P22888 (LSHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lutropin-choriogonadotropic hormone receptor
Short name=LH/CG-R

Alternative name(s):
Luteinizing hormone receptor
Short name=LHR
Short name=LSH-R

Gene names

Name:	LHCGR
Synonyms:	LCGR, LGR2, LHRHR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	699 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Gonadal and thyroid cells.
Involvement in disease	Familial male precocious puberty (FMPP) [MIM:176410]: In FMPP the receptor is constitutively activated. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.24 Ref.26 Luteinizing hormone resistance (LHR) [MIM:238320]: An autosomal recessive disorder characterized by unresponsiveness to luteinizing hormone, defective sexual development in males, and defective follicular development and ovulation, amenorrhea and infertility in females. Two forms of the disorder have been defined in males. Type 1 is a severe form characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high luteinizing hormone levels, total lack of responsiveness to luteinizing and chorionic gonadotropin hormones, lack of breast development, and absent development of secondary male sex characteristics. Type 2, a milder form, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.18 Ref.21 Ref.22 Ref.25 Ref.28 Ref.29 Ref.31 Ref.32 Ref.34
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily. Contains 6 LRR (leucine-rich) repeats. Contains 1 LRRNT domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Traceable author statement Ref.18. Source: ProtInc activation of adenylate cyclase activity Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to gonadotropin stimulus Inferred from sequence or structural similarity. Source: BHF-UCL development of secondary male sexual characteristics Inferred from electronic annotation. Source: Compara male genitalia development Traceable author statement Ref.29. Source: ProtInc male gonad development Traceable author statement Ref.18. Source: ProtInc ovarian follicle development Inferred from electronic annotation. Source: Compara phospholipase C-activating G-protein coupled receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cAMP-mediated signaling Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of inositol trisphosphate biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL regulation of steroid hormone biosynthetic process Inferred from electronic annotation. Source: Compara seminiferous tubule development Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara uterus development Inferred from electronic annotation. Source: Compara
Cellular_component	endosome Traceable author statement PubMed 10617611. Source: ProtInc integral to plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	choriogonadotropin hormone binding Inferred from sequence or structural similarity. Source: BHF-UCL choriogonadotropin hormone receptor activity Inferred from sequence or structural similarity. Source: BHF-UCL luteinizing hormone receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform Long (identifier: P22888-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P22888-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-289: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Chain

27 – 699

673

Lutropin-choriogonadotropic hormone receptor

PRO_0000012780

Regions

Topological domain

27 – 363

337

Extracellular Potential

Transmembrane

364 – 385

22

Helical; Name=1; Potential

Topological domain

386 – 395

10

Cytoplasmic Potential

Transmembrane

396 – 416

21

Helical; Name=2; Potential

Topological domain

417 – 439

23

Extracellular Potential

Transmembrane

440 – 462

23

Helical; Name=3; Potential

Topological domain

463 – 482

20

Cytoplasmic Potential

Transmembrane

483 – 505

23

Helical; Name=4; Potential

Topological domain

506 – 525

20

Extracellular Potential

Transmembrane

526 – 549

24

Helical; Name=5; Potential

Topological domain

550 – 570

21

Cytoplasmic Potential

Transmembrane

571 – 594

24

Helical; Name=6; Potential

Topological domain

595 – 605

11

Extracellular Potential

Transmembrane

606 – 627

22

Helical; Name=7; Potential

Topological domain

628 – 699

72

Cytoplasmic Potential

Domain

27 – 66

40

LRRNT

Repeat

96 – 115

20

LRR 1

Repeat

124 – 145

22

LRR 2

Repeat

149 – 171

23

LRR 3

Repeat

175 – 196

22

LRR 4

Repeat

198 – 220

23

LRR 5

Repeat

223 – 244

22

LRR 6

Amino acid modifications

Lipidation

643

1

S-palmitoyl cysteine Ref.7

Lipidation

644

1

S-palmitoyl cysteine Ref.7

Glycosylation

99

1

N-linked (GlcNAc...) Potential

Glycosylation

174

1

N-linked (GlcNAc...) Potential

Glycosylation

195

1

N-linked (GlcNAc...) Potential

Glycosylation

291

1

N-linked (GlcNAc...) Potential

Glycosylation

299

1

N-linked (GlcNAc...) Potential

Glycosylation

313

1

N-linked (GlcNAc...) Potential

Disulfide bond

439 ↔ 514

By similarity

Natural variations

Alternative sequence

227 – 289

63

Missing in isoform Short.

VSP_001962

Natural variant

18

1

Q → QLQ May be associated with earlier age of onset of breast cancer and poor prognosis.

VAR_003549

Natural variant

131

1

C → R in LHR; Leydig cell hypoplasia type 2. Ref.22

VAR_010154

Natural variant

144

1

V → F in LHR; Leydig cell hypoplasia type 1; exhibits a marked impairment of human chorionic gonadotropin binding; shows the absence of the glycosylated cell surface form; the mutant receptor is retained in the endoplasmic reticulum; mutant receptors do not migrate to the cell surface. Ref.32

VAR_062336

Natural variant

152

1

I → T in LHR; reveals a marked impairment of human chorionic gonadotropin binding and signal transduction. Ref.34

VAR_062337

Natural variant

284

1

N → S. Ref.23

VAR_003550

Natural variant

291

1

N → S.
Corresponds to variant rs12470652 [ dbSNP | Ensembl ].

VAR_055922

Natural variant

306

1

S → N. Ref.23

VAR_003551

Natural variant

312

1

N → S. Ref.1 Ref.4
Corresponds to variant rs2293275 [ dbSNP | Ensembl ].

VAR_060737

Natural variant

343

1

C → S in LHR; Leydig cell hypoplasia type 1; completely devoided of hormone-induced cAMP reporter gene activation; although initial translocation to the endoplasmic reticulum is normal translocation is halted or misrouted and the mutant does not reach the cell surface and cannot bind hormone. Ref.11

VAR_010155

Natural variant

354

1

E → K in LHR; Leydig cell hypoplasia type 1. Ref.25

VAR_003552

Natural variant

368

1

L → P in FMPP; cells expressing the mutation display up to a 12-fold increase in basal cAMP production compared with cells expressing the same number of cell surface wild-type receptor indicating constitutive activation of the mutant receptor. Ref.9

VAR_062338

Natural variant

373

1

A → V in FMPP. Ref.24

VAR_003553

Natural variant

398

1

M → T in FMPP. Ref.20

VAR_003554

Natural variant

457

1

L → R in FMPP. Ref.26

VAR_010156

Natural variant

502

1

L → P in LHR; Leydig cell hypoplasia type 1; shows reduced cAMP production and ligand binding; receptor trafficking is not affected by the mutation. Ref.31

VAR_062339

Natural variant

542

1

I → L in FMPP.

VAR_010157

Natural variant

543

1

C → R in LHR; Leydig cell hypoplasia type 1; completely devoided of hormone-induced cAMP reporter gene activation; although initial translocation to the endoplasmic reticulum is normal translocation is halted or misrouted and the mutant does not reach the cell surface and cannot bind hormone. Ref.11

VAR_010158

Natural variant

564

1

D → G in FMPP. Ref.10

VAR_010159

Natural variant

564

1

D → N in a breast cancer sample; somatic mutation. Ref.33

VAR_035764

Natural variant

568

1

A → V in FMPP. Ref.9 Ref.17

VAR_003555

Natural variant

571

1

M → I in FMPP. Ref.14

VAR_003556

Natural variant

572

1

A → V in FMPP. Ref.16

VAR_003557

Natural variant

575

1

I → L in FMPP.

VAR_010160

Natural variant

577

1

T → I in FMPP. Ref.15 Ref.19

VAR_003558

Natural variant

578

1

D → E in FMPP.

VAR_010161

Natural variant

578

1

D → G in FMPP. Ref.13 Ref.14

VAR_003559

Natural variant

578

1

D → H in Leydig cell tumor; somatic mutation; causes receptor activation and precocious puberty. Ref.30

VAR_010162

Natural variant

578

1

D → Y in FMPP.

VAR_010163

Natural variant

581

1

C → R in FMPP.

VAR_010164

Natural variant

593

1

A → P in LHR; Leydig cell hypoplasia type 1; abolishes signal transduction. Ref.18

VAR_003560

Natural variant

608 – 609

2

Missing in LHR; Leydig cell hypoplasia type 1.

VAR_003561

Natural variant

616

1

S → Y in LHR; Leydig cell hypoplasia type 1; micropenis. Ref.21

VAR_003562

Natural variant

625

1

I → K in LHR; Leydig cell hypoplasia type 2. Ref.29

VAR_003563

Experimental info

Mutagenesis

643

1

C → G: Loss of palmitoylation. Ref.7

Mutagenesis

644

1

C → G: Loss of palmitoylation. Ref.7

Sequence conflict

7

1

A → P in AAA70231. Ref.3

Sequence conflict

19

1

P → A in AAA70231. Ref.3

Sequence conflict

27 – 28

2

EA → R in AAA70231. Ref.3

Sequence conflict

44 – 51

8

CPGPTAGL → APAPRPS in AAA70231. Ref.3

Sequence conflict

68

1

A → S in AAA70231. Ref.3

Sequence conflict

124

1

R → G in AAA59515. Ref.1

Sequence conflict

124

1

R → G in CAA59234. Ref.4

Sequence conflict

262 – 263

2

RE → KQ in AAA70231. Ref.3

Sequence conflict

270

1

E → R in AAA70231. Ref.3

Sequence conflict

274

1

T → H in AAA70231. Ref.3

Sequence conflict

290

1

Q → L in AAA70231. Ref.3

Sequence conflict

311 – 323

13

Missing in AAA70231. Ref.3

Sequence conflict

448

1

F → L in AAA70231. Ref.3

Sequence conflict

540

1

F → L in AAA70231. Ref.3

Sequence conflict

649

1

E → DP in AAA70231. Ref.3

Secondary structure

1

.

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.

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699

Helix Strand Turn

Details...

Beta strand

53 – 55

3

Turn

64 – 66

3

Helix

67 – 69

3

Beta strand

77 – 79

3

Beta strand

87 – 89

3

Turn

94 – 96

3

Beta strand

102 – 104

3

Turn

111 – 113

3

Helix

117 – 119

3

Beta strand

127 – 129

3

Helix

138 – 141

4

Helix

142 – 145

4

Beta strand

146 – 149

4

Beta strand

152 – 154

3

Turn

159 – 163

5

Turn

167 – 170

4

Beta strand

178 – 180

3

Turn

189 – 195

7

Beta strand

200 – 203

4

Turn

208 – 212

5

Helix

216 – 218

3

Beta strand

226 – 228

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified December 15, 2009. Version 4. Checksum: 2E3D93F4621BA842	FASTA	699	78,643
	10 20 30 40 50 60 MKQRFSALQL LKLLLLLQPP LPRALREALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP 70 80 90 100 110 120 VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLNL SEILIQNTKN LRYIEPGAFI 130 140 150 160 170 180 NLPRLKYLSI CNTGIRKFPD VTKVFSSESN FILEICDNLH ITTIPGNAFQ GMNNESVTLK 190 200 210 220 230 240 LYGNGFEEVQ SHAFNGTTLT SLELKENVHL EKMHNGAFRG ATGPKTLDIS STKLQALPSY 250 260 270 280 290 300 GLESIQRLIA TSSYSLKKLP SRETFVNLLE ATLTYPSHCC AFRNLPTKEQ NFSHSISENF 310 320 330 340 350 360 SKQCESTVRK VNNKTLYSSM LAESELSGWD YEYGFCLPKT PRCAPEPDAF NPCEDIMGYD 370 380 390 400 410 420 FLRVLIWLIN ILAIMGNMTV LFVLLTSRYK LTVPRFLMCN LSFADFCMGL YLLLIASVDS 430 440 450 460 470 480 QTKGQYYNHA IDWQTGSGCS TAGFFTVFAS ELSVYTLTVI TLERWHTITY AIHLDQKLRL 490 500 510 520 530 540 RHAILIMLGG WLFSSLIAML PLVGVSNYMK VSICFPMDVE TTLSQVYILT ILILNVVAFF 550 560 570 580 590 600 IICACYIKIY FAVRNPELMA TNKDTKIAKK MAILIFTDFT CMAPISFFAI SAAFKVPLIT 610 620 630 640 650 660 VTNSKVLLVL FYPINSCANP FLYAIFTKTF QRDFFLLLSK FGCCKRRAEL YRRKDFSAYT 670 680 690 SNCKNGFTGS NKPSQSTLKL STLHCQGTAL LDKTRYTEC
	Isoform Short [UniParc]. Checksum: 969918F83E700C85	FASTA	636	71,615
	10 20 30 40 50 60 MKQRFSALQL LKLLLLLQPP LPRALREALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP 70 80 90 100 110 120 VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLNL SEILIQNTKN LRYIEPGAFI 130 140 150 160 170 180 NLPRLKYLSI CNTGIRKFPD VTKVFSSESN FILEICDNLH ITTIPGNAFQ GMNNESVTLK 190 200 210 220 230 240 LYGNGFEEVQ SHAFNGTTLT SLELKENVHL EKMHNGAFRG ATGPKTQNFS HSISENFSKQ 250 260 270 280 290 300 CESTVRKVNN KTLYSSMLAE SELSGWDYEY GFCLPKTPRC APEPDAFNPC EDIMGYDFLR 310 320 330 340 350 360 VLIWLINILA IMGNMTVLFV LLTSRYKLTV PRFLMCNLSF ADFCMGLYLL LIASVDSQTK 370 380 390 400 410 420 GQYYNHAIDW QTGSGCSTAG FFTVFASELS VYTLTVITLE RWHTITYAIH LDQKLRLRHA 430 440 450 460 470 480 ILIMLGGWLF SSLIAMLPLV GVSNYMKVSI CFPMDVETTL SQVYILTILI LNVVAFFIIC 490 500 510 520 530 540 ACYIKIYFAV RNPELMATNK DTKIAKKMAI LIFTDFTCMA PISFFAISAA FKVPLITVTN 550 560 570 580 590 600 SKVLLVLFYP INSCANPFLY AIFTKTFQRD FFLLLSKFGC CKRRAELYRR KDFSAYTSNC 610 620 630 KNGFTGSNKP SQSTLKLSTL HCQGTALLDK TRYTEC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of human LH/hCG receptor cDNA." Minegish T., Nakamura K., Takakura Y., Miyamoto K., Hasegawa Y., Ibuki Y., Igarashi M. Biochem. Biophys. Res. Commun. 172:1049-1054(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-312. Tissue: Ovary.
[2]	"Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species." Jia X.-C., Oikawa M., Bo M., Tanaka T., Ny T., Boime I., Hsueh A.J.W. Mol. Endocrinol. 5:759-768(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[3]	"Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing." Frazier A.L., Robbins L.S., Stork P.J., Sprengel R., Segaloff D.L., Cone R.D. Mol. Endocrinol. 4:1264-1276(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Thyroid.
[4]	"Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5' non-coding regions." Atger M., Misrahi M., Sar S., Leflem L., Dessen P., Milgrom E. Mol. Cell. Endocrinol. 111:113-123(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-GLN-18 INS AND SER-312.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Genomic distribution and gonadal mRNA expression of two human luteinizing hormone receptor exon 1 sequences in random populations." Tsai-Morris C.-H., Geng Y., Buczko E., Dehejia A., Dufau M.L. Hum. Hered. 49:48-51(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54, VARIANT LEU-GLN-18 INS.
[7]	"Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing." Munshi U.M., Clouser C.L., Peegel H., Menon K.M. Mol. Endocrinol. 19:749-758(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-643 AND CYS-644, MUTAGENESIS OF CYS-643 AND CYS-644.
[8]	"Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions." Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., Hendrickson W.A., el Tayar N. Structure 3:1341-1353(1995) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 51-232.
[9]	"Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: a novel constitutively activating mutation in the first transmembrane helix." Latronico A.C., Shinozaki H., Guerra G. Jr., Pereira M.A.A., Lemos Marini S.H.V., Baptista M.T.M., Arnhold I.J.P., Fanelli F., Mendonca B.B., Segaloff D.L. J. Clin. Endocrinol. Metab. 85:4799-4805(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FMPP PRO-368 AND VAL-568, CHARACTERIZATION OF VARIANT FMPP PRO-368.
[10]	"Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty." Leschek E.W., Chan W.-Y., Diamond D.A., Kaefer M., Jones J., Barnes K.M., Cutler G.B. Jr. J. Pediatr. 138:949-951(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP GLY-564.
[11]	"Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency." Martens J.W.M., Lumbroso S., Verhoef-Post M., Georget V., Richter-Unruh A., Szarras-Czapnik M., Romer T.E., Brunner H.G., Themmen A.P.N., Sultan C. J. Clin. Endocrinol. Metab. 87:2506-2513(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LHR SER-343 AND ARG-543, CHARACTERIZATION OF VARIANTS LHR SER-343 AND ARG-543.
[12]	"Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset." Powell B.L., Piersma D., Kevenaar M.E., van Staveren I.L., Themmen A.P.N., Iacopetta B.J., Berns E.M.J.J. J. Clin. Endocrinol. Metab. 88:1653-1657(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF VARIANT LEU-GLN-18 INS WITH AGE OF BREAST CANCER ONSET.
[13]	"A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty." Shenker A., Laue L., Kosugi S., Merendino J.J. Jr., Minegishi T., Cutler G.B. Jr. Nature 365:652-654(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP GLY-578.
[14]	"Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty." Kremer H., Mariman E., Otten B.J., Moll G.W. Jr., Stoelinga G.B.A., Wit J.M., Jansen M., Drop S.L., Faas B., Ropers H.-H., Brunner H.G. Hum. Mol. Genet. 2:1779-1783(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FMPP ILE-571 AND GLY-578.
[15]	"Characterization of heterogeneous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty." Kosugi S., van Dop C., Geffner M.E., Rabl W., Carel J.-C., Chaussain J.-L., Mori T., Merendino J.J. Jr., Shenker A. Hum. Mol. Genet. 4:183-188(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP ILE-577.
[16]	"A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty." Yano K., Saji M., Hidaka A., Moriya N., Okuno A., Kohn L.D., Cutler G.B. Jr. J. Clin. Endocrinol. Metab. 80:1162-1168(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP VAL-572.
[17]	"A novel mutation of the luteinizing hormone receptor gene causing male gonadotropin-independent precocious puberty." Latronico A.C., Anasti J., Arnhold I.J., Mendonca B.B., Domenice S., Albano M.C., Zachman K., Wajchenberg B.L., Tsigos C. J. Clin. Endocrinol. Metab. 80:2490-2494(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP VAL-568.
[18]	"Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene." Kremer H., Kraaij R., Toledo S.P.A., Post M., Fridman J.B., Hayashida C.Y., van Reen M., Milgrom E., Ropers H.-H., Mariman E., Themmen A.P.N., Brunner H.G. Nat. Genet. 9:160-164(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR PRO-593.
[19]	"A missense (T577I) mutation in the luteinizing hormone receptor gene associated with familial male-limited precocious puberty." Cocco S., Meloni A., Marini M.G., Cao A., Moi P. Hum. Mutat. 7:164-166(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP ILE-577.
[20]	"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." Evans B.A.J., Bowen D.J., Smith P.J., Clayton P.E., Gregory J.W. J. Med. Genet. 33:143-147(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP THR-398.
[21]	"Testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene." Latronico A.C., Anasti J., Arnhold I.J.P., Rapaport R., Mendonca B.B., Bloise W., Castro M., Tsigos C., Chrousos G.P. N. Engl. J. Med. 334:507-512(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR TYR-616.
[22]	"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." Misrahi M., Meduri G., Pissard S., Bouvattier C., Beau I., Loosfelt H., Jolivet A., Rappaport R., Milgrom E., Bougneres P. J. Clin. Endocrinol. Metab. 82:2159-2165(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR ARG-131.
[23]	"Polymorphisms in the coding exons of the human luteinizing hormone receptor gene." Wu S.-M., Jose M., Hallermeier K., Rennert O.M., Chan W.-Y. Hum. Mutat. 11:333-334(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LEU-GLN-18 INS; SER-284 AND ASN-306.
[24]	"A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty." Gromoll J., Partsch C.-J., Simoni M., Nordhoff V., Sippell W.G., Nieschlag E., Saxena B.B. J. Clin. Endocrinol. Metab. 83:476-480(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP VAL-373.
[25]	"A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX sisters." Stavrou S.S., Zhu Y.S., Cai L.Q., Katz M.D., Herrera C., Defillo-Ricart M., Imperato-Mcginley J. J. Clin. Endocrinol. Metab. 83:2091-2098(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR LYS-354.
[26]	"A unique constitutively activating mutation in third transmembrane helix of luteinizing hormone receptor causes sporadic male gonadotropin-independent precocious puberty." Latronico A.C., Abell A.N., Arnhold I.J., Liu X., Lins T.S., Brito V.N., Billerbeck A.E., Segaloff D.L., Mendonca B.B. J. Clin. Endocrinol. Metab. 83:2435-2440(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FMPP ARG-457.
[27]	"Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors." Rodien P., Cetani F., Costagliola S., Tonacchera M., Duprez L., Minegishi T., Govaerts C., Vassart G. J. Clin. Endocrinol. Metab. 83:4431-4434(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-GLN-18 INS.
[28]	"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." Latronico A.C., Chai Y., Arnhold I.J.P., Liu X., Mendonca B.B., Segaloff D.L. Mol. Endocrinol. 12:442-450(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR 608-LEU-VAL-609 DEL.
[29]	"A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype." Martens J.W., Verhoef-Post M., Abelin N., Ezabella M., Toledo S.P., Brunner H.G., Themmen A.P. Mol. Endocrinol. 12:775-784(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR LYS-625.
[30]	"Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor." Liu G., Duranteau L., Carel J.-C., Monroe J., Doyle D.A., Shenker A. N. Engl. J. Med. 341:1731-1736(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEYDIG CELL TUMOR HIS-578.
[31]	"A novel missense homozygous inactivating mutation in the fourth transmembrane helix of the luteinizing hormone receptor in Leydig cell hypoplasia." Leung M.Y.-K., Al-Muslim O., Wu S.-M., Aziz A., Inam S., Awadh M., Rennert O.M., Chan W.-Y. Am. J. Med. Genet. A 130:146-153(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR PRO-502, CHARACTERIZATION OF VARIANT LCH PRO-502.
[32]	"Leydig cell hypoplasia: absent luteinizing hormone receptor cell surface expression caused by a novel homozygous mutation in the extracellular domain." Richter-Unruh A., Verhoef-Post M., Malak S., Homoki J., Hauffa B.P., Themmen A.P.N. J. Clin. Endocrinol. Metab. 89:5161-5167(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR PHE-144, CHARACTERIZATION OF VARIANT LCH PHE-144.
[33]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-564.
[34]	"A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism." Qiao J., Han B., Liu B.-L., Chen X., Ru Y., Cheng K.-X., Chen F.-G., Zhao S.-X., Liang J., Lu Y.-L., Tang J.-F., Wu Y.-X., Wu W.-L., Chen J.-L., Chen M.-D., Song H.-D. Hum. Mutat. 30:E855-E865(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LHR THR-152, CHARACTERIZATION OF VARIANT LHR THR-152.
+	Additional computationally mapped references.

Web resources

GRIS

Glycoprotein-hormone Receptors Information System

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Sequence-structure-function-analysis of glycoprotein hormone receptors

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63108 mRNA. Translation: AAA59515.1.
S57793 mRNA. Translation: AAB19917.2.
M73746 mRNA. Translation: AAA70231.1.
X84753 , X84754, X84755, X84756, X84757, X84758, X84759, X84760, X84761, X84762, X84763 Genomic DNA. Translation: CAA59234.1.
AC073082 Genomic DNA. No translation available.
AC087816 Genomic DNA. No translation available.
AF082076 Genomic DNA. Translation: AAC98291.1.
AF024642 Genomic DNA. Translation: AAB88417.1.

IPI

IPI00299615.
IPI00414187.

PIR

QRHUUT. A36243.

RefSeq

NP_000224.2. NM_000233.3.

UniGene

Hs.468490.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LUT	model	-	A	51-232	[»]
1XUL	model	-	C	51-232	[»]

ProteinModelPortal

P22888.

SMR

P22888. Positions 54-356, 364-645.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000294954.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P22888.

Polymorphism databases

DMDM

281185513.

Proteomic databases

PaxDb

P22888.

PRIDE

P22888.

Protocols and materials databases

DNASU

3973.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000294954; ENSP00000294954; ENSG00000138039.

GeneID

3973.

KEGG

hsa:3973.

UCSC

uc002rwu.4. human.

Organism-specific databases

CTD

3973.

GeneCards

GC02M048825.

HGNC

HGNC:6585. LHCGR.

HPA

CAB009814.

MIM

152790. gene+phenotype.
176410. phenotype.
238320. phenotype.

neXtProt

NX_P22888.

Orphanet

96265. Leydig cell hypoplasia due to complete LH resistance.
96266. Leydig cell hypoplasia due to partial LH resistance.
3000. Testotoxicosis.

PharmGKB

PA30357.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG285844.

HOGENOM

HOG000045902.

HOVERGEN

HBG003521.

InParanoid

P22888.

KO

K04248.

OMA

NYMKVSI.

OrthoDB

EOG4K9BC3.

PhylomeDB

P22888.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6arrestinpathway. Arf6 mediated densensitization of LHCGR.
arf6cyclingpathway. Arf6 signaling events.
arf6_traffickingpathway. Arf6 trafficking events.

Reactome

REACT_111102. Signal Transduction.

SignaLink

P22888.

Gene expression databases

ArrayExpress

P22888.

Bgee

P22888.

CleanEx

HS_LHCGR.

Genevestigator

P22888.

GermOnline

ENSG00000138039. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt.
IPR000372. LRR-contain_N.
IPR026906. LRR_5.
IPR002273. LSH_rcpt.
[Graphical view]

PANTHER

PTHR24372:SF1. PTHR24372:SF1. 1 hit.

Pfam

PF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
[Graphical view]

PRINTS

PR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01144. LSHRECEPTOR.

SMART

SM00013. LRRNT. 1 hit.
[Graphical view]

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1854.

DrugBank

DB00050. Cetrorelix.
DB00097. Choriogonadotropin alfa.
DB00014. Goserelin.
DB00044. Lutropin alfa.
DB00032. Menotropins.

GenomeRNAi

3973.

NextBio

15574.

SOURCE

Search...

Entry information

Entry name

LSHR_HUMAN

Accession

Primary (citable) accession number: P22888
Secondary accession number(s): Q14751, Q15996, Q9UEW9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	December 15, 2009
Last modified:	May 29, 2013
This is version 158 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.