons." Prats H., Kaghad M., Prats A.C., Klagsbrun M., Lelias J.M., Liauzun P., Chalon P., Tauber J.P., Amalric F., Smith J.A., Caput D. Proc. Natl. Acad. Sci. U.S.A. 86:1836-1840(1989) [PubMed: 2538817] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), PROTEIN SEQUENCE OF 48-67, ALTERNATIVE INITIATION. Tissue: Hepatoma.
[5]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	NIEHS SNPs program Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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]	"Basic fibroblast growth factor gene expression." Florkiewicz R.Z., Shibata F., Barankiewicz T., Baird A., Gonzalez A.M., Florkiewicz E., Shah N. Ann. N. Y. Acad. Sci. 638:109-126(1991) [PubMed: 1785797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
[9]	"Mutations in the 5' untranslated region of the FGF-2 gene." Handschug K., Archoukieh E., Glaeser C. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114. Tissue: Blood.
[10]	"Human amniotic tumor that induces new bone formation in vivo produces growth-regulatory activity in vitro for osteoblasts identified as an extended form of basic fibroblast growth factor." Izbicka E., Dunstan C., Esparza J., Jacobs C., Sabatini M., Mundy G.R. Cancer Res. 56:633-636(1996) [PubMed: 8564983] [Abstract] Cited for: PROTEIN SEQUENCE OF 47-62 (ISOFORMS 1/3).
[11]	"A form of human basic fibroblast growth factor with an extended amino terminus." Sommer A., Brewer M.T., Thompson R.C., Moscatelli D., Presta M., Rifkin D.B. Biochem. Biophys. Res. Commun. 144:543-550(1987) [PubMed: 3579930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 54-210 (ISOFORMS 1/3), PROTEIN SEQUENCE OF 54-70; 75-82; 87-169; 174-183 AND 189-210 (ISOFORMS 1/3). Tissue: Hepatoma and Placenta.
[12]	"Amino-terminal sequence of a large form of basic fibroblast growth factor isolated from human benign prostatic hyperplastic tissue." Story M.T., Esch F., Shimasaki S., Sasse J., Jacobs S.C., Lawson R.K. Biochem. Biophys. Res. Commun. 142:702-709(1987) [PubMed: 2435284] [Abstract] Cited for: PROTEIN SEQUENCE OF 57-77.
[13]	"Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients." Watson R., Anthony F., Pickett M., Lambden P., Masson G.M., Thomas E.J. Biochem. Biophys. Res. Commun. 187:1227-1231(1992) [PubMed: 1417798] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 95-182 (ISOFORMS 1/2/3), TISSUE SPECIFICITY.
[14]	Zhang H.J., Zhang S.M., Zhuang H. Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 65-210 (ISOFORMS 1/2/3).
[15]	"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 65-94.
[16]	"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 65-90.
[17]	"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 FGF1.
[18]	"High-affinity binding of basic fibroblast growth factor and platelet-derived growth factor-AA to the core protein of the NG2 proteoglycan." Goretzki L., Burg M.A., Grako K.A., Stallcup W.B. J. Biol. Chem. 274:16831-16837(1999) [PubMed: 10358027] [Abstract] Cited for: INTERACTION WITH CSPG4.
[19]	"Enhancement of fibroblast growth factor (FGF) activity by an FGF-binding protein." Tassi E., Al-Attar A., Aigner A., Swift M.R., McDonnell K., Karavanov A., Wellstein A. J. Biol. Chem. 276:40247-40253(2001) [PubMed: 11509569] [Abstract] Cited for: INTERACTION WITH FGFBP1.
[20]	"Identification of the fibroblast growth factor (FGF)-interacting domain in a secreted FGF-binding protein by phage display." Xie B., Tassi E., Swift M.R., McDonnell K., Bowden E.T., Wang S., Ueda Y., Tomita Y., Riegel A.T., Wellstein A. J. Biol. Chem. 281:1137-1144(2006) [PubMed: 16257968] [Abstract] Cited for: INTERACTION WITH FGFBP1.
[21]	"Crystal structure of basic fibroblast growth factor at 1.6-A resolution." Ago H., Kitagawa Y., Fujishima A., Matsuura Y., Katsube Y. J. Biochem. 110:360-363(1991) [PubMed: 1769963] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
[22]	"Three-dimensional structure of human basic fibroblast growth factor." Eriksson A.E., Cousens L.S., Weaver L.H., Matthews B.W. Proc. Natl. Acad. Sci. U.S.A. 88:3441-3445(1991) [PubMed: 1707542] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[23]	"Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta." Zhang J., Cousens L.S., Barr P.J., Sprang S.R. Proc. Natl. Acad. Sci. U.S.A. 88:3446-3450(1991) [PubMed: 1849658] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[24]	"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 (2.8 ANGSTROMS).
[25]	"Refinement of the structure of human basic fibroblast growth factor at 1.6-A resolution and analysis of presumed heparin binding sites by selenate substitution." Eriksson A.E., Cousens L.S., Matthews B.W. Protein Sci. 2:1274-1284(1993) [PubMed: 7691311] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
[26]	"Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome." Ibrahimi O.A., Eliseenkova A.V., Plotnikov A.N., Yu K., Ornitz D.M., Mohammadi M. Proc. Natl. Acad. Sci. U.S.A. 98:7182-7187(2001) [PubMed: 11390973] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 79-210 IN COMPLEX WITH FGFR2.
[27]	"High-resolution solution structure of basic fibroblast growth factor determined by multidimensional heteronuclear magnetic resonance spectroscopy." Moy F.J., Seddon A.P., Boehlen P., Powers R. Biochemistry 35:13552-13561(1996) [PubMed: 8885834] [Abstract] Cited for: STRUCTURE BY NMR.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X04431 Genomic DNA. Translation: CAA28027.1.
X04432 Genomic DNA. Translation: CAA28028.1.
X04433 Genomic DNA. Translation: CAA28029.1.
M27968 mRNA. Translation: AAA52448.1.
J04513 mRNA. Translation: AAA52531.1.
J04513 mRNA. Translation: AAA52532.1.
J04513 mRNA. Translation: AAA52533.1.
AB451321 mRNA. Translation: BAG70135.1.
AB451450 mRNA. Translation: BAG70264.1.
EF506888 Genomic DNA. Translation: ABO43041.1.
CH471056 Genomic DNA. Translation: EAX05222.1.
S81809 Genomic DNA. Translation: AAB21432.2. Sequence problems.
Y13468 Genomic DNA. Translation: CAA73868.1.
M17599 mRNA. Translation: AAA52534.1.
AY820133 mRNA. Translation: AAV70487.1.
S47380 mRNA. Translation: AAD13853.1.

IPI

IPI00154603.

PIR

A32398.

RefSeq

NP_001997.5.

UniGene

Hs.284244

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BAS	X-ray	1.90	A	57-210	[»]
1BFB	X-ray	1.90	A	64-210	[»]
1BFC	X-ray	2.20	A	64-210	[»]
1BFF	X-ray	2.00	A	82-210	[»]
1BFG	X-ray	1.60	A	65-210	[»]
1BLA	NMR	-	A	56-210	[»]
1BLD	NMR	-	A	56-210	[»]
1CVS	X-ray	2.80	A/B	79-210	[»]
1EV2	X-ray	2.20	A/B/C/D	79-210	[»]
1FGA	X-ray	2.20	A	65-210	[»]
1FQ9	X-ray	3.00	A/B	79-210	[»]
1II4	X-ray	2.70	A/B/C/D	56-210	[»]
1IIL	X-ray	2.30	A/B/C/D	56-210	[»]
2BFH	X-ray	2.50	A	83-210	[»]
2FGF	X-ray	1.77	A	65-210	[»]
4FGF	X-ray	1.60	A	65-210	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:4012N.

IntAct

P09038. 5 interactions.

Proteomic databases

PRIDE

P09038.

Genome annotation databases

Ensembl

ENSG00000138685. Homo sapiens. [Contig view]

GeneID

2247.

KEGG

hsa:2247.

Organism-specific databases

GeneCards

GC04P124027.

H-InvDB

HIX0031422.

HGNC

HGNC:3676. FGF2.

HPA

CAB000125.

MIM

134920. gene.

PharmGKB

PA28115.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P09038.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
fgf_pathway. FGF signaling pathway.
glypican_1pathway. Glypican 1 network.
avb3_integrin_pathway. Integrins in angiogenesis.
syndecan_4_pathway. Syndecan-4-mediated signaling events.

Reactome

REACT_9470. Signaling by FGFR.

Gene expression databases

ArrayExpress

P09038.

Bgee

P09038.

CleanEx

HS_FGF2.

GermOnline

ENSG00000138685. Homo sapiens.

Family and domain databases

ProDom

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

PROSITE

PS00247. HBGF_FGF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00686. Pentosan Polysulfate.

NextBio

9095.

SOURCE

Search...

Entry information

Entry name

FGF2_HUMAN

Accession

Primary (citable) accession number: P09038
Secondary accession number(s): A4LBB8 , O00527, P78443, Q16443, Q5PY50, Q7KZ11, Q7KZ72, Q9UC54

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	May 26, 2009
Last modified:	June 16, 2009
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)