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   02-SEP-2026, entry version 221.
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   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 hormone
RT   beta-subunit determined by [1H]- and [15N]nuclear magnetic resonance
RT   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., 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   [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., 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: Promotes spermatogenesis and ovulation by stimulating the
CC       testes and ovaries to synthesize steroids.
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.
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.
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";
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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; 844 antibodies from 39 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; YHELHFA; -.
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; TAS:Reactome.
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   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
//