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 13-FEB-2019, entry version 186. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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; RA Sairam M.R., Li C.H.; RT "Human pituitary lutropin. Isolation, properties, and the complete RT amino 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 RT fragment 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 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 [7] 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 RT hormone beta-subunit determined by [1H]- and [15N]nuclear magnetic RT resonance spectroscopy."; RL Mol. Endocrinol. 6:904-913(1992). RN [8] 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 [9] 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 [10] 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., RA Miyazaki K., Karino K.; RT "Increased prevalence of luteinizing hormone beta-subunit variant in RT Japanese infertility patients."; RL Hum. Reprod. 13:3338-3344(1998). RN [11] 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., RA Herrera R.J., Huhtaniemi I.; RT "A novel Ala(-3)Thr mutation in the signal peptide of human RT luteinizing hormone beta-subunit: potentiation of the inositol RT phosphate signalling pathway and attenuation of the adenylate cyclase RT pathway by recombinant variant hormone."; RL Mol. Hum. Reprod. 8:201-212(2002). CC -!- FUNCTION: Promotes spermatogenesis and ovulation by stimulating CC the testes and ovaries to synthesize steroids. CC -!- SUBUNIT: Heterodimer of a common alpha chain and a unique beta CC chain which confers biological specificity to thyrotropin, CC lutropin, follitropin and gonadotropin. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Pituitary gland. CC -!- DISEASE: Hypogonadotropic hypogonadism 23 without anosmia (HH23) CC [MIM:228300]: 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. HH23 male CC patients have normal sexual differentiation, reduced or absent CC Leydig cells, reduced or absent spermatogenesis, and absence of CC spontaneous puberty. Female patients exhibit normal pubertal CC development and menarche, followed by oligomenorrhea and CC anovulatory secondary amenorrhea. {ECO:0000269|PubMed:1727547}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. 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=LHB"; 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_000894.2. DR UniGene; Hs.154704; -. DR PDB; 1M92; Model; -; A=1-141. DR PDBsum; 1M92; -. DR ProteinModelPortal; P01229; -. DR SMR; P01229; -. DR IntAct; P01229; 4. DR STRING; 9606.ENSP00000221421; -. DR GlyConnect; 350; -. DR UniCarbKB; P01229; -. DR BioMuta; LHB; -. DR DMDM; 1170834; -. DR PaxDb; P01229; -. DR PeptideAtlas; P01229; -. DR PRIDE; P01229; -. DR ProteomicsDB; 51349; -. DR DNASU; 3972; -. DR Ensembl; ENST00000221421; ENSP00000221421; ENSG00000104826. DR Ensembl; ENST00000649238; ENSP00000497294; ENSG00000104826. DR GeneID; 3972; -. DR KEGG; hsa:3972; -. DR UCSC; uc002plt.4; human. DR CTD; 3972; -. DR DisGeNET; 3972; -. DR EuPathDB; HostDB:ENSG00000104826.11; -. DR GeneCards; LHB; -. DR HGNC; HGNC:6584; LHB. DR HPA; CAB022241; -. DR HPA; CAB022707; -. DR HPA; HPA038925; -. DR MalaCards; LHB; -. DR MIM; 152780; gene. DR MIM; 228300; phenotype. DR neXtProt; NX_P01229; -. DR OpenTargets; ENSG00000104826; -. DR Orphanet; 325448; Leydig cell hypoplasia due to LHB deficiency. DR PharmGKB; PA30356; -. DR eggNOG; ENOG410J0DB; Eukaryota. DR eggNOG; ENOG4111ZSU; LUCA. DR GeneTree; ENSGT00940000163162; -. DR HOGENOM; HOG000116098; -. DR HOVERGEN; HBG006698; -. DR InParanoid; P01229; -. DR KO; K08521; -. DR OMA; TICSGHC; -. DR OrthoDB; 784427at2759; -. DR PhylomeDB; P01229; -. DR TreeFam; TF332940; -. 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 SIGNOR; P01229; -. DR GeneWiki; Luteinizing_hormone_beta_polypeptide; -. DR GenomeRNAi; 3972; -. DR PRO; PR:P01229; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000104826; Expressed in 107 organ(s), highest expression level in adenohypophysis. DR ExpressionAtlas; P01229; baseline and differential. DR Genevisible; P01229; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0008584; P:male gonad development; TAS:ProtInc. DR GO; GO:0016486; P:peptide hormone processing; TAS:Reactome. 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 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; Polymorphism; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 20 {ECO:0000269|PubMed:1191677}. FT CHAIN 21 141 Lutropin subunit beta. FT /FTId=PRO_0000011726. FT CARBOHYD 50 50 N-linked (GlcNAc...) asparagine. FT /FTId=CAR_000045. FT DISULFID 29 77 {ECO:0000250}. FT DISULFID 43 92 {ECO:0000250}. FT DISULFID 46 130 {ECO:0000250}. FT DISULFID 54 108 {ECO:0000250}. FT DISULFID 58 110 {ECO:0000250}. FT DISULFID 113 120 {ECO:0000250}. FT VARIANT 15 15 M -> I (in dbSNP:rs34247911). FT /FTId=VAR_034098. FT VARIANT 18 18 A -> T (more effective in stimulating IP3 FT but not cAMP production; FT dbSNP:rs5030775). FT {ECO:0000269|PubMed:11870227}. FT /FTId=VAR_015672. FT VARIANT 28 28 W -> R (in dbSNP:rs1800447). FT {ECO:0000269|PubMed:9886510}. FT /FTId=VAR_014589. FT VARIANT 35 35 I -> T (in dbSNP:rs34349826). FT {ECO:0000269|PubMed:9886510}. FT /FTId=VAR_014590. FT VARIANT 74 74 Q -> R (in HH23; lack of receptor FT binding; dbSNP:rs5030773). FT {ECO:0000269|PubMed:1727547}. FT /FTId=VAR_003189. FT VARIANT 122 122 G -> S (may be implicated in female FT infertility; dbSNP:rs5030774). FT {ECO:0000269|PubMed:9457942}. FT /FTId=VAR_015673. FT CONFLICT 39 39 E -> Q (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 76 76 Missing (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 132 135 HPQL -> PQH (in Ref. 2; AA sequence). FT {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 //