ID FSHB_HUMAN Reviewed; 129 AA. AC P01225; A2TF08; A5JVV3; Q14D61; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 2. DT 13-FEB-2019, entry version 197. DE RecName: Full=Follitropin subunit beta; DE AltName: Full=Follicle-stimulating hormone beta subunit; DE Short=FSH-B; DE Short=FSH-beta; DE AltName: Full=Follitropin beta chain; DE Flags: Precursor; GN Name=FSHB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2885163; DOI=10.1089/dna.1987.6.205; RA Watkins P.C., Eddy R., Beck A.K., Vellucci V., Leverone B., RA Tanzi R.E., Gusella J.F., Shows T.B.; RT "DNA sequence and regional assignment of the human follicle- RT stimulating hormone beta-subunit gene to the short arm of human RT chromosome 11."; RL DNA 6:205-212(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND RP SUBUNIT. RX PubMed=2494176; RA Keene J.L., Matzuk M.M., Otani T., Fauser B.C.J.M., Galway A.B., RA Hsueh A.J.W., Boime I.; RT "Expression of biologically active human follitropin in Chinese RT hamster ovary cells."; RL J. Biol. Chem. 264:4769-4775(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3139991; DOI=10.1210/mend-2-9-806; RA Jameson J.L., Becker C.B., Lindell C.M., Habener J.F.; RT "Human follicle-stimulating hormone beta-subunit gene encodes multiple RT messenger ribonucleic acids."; RL Mol. Endocrinol. 2:806-815(1988). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Akbari Eidgahi M.R., Shaebani A.A., Nasr R.; RT "Follicle-stimulating hormone (FSHB) beta subunit genes."; RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 19-129. RX PubMed=3151250; DOI=10.1007/BF01024882; RA Shome B., Parlow A.F., Liu W.K., Nahm H.S., Wen T., Ward D.N.; RT "A reevaluation of the amino acid sequence of human follitropin beta- RT subunit."; RL J. Protein Chem. 7:325-339(1988). RN [9] RP PRELIMINARY PROTEIN SEQUENCE OF 19-129. RX PubMed=1249074; RA Saxena B.B., Rathnam P.; RT "Amino acid sequence of the beta subunit of follicle-stimulating RT hormone from human pituitary glands."; RL J. Biol. Chem. 251:993-1005(1976). RN [10] RP PRELIMINARY PROTEIN SEQUENCE OF 19-129. RX PubMed=4835136; DOI=10.1210/jcem-39-1-203; RA Shome B., Parlow A.F.; RT "Human follicle stimulating hormone: first proposal for the amino acid RT sequence of the hormone-specific, beta subunit (hFSHb)."; RL J. Clin. Endocrinol. Metab. 39:203-205(1974). RN [11] RP FUNCTION. RX PubMed=407105; RA Maroulis G.B., Parlow A.F., Marshall J.R.; RT "Isolated follicle-stimulating hormone deficiency in man."; RL Fertil. Steril. 28:818-822(1977). RN [12] RP PRELIMINARY ASSIGNMENT OF DISULFIDE BONDS. RX PubMed=6774759; DOI=10.1016/0005-2795(80)90084-7; RA Fujiki Y., Rathnam P., Saxena B.B.; RT "Studies on the disulfide bonds in human pituitary follicle- RT stimulating hormone."; RL Biochim. Biophys. Acta 624:428-435(1980). RN [13] RP DISULFIDE BONDS. RX PubMed=11501762; DOI=10.1515/BC.2001.120; RA Amoresano A., Orru S., Siciliano R.A., De Luca E., Napoleoni R., RA Sirna A., Pucci P.; RT "Assignment of the complete disulphide bridge pattern in the human RT recombinant follitropin beta-chain."; RL Biol. Chem. 382:961-968(2001). RN [14] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF MUTANT ALA-27. RX PubMed=11222739; DOI=10.1210/mend.15.3.0603; RA Fox K.M., Dias J.A., Van Roey P.; RT "Three-dimensional structure of human follicle-stimulating hormone."; RL Mol. Endocrinol. 15:378-389(2001). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.92 ANGSTROMS) OF 19-129 IN COMPLEX WITH CGA RP AND FSHR, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-25 AND ASN-42. RX PubMed=15662415; DOI=10.1038/nature03206; RA Fan Q.R., Hendrickson W.A.; RT "Structure of human follicle-stimulating hormone in complex with its RT receptor."; RL Nature 433:269-277(2005). RN [16] {ECO:0000244|PDB:4MQW} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 19-129 IN COMPLEX WITH CGA RP AND FSHR, GLYCOSYLATION AT ASN-25 AND ASN-42, FUNCTION, SUBUNIT, RP DISULFIDE BONDS, AND MUTAGENESIS OF THR-78. RX PubMed=24692546; DOI=10.1074/jbc.M114.549592; RA Jiang X., Fischer D., Chen X., McKenna S.D., Liu H., Sriraman V., RA Yu H.N., Goutopoulos A., Arkinstall S., He X.; RT "Evidence for follicle-stimulating hormone receptor as a functional RT trimer."; RL J. Biol. Chem. 289:14273-14282(2014). RN [17] RP INVOLVEMENT IN HH24, AND FUNCTION. RX PubMed=8220432; DOI=10.1038/ng0993-83; RA Matthews C.H., Borgato S., Beck-Peccoz P., Adams M., Tone Y., RA Gambino G., Casagrande S., Tedeschini G., Benedetti A., RA Chatterjee V.K.K.; RT "Primary amenorrhoea and infertility due to a mutation in the beta- RT subunit of follicle-stimulating hormone."; RL Nat. Genet. 5:83-86(1993). RN [18] RP VARIANT HH24 GLY-69. RX PubMed=9271483; DOI=10.1056/NEJM199708283370905; RA Layman L.C., Lee E.-J., Peak D.B., Namnoum A.B., Vu K.V., RA van Lingen B.L., Gray M.R., McDonough P.G., Reindollar R.H., RA Jameson J.L.; RT "Delayed puberty and hypogonadism caused by mutations in the follicle- RT stimulating hormone beta-subunit gene."; RL N. Engl. J. Med. 337:607-611(1997). RN [19] RP INVOLVEMENT IN HH24. RX PubMed=9280841; DOI=10.1056/NEJM199708283370918; RA Matthews C., Chatterjee V.K.; RT "Isolated deficiency of follicle-stimulating hormone re-revisited."; RL N. Engl. J. Med. 337:642-642(1997). RN [20] RP VARIANT ILE-20. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [21] RP ERRATUM. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). CC -!- FUNCTION: Together with the alpha chain CGA constitutes CC follitropin, the follicle-stimulating hormone, and provides its CC biological specificity to the hormone heterodimer. Binds FSHR, a G CC protein-coupled receptor, on target cells to activate downstream CC signaling pathways (PubMed:2494176, PubMed:24692546). Follitropin CC is involved in follicle development and spermatogenesis in CC reproductive organs (PubMed:407105, PubMed:8220432). CC {ECO:0000269|PubMed:24692546, ECO:0000269|PubMed:2494176, CC ECO:0000269|PubMed:407105, ECO:0000269|PubMed:8220432}. CC -!- SUBUNIT: Heterodimer. The active follitropin is a heterodimer CC composed of an alpha chain/CGA shared with other hormones and a CC unique beta chain/FSHB shown here. {ECO:0000269|PubMed:15662415, CC ECO:0000269|PubMed:24692546, ECO:0000269|PubMed:2494176}. CC -!- INTERACTION: CC P01215:CGA; NbExp=4; IntAct=EBI-1030645, EBI-718913; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2494176}. CC Note=Efficient secretion requires dimerization with CGA. CC {ECO:0000269|PubMed:2494176}. CC -!- DISEASE: Hypogonadotropic hypogonadism 24 without anosmia (HH24) CC [MIM:229070]: A form of hypogonadotropic hypogonadism, a group of CC disorders characterized by absent or incomplete sexual maturation CC by the age of 18 years, in conjunction with low levels of CC circulating gonadotropins and testosterone and no other CC abnormalities of the hypothalamic-pituitary axis. HH24 is CC characterized by primary amenorrhea in women, oligo or azoospermia CC with low to normal testosterone levels in men, and infertility. CC {ECO:0000269|PubMed:8220432, ECO:0000269|PubMed:9271483, CC ECO:0000269|PubMed:9280841}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- PHARMACEUTICAL: Available under the names Gonal-F or Metrodin HP CC (Serono) and Puregon (Organon). Used in the treatment of CC infertility in women with proven hypopituitarism or who have not CC responded to clomifene; or in superovulation treatment for CC assisted conception (such as in vitro fertilization). Metrodin HP CC is also used in the treatment of hypogonadotrophic hypogonadism in CC men for the stimulation of spermatogenesis. CC -!- SIMILARITY: Belongs to the glycoprotein hormones subunit beta CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and CC polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=FSHB"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Follicle-stimulating hormone CC entry; CC URL="https://en.wikipedia.org/wiki/Follicle_stimulating_hormone"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; M16647; AAA52476.1; -; Genomic_DNA. DR EMBL; M16646; AAA52476.1; JOINED; Genomic_DNA. DR EMBL; M24540; AAA52470.1; -; Genomic_DNA. DR EMBL; M24539; AAA52470.1; JOINED; Genomic_DNA. DR EMBL; M54914; AAB02868.1; -; Genomic_DNA. DR EMBL; M54913; AAB02868.1; JOINED; Genomic_DNA. DR EMBL; EF198021; ABM88373.1; -; Genomic_DNA. DR EMBL; EF585489; ABQ57401.1; -; mRNA. DR EMBL; EF585490; ABQ57402.1; -; Genomic_DNA. DR EMBL; EU081884; ABU96749.1; -; Genomic_DNA. DR EMBL; EU081885; ABU96750.1; -; Genomic_DNA. DR EMBL; AL358944; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68260.1; -; Genomic_DNA. DR EMBL; BC113488; AAI13489.1; -; mRNA. DR EMBL; BC113490; AAI13491.1; -; mRNA. DR CCDS; CCDS7868.1; -. DR PIR; A40920; FTHUB. DR RefSeq; NP_000501.1; NM_000510.2. DR RefSeq; NP_001018090.1; NM_001018080.1. DR UniGene; Hs.36975; -. DR PDB; 1FL7; X-ray; 3.00 A; B/D=19-129. DR PDB; 1XWD; X-ray; 2.92 A; B/E=19-129. DR PDB; 4AY9; X-ray; 2.50 A; B/E/H=19-129. DR PDB; 4MQW; X-ray; 2.90 A; B/E/H=19-129. DR PDBsum; 1FL7; -. DR PDBsum; 1XWD; -. DR PDBsum; 4AY9; -. DR PDBsum; 4MQW; -. DR ProteinModelPortal; P01225; -. DR SMR; P01225; -. DR BioGrid; 108766; 1. DR DIP; DIP-35604N; -. DR ELM; P01225; -. DR IntAct; P01225; 3. DR STRING; 9606.ENSP00000254122; -. DR GlyConnect; 165; -. DR iPTMnet; P01225; -. DR PhosphoSitePlus; P01225; -. DR SwissPalm; P01225; -. DR UniCarbKB; P01225; -. DR BioMuta; FSHB; -. DR DMDM; 120552; -. DR PaxDb; P01225; -. DR PeptideAtlas; P01225; -. DR PRIDE; P01225; -. DR ProteomicsDB; 51348; -. DR DNASU; 2488; -. DR Ensembl; ENST00000254122; ENSP00000254122; ENSG00000131808. DR Ensembl; ENST00000417547; ENSP00000416606; ENSG00000131808. DR Ensembl; ENST00000533718; ENSP00000433424; ENSG00000131808. DR GeneID; 2488; -. DR KEGG; hsa:2488; -. DR UCSC; uc001msl.4; human. DR CTD; 2488; -. DR DisGeNET; 2488; -. DR EuPathDB; HostDB:ENSG00000131808.10; -. DR GeneCards; FSHB; -. DR HGNC; HGNC:3964; FSHB. DR HPA; CAB023410; -. DR HPA; HPA069703; -. DR MalaCards; FSHB; -. DR MIM; 136530; gene. DR MIM; 229070; phenotype. DR neXtProt; NX_P01225; -. DR OpenTargets; ENSG00000131808; -. DR Orphanet; 52901; Isolated follicle stimulating hormone deficiency. DR PharmGKB; PA28382; -. DR eggNOG; ENOG410IWHY; Eukaryota. DR eggNOG; ENOG4111ZSU; LUCA. DR GeneTree; ENSGT00940000160051; -. DR HOGENOM; HOG000116098; -. DR HOVERGEN; HBG006698; -. DR InParanoid; P01225; -. DR KO; K05250; -. DR OMA; AVEKEEC; -. DR OrthoDB; 101221at2759; -. DR PhylomeDB; P01225; -. DR TreeFam; TF332940; -. DR Reactome; R-HSA-209822; Glycoprotein hormones. DR Reactome; R-HSA-375281; Hormone ligand-binding receptors. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR SABIO-RK; P01225; -. DR SIGNOR; P01225; -. DR EvolutionaryTrace; P01225; -. DR GeneWiki; FSHB; -. DR GenomeRNAi; 2488; -. DR PRO; PR:P01225; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000131808; Expressed in 38 organ(s), highest expression level in pituitary gland. DR ExpressionAtlas; P01225; baseline and differential. DR Genevisible; P01225; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0016914; C:follicle-stimulating hormone complex; IDA:UniProtKB. DR GO; GO:0016913; F:follicle-stimulating hormone activity; IDA:UniProtKB. DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc. DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc. DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0016486; P:peptide hormone processing; TAS:Reactome. DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; NAS:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; NAS:BHF-UCL. DR GO; GO:0010893; P:positive regulation of steroid biosynthetic process; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; NAS:BHF-UCL. DR GO; GO:0006701; P:progesterone biosynthetic process; TAS:BHF-UCL. DR GO; GO:0045670; P:regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0010469; P:regulation of signaling receptor activity; IDA:UniProtKB. DR GO; GO:0060011; P:Sertoli cell proliferation; IEA:Ensembl. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEP:BHF-UCL. DR CDD; cd00069; GHB_like; 1. DR Gene3D; 2.10.90.10; -; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR006208; Glyco_hormone_CN. DR InterPro; IPR001545; Gonadotropin_bsu. DR InterPro; IPR018245; Gonadotropin_bsu_CS. DR PANTHER; PTHR11515; PTHR11515; 1. DR Pfam; PF00007; Cys_knot; 1. DR SMART; SM00068; GHB; 1. DR SUPFAM; SSF57501; SSF57501; 1. DR PROSITE; PS00261; GLYCO_HORMONE_BETA_1; 1. DR PROSITE; PS00689; GLYCO_HORMONE_BETA_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Disease mutation; Disulfide bond; Glycoprotein; Hormone; KW Hypogonadotropic hypogonadism; Pharmaceutical; Polymorphism; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 18 {ECO:0000269|PubMed:3151250}. FT CHAIN 19 129 Follitropin subunit beta. FT /FTId=PRO_0000011711. FT CARBOHYD 25 25 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:4835136}. FT CARBOHYD 42 42 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:4835136}. FT DISULFID 21 69 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:24692546}. FT DISULFID 35 84 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:24692546}. FT DISULFID 38 122 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:24692546}. FT DISULFID 46 100 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:24692546}. FT DISULFID 50 102 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:24692546}. FT DISULFID 105 112 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:24692546}. FT VARIANT 20 20 S -> I (in dbSNP:rs6170). FT {ECO:0000269|PubMed:10391209}. FT /FTId=VAR_012047. FT VARIANT 69 69 C -> G (in HH24; dbSNP:rs5030776). FT {ECO:0000269|PubMed:9271483}. FT /FTId=VAR_033015. FT MUTAGEN 78 78 T->E: Increased activation of the FT follicle-stimulating hormone signaling FT pathway. {ECO:0000269|PubMed:24692546}. FT STRAND 21 32 {ECO:0000244|PDB:4AY9}. FT HELIX 33 35 {ECO:0000244|PDB:4AY9}. FT STRAND 37 53 {ECO:0000244|PDB:4AY9}. FT STRAND 68 81 {ECO:0000244|PDB:4AY9}. FT STRAND 85 87 {ECO:0000244|PDB:4MQW}. FT STRAND 90 103 {ECO:0000244|PDB:4AY9}. FT TURN 107 109 {ECO:0000244|PDB:4AY9}. FT STRAND 110 114 {ECO:0000244|PDB:4AY9}. SQ SEQUENCE 129 AA; 14700 MW; 9D2AF00DD76B8E2B CRC64; MKTLQFFFLF CCWKAICCNS CELTNITIAI EKEECRFCIS INTTWCAGYC YTRDLVYKDP ARPKIQKTCT FKELVYETVR VPGCAHHADS LYTYPVATQC HCGKCDSDST DCTVRGLGPS YCSFGEMKE //