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PR01144

Identifier
LSHRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01144
No. of Motifs
10
Creation Date
12-MAR-1999
Title
Lutropin-choriogonadotropic hormone receptor precursor signature 
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00373 GLYCHORMONER
INTERPRO; IPR002273
GCRDB; GCR_1214; GCR_1222; GCR_0106; GCR_0608; GCR_0138; GCR_0139

GCRDB; GCR_0612
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. WATSON, S. AND ARKINSTALL, S.
Glycoprotein hormones.
In THE G-PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, pp142-149.
 
7. JIANG, X., DREANO, M., BUCKLER, D.R., CHENG, S., YTHIER, A., WU, H.,
HENDRICKSON, W.A. AND EL TAYAR, N.
Structural predictions for the ligand-binding region of glycoprotein hormone
receptors and the nature of hormone-receptor interactions.
STRUCTURE 3 1341-1353 (1995).
 
8. SHENKER, A., LAUE, L., KOSUGI, S., MERENDINO, J.J. JR., MINEGISHI, T.
AND CUTLER, G.B. 
A constitutively activating mutation of the luteinizing hormone receptor in 
familial male precocious puberty.
NATURE 365 652-654 (1993). 

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that 
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the 
sequence level, on the basis of which they can be separated into distinct 
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship, 
but between which there is no statistically significant similarity in 
sequence [1]. The currently known clan members include the rhodopsin-like 
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
 
The rhodopsin-like GPCRs themselves represent a widespread protein family 
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary 
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural 
framework comprising 7 transmembrane (TM) helices [3-5]. 
 
The gonadotrophins (luteinising hormone, choriogonadotrophin, follicle-
stimulating hormone) and thyroid-stimulating hormone are heterotrimeric
glycoproteins composed of a common alpha-subunit and distinct beta-subunits
[6]. The carbohydrate moiety of the glycoproteins has an essential role in
receptor recognition. The receptors share close sequence similarity, and
are characterised by large extracellular domains believed to be involved
in hormone binding via leucine-rich repeats (LRR) [7]. Modelling of this
portion of the receptors suggests that they contain three-dimensional
structures similar to that of porcine ribonuclease inhibitor [7].
 
The beta subunits of LH (also known as lupotrophin) and hCG are closely
related in sequence and elicit their biological actions via the same 
receptor [6]. LH is released from the anterior pituitary under the
influence of gonadotrophin-releasing hormone and progesterones [6]. CG is
released by the placenta during pregnancy [6]. In females, LH stimulates
ovulation and is the major hormone involved in the regulation of 
progesterone secretion by the corpus luteum [6]. In males, it stimulates 
Leydig cells to secrete androgens, particularly testosterone. The receptor
is found in organs involved in reproductive physiology, including testicular
Leydig cells, ovarian theca, granulosa, luteal and interstitial cells [6].
The receptor activates adenylyl cyclase through Gs and stimulates the
phosphoinositide pathway through a pertussis-toxin-insensitive G protein [6].
 
Familial male precocious puberty (FMPP) is a gonadotropin-independent
disorder that is inherited in an autosomal dominant, male-limited pattern
[8]. Affected males generally exhibit signs of puberty by age 4 [8].
Testosterone production and Leydig cell hyperplasia occur in the context of
prepubertal levels of luteinising hormone (LH). FMPP was thought to be due
to a mutant receptor activated in the presence of little or no agonist. A 
single A-G base change that results in substitution of glycine for aspartate 
at position 578 in LH receptor TM domain 6 was found in affected individuals
from eight different families [8]. Linkage of the mutation to FMPP was
supported by restriction-digest analysis [8]. Further results suggest that
autonomous Leydig cell activity in FMPP is caused by a constitutively
activated LH receptor [8]. 
 
LSHRECEPTOR is a 10-element fingerprint that provides a signature for the
lutropin-choriogonadotropic hormone receptors. The fingerprint was derived
from an initial alignment of 6 sequences: the motifs were drawn from 
conserved regions spanning virtually the full alignment length, focusing on 
those sections that characterise the LH/CG hormone receptors but distinguish
them from the rest of the glycoprotein hormone receptor family - motifs 1-8
reside within the N-terminal half of the alignment, prior to the TM domains;
and motifs 9 and 10 lie at the C-terminus. Two iterations on SPTR37_9f were
required to reach convergence, at which point a true set comprising 8 
sequences was identfied. 
Summary Information
8 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
108888888888
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
LSHR_BOVIN    LSHR_CALJA    LSHR_HUMAN    LSHR_MOUSE    
LSHR_PIG LSHR_RAT Q14751 Q15996
Sequence Titles
LSHR_BOVIN  Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) (LSH- R) (Luteinizing hormone receptor) - Bos taurus (Bovine). 
LSHR_CALJA Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) (LSH- R) (Luteinizing hormone receptor) - Callithrix jacchus (Common marmoset).
LSHR_HUMAN Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) (LSH- R) (Luteinizing hormone receptor) (LHR) - Homo sapiens (Human).
LSHR_MOUSE Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) (LSH- R) (Luteinizing hormone receptor) - Mus musculus (Mouse).
LSHR_PIG Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) (LSH- R) (Luteinizing hormone receptor) - Sus scrofa (Pig).
LSHR_RAT Lutropin-choriogonadotropic hormone receptor precursor (LH/CG-R) (LSH- R) (Luteinizing hormone receptor) - Rattus norvegicus (Rat).
Q14751 LUTEINISING HORMONE-CHORIOGONADOTROPIN RECEPTOR - HOMO SAPIENS (HUMAN).
Q15996 LUTEINIZING HORMONE RECEPTOR - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_9f  2  9    NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
CPEPCNCVPDGALRCPGPT LSHR_HUMAN 30 30 -
CPEPCSCPPDGALRCPGPQ LSHR_BOVIN 32 32 -
CPEPCSCRPDGALRCPGPR LSHR_PIG 30 30 -
CPEPCNCTPDGALRCPGPG LSHR_CALJA 34 34 -
CPEPCDCAPDGALRCPGPR LSHR_RAT 34 34 -
CPEPCDCAPDGALRCPGPR LSHR_MOUSE 34 34 -

Motif 2 width=17
Element Seqn Id St Int Rpt
AGLTRLSLAYLPVKVIP LSHR_HUMAN 49 0 -
AGLSRLSLTYLPIKVIP LSHR_BOVIN 51 0 -
AGLSRLSLTYLPIKVIP LSHR_PIG 49 0 -
AGLTRLSLAYLPVKVIP LSHR_CALJA 53 0 -
AGLARLSLTYLPVKVIP LSHR_RAT 53 0 -
AGLARLSLTYLPVKVIP LSHR_MOUSE 53 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
LLNLSEILIQNTKNL LSHR_HUMAN 97 31 -
LLNLSEILIQNTKNL LSHR_BOVIN 99 31 -
LLNLSEILIQNTKNL LSHR_PIG 97 31 -
LLNLSEILIQNTKNL LSHR_CALJA 101 31 -
LLNLSELLIQNTKNL LSHR_RAT 101 31 -
LLNLSEILIQNTKNL LSHR_MOUSE 101 31 -

Motif 4 width=12
Element Seqn Id St Int Rpt
DVTKVFSSESNF LSHR_HUMAN 140 28 -
DVTKIFSSEFNF LSHR_BOVIN 142 28 -
DVTKIFSSEFNF LSHR_PIG 140 28 -
DVTKIFSSETNF LSHR_CALJA 144 28 -
DVTKISSSEFNF LSHR_RAT 144 28 -
DVSKISSSEFNF LSHR_MOUSE 144 28 -

Motif 5 width=22
Element Seqn Id St Int Rpt
TTLTSLELKENVHLEKMHNGAF LSHR_HUMAN 197 45 -
TTLISLELKENARLEKMHNDAF LSHR_BOVIN 199 45 -
TTLISLELKENAHLKKMHNDAF LSHR_PIG 197 45 -
TTVISLVLKENVHLERIHNGAF LSHR_CALJA 201 45 -
TTLISLELKENIYLEKMHSGAF LSHR_RAT 201 45 -
TTLISLELKENIYLEKMHSGTF LSHR_MOUSE 201 45 -

Motif 6 width=13
Element Seqn Id St Int Rpt
SIQRLIATSSYSL LSHR_HUMAN 244 25 -
SIQTLIATSSYSL LSHR_BOVIN 246 25 -
SIQTLIATSSYSL LSHR_PIG 244 25 -
SIQTLIATSSYSL LSHR_CALJA 248 25 -
SIQTLIALSSYSL LSHR_RAT 248 25 -
SIQTLIATSSYSL LSHR_MOUSE 248 25 -

Motif 7 width=14
Element Seqn Id St Int Rpt
SMLAESELSGWDYE LSHR_HUMAN 319 62 -
AIFAESELSGWDYD LSHR_BOVIN 321 62 -
AIFAESELSDWDYD LSHR_PIG 319 62 -
AIFAESGQSGWDYD LSHR_CALJA 296 35 -
AIFEENELSGWDYD LSHR_RAT 323 62 -
AIFEENELSGWDYD LSHR_MOUSE 323 62 -

Motif 8 width=15
Element Seqn Id St Int Rpt
YGFCLPKTPRCAPEP LSHR_HUMAN 333 0 -
YGFCLPKTLQCAPEP LSHR_BOVIN 335 0 -
YGFCSPKTLQCAPEP LSHR_PIG 333 0 -
YGFHLPKTPRCAPEP LSHR_CALJA 310 0 -
YGFCSPKTLQCAPEP LSHR_RAT 337 0 -
YDFCSPKTLQCTPEP LSHR_MOUSE 337 0 -

Motif 9 width=16
Element Seqn Id St Int Rpt
CKRRAELYRRKDFSAY LSHR_HUMAN 644 296 -
CKYRAELYRRKDFSAY LSHR_BOVIN 646 296 -
CKHQAELYRRKDFSAY LSHR_PIG 644 296 -
CKHRAELYRRKDFSAY LSHR_CALJA 621 296 -
CKRRAELYRRKEFSAY LSHR_RAT 648 296 -
CKHRAELYRRKEFSAC LSHR_MOUSE 648 296 -

Motif 10 width=23
Element Seqn Id St Int Rpt
KNGFTGSNKPSQSTLKLSTLHCQ LSHR_HUMAN 664 4 -
KNGFTGSNKPSRSTFKLTTLQCQ LSHR_BOVIN 666 4 -
KNGFTGSNKPSRSTLKLTTLQCQ LSHR_PIG 661 1 -
KNGFTGSSKPSQSTLKLPALHCQ LSHR_CALJA 641 4 -
KNGFPGASKPSQATLKLSTVHCQ LSHR_RAT 668 4 -
KNGFPRSSKPSQAALKLSIVHCQ LSHR_MOUSE 668 4 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
CPEPCNCVPDGALRCPGPT LSHR_HUMAN 30 30 -
CPEPCNCVPDGALRCPGPT Q15996 30 30 -
CPEPCNCVPDGALRCPGPT Q14751 32 32 -
CPEPCSCPPDGALRCPGPQ LSHR_BOVIN 32 32 -
CPEPCSCRPDGALRCPGPR LSHR_PIG 30 30 -
CPEPCNCTPDGALRCPGPG LSHR_CALJA 34 34 -
CPEPCDCAPDGALRCPGPR LSHR_RAT 34 34 -
CPEPCDCAPDGALRCPGPR LSHR_MOUSE 34 34 -

Motif 2 width=17
Element Seqn Id St Int Rpt
AGLTRLSLAYLPVKVIP LSHR_HUMAN 49 0 -
AGLTRLSLAYLPVKVIP Q15996 49 0 -
AGLTRLSLAYLPVKVIP Q14751 51 0 -
AGLSRLSLTYLPIKVIP LSHR_BOVIN 51 0 -
AGLSRLSLTYLPIKVIP LSHR_PIG 49 0 -
AGLTRLSLAYLPVKVIP LSHR_CALJA 53 0 -
AGLARLSLTYLPVKVIP LSHR_RAT 53 0 -
AGLARLSLTYLPVKVIP LSHR_MOUSE 53 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
LLNLSEILIQNTKNL LSHR_HUMAN 97 31 -
LLNLSEILIQNTKNL Q15996 97 31 -
LLNLSEILIQNTKNL Q14751 99 31 -
LLNLSEILIQNTKNL LSHR_BOVIN 99 31 -
LLNLSEILIQNTKNL LSHR_PIG 97 31 -
LLNLSEILIQNTKNL LSHR_CALJA 101 31 -
LLNLSELLIQNTKNL LSHR_RAT 101 31 -
LLNLSEILIQNTKNL LSHR_MOUSE 101 31 -

Motif 4 width=12
Element Seqn Id St Int Rpt
DVTKVFSSESNF LSHR_HUMAN 140 28 -
DVTKVFSSESNF Q15996 140 28 -
DVTKVFSSESNF Q14751 142 28 -
DVTKIFSSEFNF LSHR_BOVIN 142 28 -
DVTKIFSSEFNF LSHR_PIG 140 28 -
DVTKIFSSETNF LSHR_CALJA 144 28 -
DVTKISSSEFNF LSHR_RAT 144 28 -
DVSKISSSEFNF LSHR_MOUSE 144 28 -

Motif 5 width=22
Element Seqn Id St Int Rpt
TTLTSLELKENVHLEKMHNGAF LSHR_HUMAN 197 45 -
TTLTSLELKENVHLEKMHNGAF Q15996 197 45 -
TTLTSLELKENVHLEKMHNGAF Q14751 199 45 -
TTLISLELKENARLEKMHNDAF LSHR_BOVIN 199 45 -
TTLISLELKENAHLKKMHNDAF LSHR_PIG 197 45 -
TTVISLVLKENVHLERIHNGAF LSHR_CALJA 201 45 -
TTLISLELKENIYLEKMHSGAF LSHR_RAT 201 45 -
TTLISLELKENIYLEKMHSGTF LSHR_MOUSE 201 45 -

Motif 6 width=13
Element Seqn Id St Int Rpt
SIQRLIATSSYSL LSHR_HUMAN 244 25 -
SIQRLIATSSYSL Q15996 244 25 -
SIQRLIATSSYSL Q14751 246 25 -
SIQTLIATSSYSL LSHR_BOVIN 246 25 -
SIQTLIATSSYSL LSHR_PIG 244 25 -
SIQTLIATSSYSL LSHR_CALJA 248 25 -
SIQTLIALSSYSL LSHR_RAT 248 25 -
SIQTLIATSSYSL LSHR_MOUSE 248 25 -

Motif 7 width=14
Element Seqn Id St Int Rpt
SMLAESELSGWDYE LSHR_HUMAN 319 62 -
SMLAESELSGWDYE Q15996 319 62 -
SMLAESELSGWDYE Q14751 321 62 -
AIFAESELSGWDYD LSHR_BOVIN 321 62 -
AIFAESELSDWDYD LSHR_PIG 319 62 -
AIFAESGQSGWDYD LSHR_CALJA 296 35 -
AIFEENELSGWDYD LSHR_RAT 323 62 -
AIFEENELSGWDYD LSHR_MOUSE 323 62 -

Motif 8 width=15
Element Seqn Id St Int Rpt
YGFCLPKTPRCAPEP LSHR_HUMAN 333 0 -
YGFCLPKTPRCAPEP Q15996 333 0 -
YGFCLPKTPRCAPEP Q14751 335 0 -
YGFCLPKTLQCAPEP LSHR_BOVIN 335 0 -
YGFCSPKTLQCAPEP LSHR_PIG 333 0 -
YGFHLPKTPRCAPEP LSHR_CALJA 310 0 -
YGFCSPKTLQCAPEP LSHR_RAT 337 0 -
YDFCSPKTLQCTPEP LSHR_MOUSE 337 0 -

Motif 9 width=16
Element Seqn Id St Int Rpt
CKRRAELYRRKDFSAY LSHR_HUMAN 644 296 -
CKRRAELYRRKDFSAY Q15996 644 296 -
CKRRAELYRRKDFSAY Q14751 646 296 -
CKYRAELYRRKDFSAY LSHR_BOVIN 646 296 -
CKHQAELYRRKDFSAY LSHR_PIG 644 296 -
CKHRAELYRRKDFSAY LSHR_CALJA 621 296 -
CKRRAELYRRKEFSAY LSHR_RAT 648 296 -
CKHRAELYRRKEFSAC LSHR_MOUSE 648 296 -

Motif 10 width=23
Element Seqn Id St Int Rpt
KNGFTGSNKPSQSTLKLSTLHCQ LSHR_HUMAN 664 4 -
KNGFTGSNKPSQSTLKLSTLHCQ Q15996 664 4 -
KNGFTGSNKPSQSTLKLSTLHCQ Q14751 666 4 -
KNGFTGSNKPSRSTFKLTTLQCQ LSHR_BOVIN 666 4 -
KNGFTGSNKPSRSTLKLTTLQCQ LSHR_PIG 661 1 -
KNGFTGSSKPSQSTLKLPALHCQ LSHR_CALJA 641 4 -
KNGFPGASKPSQATLKLSTVHCQ LSHR_RAT 668 4 -
KNGFPRSSKPSQAALKLSIVHCQ LSHR_MOUSE 668 4 -