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PR00751

Identifier
THYROLIBRINR  [View Relations]  [View Alignment]  
Accession
PR00751
No. of Motifs
11
Creation Date
09-SEP-1997  (UPDATE 15-JUN-1999)
Title
Thyrotrophin-releasing hormone receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN

INTERPRO; IPR002120
GCRDB; GCR_0306; GCR_0431; GCR_0691; GCR_0765; GCR_0799; GCR_0880

GCRDB; GCR_0099
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.
Thyrotrophin-releasing hormone.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.275-277.

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]. 
 
Thyrotrophin-releasing hormone (thyroliberin) (TRH) stimulates synthesis
and release of thyroid-stimulating hormone in the anterior pituitary [6].
It also stimulates synthesis and release of prolactin. In the CNS, TRH 
stimulates a number of behavioural and pharmacological actions, including
increased turnover of catecholamines in the nucleus accumbens [6]. TRH
receptors are found in high levels in the anterior pituitary, and are also
found in the retina and in certain areas of the brain [6]. The receptors
activate phosphoinositide metabolism through a pertussis-toxin-insensitive
G protein, probably of the Gq/G11 class [6].
 
THYROLIBRINR is an 11-element fingerprint that provides a signature for
thyrotrophin-releasing hormone receptors. The fingerprint was derived from
an initial alignment of 6 sequences: the motifs were drawn from conserved
sections within either loop or TM regions, focusing on those areas of the
alignment that characterise the TRH receptors but distinguish them from
the rest of the rhodopsin-like superfamily - motifs 1 and 2 span the
N-terminus; motif 3 spans the first external loop; motif 4 spans the second
external loop; motif 5 lies in the second external loop; motif 6 lies at
the N-terminus of TM domain 5; motifs 7 and 8 lie in the third cytoplasmic
loop; motif 9 lies in the third external loop; and motifs 10 and 11 lie at
the C-terminus. A single iteration on OWL29.4 was required to reach
convergence, no further sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 5 sequences, and 3
partial matches.
Summary Information
   5 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
1155555555555
1000000000000
900000000000
800000000000
700000000000
600000000000
501110100100
400000000000
300000000000
200000000000
1234567891011
True Positives
O46639        TRFR_HUMAN    TRFR_MOUSE    TRFR_RAT      
TRFR_SHEEP
True Positive Partials
Codes involving 5 elements
O88820
Codes involving 0 elements
O93603
Sequence Titles
O46639      THYROTROPIN-RELEASING HORMONE RECEPTOR - BOS TAURUS (BOVINE). 
TRFR_HUMAN Thyrotropin-releasing hormone receptor (TRH-R) (Thyroliberin receptor) - Homo sapiens (Human).
TRFR_MOUSE Thyrotropin-releasing hormone receptor (TRH-R) (Thyroliberin receptor) - Mus musculus (Mouse).
TRFR_RAT Thyrotropin-releasing hormone receptor (TRH-R) (Thyroliberin receptor) - Rattus norvegicus (Rat).
TRFR_SHEEP Thyrotropin-releasing hormone receptor (TRH-R) (Thyroliberin receptor) - Ovis aries (Sheep).

O88820 G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat).

O93603 THYROTROPIN RELEASING HORMONE RECEPTOR - GALLUS GALLUS (CHICKEN).
Scan History
OWL29_4    1  25   NSINGLE    
SPTR37_9f 2 30 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
NDTVSEMNQTELQPQAAVAL TRFR_MOUSE 3 3 -
NETVSELNQTELPPQVAVAL TRFR_RAT 3 3 -
NETVSELNQTQLQPRAVVAL TRFR_HUMAN 3 3 -
NETVSELNQTELPPQVAVAL S69161 3 3 -
NETGSELNQTQLQPRAVVAL OATRHRECP 3 3 -
NETVSELNQTELPPQVAVAL S69160 3 3 -

Motif 2 width=17
Element Seqn Id St Int Rpt
EYQVVTILLVVIICGLG TRFR_MOUSE 23 0 -
EYQVVTILLVVVICGLG TRFR_RAT 23 0 -
EYQVVTILLVLIICGLG TRFR_HUMAN 23 0 -
EYQVVTILLVVVICGLG S69160 23 0 -
EYQVVTILLVVVICGLG S69161 23 0 -
EYQVVTILLVLIICGLG OATRHRECP 23 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
GLPNITDSIYGSWVYGYVGCLC OATRHRECP 79 39 -
GLPNITDSIYGSWVYGYVGCLC S69160 79 39 -
GLPNITDSIYGSWVYGYVGCLC S69161 79 39 -
GLPNITDSIYGSWVYGYVGCLC TRFR_HUMAN 79 39 -
GLPNITDSIYGSWVYGYVGCLC TRFR_RAT 79 39 -
GLPNITDSIYGSWVYGYVGCLC TRFR_MOUSE 79 39 -

Motif 4 width=17
Element Seqn Id St Int Rpt
CHPIKAQFLCTFSRAKK TRFR_MOUSE 128 27 -
CHPIKAQFLCTFSRAKK S69161 128 27 -
CHPIKAQFLCTFSRAKK S69160 128 27 -
CHPIKAQFLCTFSRAKK OATRHRECP 128 27 -
CHPIKAQFLCTFSRAKK TRFR_HUMAN 128 27 -
CHPIKAQFLCTFSRAKK TRFR_RAT 128 27 -

Motif 5 width=17
Element Seqn Id St Int Rpt
STYKDAIVISCGYKISR S69160 169 24 -
STYKNAVVVSCGYKISR TRFR_MOUSE 169 24 -
STYKDAIVISCGYKISR TRFR_RAT 169 24 -
STYKDAIVISCGYKISR TRFR_HUMAN 169 24 -
STYKDAIVVSCGYKISR OATRHRECP 169 24 -
STYKDAIVISCGYKISR S69161 169 24 -

Motif 6 width=15
Element Seqn Id St Int Rpt
RNYYSPIYLMDFGVF TRFR_MOUSE 185 -1 -
RNYYSPIYLMDFGVF TRFR_RAT 185 -1 -
RNYYSPIYLMDFGVF TRFR_HUMAN 185 -1 -
RNYYSPIYLMDFGVF S69160 185 -1 -
RNYYSPIYLMDFGVF S69161 185 -1 -
RNYYSPIYLMDFGVF OATRHRECP 185 -1 -

Motif 7 width=20
Element Seqn Id St Int Rpt
LFLNPIPSDPKENSKMWKND TRFR_MOUSE 218 18 -
LFLNPTPSDPKENSKTWKND S69161 218 18 -
LFLSPIPSDPKENSNTWKND OATRHRECP 218 18 -
LFLNPIPSDPKENSKTWKND TRFR_HUMAN 218 18 -
LFLNPIPSDPKENSKTWKND TRFR_RAT 218 18 -
LFLNPTPSDPKENSKTWKND S69160 218 18 -

Motif 8 width=18
Element Seqn Id St Int Rpt
NRCFNSTVSSRKQVTKML TRFR_MOUSE 251 13 -
NRCFNSTVSSRKQVTKML TRFR_RAT 251 13 -
NRCFNSTVSSRKQVTKML TRFR_HUMAN 251 13 -
NRYFNSTVSSRKQVTKML OATRHRECP 251 13 -
NRCFNSTVSSRKQVTKML S69160 251 13 -
NRCFNSTVSSRKQVTKML S69161 251 13 -

Motif 9 width=18
Element Seqn Id St Int Rpt
SSPFQENWFLLFCRICIY TRFR_MOUSE 293 24 -
SSPFQENWFLLFCRICIY OATRHRECP 293 24 -
SSPFQENWFLLFCRICIY S69161 293 24 -
SSPFQENWFLLFCRICIY S69160 293 24 -
SSPFQENWFLLFCRICIY TRFR_HUMAN 293 24 -
SSPFQENWFLLFCRICIY TRFR_RAT 293 24 -

Motif 10 width=26
Element Seqn Id St Int Rpt
RKLCNCKQKPVEKPANYSVALNYSVI OATRHRECP 332 21 -
RKLCNCKQKPTEKAANYSVALNYSVI TRFR_MOUSE 332 21 -
RKLCNCKQKPTEKAANYSVALNYSVI TRFR_RAT 332 21 -
RKLCNCKQKPTEKPANYSVALNYSVI TRFR_HUMAN 332 21 -
RKLCNCKQKPTEKAANYSVALNYSVI S69160 332 21 -
RKLCNCKQKPTEKAANYSVALNYSVI S69161 332 21 -

Motif 11 width=19
Element Seqn Id St Int Rpt
KESDRFSTELEDITVTDTY TRFR_MOUSE 358 0 -
KESDRFSTELDDITVTDTR S69161 358 0 -
KESDRFSTELDDITVTDTY S69160 358 0 -
KESDHFSTELDDITVTDTY TRFR_HUMAN 358 0 -
KESDRFSTELDDITVTDTY TRFR_RAT 358 0 -
KESDHFSTELDDITVTDTY OATRHRECP 358 0 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
NETVSELNQTQLQPRAVVAL TRFR_HUMAN 3 3 -
NETGSELNQTQLQPRAVVAL TRFR_SHEEP 3 3 -
NETGSELNQTQLQPRAVVAL O46639 3 3 -
NETVSELNQTELPPQVAVAL TRFR_RAT 3 3 -
NDTVSEMNQTELQPQAAVAL TRFR_MOUSE 3 3 -

Motif 2 width=17
Element Seqn Id St Int Rpt
EYQVVTILLVLIICGLG TRFR_HUMAN 23 0 -
EYQVVTILLVLIICGLG TRFR_SHEEP 23 0 -
EYQVVTILLVLIICGLG O46639 23 0 -
EYQVVTILLVVVICGLG TRFR_RAT 23 0 -
EYQVVTILLVVIICGLG TRFR_MOUSE 23 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
GLPNITDSIYGSWVYGYVGCLC TRFR_HUMAN 79 39 -
GLPNITDSIYGSWVYGYVGCLC TRFR_SHEEP 79 39 -
GLPNITDSIYGSWVYGYVGCLC O46639 79 39 -
GLPNITDSIYGSWVYGYVGCLC TRFR_RAT 79 39 -
GLPNITDSIYGSWVYGYVGCLC TRFR_MOUSE 79 39 -

Motif 4 width=17
Element Seqn Id St Int Rpt
CHPIKAQFLCTFSRAKK TRFR_HUMAN 128 27 -
CHPIKAQFLCTFSRAKK TRFR_SHEEP 128 27 -
CHPIKAQFLCTFSRAKK O46639 128 27 -
CHPIKAQFLCTFSRAKK TRFR_RAT 128 27 -
CHPIKAQFLCTFSRAKK TRFR_MOUSE 128 27 -

Motif 5 width=17
Element Seqn Id St Int Rpt
STYKDAIVISCGYKISR TRFR_HUMAN 169 24 -
STYKDAIVVSCGYKISR TRFR_SHEEP 169 24 -
STYKDAIVVSCGYKISR O46639 169 24 -
STYKDAIVISCGYKISR TRFR_RAT 169 24 -
STYKNAVVVSCGYKISR TRFR_MOUSE 169 24 -

Motif 6 width=15
Element Seqn Id St Int Rpt
RNYYSPIYLMDFGVF TRFR_HUMAN 185 -1 -
RNYYSPIYLMDFGVF TRFR_SHEEP 185 -1 -
RNYYSPIYLMDFGVF O46639 185 -1 -
RNYYSPIYLMDFGVF TRFR_RAT 185 -1 -
RNYYSPIYLMDFGVF TRFR_MOUSE 185 -1 -

Motif 7 width=20
Element Seqn Id St Int Rpt
LFLNPIPSDPKENSKTWKND TRFR_HUMAN 218 18 -
LFLSPIPSDPKENSNTWKND TRFR_SHEEP 218 18 -
LFLNPIPSDPKENSNMWKND O46639 218 18 -
LFLNPIPSDPKENSKTWKND TRFR_RAT 218 18 -
LFLNPIPSDPKENSKMWKND TRFR_MOUSE 218 18 -

Motif 8 width=18
Element Seqn Id St Int Rpt
NRCFNSTVSSRKQVTKML TRFR_HUMAN 251 13 -
NRYFNSTVSSRKQVTKML TRFR_SHEEP 251 13 -
NRYFNSTVSSRKQVTKML O46639 251 13 -
NRCFNSTVSSRKQVTKML TRFR_RAT 251 13 -
NRCFNSTVSSRKQVTKML TRFR_MOUSE 251 13 -

Motif 9 width=18
Element Seqn Id St Int Rpt
SSPFQENWFLLFCRICIY TRFR_HUMAN 293 24 -
SSPFQENWFLLFCRICIY TRFR_SHEEP 293 24 -
SSPFQENWFLLFCRICIY O46639 293 24 -
SSPFQENWFLLFCRICIY TRFR_RAT 293 24 -
SSPFQENWFLLFCRICIY TRFR_MOUSE 293 24 -

Motif 10 width=26
Element Seqn Id St Int Rpt
RKLCNCKQKPTEKPANYSVALNYSVI TRFR_HUMAN 332 21 -
RKLCNCKQKPVEKPANYSVALNYSVI TRFR_SHEEP 332 21 -
RKLCNCKQKPVEKPANYSVALSYSVI O46639 332 21 -
RKLCNCKQKPTEKAANYSVALNYSVI TRFR_RAT 332 21 -
RKLCNCKQKPTEKAANYSVALNYSVI TRFR_MOUSE 332 21 -

Motif 11 width=19
Element Seqn Id St Int Rpt
KESDHFSTELDDITVTDTY TRFR_HUMAN 358 0 -
KESDHFSTELDDITVTDTY TRFR_SHEEP 358 0 -
KESDRFSTELDDVTVTDTY O46639 358 0 -
KESDRFSTELDDITVTDTY TRFR_RAT 358 0 -
KESDRFSTELEDITVTDTY TRFR_MOUSE 358 0 -