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PR01471

Identifier
HISTAMINEH3R  [View Relations]  [View Alignment]  
Accession
PR01471
No. of Motifs
8
Creation Date
19-FEB-2001
Title
Histamine H3 receptor 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.
Histamine.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994,
PP.152-158.
 
7. LOVENBERG, T.W., ROLAND, B.L., WILSON, S.J., JIANG, X., PYATI, J., HUVAT,
A., JACKSON, M.R. AND ERLANDER, M.G.
Cloning and functional expression of the human histamine H3 receptor.
MOL.PHARMACOL. 55 1101-1107 (1999).

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine,
paracrine 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]. 
     
Histamine is distributed within mast cells in all peripheral tissues and 
is a well-characterised mediator of inflammation and allergy [6]. It also
regulates release of gastric acid from parietal cells in the gastric mucosa.
H3 receptors function as presynaptic autoreceptors on histamine-containing
neurones. They are expressed abundantly in the central nervous system, with
highest levels found in the thalamus, caudate nucleus and cortex. High
levels of expression are also found in the hypothalamus, hippocampus and
olfactory tubercle. In the periphery, low levels of H3 have been detected in
the human small intestine, testis and prostate but not in a number of other
tissues tested, including the heart, lung and spleen [7]. Binding of 
histamine to H3 receptors results in inhibition of forskolin-stimulated cAMP
accumulation, suggesting coupling to a G protein of the Gi class [7].
 
HISTAMINEH3R is an 8-element fingerprint that provides a signature for the
histamine H3 receptors. The fingerprint was derived from an initial 
alignment of 5 sequences: the motifs were drawn from conserved sections
within the N-terminus and loop regions, focusing on those regions of the 
alignment that characterise the histamine H3 receptors but distinguish them 
from the rest of the histamine receptor family - motif 1 is located in the
N-terminus; motif 2 spans part of the N-terminus leading into TM domain 1;
motifs 3 and 4 span the second external loop; motifs 5 and 6 span the
N-terminal region of the third cytoplasmic loop; motif 7 encodes the
C-terminus of the third cytoplasmic loop; and motif 8 resides at the
C-terminus of TM domain 6, leading into the third external loop. Two 
iterations on SPTR39_15f were required to reach convergence, at which point
a true set comprising 7 sequences was identified.
Summary Information
7 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
877777777
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
Q9JI35        Q9JI36        Q9QYN6        Q9QYN7        
Q9QYN8 Q9QYN9 Q9Y5N1
Sequence Titles
Q9JI35      HISTAMINE H3 RECEPTOR H3S ISOFORM - Cavia porcellus (Guinea pig). 
Q9JI36 HISTAMINE H3 RECEPTOR H3L ISOFORM - Cavia porcellus (Guinea pig).
Q9QYN6 G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat).
Q9QYN7 G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat).
Q9QYN8 G PROTEIN-COUPLED RECEPTOR (HISTAMINE H3 RECEPTOR) - Rattus norvegicus (Rat).
Q9QYN9 G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat).
Q9Y5N1 HISTAMINE H3 RECEPTOR - Homo sapiens (Human).
Scan History
SPTR39_15f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
MERAPPDGLMNASGTLAGE Q9QYN6 1 1 -
MERAPPDGLMNASGTLAGE Q9QYN9 1 1 -
MERAPPDGLMNASGTLAGE Q9QYN8 1 1 -
MERAPPDGLMNASGTLAGE Q9QYN7 1 1 -
MERAPPDGPLNASGALAGD Q9Y5N1 1 1 -

Motif 2 width=19
Element Seqn Id St Int Rpt
AAAAGGARGFSAAWTAVLA Q9QYN6 20 0 -
AAAAGGARGFSAAWTAVLA Q9QYN9 20 0 -
AAAAGGARGFSAAWTAVLA Q9QYN8 20 0 -
AAAAGGARGFSAAWTAVLA Q9QYN7 20 0 -
AAAAGGARGFSAAWTAVLA Q9Y5N1 20 0 -

Motif 3 width=21
Element Seqn Id St Int Rpt
YGPAILSWEYLSGGSSIPEGH Q9QYN6 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9QYN9 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9QYN8 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9QYN7 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9Y5N1 167 128 -

Motif 4 width=19
Element Seqn Id St Int Rpt
CYAEFFYNWYFLITASTLE Q9QYN6 188 0 -
CYAEFFYNWYFLITASTLE Q9QYN9 188 0 -
CYAEFFYNWYFLITASTLE Q9QYN8 188 0 -
CYAEFFYNWYFLITASTLE Q9QYN7 188 0 -
CYAEFFYNWYFLITASTLE Q9Y5N1 188 0 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GPEPPPDAQPSPPPAP Q9QYN6 240 33 -
GPEPPPDAQPSPPPAP Q9QYN9 240 33 -
GPEPPPDAQPSPPPAP Q9QYN8 240 33 -
GPEPPPDAQPSPPPAP Q9QYN7 240 33 -
GPEPPPEAQPSPPPPP Q9Y5N1 241 34 -

Motif 6 width=16
Element Seqn Id St Int Rpt
CWGCWPKGHGEAMPLH Q9QYN6 258 2 -
CWGCWPKGHGEAMPLH Q9QYN9 258 2 -
CWGCWPKGHGEAMPLH Q9QYN8 258 2 -
CWGCWPKGHGEAMPLH Q9QYN7 258 2 -
CWGCWQKGHGEAMPLH Q9Y5N1 258 1 -

Motif 7 width=27
Element Seqn Id St Int Rpt
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN6 276 2 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN9 276 2 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN8 324 50 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN7 292 18 -
SKPSASSASLEKRMKMVSQSFTQRFRL Q9Y5N1 324 50 -

Motif 8 width=17
Element Seqn Id St Int Rpt
LLMIIRAACHGRCIPDY Q9QYN6 328 25 -
LLMIIRAACHGRCIPDY Q9QYN9 328 25 -
LLMIIRAACHGRCIPDY Q9QYN8 376 25 -
LLMIIRAACHGRCIPDY Q9QYN7 344 25 -
LLMIIRAACHGHCVPDY Q9Y5N1 376 25 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
MERAPPDGLMNASGTLAGE Q9QYN6 1 1 -
MERAPPDGLMNASGTLAGE Q9QYN9 1 1 -
MERAPPDGLMNASGTLAGE Q9QYN8 1 1 -
MERAPPDGLMNASGTLAGE Q9QYN7 1 1 -
MERAPPDGPLNASGALAGD Q9Y5N1 1 1 -
MERAPPDGLMNASGALAGE Q9JI35 1 1 -
MERAPPDGLMNASGALAGE Q9JI36 1 1 -

Motif 2 width=19
Element Seqn Id St Int Rpt
AAAAGGARGFSAAWTAVLA Q9QYN6 20 0 -
AAAAGGARGFSAAWTAVLA Q9QYN9 20 0 -
AAAAGGARGFSAAWTAVLA Q9QYN8 20 0 -
AAAAGGARGFSAAWTAVLA Q9QYN7 20 0 -
AAAAGGARGFSAAWTAVLA Q9Y5N1 20 0 -
AAAAGGARTFSAAWTAVLA Q9JI35 21 1 -
AAAAGGARTFSAAWTAVLA Q9JI36 21 1 -

Motif 3 width=21
Element Seqn Id St Int Rpt
YGPAILSWEYLSGGSSIPEGH Q9QYN6 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9QYN9 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9QYN8 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9QYN7 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9Y5N1 167 128 -
YGPAILSWEYLSGGSSIPEGH Q9JI35 168 128 -
YGPAILSWEYLSGGSSIPEGH Q9JI36 168 128 -

Motif 4 width=19
Element Seqn Id St Int Rpt
CYAEFFYNWYFLITASTLE Q9QYN6 188 0 -
CYAEFFYNWYFLITASTLE Q9QYN9 188 0 -
CYAEFFYNWYFLITASTLE Q9QYN8 188 0 -
CYAEFFYNWYFLITASTLE Q9QYN7 188 0 -
CYAEFFYNWYFLITASTLE Q9Y5N1 188 0 -
CYAEFFYNWYFLITASTLE Q9JI35 189 0 -
CYAEFFYNWYFLITASTLE Q9JI36 189 0 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GPEPPPDAQPSPPPAP Q9QYN6 240 33 -
GPEPPPDAQPSPPPAP Q9QYN9 240 33 -
GPEPPPDAQPSPPPAP Q9QYN8 240 33 -
GPEPPPDAQPSPPPAP Q9QYN7 240 33 -
GPEPPPEAQPSPPPPP Q9Y5N1 241 34 -
GPDPLPEAQSSPPQPP Q9JI35 242 34 -
GPDPLPEAQSSPPQPP Q9JI36 242 34 -

Motif 6 width=16
Element Seqn Id St Int Rpt
CWGCWPKGHGEAMPLH Q9QYN6 258 2 -
CWGCWPKGHGEAMPLH Q9QYN9 258 2 -
CWGCWPKGHGEAMPLH Q9QYN8 258 2 -
CWGCWPKGHGEAMPLH Q9QYN7 258 2 -
CWGCWQKGHGEAMPLH Q9Y5N1 258 1 -
CWGCWPKGQGESMPLH Q9JI35 260 2 -
CWGCWPKGQGESMPLH Q9JI36 260 2 -

Motif 7 width=27
Element Seqn Id St Int Rpt
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN6 276 2 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN9 276 2 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN8 324 50 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9QYN7 292 18 -
SKPSASSASLEKRMKMVSQSFTQRFRL Q9Y5N1 324 50 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9JI35 294 18 -
SKPSASSASLEKRMKMVSQSITQRFRL Q9JI36 324 48 -

Motif 8 width=17
Element Seqn Id St Int Rpt
LLMIIRAACHGRCIPDY Q9QYN6 328 25 -
LLMIIRAACHGRCIPDY Q9QYN9 328 25 -
LLMIIRAACHGRCIPDY Q9QYN8 376 25 -
LLMIIRAACHGRCIPDY Q9QYN7 344 25 -
LLMIIRAACHGHCVPDY Q9Y5N1 376 25 -
LLMIIRAACHGHCVPDY Q9JI35 346 25 -
LLMIIRAACHGHCVPDY Q9JI36 376 25 -