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PR01654

Identifier
TRHRECEPTOR2  [View Relations]  [View Alignment]  
Accession
PR01654
No. of Motifs
6
Creation Date
20-DEC-2001
Title
Thyrotropin-releasing hormone receptor 2 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
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.
 
7. CAO, J., O'DONNELL, D., VU, H., PAYZA, K., POU, C., GODBOUT, C.,
JAKOB, A., PELLETIER, M., LEMBO, P., AHMAD, S. AND WALKER, P.
Cloning and characterization of a cDNA encoding a novel subtype of rat
thyrotropin-releasing hormone receptor.
J.BIOL.CHEM. 273(48) 32281-32287 (1998).

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]. 
 
Thyrotropin-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]. 
 
A second receptor for thyrotropin-releasing hormone has been identified [7].
TRHR2 is expressed in the brain and spinal cord, with highest levels in the
pontine nucleus, thalamus and cerebellar cortex. Moderate expression was
also found in the anterior olfactory nucleus, neocortex, superior and
inferior colliculi, central grey and in several other brainstem nuclei. In
contrast to TRHR1, no expression was found in the pituitary. In the spinal
cord, TRHR2 expression was detected only in the dorsal horn [7]. The
distribution of TRHR2 suggests a role for the receptor in somatosensory,
antinociceptive and motor functions. Binding of TRH to the receptor leads to
activation of phospholipase C through coupling to Gq proteins [7].
 
TRHRECEPTOR2 is a 6-element fingerprint that provides a signature for the
thyrotropin-releasing hormone receptor 2. The fingerprint was derived from
an initial alignment of 5 sequences: the motifs were drawn from conserved
sections within N- and C-terminal and loop regions, focusing on those areas
of the alignment that characterise the type 2 thyrotropin-releasing hormone
receptors but distinguish them from the rest of the thyrotropin-releasing
hormone receptor family - motifs 1 and 2 reside at the N-terminus; motif 3
spans the first external loop; motif 4 lies in the second cytoplasmic loop;
motif 5 encodes the second external loop; and motif 6 is located in the
C-terminus. Two iterations on SPTR40_18f were required to reach convergence,
at which point a true set comprising 6 sequences was identified.
Summary Information
6 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
6666666
5000000
4000000
3000000
2000000
123456
True Positives
O88820        Q9DDR0        Q9DFA9        Q9ERT2        
Q9QWW3 Q9R297
Sequence Titles
O88820      G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat). 
Q9DDR0 THYROTROPIN-RELEASING HORMONE RECEPTOR 2 - Xenopus laevis (African clawed frog).
Q9DFA9 THYROTROPIN-RELEASING HORMONE RECEPTOR 2 - Catostomus commersoni (White sucker).
Q9ERT2 THYROTROPIN-RELEASING HORMONE RECEPTOR 2 - Mus musculus (Mouse).
Q9QWW3 THYROTROPIN RELEASING HORMONE RECEPTOR-2 - Rattus norvegicus (Rat).
Q9R297 THYROTROPIN-RELEASING HORMONE RECEPTOR 2 - Rattus norvegicus (Rat).
Scan History
SPTR40_18f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
MDGPSNVSLI O88820 1 1 -
MDGPSNVSLI Q9R297 1 1 -
MDGPSNVSLV Q9ERT2 1 1 -
FDSPTNISLA Q9DDR0 7 7 -
MDTPTNISLV Q9DFA9 9 9 -

Motif 2 width=17
Element Seqn Id St Int Rpt
HGDTTLGLPEYKVVSVF O88820 11 0 -
HGDTTLGLPEYKVVSVF Q9R297 11 0 -
HGDTTLGLPEYKVVSVL Q9ERT2 11 0 -
NHDIVFSMNEYKAISVF Q9DDR0 17 0 -
SGDAVSESLEYKTISVF Q9DFA9 20 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
HWIYGRAGCLGITYF O88820 87 59 -
HWIYGRAGCLGITYF Q9R297 87 59 -
HWIYGHAGCLGITYF Q9ERT2 87 59 -
TWIYGHAGCLGITYF Q9DDR0 93 59 -
TWVYGHAGCLGITYF Q9DFA9 96 59 -

Motif 4 width=10
Element Seqn Id St Int Rpt
LRAQTVCTVA O88820 128 26 -
LRAQTVCTVA Q9R297 128 26 -
MRAQTVCTVA Q9ERT2 128 26 -
MRAKTVCTVS Q9DDR0 134 26 -
MRAQTVCTVS Q9DFA9 137 26 -

Motif 5 width=14
Element Seqn Id St Int Rpt
NVRDNQRLECGYKV O88820 164 26 -
NVRDNQRLECGYKV Q9R297 164 26 -
NVRDNQRLECGYKV Q9ERT2 164 26 -
HVNKSQQVECGYKV Q9DDR0 170 26 -
QVNQEGRVQCGYRV Q9DFA9 173 26 -

Motif 6 width=16
Element Seqn Id St Int Rpt
AAGPQRRAARVLTSNY O88820 324 146 -
AAGPQRRAARVLTSNY Q9R297 324 146 -
AAGSQRRAACAPTSNY Q9ERT2 327 149 -
HEETQRRSMYMTTTSY Q9DDR0 343 159 -
RDDGHQRSLSMLQSGY Q9DFA9 344 157 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
MDGPSNVSLI O88820 1 1 -
MDGPSNVSLI Q9R297 1 1 -
MDGPSNVSLI Q9QWW3 1 1 -
MDGPSNVSLV Q9ERT2 1 1 -
FDSPTNISLA Q9DDR0 7 7 -
MDTPTNISLV Q9DFA9 9 9 -

Motif 2 width=17
Element Seqn Id St Int Rpt
HGDTTLGLPEYKVVSVF O88820 11 0 -
HGDTTLGLPEYKVVSVF Q9R297 11 0 -
HGDTTLGLPEYKVVSVF Q9QWW3 11 0 -
HGDTTLGLPEYKVVSVL Q9ERT2 11 0 -
NHDIVFSMNEYKAISVF Q9DDR0 17 0 -
SGDAVSESLEYKTISVF Q9DFA9 20 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
HWIYGRAGCLGITYF O88820 87 59 -
HWIYGRAGCLGITYF Q9R297 87 59 -
HWIYGRAGCLGITYF Q9QWW3 87 59 -
HWIYGHAGCLGITYF Q9ERT2 87 59 -
TWIYGHAGCLGITYF Q9DDR0 93 59 -
TWVYGHAGCLGITYF Q9DFA9 96 59 -

Motif 4 width=10
Element Seqn Id St Int Rpt
LRAQTVCTVA O88820 128 26 -
LRAQTVCTVA Q9R297 128 26 -
LRAQTVCTVA Q9QWW3 128 26 -
MRAQTVCTVA Q9ERT2 128 26 -
MRAKTVCTVS Q9DDR0 134 26 -
MRAQTVCTVS Q9DFA9 137 26 -

Motif 5 width=14
Element Seqn Id St Int Rpt
NVRDNQRLECGYKV O88820 164 26 -
NVRDNQRLECGYKV Q9R297 164 26 -
NVRDNQRLECGYKV Q9QWW3 164 26 -
NVRDNQRLECGYKV Q9ERT2 164 26 -
HVNKSQQVECGYKV Q9DDR0 170 26 -
QVNQEGRVQCGYRV Q9DFA9 173 26 -

Motif 6 width=16
Element Seqn Id St Int Rpt
AAGPQRRAARVLTSNY O88820 324 146 -
AAGPQRRAARVLTSNY Q9R297 324 146 -
AAGPQRRAARVLTSNY Q9QWW3 324 146 -
AAGSQRRAACAPTSNY Q9ERT2 327 149 -
HEETQRRSMYMTTTSY Q9DDR0 343 159 -
RDDGHQRSLSMLQSGY Q9DFA9 344 157 -