ID LSHB_HUMAN Reviewed; 141 AA. AC P01229; Q9UDI0; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 3. DT 04-NOV-2026, entry version 222. DE RecName: Full=Lutropin subunit beta; DE Short=Lutropin beta chain; DE AltName: Full=Luteinizing hormone subunit beta; DE Short=LH-B; DE Short=LSH-B; DE Short=LSH-beta; DE Flags: Precursor; GN Name=LHB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6690982; DOI=10.1038/307037a0; RA Talmadge K., Vamvakopoulos N.C., Fiddes J.C.; RT "Evolution of the genes for the beta subunits of human chorionic RT gonadotropin and luteinizing hormone."; RL Nature 307:37-40(1984). RN [2] RP PROTEIN SEQUENCE OF 21-141. RX PubMed=1191677; DOI=10.1016/0005-2795(75)90340-2; RA Sairam M.R., Li C.H.; RT "Human pituitary lutropin. Isolation, properties, and the complete amino RT acid sequence of the beta-subunit."; RL Biochim. Biophys. Acta 412:70-81(1975). RN [3] RP PRELIMINARY PROTEIN SEQUENCE OF 21-141. RX PubMed=4685398; DOI=10.1210/jcem-36-3-618; RA Shome B., Parlow A.F.; RT "The primary structure of the hormone-specific, beta subunit of human RT pituitary luteinizing hormone (hLH)."; RL J. Clin. Endocrinol. Metab. 36:618-621(1973). RN [4] RP PROTEIN SEQUENCE OF 26-40 AND 75-89. RC TISSUE=Pituitary; RX PubMed=7689962; DOI=10.1210/endo.133.3.7689962; RA Birken S., Chen Y., Gawinowicz M.A., Agosto G.M., Canfield R.E., RA Hartree A.S.; RT "Structure and significance of human luteinizing hormone-beta core fragment RT purified from human pituitary extracts."; RL Endocrinology 133:985-989(1993). RN [5] RP PRELIMINARY PARTIAL PROTEIN SEQUENCE. RX PubMed=4719207; DOI=10.1016/0014-5793(73)80534-4; RA Closset J., Hennen G., Lequin R.M.; RT "Human luteinizing hormone. The amino acid sequence of the subunit."; RL FEBS Lett. 29:97-100(1973). RN [6] RP FUNCTION. RX PubMed=15677709; DOI=10.1210/me.2004-0410; RA Galet C., Ascoli M.; RT "The differential binding affinities of the luteinizing hormone RT (LH)/choriogonadotropin receptor for LH and choriogonadotropin are dictated RT by different extracellular domain residues."; RL Mol. Endocrinol. 19:1263-1276(2005). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17761593; DOI=10.1056/nejmoa071999; RA Lofrano-Porto A., Barra G.B., Giacomini L.A., Nascimento P.P., RA Latronico A.C., Casulari L.A., da Rocha Neves A.; RT "Luteinizing hormone beta mutation and hypogonadism in men and women."; RL N. Engl. J. Med. 357:897-904(2007). RN [8] RP FUNCTION, INTERACTION WITH CGA, AND MUTAGENESIS OF CYS-46. RX PubMed=24692561; DOI=10.1074/jbc.m113.535609; RA Bernard M.P., Lin W., Kholodovych V., Moyle W.R.; RT "Human lutropin (hLH) and choriogonadotropin (CG) are assembled by RT different pathways: a model of hLH assembly."; RL J. Biol. Chem. 289:14360-14369(2014). RN [9] RP STRUCTURE OF CARBOHYDRATE. RX PubMed=1991473; DOI=10.1111/j.1432-1033.1991.tb15702.x; RA Weisshaar G., Hiyama J., Renwick A.G.C., Nimtz M.; RT "NMR investigations of the N-linked oligosaccharides at individual RT glycosylation sites of human lutropin."; RL Eur. J. Biochem. 195:257-268(1991). RN [10] RP STRUCTURE BY NMR OF 58-77. RX PubMed=1495492; DOI=10.1210/mend.6.6.1495492; RA Keutmann H.T., Hua Q.-X., Weiss M.A.; RT "Structure of a receptor-binding fragment from human luteinizing hormone RT beta-subunit determined by [1H]- and [15N]nuclear magnetic resonance RT spectroscopy."; RL Mol. Endocrinol. 6:904-913(1992). RN [11] RP INVOLVEMENT IN HH23, AND VARIANT HH23 ARG-74. RX PubMed=1727547; DOI=10.1056/nejm199201163260306; RA Weiss J., Axelrod L., Whitcomb R.W., Harris P.E., Crowley W.F. Jr., RA Jameson J.L.; RT "Hypogonadism caused by a single amino acid substitution in the beta RT subunit of luteinizing hormone."; RL N. Engl. J. Med. 326:179-183(1992). RN [12] RP VARIANT SER-122. RX PubMed=9457942; DOI=10.1016/s0015-0282(97)00445-7; RA Liao W.X., Roy A.C., Chan C., Arulkumaran S., Ratnam S.S.; RT "A new molecular variant of luteinizing hormone associated with female RT infertility."; RL Fertil. Steril. 69:102-106(1998). RN [13] RP VARIANTS ARG-28 AND THR-35. RX PubMed=9886510; DOI=10.1093/humrep/13.12.3338; RA Takahashi K., Kurioka H., Ozaki T., Kanasaki H., Kohsaka M., Miyazaki K., RA Karino K.; RT "Increased prevalence of luteinizing hormone beta-subunit variant in RT Japanese infertility patients."; RL Hum. Reprod. 13:3338-3344(1998). RN [14] RP VARIANT THR-18. RX PubMed=11870227; DOI=10.1093/molehr/8.3.201; RA Jiang M., Lamminen T., Pakarinen P., Hellman J., Manna P., Herrera R.J., RA Huhtaniemi I.; RT "A novel Ala(-3)Thr mutation in the signal peptide of human luteinizing RT hormone beta-subunit: potentiation of the inositol phosphate signalling RT pathway and attenuation of the adenylate cyclase pathway by recombinant RT variant hormone."; RL Mol. Hum. Reprod. 8:201-212(2002). CC -!- FUNCTION: Hormone-specific beta subunit of luteinizing hormone (LH), a CC pituitary glycoprotein hormone (PubMed:24692561). Assembles non- CC covalently with the common glycoprotein hormone alpha subunit (CGA) to CC form the biologically active LH heterodimer; the alpha subunit CC contributes to correct folding and assembly of the beta subunit CC (PubMed:24692561). Binds and activates the G protein-coupled receptor CC LHCGR on gonadal target cells (PubMed:15677709). In turn, triggers Gs- CC mediated cAMP production, PKA/CREB activation and steroidogenic gene CC expression such as STAR, leading to steroidogenesis (By similarity). In CC males, promotes Leydig cell development and maturation and testicular CC androgen (testosterone) production; while in females, drives ovulation, CC corpus luteum formation and ovarian progesterone and estradiol output CC (PubMed:17761593). In the ovary, the preovulatory LH surge acts on CC preovulatory granulosa cells to transiently and cAMP-dependently induce CC the progesterone receptor (PGR), a transcription factor required for CC follicular rupture and ovulation (By similarity). Required for CC postnatal gonadal maturation and fertility in both sexes CC (PubMed:17761593). {ECO:0000250|UniProtKB:O09108, CC ECO:0000250|UniProtKB:P01230, ECO:0000269|PubMed:15677709, CC ECO:0000269|PubMed:17761593, ECO:0000269|PubMed:24692561}. CC -!- SUBUNIT: Heterodimer of a common alpha chain and a unique beta chain CC which confers biological specificity to thyrotropin, lutropin, CC follitropin and gonadotropin. {ECO:0000269|PubMed:24692561}. CC -!- INTERACTION: CC P01229; Q13643: FHL3; NbExp=3; IntAct=EBI-11659791, EBI-741101; CC P01229; Q9P121-3: NTM; NbExp=3; IntAct=EBI-11659791, EBI-12027160; CC P01229; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-11659791, EBI-744081; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17761593}. CC -!- TISSUE SPECIFICITY: Pituitary gland. CC -!- DISEASE: Hypogonadotropic hypogonadism 23 with or without anosmia CC (HH23) [MIM:228300]: A form of hypogonadotropic hypogonadism, a group CC of disorders characterized by absent or incomplete sexual maturation by CC the age of 18 years, in conjunction with low levels of circulating CC gonadotropins and testosterone and no other abnormalities of the CC hypothalamic-pituitary axis. HH23 male patients have normal sexual CC differentiation, reduced or absent Leydig cells, reduced or absent CC spermatogenesis, and absence of spontaneous puberty. Female patients CC exhibit normal pubertal development and menarche, followed by CC oligomenorrhea and anovulatory secondary amenorrhea. CC {ECO:0000269|PubMed:1727547}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the glycoprotein hormones subunit beta family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Luteinizing hormone entry; CC URL="https://en.wikipedia.org/wiki/Luteinizing_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; X00264; CAA25067.1; -; Genomic_DNA. DR EMBL; S71273; AAD14960.1; ALT_SEQ; Genomic_DNA. DR CCDS; CCDS12748.1; -. DR PIR; I37994; UTHUB. DR RefSeq; NP_000885.1; NM_000894.3. DR AlphaFoldDB; P01229; -. DR SMR; P01229; -. DR BioGRID; 110160; 4. DR ComplexPortal; CPX-6097; Luteinizing hormone complex. DR FunCoup; P01229; 720. DR IntAct; P01229; 5. DR NDEx; IQUERY-CP-LHB; 3 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000497294; -. DR GlyConnect; P01229; 18 N-Linked glycans (1 site). DR GlyCosmos; P01229; 1 site, 32 glycans. DR GlyGen; P01229; 1 site, 32 N-linked glycans (1 site). DR iPTMnet; P01229; -. DR BioMuta; LHB; -. DR DMDM; 1170834; -. DR MassIVE; P01229; -. DR PaxDb; 9606-ENSP00000497294; -. DR PeptideAtlas; P01229; -. DR ProteomicsDB; 51349; -. DR Antibodypedia; 18479; 890 antibodies from 41 providers. DR DNASU; 3972; -. DR Ensembl; ENST00000649238.3; ENSP00000497294.2; ENSG00000104826.15. DR GeneID; 3972; -. DR KEGG; hsa:3972; -. DR MANE-Select; ENST00000649238.3; ENSP00000497294.2; NM_000894.3; NP_000885.1. DR UCSC; uc002plt.4; human. DR AGR; HGNC:6584; -. DR ClinPGx; PA30356; -. DR CTD; 3972; -. DR DisGeNET; 3972; -. DR GeneCards; LHB; -. DR HGNC; HGNC:6584; LHB. DR HPA; ENSG00000104826; Tissue enriched (pituitary). DR MalaCards; LHB; -. DR MIM; 152780; gene. DR MIM; 228300; phenotype. DR OpenTargets; ENSG00000104826; -. DR Orphanet; 325448; Leydig cell hypoplasia due to LHB deficiency. DR VEuPathDB; HostDB:ENSG00000104826; -. DR eggNOG; ENOG502S49V; Eukaryota. DR GeneTree; ENSGT00940000163162; -. DR HOGENOM; CLU_126319_0_0_1; -. DR InParanoid; P01229; -. DR OMA; AAENEVC; -. DR OrthoDB; 9525526at2759; -. DR PAN-GO; P01229; 4 GO annotations based on evolutionary models. DR PhylomeDB; P01229; -. DR PathwayCommons; P01229; -. DR Reactome; R-HSA-193048; Androgen biosynthesis. DR Reactome; R-HSA-193993; Mineralocorticoid biosynthesis. 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 Reactome; R-HSA-975578; Reactions specific to the complex N-glycan synthesis pathway. DR SignaLink; P01229; -. DR SIGNOR; P01229; -. DR Agora; ENSG00000104826; -. DR BioGRID-ORCS; 3972; 7 hits in 1137 CRISPR screens. DR GeneWiki; Luteinizing_hormone_beta_polypeptide; -. DR GenomeRNAi; 3972; -. DR Pharos; P01229; Tbio. DR PRO; PR:P01229; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P01229; protein. DR Bgee; ENSG00000104826; Expressed in adenohypophysis and 124 other cell types or tissues. DR ExpressionAtlas; P01229; baseline and differential. DR GO; GO:0005576; C:extracellular region; IBA:GO_Central. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0061696; C:pituitary gonadotropin complex; NAS:ComplexPortal. DR GO; GO:0005179; F:hormone activity; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0009755; P:hormone-mediated signaling pathway; NAS:ComplexPortal. DR GO; GO:0042700; P:luteinizing hormone signaling pathway; IBA:GO_Central. DR GO; GO:0008584; P:male gonad development; TAS:ProtInc. DR GO; GO:0001541; P:ovarian follicle development; IBA:GO_Central. DR GO; GO:0006701; P:progesterone biosynthetic process; TAS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd00069; GHB_like; 1. DR FunFam; 2.10.90.10:FF:000007; Luteinizing hormone beta subunit; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 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; GLYCOPROTEIN HORMONE BETA CHAIN; 1. DR PANTHER; PTHR11515:SF11; LUTROPIN SUBUNIT BETA; 1. DR Pfam; PF00007; Cys_knot; 1. DR SMART; SM00068; GHB; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR PROSITE; PS00261; GLYCO_HORMONE_BETA_1; 1. DR PROSITE; PS00689; GLYCO_HORMONE_BETA_2; 1. PE 1: Evidence at protein level; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Hormone; Hypogonadotropic hypogonadism; Proteomics identification; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..20 FT /evidence="ECO:0000269|PubMed:1191677" FT CHAIN 21..141 FT /note="Lutropin subunit beta" FT /id="PRO_0000011726" FT CARBOHYD 50 FT /note="N-linked (GlcNAc...) asparagine" FT /id="CAR_000045" FT DISULFID 29..77 FT /evidence="ECO:0000250" FT DISULFID 43..92 FT /evidence="ECO:0000250" FT DISULFID 46..130 FT /evidence="ECO:0000250" FT DISULFID 54..108 FT /evidence="ECO:0000250" FT DISULFID 58..110 FT /evidence="ECO:0000250" FT DISULFID 113..120 FT /evidence="ECO:0000250" FT VARIANT 15 FT /note="M -> I (in dbSNP:rs34247911)" FT /id="VAR_034098" FT VARIANT 18 FT /note="A -> T (more effective in stimulating IP3 but not FT cAMP production; dbSNP:rs5030775)" FT /evidence="ECO:0000269|PubMed:11870227" FT /id="VAR_015672" FT VARIANT 28 FT /note="W -> R (in dbSNP:rs1800447)" FT /evidence="ECO:0000269|PubMed:9886510" FT /id="VAR_014589" FT VARIANT 35 FT /note="I -> T (in dbSNP:rs34349826)" FT /evidence="ECO:0000269|PubMed:9886510" FT /id="VAR_014590" FT VARIANT 74 FT /note="Q -> R (in HH23; lack of receptor binding; FT dbSNP:rs5030773)" FT /evidence="ECO:0000269|PubMed:1727547" FT /id="VAR_003189" FT VARIANT 122 FT /note="G -> S (may be implicated in female infertility; FT dbSNP:rs5030774)" FT /evidence="ECO:0000269|PubMed:9457942" FT /id="VAR_015673" FT MUTAGEN 46 FT /note="C->A: About 50% loss of heterodimerization with FT CGA." FT /evidence="ECO:0000269|PubMed:24692561" FT CONFLICT 39 FT /note="E -> Q (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 76 FT /note="Missing (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 132..135 FT /note="HPQL -> PQH (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 141 AA; 15345 MW; E411766253113F7C CRC64; MEMLQGLLLL LLLSMGGAWA SREPLRPWCH PINAILAVEK EGCPVCITVN TTICAGYCPT MMRVLQAVLP PLPQVVCTYR DVRFESIRLP GCPRGVDPVV SFPVALSCRC GPCRRSTSDC GGPKDHPLTC DHPQLSGLLF L //