ID LSHR_HUMAN STANDARD; PRT; 699 AA. AC P22888; Q14751; Q15996; Q9UEW9; DT 01-AUG-1991 (Rel. 19, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-SEP-2003 (Rel. 42, Last annotation update) DE Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) DE (LSH-R) (Luteinizing hormone receptor) (LHR). GN LHCGR OR LHRHR OR LCGR. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Ovary; RX MEDLINE=91058534; PubMed=2244890; RA Minegish T., Nakamura K., Takakura Y., Miyamoto K., Hasegawa Y., RA Ibuki Y., Igarashi M.; RT "Cloning and sequencing of human LH/hCG receptor cDNA."; RL Biochem. Biophys. Res. Commun. 172:1049-1054(1990). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Ovary; RX MEDLINE=92017881; PubMed=1922095; RA Jia X.-C., Oikawa M., Bo M., Tanaka T., Ny T., Boime I., Hsueh A.J.W.; RT "Expression of human luteinizing hormone (LH) receptor: interaction RT with LH and chorionic gonadotropin from human but not equine, rat, RT and ovine species."; RL Mol. Endocrinol. 5:759-768(1991). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Thyroid; RX MEDLINE=91155962; PubMed=2293030; RA Frazier A.L., Robbins L.S., Stork P.J., Sprengel R., Segaloff D.L., RA Cone R.D.; RT "Isolation of TSH and LH/CG receptor cDNAs from human thyroid: RT regulation by tissue specific splicing."; RL Mol. Endocrinol. 4:1264-1276(1990). RN [4] RP SEQUENCE FROM N.A., AND VARIANT LEU-GLN-18 INS. RX MEDLINE=96023956; PubMed=7556872; RA Atger M., Misrahi M., Sar S., Leflem L., Dessen P., Milgrom E.; RT "Structure of the human luteinizing hormone-choriogonadotropin RT receptor gene: unusual promoter and 5' non-coding regions."; RL Mol. Cell. Endocrinol. 111:113-123(1995). RN [5] RP SEQUENCE OF 1-54 FROM N.A., AND VARIANT LEU-GLN-18 INS. RX MEDLINE=99077869; PubMed=9858858; RA Tsai-Morris C.-H., Geng Y., Buczko E., Dehejia A., Dufau M.L.; RT "Genomic distribution and gonadal mRNA expression of two human RT luteinizing hormone receptor exon 1 sequences in random RT populations."; RL Hum. Hered. 49:48-51(1999). RN [6] RP 3D-STRUCTURE MODELING OF 51-232. RX MEDLINE=96363672; PubMed=8747461; RA Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., RA Hendrickson W.A., el Tayar N.; RT "Structural predictions for the ligand-binding region of glycoprotein RT hormone receptors and the nature of hormone-receptor interactions."; RL Structure 3:1341-1353(1995). RN [7] RP VARIANT FMPP GLY-578. RX MEDLINE=94019815; PubMed=7692306; RA Shenker A., Laue L., Kosugi S., Merendino J.J. Jr., Minegishi T., RA Cutler G.B. Jr.; RT "A constitutively activating mutation of the luteinizing hormone RT receptor in familial male precocious puberty."; RL Nature 365:652-654(1993). RN [8] RP VARIANTS FMPP ILE-571 AND GLY-578. RX MEDLINE=94108425; PubMed=8281137; RA Kremer H., Mariman E., Otten B.J., Moll G.W. Jr., Stoelinga G.B.A., RA Wit J.M., Jansen M., Drop S.L., Faas B., Ropers H.-H., Brunner H.G.; RT "Cosegregation of missense mutations of the luteinizing hormone RT receptor gene with familial male-limited precocious puberty."; RL Hum. Mol. Genet. 2:1779-1783(1993). RN [9] RP VARIANT FMPP ILE-577. RX MEDLINE=95276728; PubMed=7757065; RA Kosugi S., van Dop C., Geffner M.E., Rabl W., Carel J.-C., RA Chaussain J.-L., Mori T., Merendino J.J. Jr., Shenker A.; RT "Characterization of heterogeneous mutations causing constitutive RT activation of the luteinizing hormone receptor in familial male RT precocious puberty."; RL Hum. Mol. Genet. 4:183-188(1995). RN [10] RP VARIANT FMPP VAL-572. RX MEDLINE=95229804; PubMed=7714085; RA Yano K., Saji M., Hidaka A., Moriya N., Okuno A., Kohn L.D., RA Cutler G.B. Jr.; RT "A new constitutively activating point mutation in the luteinizing RT hormone/choriogonadotropin receptor gene in cases of male-limited RT precocious puberty."; RL J. Clin. Endocrinol. Metab. 80:1162-1168(1995). RN [11] RP VARIANT FMPP VAL-568. RX MEDLINE=95355560; PubMed=7629248; RA Latronico A.C., Anasti J., Arnhold I.J., Mendonca B.B., Domenice S., RA Albano M.C., Zachman K., Wajchenberg B.L., Tsigos C.; RT "A novel mutation of the luteinizing hormone receptor gene causing RT male gonadotropin-independent precocious puberty."; RL J. Clin. Endocrinol. Metab. 80:2490-2494(1995). RN [12] RP VARIANT LCH PRO-593. RX MEDLINE=95235561; PubMed=7719343; RA Kremer H., Kraaij R., Toledo S.P.A., Post M., Fridman J.B., RA Hayashida C.Y., van Reen M., Milgrom E., Ropers H.-H., Mariman E., RA Themmen A.P.N., Brunner H.G.; RT "Male pseudohermaphroditism due to a homozygous missense mutation of RT the luteinizing hormone receptor gene."; RL Nat. Genet. 9:160-164(1995). RN [13] RP VARIANT FMPP ILE-577. RX MEDLINE=96233936; PubMed=8829636; RA Cocco S., Meloni A., Marini M.G., Cao A., Moi P.; RT "A missense (T577I) mutation in the luteinizing hormone receptor gene RT associated with familial male-limited precocious puberty."; RL Hum. Mutat. 7:164-166(1996). RN [14] RP VARIANT FMPP THR-398. RX MEDLINE=97083378; PubMed=8929952; RA Evans B.A.J., Bowen D.J., Smith P.J., Clayton P.E., Gregory J.W.; RT "A new point mutation in the luteinising hormone receptor gene in RT familial and sporadic male limited precocious puberty: genotype does RT not always correlate with phenotype."; RL J. Med. Genet. 33:143-147(1996). RN [15] RP VARIANT LCH TYR-616. RX MEDLINE=96157015; PubMed=8559204; RA Latronico A.C., Anasti J., Arnhold I.J.P., Rapaport R., Mendonca B.B., RA Bloise W., Castro M., Tsigos C., Chrousos G.P.; RT "Brief report: testicular and ovarian resistance to luteinizing RT hormone caused by inactivating mutations of the luteinizing RT hormone-receptor gene."; RL New Engl. J. Med. 334:507-512(1996). RN [16] RP VARIANT LCH ARG-131. RX MEDLINE=97358168; PubMed=9215288; RA Misrahi M., Meduri G., Pissard S., Bouvattier C., Beau I., RA Loosfelt H., Jolivet A., Rappaport R., Milgrom E., Bougneres P.; RT "Comparison of immunocytochemical and molecular features with the RT phenotype in a case of incomplete male pseudohermaphroditism RT associated with a mutation of the luteinizing hormone receptor."; RL J. Clin. Endocrinol. Metab. 82:2159-2165(1997). RN [17] RP VARIANTS LEU-GLN-18 INS; SER-284 AND ASN-306. RA Wu S.-M., Jose M., Hallermeier K., Rennert O.M., Chan W.-Y.; RT "Polymorphisms in the coding exons of the human luteinizing hormone RT receptor gene."; RL Hum. Mutat. 11:333-334(1998). RN [18] RP VARIANT FMPP VAL-373. RX MEDLINE=98128689; PubMed=9467560; RA Gromoll J., Partsch C.-J., Simoni M., Nordhoff V., Sippell W.G., RA Nieschlag E., Saxena B.B.; RT "A mutation in the first transmembrane domain of the lutropin receptor RT causes male precocious puberty."; RL J. Clin. Endocrinol. Metab. 83:476-480(1998). RN [19] RP VARIANT LCH LYS-354. RX MEDLINE=98289384; PubMed=9626144; RA Stavrou S.S., Zhu Y.S., Cai L.Q., Katz M.D., Herrera C., RA Defillo-Ricart M., Imperato-Mcginley J.; RT "A novel mutation of the human luteinizing hormone receptor in 46XY RT and 46XX sisters."; RL J. Clin. Endocrinol. Metab. 83:2091-2098(1998). RN [20] RP VARIANT FMPP ARG-457. RX MEDLINE=98326270; PubMed=9661624; RA Latronico A.C., Abell A.N., Arnhold I.J., Liu X., Lins T.S., RA Brito V.N., Billerbeck A.E., Segaloff D.L., Mendonca B.B.; RT "A unique constitutively activating mutation in third transmembrane RT helix of luteinizing hormone receptor causes sporadic male RT gonadotropin-independent precocious puberty."; RL J. Clin. Endocrinol. Metab. 83:2435-2440(1998). RN [21] RP VARIANT LEU-GLN-18 INS. RX MEDLINE=99067115; PubMed=9851790; RA Rodien P., Cetani F., Costagliola S., Tonacchera M., Duprez L., RA Minegishi T., Govaerts C., Vassart G.; RT "Evidences for an allelic variant of the human LC/CG receptor rather RT than a gene duplication: functional comparison of wild-type and RT variant receptors."; RL J. Clin. Endocrinol. Metab. 83:4431-4434(1998). RN [22] RP VARIANT LCH 608-LEU-VAL-609 DEL. RX MEDLINE=98173094; PubMed=9514160; RA Latronico A.C., Chai Y., Arnhold I.J.P., Liu X., Mendonca B.B., RA Segaloff D.L.; RT "A homozygous microdeletion in helix 7 of the luteinizing hormone RT receptor associated with familial testicular and ovarian resistance is RT due to both decreased cell surface expression and impaired effector RT activation by the cell surface receptor."; RL Mol. Endocrinol. 12:442-450(1998). RN [23] RP VARIANT LCH LYS-625. RX MEDLINE=98289955; PubMed=9626653; RA Martens J.W., Verhoef-Post M., Abelin N., Ezabella M., Toledo S.P., RA Brunner H.G., Themmen A.P.; RT "A homozygous mutation in the luteinizing hormone receptor causes RT partial Leydig cell hypoplasia: correlation between receptor activity RT and phenotype."; RL Mol. Endocrinol. 12:775-784(1998). RN [24] RP VARIANT LEYDIG CELL TUMOR HIS-578. RX MEDLINE=20037768; PubMed=10580072; RA Liu G., Duranteau L., Carel J.-C., Monroe J., Doyle D.A., Shenker A.; RT "Leydig-cell tumors caused by an activating mutation of the gene RT encoding the luteinizing hormone receptor."; RL New Engl. J. Med. 341:1731-1736(1999). CC -!- FUNCTION: RECEPTOR FOR LUTROPIN-CHORIOGONADOTROPIC HORMONE. THE CC ACTIVITY OF THIS RECEPTOR IS MEDIATED BY G PROTEINS WHICH ACTIVATE CC ADENYLATE CYCLASE. CC -!- SUBCELLULAR LOCATION: Integral membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist; CC Name=Long; CC IsoId=P22888-1; Sequence=Displayed; CC Name=Short; CC IsoId=P22888-2; Sequence=VSP_001962; CC -!- TISSUE SPECIFICITY: GONADAL AND THYROID CELLS. CC -!- DISEASE: Defects in LHCGR are a cause of familial male precocious CC puberty (FMPP) [MIM:176410], also known as testotoxicosis. In FMPP CC the receptor is constitutively activated. CC -!- DISEASE: Defects in LHCGR are a cause of Leydig cell hypoplasia; CC (LCH) [MIM:152790], an autosomal recessive disease characterized CC by male pseudohermaphroditism. In LCH the testes are small with CC marked immaturity of the leydig cells which correlates with CC undetectable plasma testosterone levels and elevated CC gonadotropins. CC -!- SIMILARITY: BELONGS TO FAMILY 1 OF G-PROTEIN COUPLED RECEPTORS. CC FSH/LSH/TSH SUBFAMILY. CC -!- SIMILARITY: Contains 7 leucine-rich (LRR) repeats. CC -!- DATABASE: NAME=Human luteinizing hormone receptor mutation db; CC WWW="http://www.eur.nl/fgg/endov/lhr.html". 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; M73746; AAA70231.1; -. DR EMBL; S57793; AAB19917.2; -. DR EMBL; M63108; AAA59515.1; -. DR EMBL; X84753; CAA59234.1; -. DR EMBL; X84754; CAA59234.1; JOINED. DR EMBL; X84755; CAA59234.1; JOINED. DR EMBL; X84756; CAA59234.1; JOINED. DR EMBL; X84757; CAA59234.1; JOINED. DR EMBL; X84758; CAA59234.1; JOINED. DR EMBL; X84759; CAA59234.1; JOINED. DR EMBL; X84760; CAA59234.1; JOINED. DR EMBL; X84761; CAA59234.1; JOINED. DR EMBL; X84762; CAA59234.1; JOINED. DR EMBL; X84763; CAA59234.1; JOINED. DR EMBL; AF082076; AAC98291.1; -. DR EMBL; AF024642; AAB88417.1; -. DR PIR; A23728; A23728. DR PIR; A36243; A36243. DR PIR; B36243; B36243. DR PIR; B36120; B36120. DR PDB; 1LUT; 21-APR-97. DR Genew; HGNC:6585; LHCGR. DR MIM; 152790; -. DR MIM; 176410; -. DR GO; GO:0005768; C:endosome; TAS. DR GO; GO:0005887; C:integral to plasma membrane; TAS. DR GO; GO:0015029; F:internalization receptor activity; TAS. DR GO; GO:0007187; P:G-protein signaling, coupled to cyclic nucl...; TAS. DR GO; GO:0007485; P:male genital morphogenesis (sensu Holometab...; TAS. DR GO; GO:0008584; P:male gonad development; TAS. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR001611; LRR. DR InterPro; IPR000372; LRR_Nterm. DR Pfam; PF00001; 7tm_1; 1. DR Pfam; PF00560; LRR; 3. DR PRINTS; PR00237; GPCRRHODOPSN. DR SMART; SM00013; LRRNT; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. KW G-protein coupled receptor; Transmembrane; Glycoprotein; Signal; KW Phosphorylation; Repeat; Leucine-rich repeat; Alternative splicing; KW Disease mutation; Polymorphism; 3D-structure. FT SIGNAL 1 26 POTENTIAL. FT CHAIN 27 699 LUTROPIN-CHORIOGONADOTROPIC HORMONE FT RECEPTOR. FT DOMAIN 27 363 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 364 385 1 (POTENTIAL). FT DOMAIN 386 395 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 396 416 2 (POTENTIAL). FT DOMAIN 417 439 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 440 462 3 (POTENTIAL). FT DOMAIN 463 482 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 483 505 4 (POTENTIAL). FT DOMAIN 506 525 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 526 549 5 (POTENTIAL). FT DOMAIN 550 570 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 571 594 6 (POTENTIAL). FT DOMAIN 595 605 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 606 627 7 (POTENTIAL). FT DOMAIN 628 699 CYTOPLASMIC (POTENTIAL). FT REPEAT 48 71 LRR 1. FT REPEAT 97 121 LRR 2. FT REPEAT 122 147 LRR 3. FT REPEAT 149 171 LRR 4. FT REPEAT 172 196 LRR 5. FT REPEAT 197 220 LRR 6. FT REPEAT 221 244 LRR 7. FT DISULFID 439 514 BY SIMILARITY. FT CARBOHYD 99 99 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 174 174 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 195 195 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 291 291 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 299 299 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 313 313 N-LINKED (GLCNAC...) (POTENTIAL). FT VARSPLIC 227 289 Missing (in isoform Short). FT /FTId=VSP_001962. FT VARIANT 18 18 Q -> QLQ. FT /FTId=VAR_003549. FT VARIANT 131 131 C -> R (in LCH). FT /FTId=VAR_010154. FT VARIANT 284 284 N -> S. FT /FTId=VAR_003550. FT VARIANT 306 306 S -> N. FT /FTId=VAR_003551. FT VARIANT 343 343 C -> S (in LCH). FT /FTId=VAR_010155. FT VARIANT 354 354 E -> K (in LCH). FT /FTId=VAR_003552. FT VARIANT 373 373 A -> V (in FMPP). FT /FTId=VAR_003553. FT VARIANT 398 398 M -> T (in FMPP). FT /FTId=VAR_003554. FT VARIANT 457 457 L -> R (in FMPP). FT /FTId=VAR_010156. FT VARIANT 542 542 I -> L (in FMPP). FT /FTId=VAR_010157. FT VARIANT 543 543 C -> R (in FMPP). FT /FTId=VAR_010158. FT VARIANT 564 564 D -> G (in FMPP). FT /FTId=VAR_010159. FT VARIANT 568 568 A -> V (in FMPP). FT /FTId=VAR_003555. FT VARIANT 571 571 M -> I (in FMPP). FT /FTId=VAR_003556. FT VARIANT 572 572 A -> V (in FMPP). FT /FTId=VAR_003557. FT VARIANT 575 575 I -> L (in FMPP). FT /FTId=VAR_010160. FT VARIANT 577 577 T -> I (in FMPP). FT /FTId=VAR_003558. FT VARIANT 578 578 D -> E (in FMPP). FT /FTId=VAR_010161. FT VARIANT 578 578 D -> G (in FMPP). FT /FTId=VAR_003559. FT VARIANT 578 578 D -> H (in Leydig cell tumor; somatic FT mutation; causes receptor activation and FT precocious puberty). FT /FTId=VAR_010162. FT VARIANT 578 578 D -> Y (in FMPP). FT /FTId=VAR_010163. FT VARIANT 581 581 C -> R (in FMPP). FT /FTId=VAR_010164. FT VARIANT 593 593 A -> P (in LCH; abolishes signal FT transduction). FT /FTId=VAR_003560. FT VARIANT 608 609 Missing (in LCH). FT /FTId=VAR_003561. FT VARIANT 616 616 S -> Y (in LCH; micropenis). FT /FTId=VAR_003562. FT VARIANT 625 625 I -> K (in LCH). FT /FTId=VAR_003563. FT CONFLICT 7 7 A -> P (IN REF. 3). FT CONFLICT 19 19 P -> A (IN REF. 3). FT CONFLICT 27 28 EA -> R (IN REF. 3). FT CONFLICT 44 51 CPGPTAGL -> APAPRPS (IN REF. 3). FT CONFLICT 68 68 A -> S (IN REF. 3). FT CONFLICT 124 124 R -> G (IN REF. 1 AND 4). FT CONFLICT 262 263 RE -> KQ (IN REF. 3). FT CONFLICT 270 270 E -> R (IN REF. 3). FT CONFLICT 274 274 T -> H (IN REF. 3). FT CONFLICT 290 290 Q -> L (IN REF. 3). FT CONFLICT 311 323 MISSING (IN REF. 3). FT CONFLICT 312 312 S -> N (IN REF. 2). FT CONFLICT 448 448 F -> L (IN REF. 3). FT CONFLICT 540 540 F -> L (IN REF. 3). FT CONFLICT 546 546 Y -> T (IN REF. 2). FT CONFLICT 649 649 E -> DP (IN REF. 3). FT STRAND 53 55 FT TURN 57 58 FT TURN 64 66 FT HELIX 67 69 FT TURN 70 70 FT STRAND 77 79 FT TURN 81 82 FT TURN 94 96 FT STRAND 102 104 FT TURN 111 113 FT HELIX 117 119 FT TURN 120 120 FT STRAND 127 129 FT HELIX 138 141 FT HELIX 142 145 FT TURN 146 147 FT STRAND 152 154 FT TURN 156 157 FT TURN 159 163 FT TURN 167 170 FT STRAND 178 180 FT TURN 182 183 FT TURN 189 195 FT STRAND 201 203 FT TURN 208 212 FT HELIX 216 218 FT TURN 219 220 FT STRAND 226 228 FT TURN 230 231 SQ SEQUENCE 699 AA; 78615 MW; 16F9980BB0ED7146 CRC64; MKQRFSALQL LKLLLLLQPP LPRALREALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLNL SEILIQNTKN LRYIEPGAFI NLPRLKYLSI CNTGIRKFPD VTKVFSSESN FILEICDNLH ITTIPGNAFQ GMNNESVTLK LYGNGFEEVQ SHAFNGTTLT SLELKENVHL EKMHNGAFRG ATGPKTLDIS STKLQALPSY GLESIQRLIA TSSYSLKKLP SRETFVNLLE ATLTYPSHCC AFRNLPTKEQ NFSHSISENF SKQCESTVRK VSNKTLYSSM LAESELSGWD YEYGFCLPKT PRCAPEPDAF NPCEDIMGYD FLRVLIWLIN ILAIMGNMTV LFVLLTSRYK LTVPRFLMCN LSFADFCMGL YLLLIASVDS QTKGQYYNHA IDWQTGSGCS TAGFFTVFAS ELSVYTLTVI TLERWHTITY AIHLDQKLRL RHAILIMLGG WLFSSLIAML PLVGVSNYMK VSICFPMDVE TTLSQVYILT ILILNVVAFF IICACYIKIY FAVRNPELMA TNKDTKIAKK MAILIFTDFT CMAPISFFAI SAAFKVPLIT VTNSKVLLVL FYPINSCANP FLYAIFTKTF QRDFFLLLSK FGCCKRRAEL YRRKDFSAYT SNCKNGFTGS NKPSQSTLKL STLHCQGTAL LDKTRYTEC //