P19883 (FST_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Follistatin
Short name=FS

Alternative name(s):
Activin-binding protein

Gene names

Name:

FST

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	344 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	Binds directly to activin and functions as an activin antagonist. Specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (FSH).
Subunit structure	Monomer Potential.
Subcellular location	Secreted.
Tissue specificity	Isoform 1 is the predominant isoform in serum but is undetectable in follicular fluid. Ref.6
Sequence similarities	Contains 3 follistatin-like domains. Contains 3 Kazal-like domains. Contains 1 TB (TGF-beta binding) domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from electronic annotation. Source: Compara female gonad development Inferred from electronic annotation. Source: Compara gamete generation Inferred from electronic annotation. Source: Compara hair follicle morphogenesis Inferred from electronic annotation. Source: Compara hematopoietic progenitor cell differentiation Inferred from direct assay PubMed 15451575. Source: UniProtKB keratinocyte proliferation Inferred from electronic annotation. Source: Compara negative regulation of activin receptor signaling pathway Inferred from direct assay PubMed 11948405PubMed 12697670. Source: UniProtKB negative regulation of cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of follicle-stimulating hormone secretion Non-traceable author statement. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12702211. Source: UniProtKB odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara pattern specification process Inferred from electronic annotation. Source: Compara positive regulation of hair follicle development Inferred from direct assay PubMed 12514121. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular region Non-traceable author statement. Source: UniProtKB nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	signal transducer activity Non-traceable author statement PubMed 12702211. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANG	P03950	3	EBI-1571188,EBI-525291

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P19883-1)

Also known as: FS315; FS-315;

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 2 (identifier: P19883-2)

Also known as: FS288; FS-288;

The sequence of this isoform differs from the canonical sequence as follows:
     318-344: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Ref.5

Chain

30 – 344

315

Follistatin

PRO_0000010103

Regions

Domain

30 – 103

74

TB

Domain

94 – 117

24

Follistatin-like 1

Domain

112 – 166

55

Kazal-like 1

Domain

167 – 190

24

Follistatin-like 2

Domain

186 – 241

56

Kazal-like 2

Domain

244 – 268

25

Follistatin-like 3

Domain

264 – 318

55

Kazal-like 3

Compositional bias

321 – 333

13

Asp/Glu-rich (highly acidic)

Amino acid modifications

Glycosylation

124

1

N-linked (GlcNAc...) Potential

Glycosylation

288

1

N-linked (GlcNAc...) Potential

Disulfide bond

32 ↔ 55

Ref.7 Ref.8 Ref.9

Disulfide bond

42 ↔ 88

Ref.7 Ref.8 Ref.9

Disulfide bond

56 ↔ 91

Ref.7 Ref.8 Ref.9

Disulfide bond

95 ↔ 106

Ref.7 Ref.8 Ref.9

Disulfide bond

100 ↔ 116

Ref.7 Ref.8 Ref.9

Disulfide bond

118 ↔ 150

Ref.7 Ref.8 Ref.9

Disulfide bond

122 ↔ 143

Ref.7 Ref.8 Ref.9

Disulfide bond

132 ↔ 164

Ref.7 Ref.8 Ref.9

Disulfide bond

192 ↔ 225

Ref.7 Ref.8 Ref.9

Disulfide bond

196 ↔ 218

Ref.7 Ref.8 Ref.9

Disulfide bond

207 ↔ 239

Ref.7 Ref.8 Ref.9

Disulfide bond

270 ↔ 302

Ref.7 Ref.8 Ref.9

Disulfide bond

274 ↔ 295

Ref.7 Ref.8 Ref.9

Disulfide bond

284 ↔ 316

Ref.7 Ref.8 Ref.9

Natural variations

Alternative sequence

318 – 344

27

Missing in isoform 2.

VSP_001565

Natural variant

152

1

E → Q.
Corresponds to variant rs11745088 [ dbSNP | Ensembl ].

VAR_049091

Secondary structure

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344

Helix Strand Turn

Details...

Beta strand

31 – 36

6

Beta strand

42 – 49

8

Helix

52 – 55

4

Beta strand

64 – 66

3

Helix

72 – 81

10

Beta strand

82 – 87

6

Beta strand

89 – 91

3

Beta strand

93 – 95

3

Beta strand

104 – 108

5

Turn

110 – 112

3

Beta strand

114 – 118

5

Helix

123 – 125

3

Beta strand

131 – 133

3

Beta strand

138 – 141

4

Helix

142 – 151

10

Beta strand

158 – 163

6

Beta strand

166 – 168

3

Beta strand

178 – 181

4

Beta strand

185 – 190

6

Beta strand

202 – 204

3

Beta strand

206 – 208

3

Beta strand

213 – 216

4

Helix

217 – 227

11

Beta strand

233 – 237

5

Helix

245 – 247

3

Turn

251 – 253

3

Beta strand

255 – 259

5

Turn

260 – 263

4

Beta strand

264 – 268

5

Beta strand

283 – 285

3

Beta strand

290 – 293

4

Helix

294 – 304

11

Beta strand

310 – 314

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (FS315) (FS-315) [UniParc]. Last modified October 10, 2002. Version 2. Checksum: D9BB45055D84AC90	FASTA	344	38,007
	10 20 30 40 50 60 MVRARHQPGG LCLLLLLLCQ FMEDRSAQAG NCWLRQAKNG RCQVLYKTEL SKEECCSTGR 70 80 90 100 110 120 LSTSWTEEDV NDNTLFKWMI FNGGAPNCIP CKETCENVDC GPGKKCRMNK KNKPRCVCAP 130 140 150 160 170 180 DCSNITWKGP VCGLDGKTYR NECALLKARC KEQPELEVQY QGRCKKTCRD VFCPGSSTCV 190 200 210 220 230 240 VDQTNNAYCV TCNRICPEPA SSEQYLCGND GVTYSSACHL RKATCLLGRS IGLAYEGKCI 250 260 270 280 290 300 KAKSCEDIQC TGGKKCLWDF KVGRGRCSLC DELCPDSKSD EPVCASDNAT YASECAMKEA 310 320 330 340 ACSSGVLLEV KHSGSCNSIS EDTEEEEEDE DQDYSFPISS ILEW
	Isoform 2 (FS288) (FS-288) [UniParc]. Checksum: B516643224C7F8FF	FASTA	317	34,803
	10 20 30 40 50 60 MVRARHQPGG LCLLLLLLCQ FMEDRSAQAG NCWLRQAKNG RCQVLYKTEL SKEECCSTGR 70 80 90 100 110 120 LSTSWTEEDV NDNTLFKWMI FNGGAPNCIP CKETCENVDC GPGKKCRMNK KNKPRCVCAP 130 140 150 160 170 180 DCSNITWKGP VCGLDGKTYR NECALLKARC KEQPELEVQY QGRCKKTCRD VFCPGSSTCV 190 200 210 220 230 240 VDQTNNAYCV TCNRICPEPA SSEQYLCGND GVTYSSACHL RKATCLLGRS IGLAYEGKCI 250 260 270 280 290 300 KAKSCEDIQC TGGKKCLWDF KVGRGRCSLC DELCPDSKSD EPVCASDNAT YASECAMKEA 310 ACSSGVLLEV KHSGSCN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the human follistatin precursor and its genomic organization." Shimasaki S., Koga M., Esch F., Cooksey K., Mercado M., Koba A., Ueno N., Ying S.-Y., Ling N., Guillemin R. Proc. Natl. Acad. Sci. U.S.A. 85:4218-4222(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 1). Tissue: Pancreas.
[5]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 30-44.
[6]	"Differential distribution of follistatin isoforms: application of a new FS315-specific immunoassay." Schneyer A.L., Wang Q., Sidis Y., Sluss P.M. J. Clin. Endocrinol. Metab. 89:5067-5075(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding." Thompson T.B., Lerch T.F., Cook R.W., Woodruff T.K., Jardetzky T.S. Dev. Cell 9:535-543(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-317 IN COMPLEX WITH ACTIVIN A, DISULFIDE BONDS.
[8]	"Structural and biophysical coupling of heparin and activin binding to follistatin isoform functions." Lerch T.F., Shimasaki S., Woodruff T.K., Jardetzky T.S. J. Biol. Chem. 282:15930-15939(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 30-344 IN COMPLEX WITH ACTIVIN A, DISULFIDE BONDS.
[9]	"The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding." Cash J.N., Rejon C.A., McPherron A.C., Bernard D.J., Thompson T.B. EMBO J. 28:2662-2676(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 30-317 IN COMPLEX WITH MOUSE GDF8, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M19481, M19480 Genomic DNA. Translation: AAA35851.1.
AB451330 mRNA. Translation: BAG70144.1.
AB451474 mRNA. Translation: BAG70288.1.
CH471123 Genomic DNA. Translation: EAW54880.1.
BC004107 mRNA. Translation: AAH04107.1.

IPI

IPI00021081.
IPI00217070.
IPI00217071.

PIR

A32141.

RefSeq

NP_006341.1. NM_006350.3.
NP_037541.1. NM_013409.2.

UniGene

Hs.9914.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B0U	X-ray	2.80	C/D	30-317	[»]
2P6A	X-ray	3.40	C/D	30-344	[»]
3HH2	X-ray	2.15	C/D	30-317	[»]

ProteinModelPortal

P19883.

ModBase

Search...

Protein-protein interaction databases

IntAct

P19883. 3 interactions.

STRING

9606.ENSP00000256759.

Protein family/group databases

MEROPS

I01.966.

Polymorphism databases

DMDM

23831079.

Proteomic databases

PaxDb

P19883.

PRIDE

P19883.

Protocols and materials databases

DNASU

10468.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256759; ENSP00000256759; ENSG00000134363.
ENST00000396947; ENSP00000380151; ENSG00000134363.

GeneID

10468.

KEGG

hsa:10468.

UCSC

uc003jpc.3. human.

Organism-specific databases

CTD

10468.

GeneCards

GC05P052776.

HGNC

HGNC:3971. FST.

HPA

CAB026025.
HPA018155.

MIM

136470. gene.

neXtProt

NX_P19883.

Orphanet

3185. Stein-Leventhal syndrome.

PharmGKB

PA28388.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG267610.

HOGENOM

HOG000261649.

HOVERGEN

HBG051666.

InParanoid

P19883.

KO

K04661.

OMA

EAVCASD.

OrthoDB

EOG4QRH47.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P19883.

Bgee

P19883.

CleanEx

HS_FST.

Genevestigator

P19883.

GermOnline

ENSG00000134363. Homo sapiens.

Family and domain databases

InterPro

IPR003645. Fol_N.
IPR015369. Follistatin/Osteonectin_EGF.
IPR002350. Kazal_dom.
IPR017878. TB_dom.
[Graphical view]

Pfam

PF09289. FOLN. 1 hit.
PF00050. Kazal_1. 3 hits.
[Graphical view]

SMART

SM00274. FOLN. 3 hits.
SM00280. KAZAL. 3 hits.
[Graphical view]

PROSITE

PS00282. KAZAL_1. False negative.
PS51465. KAZAL_2. 3 hits.
PS51364. TB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P19883.

GenomeRNAi

10468.

NextBio

39699.

SOURCE

Search...

Entry information

Entry name

FST_HUMAN

Accession

Primary (citable) accession number: P19883
Secondary accession number(s): B5BU94, Q9BTH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 10, 2002
Last modified:	May 1, 2013
This is version 140 of the entry and version 2 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.