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PR01846

Identifier
TRHRFAMILY  [View Relations]  [View Alignment]  
Accession
PR01846
No. of Motifs
8
Creation Date
05-OCT-2002
Title
Thyrotropin-releasing hormone receptor family 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.

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].
 
TRHRFAMILY is an 8-element fingerprint that provides a signature for the
thyrotropin-releasing hormone receptor family. The fingerprint was derived
from an initial alignment of 8 sequences: the motifs were drawn from
conserved sections within loop and TM regions, focusing on those areas of
the alignment that characterise the thyrotropin-releasing hormone receptors
but distinguish them from the rest of rhodopsin-like superfamily - motif 1
encodes the C-terminal portion of TM domain 2 and the first external loop;
motif 2 spans the external and central regions of TM domain 3; motif 3 is
located in the N-terminal section of TM domain 5; motif 4 resides at the
C-terminus of TM domain 5; motif 5 encodes the N-terminal portion of TM
domain 6; motif 6 spans the third external loop; motif 7 resides in the
external and central sections of TM domain 7; and motif 8 lies in the
initial portion of the C-terminus. Two iterations on SPTR40_20f were
required to reach convergence, at which point a true set comprising 14
sequences was identified. Two partial matches were also found: Q9VDC4 and
Q95YD7, receptors from D.melanogaster and C.elegans, respectively, that
are most closely related to the thyrotropin-releasing hormone receptors and
may be members of the family.
Summary Information
  14 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
2 codes involving 2 elements
Composite Feature Index
81414141414141414
700000000
600000000
500000000
400000000
300000000
201000012
12345678
True Positives
O46639        O88820        O93603        Q9DDR0        
Q9DDR1 Q9DFA9 Q9DFB0 Q9ERT2
Q9QWW3 Q9R297 TRFR_HUMAN TRFR_MOUSE
TRFR_RAT TRFR_SHEEP
True Positive Partials
Codes involving 2 elements
Q95YD7 Q9VDC4
Sequence Titles
O46639      THYROTROPIN-RELEASING HORMONE RECEPTOR - BOS TAURUS (BOVINE). 
O88820 G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat).
O93603 THYROTROPIN RELEASING HORMONE RECEPTOR - GALLUS GALLUS (CHICKEN).
Q9DDR0 THYROTROPIN-RELEASING HORMONE RECEPTOR 2 - Xenopus laevis (African clawed frog).
Q9DDR1 THYROTROPIN-RELEASING HORMONE RECEPTOR 1 - Xenopus laevis (African clawed frog).
Q9DFA9 THYROTROPIN-RELEASING HORMONE RECEPTOR 2 - Catostomus commersoni (White sucker).
Q9DFB0 THYROTROPIN-RELEASING HORMONE RECEPTOR 1 - 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).
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).

Q95YD7 HYPOTHETICAL 44.0 KDA PROTEIN - Caenorhabditis elegans.
Q9VDC4 CG5911 PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR40_20f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GLPNITDSIYGSWVYG TRFR_HUMAN 79 79 -
GLPNITDSIYGSWVYG TRFR_MOUSE 79 79 -
GLPNITDSIYGSWVYG TRFR_RAT 79 79 -
GLPNVSDSLVGHWIYG Q9ERT2 76 76 -
GLPNVSDSLVGHWIYG O88820 76 76 -
GLPNVSDSLVGHWIYG Q9R297 76 76 -
GLPNVSDSLAGTWIYG Q9DDR0 82 82 -
GLPNISESLMATWVYG Q9DFA9 85 85 -

Motif 2 width=17
Element Seqn Id St Int Rpt
GCLCITYLQYLGINASS TRFR_HUMAN 97 2 -
GCLCITYLQYLGINASS TRFR_MOUSE 97 2 -
GCLCITYLQYLGINASS TRFR_RAT 97 2 -
GCLGITYFQYLGINVSS Q9ERT2 94 2 -
GCLGITYFQYLGINVSS O88820 94 2 -
GCLGITYFQYLGINVSS Q9R297 94 2 -
GCLGITYFQYLGINASS Q9DDR0 100 2 -
GCLGITYFQYLGINVSS Q9DFA9 103 2 -

Motif 3 width=11
Element Seqn Id St Int Rpt
PIYLMDFGVFY TRFR_HUMAN 190 76 -
PIYLMDFGVFY TRFR_MOUSE 190 76 -
PIYLMDFGVFY TRFR_RAT 190 76 -
PIYLLDFAVFF Q9ERT2 184 73 -
PIYLLDFAVFF O88820 184 73 -
PIYLLDFAVFF Q9R297 184 73 -
PIYLADFAIFY Q9DDR0 190 73 -
PIYLIDFAIFY Q9DFA9 193 73 -

Motif 4 width=12
Element Seqn Id St Int Rpt
YGFIARILFLNP TRFR_HUMAN 211 10 -
YGFIARILFLNP TRFR_MOUSE 211 10 -
YGFIARILFLNP TRFR_RAT 211 10 -
YGFIGRILFQSP Q9ERT2 205 10 -
YGLIGRILFQSP O88820 205 10 -
YGLIGRILFQSP Q9R297 205 10 -
YGLIGRILFLSP Q9DDR0 211 10 -
YGLIARIMYLNP Q9DFA9 214 10 -

Motif 5 width=10
Element Seqn Id St Int Rpt
SSRKQVTKML TRFR_HUMAN 259 36 -
SSRKQVTKML TRFR_MOUSE 259 36 -
SSRKQVTKML TRFR_RAT 259 36 -
SSRKQATRML Q9ERT2 247 30 -
SSRKQATRML O88820 244 27 -
SSRKQATRML Q9R297 244 27 -
SSRKQVTKML Q9DDR0 263 40 -
SSRKQVTKML Q9DFA9 264 38 -

Motif 6 width=11
Element Seqn Id St Int Rpt
VNSFLSSPFQE TRFR_HUMAN 288 19 -
VNSFLSSPFQE TRFR_MOUSE 288 19 -
VNSFLSSPFQE TRFR_RAT 288 19 -
LNSFLARPFLD Q9ERT2 276 19 -
LNSFVAQPFLD O88820 273 19 -
LNSFVAQPFLD Q9R297 273 19 -
VNSFMDKPYLD Q9DDR0 292 19 -
INSFMSTPYLD Q9DFA9 293 19 -

Motif 7 width=12
Element Seqn Id St Int Rpt
LLFCRICIYLNS TRFR_HUMAN 302 3 -
LLFCRICIYLNS TRFR_MOUSE 302 3 -
LLFCRICIYLNS TRFR_RAT 302 3 -
LLFCRTCVYTNS Q9ERT2 290 3 -
LLFCRTCVYTNS O88820 287 3 -
LLFCRTCVYTNS Q9R297 287 3 -
LLFCRICVYANS Q9DDR0 306 3 -
LLFCRTCIYANS Q9DFA9 307 3 -

Motif 8 width=14
Element Seqn Id St Int Rpt
SQKFRAAFRKLCNC TRFR_HUMAN 324 10 -
SQKFRAAFRKLCNC TRFR_MOUSE 324 10 -
SQKFRAAFRKLCNC TRFR_RAT 324 10 -
SQKFRAAFLKLCWC Q9ERT2 312 10 -
SQKFRAAFLKLCWC O88820 309 10 -
SQKFRAAFLKLCWC Q9R297 309 10 -
SQKFRTAFKRLCKC Q9DDR0 328 10 -
SQKFRSAFRGLYHC Q9DFA9 329 10 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GLPNITDSIYGSWVYG O46639 79 79 -
GLPNITDSIYGSWVYG TRFR_HUMAN 79 79 -
GLPNITDSIYGSWVYG TRFR_MOUSE 79 79 -
GLPNITDSIYGSWVYG TRFR_RAT 79 79 -
GLPNITDSIYGSWVYG TRFR_SHEEP 79 79 -
GLPNITESLYKSWVYG O93603 81 81 -
GLPNVSDSLVGHWIYG Q9ERT2 76 76 -
GLPNVSDSLVGHWIYG O88820 76 76 -
GLPNVSDSLVGHWIYG Q9R297 76 76 -
GLPNVSDSLVGHWIYG Q9QWW3 76 76 -
GLPNITESVYGSWVYG Q9DDR1 79 79 -
GLPNVSDSLAGTWIYG Q9DDR0 82 82 -
GLPNISESLMATWVYG Q9DFA9 85 85 -
GLPNITESLFGQWVYG Q9DFB0 79 79 -

Motif 2 width=17
Element Seqn Id St Int Rpt
GCLCITYLQYLGINASS O46639 97 2 -
GCLCITYLQYLGINASS TRFR_HUMAN 97 2 -
GCLCITYLQYLGINASS TRFR_MOUSE 97 2 -
GCLCITYLQYLGINASS TRFR_RAT 97 2 -
GCLCITYLQYLGINASS TRFR_SHEEP 97 2 -
GCLCITYLQYLGINASS O93603 99 2 -
GCLGITYFQYLGINVSS Q9ERT2 94 2 -
GCLGITYFQYLGINVSS O88820 94 2 -
GCLGITYFQYLGINVSS Q9R297 94 2 -
GCLGITYFQYLGINVSS Q9QWW3 94 2 -
GCLCITYLQYLGINASS Q9DDR1 97 2 -
GCLGITYFQYLGINASS Q9DDR0 100 2 -
GCLGITYFQYLGINVSS Q9DFA9 103 2 -
GCLSITYFQYLGINASS Q9DFB0 97 2 -

Motif 3 width=11
Element Seqn Id St Int Rpt
PIYLMDFGVFY O46639 190 76 -
PIYLMDFGVFY TRFR_HUMAN 190 76 -
PIYLMDFGVFY TRFR_MOUSE 190 76 -
PIYLMDFGVFY TRFR_RAT 190 76 -
PIYLMDFGVFY TRFR_SHEEP 190 76 -
PIYMMDFGIFY O93603 192 76 -
PIYLLDFAVFF Q9ERT2 184 73 -
PIYLLDFAVFF O88820 184 73 -
PIYLLDFAVFF Q9R297 184 73 -
PIYLLDFAVFF Q9QWW3 184 73 -
PIYLIDFGIFY Q9DDR1 190 76 -
PIYLADFAIFY Q9DDR0 190 73 -
PIYLIDFAIFY Q9DFA9 193 73 -
PIYFTDFAVFY Q9DFB0 190 76 -

Motif 4 width=12
Element Seqn Id St Int Rpt
YGFIARILFLNP O46639 211 10 -
YGFIARILFLNP TRFR_HUMAN 211 10 -
YGFIARILFLNP TRFR_MOUSE 211 10 -
YGFIARILFLNP TRFR_RAT 211 10 -
YGFIARILFLSP TRFR_SHEEP 211 10 -
YGLIARILFLNP O93603 213 10 -
YGFIGRILFQSP Q9ERT2 205 10 -
YGLIGRILFQSP O88820 205 10 -
YGLIGRILFQSP Q9R297 205 10 -
YGLIGRILFQSP Q9QWW3 205 10 -
YGLIARILFLNP Q9DDR1 211 10 -
YGLIGRILFLSP Q9DDR0 211 10 -
YGLIARIMYLNP Q9DFA9 214 10 -
YGLIARILFLNP Q9DFB0 211 10 -

Motif 5 width=10
Element Seqn Id St Int Rpt
SSRKQVTKML O46639 259 36 -
SSRKQVTKML TRFR_HUMAN 259 36 -
SSRKQVTKML TRFR_MOUSE 259 36 -
SSRKQVTKML TRFR_RAT 259 36 -
SSRKQVTKML TRFR_SHEEP 259 36 -
ASRRQVTKML O93603 261 36 -
SSRKQATRML Q9ERT2 247 30 -
SSRKQATRML O88820 244 27 -
SSRKQATRML Q9R297 244 27 -
SSRKQATRML Q9QWW3 244 27 -
ASRRQVTKML Q9DDR1 259 36 -
SSRKQVTKML Q9DDR0 263 40 -
SSRKQVTKML Q9DFA9 264 38 -
ASRRQVTKML Q9DFB0 257 34 -

Motif 6 width=11
Element Seqn Id St Int Rpt
VNSFLSSPFQE O46639 288 19 -
VNSFLSSPFQE TRFR_HUMAN 288 19 -
VNSFLSSPFQE TRFR_MOUSE 288 19 -
VNSFLSSPFQE TRFR_RAT 288 19 -
VNSFLSSPFQE TRFR_SHEEP 288 19 -
VNSFLSSPFQE O93603 290 19 -
LNSFLARPFLD Q9ERT2 276 19 -
LNSFVAQPFLD O88820 273 19 -
LNSFVAQPFLD Q9R297 273 19 -
LNSFVAQPFLD Q9QWW3 273 19 -
VNSFLSRPYLQ Q9DDR1 288 19 -
VNSFMDKPYLD Q9DDR0 292 19 -
INSFMSTPYLD Q9DFA9 293 19 -
VNSFLKDAYLD Q9DFB0 286 19 -

Motif 7 width=12
Element Seqn Id St Int Rpt
LLFCRICIYLNS O46639 302 3 -
LLFCRICIYLNS TRFR_HUMAN 302 3 -
LLFCRICIYLNS TRFR_MOUSE 302 3 -
LLFCRICIYLNS TRFR_RAT 302 3 -
LLFCRICIYLNS TRFR_SHEEP 302 3 -
LLFCRICIYLNS O93603 304 3 -
LLFCRTCVYTNS Q9ERT2 290 3 -
LLFCRTCVYTNS O88820 287 3 -
LLFCRTCVYTNS Q9R297 287 3 -
LLFCRTCVYTNS Q9QWW3 287 3 -
VLFCRICIYLNS Q9DDR1 302 3 -
LLFCRICVYANS Q9DDR0 306 3 -
LLFCRTCIYANS Q9DFA9 307 3 -
LLFCRLCVYMNS Q9DFB0 300 3 -

Motif 8 width=14
Element Seqn Id St Int Rpt
SQKFRAAFRKLCNC O46639 324 10 -
SQKFRAAFRKLCNC TRFR_HUMAN 324 10 -
SQKFRAAFRKLCNC TRFR_MOUSE 324 10 -
SQKFRAAFRKLCNC TRFR_RAT 324 10 -
SQKFRAAFRKLCNC TRFR_SHEEP 324 10 -
SQKFRAAFRKLCNC O93603 326 10 -
SQKFRAAFLKLCWC Q9ERT2 312 10 -
SQKFRAAFLKLCWC O88820 309 10 -
SQKFRAAFLKLCWC Q9R297 309 10 -
SQKFRAAFLKLCWC Q9QWW3 309 10 -
SQKFRAAFQKLCKC Q9DDR1 324 10 -
SQKFRTAFKRLCKC Q9DDR0 328 10 -
SQKFRSAFRGLYHC Q9DFA9 329 10 -
SQKFRAAFHKLCHC Q9DFB0 322 10 -