Lutropin-choriogonadotropic hormone receptor

Details

Name
Lutropin-choriogonadotropic hormone receptor
Synonyms
  • LCGR
  • LGR2
  • LH/CG-R
  • LHR
  • LHRHR
  • LSH-R
  • Luteinizing hormone receptor
Gene Name
LHCGR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036957|Lutropin-choriogonadotropic hormone receptor
MKQRFSALQLLKLLLLLQPPLPRALREALCPEPCNCVPDGALRCPGPTAGLTRLSLAYLP
VKVIPSQAFRGLNEVIKIEISQIDSLERIEANAFDNLLNLSEILIQNTKNLRYIEPGAFI
NLPRLKYLSICNTGIRKFPDVTKVFSSESNFILEICDNLHITTIPGNAFQGMNNESVTLK
LYGNGFEEVQSHAFNGTTLTSLELKENVHLEKMHNGAFRGATGPKTLDISSTKLQALPSY
GLESIQRLIATSSYSLKKLPSRETFVNLLEATLTYPSHCCAFRNLPTKEQNFSHSISENF
SKQCESTVRKVNNKTLYSSMLAESELSGWDYEYGFCLPKTPRCAPEPDAFNPCEDIMGYD
FLRVLIWLINILAIMGNMTVLFVLLTSRYKLTVPRFLMCNLSFADFCMGLYLLLIASVDS
QTKGQYYNHAIDWQTGSGCSTAGFFTVFASELSVYTLTVITLERWHTITYAIHLDQKLRL
RHAILIMLGGWLFSSLIAMLPLVGVSNYMKVSICFPMDVETTLSQVYILTILILNVVAFF
IICACYIKIYFAVRNPELMATNKDTKIAKKMAILIFTDFTCMAPISFFAISAAFKVPLIT
VTNSKVLLVLFYPINSCANPFLYAIFTKTFQRDFFLLLSKFGCCKRRAELYRRKDFSAYT
SNCKNGFTGSNKPSQSTLKLSTLHCQGTALLDKTRYTEC
Number of residues
699
Molecular Weight
78642.01
Theoretical pI
8.58
GO Classification
Functions
choriogonadotropin hormone binding / choriogonadotropin hormone receptor activity / G-protein coupled peptide receptor activity / luteinizing hormone receptor activity
Processes
activation of adenylate cyclase activity / adenylate cyclase-activating G-protein coupled receptor signaling pathway / cellular response to gonadotropin stimulus / cognition / female gonad development / G-protein coupled receptor signaling pathway / G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hormone-mediated signaling pathway / luteinizing hormone signaling pathway / male genitalia development / male gonad development / ovulation cycle process / phospholipase C-activating G-protein coupled receptor signaling pathway / positive regulation of cAMP-mediated signaling / positive regulation of inositol trisphosphate biosynthetic process / spermatogenesis / uterus development
Components
endosome / integral component of plasma membrane / plasma membrane
General Function
Luteinizing hormone receptor activity
Specific Function
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Pfam Domain Function
Transmembrane Regions
364-385 396-416 440-462 483-505 526-549 571-594 606-627
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010174|Lutropin-choriogonadotropic hormone receptor (LHCGR)
ATGAAGCAGCGGTTCTCGGCGCTGCAGCTGCTGAAGCTGCTGCTGCTGCTGCAGCCGCCG
CTGCCACGAGCGCTGCGCGAGGCGCTCTGCCCTGAGCCCTGCAACTGCGTGCCCGACGGC
GCCCTGCGCTGCCCCGGCCCCACGGCCGGTCTCACTCGACTATCACTTGCCTACCTCCCT
GTCAAAGTGATCCCATCTCAAGCTTTCAGAGGACTTAATGAGGTCATAAAAATTGAAATC
TCTCAGATTGATTCCCTGGAAAGGATAGAAGCTAATGCCTTTGACAACCTCCTCAATTTG
TCTGAAATACTGATCCAGAACACCAAAAATCTGAGATACATTGAGCCCGGAGCATTTATA
AATCTTCCCCGATTAAAATACTTGAGCATCTGTAACACAGGCATCAGAAAGTTTCCAGAT
GTTACGAAGGTCTTCTCCTCTGAATCAAATTTCATTCTGGAAATTTGTGATAACTTACAC
ATAACCACCATACCAGGAAATGCTTTTCAAGGGATGAATAATGAATCTGTAACACTCAAA
CTATATGGAAATGGATTTGAAGAAGTACAAAGTCATGCATTCAATGGGACGACACTGACT
TCACTGGAGCTAAAGGAAAACGTACATCTGGAGAAGATGCACAATGGAGCCTTCCGTGGG
GCCACAGGGCCGAAAACCTTGGATATTTCTTCCACCAAATTGCAGGCCCTGCCGAGCTAT
GGCCTAGAGTCCATTCAGAGGCTAATTGCCACGTCATCCTATTCTCTAAAAAAATTGCCA
TCAAGAGAAACATTTGTCAATCTCCTGGAGGCCACGTTGACTTACCCCAGCCACTGCTGT
GCTTTTAGAAACTTGCCAACAAAAGAACAGAATTTTTCACATTCCATTTCTGAAAACTTT
TCCAAACAATGTGAAAGCACAGTAAGGAAAGTGAATAACAAAACACTTTATTCTTCCATG
CTTGCTGAGAGTGAACTGAGTGGCTGGGACTATGAATATGGTTTCTGCTTACCCAAGACA
CCCCGATGTGCTCCTGAACCAGATGCTTTTAATCCCTGTGAAGATATTATGGGCTATGAC
TTCCTTAGGGTCCTGATTTGGCTGATTAATATTCTAGCCATCATGGGAAACATGACTGTT
CTTTTTGTTCTCCTGACAAGTCGTTACAAACTTACAGTGCCTCGTTTTCTCATGTGCAAT
CTCTCCTTTGCAGACTTTTGCATGGGGCTCTATCTGCTGCTCATAGCCTCAGTTGATTCC
CAAACCAAGGGCCAGTACTATAACCATGCCATAGACTGGCAGACAGGGAGTGGGTGCAGC
ACTGCTGGCTTTTTCACTGTATTCGCAAGTGAACTTTCTGTCTACACCCTCACCGTCATC
ACTCTAGAAAGATGGCACACCATCACCTATGCTATTCACCTGGACCAAAAGCTGCGATTA
AGACATGCCATTCTGATTATGCTTGGAGGATGGCTCTTTTCTTCTCTAATTGCTATGTTG
CCCCTTGTCGGTGTCAGCAATTACATGAAGGTCAGTATTTGCTTCCCCATGGATGTGGAA
ACCACTCTCTCACAAGTCTATATATTAACCATCCTGATTCTCAATGTGGTGGCCTTCTTC
ATAATTTGTGCTTGCTACATTAAAATTTATTTTGCAGTTCGAAACCCAGAATTAATGGCT
ACCAATAAAGATACAAAGATTGCTAAGAAAATGGCAATCCTCATCTTCACCGATTTCACC
TGCATGGCACCTATCTCTTTTTTTGCCATCTCAGCTGCCTTCAAAGTACCTCTTATCACA
GTAACCAACTCTAAAGTTTTACTGGTTCTTTTTTATCCCATCAATTCTTGTGCCAATCCA
TTTCTGTATGCAATATTCACTAAGACATTCCAAAGAGATTTCTTTCTTTTGCTGAGCAAA
TTTGGCTGCTGTAAACGTCGGGCTGAACTTTATAGAAGGAAAGATTTTTCAGCTTACACC
TCCAACTGCAAAAATGGCTTCACTGGATCAAATAAGCCTTCTCAATCCACCTTGAAGTTG
TCCACATTGCACTGTCAAGGTACAGCTCTCCTAGACAAGACTCGCTACACAGAGTGTTAA
Chromosome Location
2
Locus
2p21
External Identifiers
ResourceLink
UniProtKB IDP22888
UniProtKB Entry NameLSHR_HUMAN
GenBank Protein ID903746
GenBank Gene IDM73746
GenAtlas IDLHCGR
HGNC IDHGNC:6585
General References
  1. Minegishi T, Nakamura K, Takakura Y, Miyamoto K, Hasegawa Y, Ibuki Y, Igarashi M, Minegish T [corrected to Minegishi T]: Cloning and sequencing of human LH/hCG receptor cDNA. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1049-54. [PubMed:2244890]
  2. Jia XC, Oikawa M, Bo M, Tanaka T, Ny T, Boime I, Hsueh AJ: Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species. Mol Endocrinol. 1991 Jun;5(6):759-68. [PubMed:1922095]
  3. Frazier AL, Robbins LS, Stork PJ, Sprengel R, Segaloff DL, Cone RD: Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing. Mol Endocrinol. 1990 Aug;4(8):1264-76. [PubMed:2293030]
  4. Atger M, Misrahi M, Sar S, Le Flem L, Dessen P, Milgrom E: Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5' non-coding regions. Mol Cell Endocrinol. 1995 Jun;111(2):113-23. [PubMed:7556872]
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  6. Tsai-Morris CH, Geng Y, Buczko E, Dehejia A, Dufau ML: Genomic distribution and gonadal mRNA expression of two human luteinizing hormone receptor exon 1 sequences in random populations. Hum Hered. 1999 Jan;49(1):48-51. [PubMed:9858858]
  7. Munshi UM, Clouser CL, Peegel H, Menon KM: Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing. Mol Endocrinol. 2005 Mar;19(3):749-58. Epub 2004 Nov 11. [PubMed:15539429]
  8. Jiang X, Dreano M, Buckler DR, Cheng S, Ythier A, Wu H, Hendrickson WA, el Tayar N: Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions. Structure. 1995 Dec 15;3(12):1341-53. [PubMed:8747461]
  9. Latronico AC, Shinozaki H, Guerra G Jr, Pereira MA, Lemos Marini SH, Baptista MT, Arnhold IJ, Fanelli F, Mendonca BB, Segaloff DL: Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: a novel constitutively activating mutation in the first transmembrane helix. J Clin Endocrinol Metab. 2000 Dec;85(12):4799-805. [PubMed:11134146]
  10. Leschek EW, Chan WY, Diamond DA, Kaefer M, Jones J, Barnes KM, Cutler GB Jr: Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty. J Pediatr. 2001 Jun;138(6):949-51. [PubMed:11391350]
  11. Martens JW, Lumbroso S, Verhoef-Post M, Georget V, Richter-Unruh A, Szarras-Czapnik M, Romer TE, Brunner HG, Themmen AP, Sultan Ch: Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency. J Clin Endocrinol Metab. 2002 Jun;87(6):2506-13. [PubMed:12050206]
  12. Powell BL, Piersma D, Kevenaar ME, van Staveren IL, Themmen AP, Iacopetta BJ, Berns EM: Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset. J Clin Endocrinol Metab. 2003 Apr;88(4):1653-7. [PubMed:12679452]
  13. Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr: A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature. 1993 Oct 14;365(6447):652-4. [PubMed:7692306]
  14. Kremer H, Mariman E, Otten BJ, Moll GW Jr, Stoelinga GB, Wit JM, Jansen M, Drop SL, Faas B, Ropers HH, et al.: Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty. Hum Mol Genet. 1993 Nov;2(11):1779-83. [PubMed:8281137]
  15. Kosugi S, Van Dop C, Geffner ME, Rabl W, Carel JC, Chaussain JL, Mori T, Merendino JJ Jr, Shenker A: Characterization of heterogeneous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty. Hum Mol Genet. 1995 Feb;4(2):183-8. [PubMed:7757065]
  16. Yano K, Saji M, Hidaka A, Moriya N, Okuno A, Kohn LD, Cutler GB Jr: A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty. J Clin Endocrinol Metab. 1995 Apr;80(4):1162-8. [PubMed:7714085]
  17. Latronico AC, Anasti J, Arnhold IJ, Mendonca BB, Domenice S, Albano MC, Zachman K, Wajchenberg BL, Tsigos C: A novel mutation of the luteinizing hormone receptor gene causing male gonadotropin-independent precocious puberty. J Clin Endocrinol Metab. 1995 Aug;80(8):2490-4. [PubMed:7629248]
  18. Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, van Reen M, Milgrom E, Ropers HH, Mariman E, et al.: Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995 Feb;9(2):160-4. [PubMed:7719343]
  19. Cocco S, Meloni A, Marini MG, Cao A, Moi P: A missense (T577I) mutation in the luteinizing hormone receptor gene associated with familial male-limited precocious puberty. Hum Mutat. 1996;7(2):164-6. [PubMed:8829636]
  20. Evans BA, Bowen DJ, Smith PJ, Clayton PE, Gregory JW: A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype. J Med Genet. 1996 Feb;33(2):143-7. [PubMed:8929952]
  21. Latronico AC, Anasti J, Arnhold IJ, Rapaport R, Mendonca BB, Bloise W, Castro M, Tsigos C, Chrousos GP: Brief report: testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N Engl J Med. 1996 Feb 22;334(8):507-12. [PubMed:8559204]
  22. Misrahi M, Meduri G, Pissard S, Bouvattier C, Beau I, Loosfelt H, Jolivet A, Rappaport R, Milgrom E, Bougneres P: Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor. J Clin Endocrinol Metab. 1997 Jul;82(7):2159-65. [PubMed:9215288]
  23. Wu SM, Jose M, Hallermeier K, Rennert OM, Chan WY: Polymorphisms in the coding exons of the human luteinizing hormone receptor gene. Mutations in brief no. 124. Online. Hum Mutat. 1998;11(4):333-4. [PubMed:10215412]
  24. Gromoll J, Partsch CJ, Simoni M, Nordhoff V, Sippell WG, Nieschlag E, Saxena BB: A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty. J Clin Endocrinol Metab. 1998 Feb;83(2):476-80. [PubMed:9467560]
  25. Stavrou SS, Zhu YS, Cai LQ, Katz MD, Herrera C, Defillo-Ricart M, Imperato-McGinley J: A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX sisters. J Clin Endocrinol Metab. 1998 Jun;83(6):2091-8. [PubMed:9626144]
  26. Latronico AC, Abell AN, Arnhold IJ, Liu X, Lins TS, Brito VN, Billerbeck AE, Segaloff DL, Mendonca BB: A unique constitutively activating mutation in third transmembrane helix of luteinizing hormone receptor causes sporadic male gonadotropin-independent precocious puberty. J Clin Endocrinol Metab. 1998 Jul;83(7):2435-40. [PubMed:9661624]
  27. Rodien P, Cetani F, Costagliola S, Tonacchera M, Duprez L, Minegishi T, Govaerts C, Vassart G: Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors. J Clin Endocrinol Metab. 1998 Dec;83(12):4431-4. [PubMed:9851790]
  28. Latronico AC, Chai Y, Arnhold IJ, Liu X, Mendonca BB, Segaloff DL: A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor. Mol Endocrinol. 1998 Mar;12(3):442-50. [PubMed:9514160]
  29. Martens JW, Verhoef-Post M, Abelin N, Ezabella M, Toledo SP, Brunner HG, Themmen AP: A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype. Mol Endocrinol. 1998 Jun;12(6):775-84. [PubMed:9626653]
  30. Liu G, Duranteau L, Carel JC, Monroe J, Doyle DA, Shenker A: Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med. 1999 Dec 2;341(23):1731-6. [PubMed:10580072]
  31. Leung MY, Al-Muslim O, Wu SM, Aziz A, Inam S, Awadh M, Rennert OM, Chan WY: A novel missense homozygous inactivating mutation in the fourth transmembrane helix of the luteinizing hormone receptor in leydig cell hypoplasia. Am J Med Genet A. 2004 Oct 1;130A(2):146-53. [PubMed:15372531]
  32. Richter-Unruh A, Verhoef-Post M, Malak S, Homoki J, Hauffa BP, Themmen AP: Leydig cell hypoplasia: absent luteinizing hormone receptor cell surface expression caused by a novel homozygous mutation in the extracellular domain. J Clin Endocrinol Metab. 2004 Oct;89(10):5161-7. [PubMed:15472221]
  33. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974]
  34. Qiao J, Han B, Liu BL, Chen X, Ru Y, Cheng KX, Chen FG, Zhao SX, Liang J, Lu YL, Tang JF, Wu YX, Wu WL, Chen JL, Chen MD, Song HD: A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Hum Mutat. 2009 Sep;30(9):E855-65. doi: 10.1002/humu.21072. [PubMed:19551906]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00014GoserelinapprovedyesagonistDetails
DB00044Lutropin alfaapprovedyesagonistDetails
DB00050Cetrorelixapproved, investigationalunknownDetails
DB00032MenotropinsapprovedyesDetails
DB00097Choriogonadotropin alfaapprovedyesDetails
DB06719Buserelinapproved, investigationalyesDetails
DB09126Chorionic Gonadotropin (Human)approved, vet_approvedyesligandDetails