LSHB_HUMAN
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 03-AUG-2022, entry version 203.
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;
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=SHMPD; Note=The Singapore human mutation and
CC polymorphism database;
CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=C&genename=LHB";
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_000894.2.
DR AlphaFoldDB; P01229; -.
DR SMR; P01229; -.
DR BioGRID; 110160; 4.
DR ComplexPortal; CPX-6097; Luteinizing hormone complex.
DR IntAct; P01229; 4.
DR STRING; 9606.ENSP00000221421; -.
DR GlyConnect; 350; 18 N-Linked glycans (1 site).
DR GlyGen; P01229; 1 site, 32 N-linked glycans (1 site).
DR BioMuta; LHB; -.
DR DMDM; 1170834; -.
DR MassIVE; P01229; -.
DR PaxDb; P01229; -.
DR PeptideAtlas; P01229; -.
DR PRIDE; P01229; -.
DR ProteomicsDB; 51349; -.
DR Antibodypedia; 18479; 808 antibodies from 35 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 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 neXtProt; NX_P01229; -.
DR OpenTargets; ENSG00000104826; -.
DR Orphanet; 325448; Leydig cell hypoplasia due to LHB deficiency.
DR PharmGKB; PA30356; -.
DR VEuPathDB; HostDB:ENSG00000104826; -.
DR eggNOG; ENOG502S49V; Eukaryota.
DR GeneTree; ENSGT00940000163162; -.
DR HOGENOM; CLU_126319_0_0_1; -.
DR InParanoid; P01229; -.
DR OMA; NSICAGY; -.
DR OrthoDB; 1362225at2759; -.
DR PhylomeDB; P01229; -.
DR TreeFam; TF332940; -.
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-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-975578; Reactions specific to the complex N-glycan synthesis pathway.
DR SignaLink; P01229; -.
DR SIGNOR; P01229; -.
DR BioGRID-ORCS; 3972; 7 hits in 1061 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 122 other tissues.
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:0061696; C:pituitary gonadotropin complex; IC:ComplexPortal.
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; IC:ComplexPortal.
DR GO; GO:0008584; P:male gonad development; TAS:ProtInc.
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 Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Hormone; Hypogonadotropic hypogonadism; Reference proteome; Secreted;
KW 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
