P01225 (FSHB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Follitropin subunit beta

Alternative name(s):
Follicle-stimulating hormone beta subunit
Short name=FSH-B
Short name=FSH-beta
Follitropin beta chain

Gene names

Name:

FSHB

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	129 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 development of follicle and spermatogenesis in the reproductive organs.
Subunit structure	Heterodimer of a common alpha chain and a unique beta chain which confers biological specificity to thyrotropin, lutropin, follitropin and gonadotropin.
Subcellular location	Secreted.
Involvement in disease	Isolated follicle-stimulating hormone deficiency (IFSHD) [MIM:229070]: Selective follicle-stimulating hormone deficiency is an uncommon cause of infertility, producing amenorrhea and hypogonadism in women and oligo or azoospermia with normal testosterone levels in normally virilised men. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17
Pharmaceutical use	Available under the names Gonal-F or Metrodin HP (Serono) and Puregon (Organon). Used in the treatment of infertility in women with proven hypopituitarism or who have not responded to clomifene; or in superovulation treatment for assisted conception (such as in vitro fertilization). Metrodin HP is also used in the treatment of hypogonadotrophic hypogonadism in men for the stimulation of spermatogenesis.
Sequence similarities	Belongs to the glycoprotein hormones subunit beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Hormone
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell proliferation Inferred from electronic annotation. Source: Compara cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome female gamete generation Traceable author statement Ref.15. Source: ProtInc female pregnancy Traceable author statement Ref.15. Source: ProtInc ovarian follicle development Non-traceable author statement. Source: UniProtKB peptide hormone processing Traceable author statement. Source: Reactome positive regulation of cell migration Non-traceable author statement PubMed 20613903. Source: BHF-UCL positive regulation of cell proliferation Non-traceable author statement PubMed 20613903. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Non-traceable author statement PubMed 20613903. Source: BHF-UCL progesterone biosynthetic process Traceable author statement PubMed 14557487. Source: BHF-UCL spermatogenesis Non-traceable author statement. Source: UniProtKB transforming growth factor beta receptor signaling pathway Inferred from expression pattern PubMed 14557487. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from direct assay PubMed 14602737. Source: UniProtKB extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB
Molecular_function	follicle-stimulating hormone activity Non-traceable author statement. Source: UniProtKB protein heterodimerization activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CGA	P01215	2	EBI-1030645,EBI-718913

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.8 Ref.9 Ref.10

Chain

19 – 129

111

Follitropin subunit beta

PRO_0000011711

Amino acid modifications

Glycosylation

25

1

N-linked (GlcNAc...) Ref.10 Ref.14

Glycosylation

42

1

N-linked (GlcNAc...) Ref.10 Ref.14

Disulfide bond

21 ↔ 69

Ref.11 Ref.12 Ref.14

Disulfide bond

35 ↔ 84

Ref.11 Ref.12 Ref.14

Disulfide bond

38 ↔ 122

Ref.11 Ref.12 Ref.14

Disulfide bond

46 ↔ 100

Ref.11 Ref.12 Ref.14

Disulfide bond

50 ↔ 102

Ref.11 Ref.12 Ref.14

Disulfide bond

105 ↔ 112

Ref.11 Ref.12 Ref.14

Natural variations

Natural variant

20

1

S → I. Ref.18
Corresponds to variant rs6170 [ dbSNP | Ensembl ].

VAR_012047

Natural variant

69

1

C → G in IFSHD. Ref.16
Corresponds to variant rs5030776 [ dbSNP | Ensembl ].

VAR_033015

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

129

Helix Strand Turn

Details...

Beta strand

21 – 32

12

Helix

33 – 35

3

Beta strand

37 – 53

17

Beta strand

68 – 81

14

Beta strand

90 – 103

14

Turn

107 – 109

3

Beta strand

110 – 114

5

Sequences

	Sequence		Length	Mass (Da)
	P01225 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: 9D2AF00DD76B8E2B	FASTA	129	14,700
	10 20 30 40 50 60 MKTLQFFFLF CCWKAICCNS CELTNITIAI EKEECRFCIS INTTWCAGYC YTRDLVYKDP 70 80 90 100 110 120 ARPKIQKTCT FKELVYETVR VPGCAHHADS LYTYPVATQC HCGKCDSDST DCTVRGLGPS YCSFGEMKE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence and regional assignment of the human follicle-stimulating hormone beta-subunit gene to the short arm of human chromosome 11." Watkins P.C., Eddy R., Beck A.K., Vellucci V., Leverone B., Tanzi R.E., Gusella J.F., Shows T.B. DNA 6:205-212(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Expression of biologically active human follitropin in Chinese hamster ovary cells." Keene J.L., Matzuk M.M., Otani T., Fauser B.C.J.M., Galway A.B., Hsueh A.J.W., Boime I. J. Biol. Chem. 264:4769-4775(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Human follicle-stimulating hormone beta-subunit gene encodes multiple messenger ribonucleic acids." Jameson J.L., Becker C.B., Lindell C.M., Habener J.F. Mol. Endocrinol. 2:806-815(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Follicle-stimulating hormone (FSHB) beta subunit genes." Akbari Eidgahi M.R., Shaebani A.A., Nasr R. Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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].
[8]	"A reevaluation of the amino acid sequence of human follitropin beta-subunit." Shome B., Parlow A.F., Liu W.K., Nahm H.S., Wen T., Ward D.N. J. Protein Chem. 7:325-339(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-129.
[9]	"Amino acid sequence of the beta subunit of follicle-stimulating hormone from human pituitary glands." Saxena B.B., Rathnam P. J. Biol. Chem. 251:993-1005(1976) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-129.
[10]	"Human follicle stimulating hormone: first proposal for the amino acid sequence of the hormone-specific, beta subunit (hFSHb)." Shome B., Parlow A.F. J. Clin. Endocrinol. Metab. 39:203-205(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-129.
[11]	"Studies on the disulfide bonds in human pituitary follicle-stimulating hormone." Fujiki Y., Rathnam P., Saxena B.B. Biochim. Biophys. Acta 624:428-435(1980) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY ASSIGNMENT OF DISULFIDE BONDS.
[12]	"Assignment of the complete disulphide bridge pattern in the human recombinant follitropin beta-chain." Amoresano A., Orru S., Siciliano R.A., De Luca E., Napoleoni R., Sirna A., Pucci P. Biol. Chem. 382:961-968(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[13]	"Three-dimensional structure of human follicle-stimulating hormone." Fox K.M., Dias J.A., Van Roey P. Mol. Endocrinol. 15:378-389(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF MUTANT ALA-27.
[14]	"Structure of human follicle-stimulating hormone in complex with its receptor." Fan Q.R., Hendrickson W.A. Nature 433:269-277(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.92 ANGSTROMS) OF 19-129 IN COMPLEX WITH CGA AND FSHR, DISULFIDE BONDS, GLYCOSYLATION AT ASN-25 AND ASN-42.
[15]	"Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone." Matthews C.H., Borgato S., Beck-Peccoz P., Adams M., Tone Y., Gambino G., Casagrande S., Tedeschini G., Benedetti A., Chatterjee V.K.K. Nat. Genet. 5:83-86(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN IFSHD.
[16]	"Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone beta-subunit gene." Layman L.C., Lee E.-J., Peak D.B., Namnoum A.B., Vu K.V., van Lingen B.L., Gray M.R., McDonough P.G., Reindollar R.H., Jameson J.L. N. Engl. J. Med. 337:607-611(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT IFSHD GLY-69.
[17]	"Isolated deficiency of follicle-stimulating hormone re-revisited." Matthews C., Chatterjee V.K. N. Engl. J. Med. 337:642-642(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN IFSHD.
[18]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-20.
[19]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Web resources

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Follicle-stimulating hormone entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16647, M16646 Genomic DNA. Translation: AAA52476.1.
M24540, M24539 Genomic DNA. Translation: AAA52470.1.
M54914, M54913 Genomic DNA. Translation: AAB02868.1.
EF198021 Genomic DNA. Translation: ABM88373.1.
EF585489 mRNA. Translation: ABQ57401.1.
EF585490 Genomic DNA. Translation: ABQ57402.1.
EU081884 Genomic DNA. Translation: ABU96749.1.
EU081885 Genomic DNA. Translation: ABU96750.1.
AL358944 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68260.1.
BC113488 mRNA. Translation: AAI13489.1.
BC113490 mRNA. Translation: AAI13491.1.

IPI

IPI00000853.

PIR

FTHUB. A40920.

RefSeq

NP_000501.1. NM_000510.2.
NP_001018090.1. NM_001018080.1.

UniGene

Hs.36975.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FL7	X-ray	3.00	B/D	19-129	[»]
1XWD	X-ray	2.92	B/E	19-129	[»]
4AY9	X-ray	2.50	B/E/H	19-129	[»]

ProteinModelPortal

P01225.

ModBase

Search...

Protein-protein interaction databases

IntAct

P01225. 2 interactions.

STRING

9606.ENSP00000254122.

PTM databases

GlycoSuiteDB

P01225.

Polymorphism databases

DMDM

120552.

Proteomic databases

PaxDb

P01225.

PeptideAtlas

P01225.

PRIDE

P01225.

Protocols and materials databases

DNASU

2488.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254122; ENSP00000254122; ENSG00000131808.
ENST00000417547; ENSP00000416606; ENSG00000131808.
ENST00000533718; ENSP00000433424; ENSG00000131808.

GeneID

2488.

KEGG

hsa:2488.

UCSC

uc001msl.3. human.

Organism-specific databases

CTD

2488.

GeneCards

GC11P030210.

HGNC

HGNC:3964. FSHB.

MIM

136530. gene.
229070. phenotype.

neXtProt

NX_P01225.

Orphanet

52901. Isolated follicle stimulating hormone deficiency.

PharmGKB

PA28382.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41629.

HOGENOM

HOG000116098.

HOVERGEN

HBG006698.

InParanoid

P01225.

KO

K05250.

OMA

TWCAGYC.

OrthoDB

EOG42NJ1N.

PhylomeDB

P01225.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P01225.

Bgee

P01225.

CleanEx

HS_FSHB.

Genevestigator

P01225.

GermOnline

ENSG00000131808. Homo sapiens.

Family and domain databases

InterPro

IPR006208. Cys_knot.
IPR001545. Gonadotropin_bsu.
IPR018245. Gonadotropin_bsu_CS.
[Graphical view]

PANTHER

PTHR11515. PTHR11515. 1 hit.

Pfam

PF00007. Cys_knot. 1 hit.
[Graphical view]

SMART

SM00068. GHB. 1 hit.
[Graphical view]

PROSITE

PS00261. GLYCO_HORMONE_BETA_1. 1 hit.
PS00689. GLYCO_HORMONE_BETA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00066. Follitropin beta.
DB00024. Thyrotropin Alfa.
DB00094. Urofollitropin.

EvolutionaryTrace

P01225.

GenomeRNAi

2488.

NextBio

9829.

SOURCE

Search...

Entry information

Entry name

FSHB_HUMAN

Accession

Primary (citable) accession number: P01225
Secondary accession number(s): A2TF08, A5JVV3, Q14D61

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 144 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.