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PR01726

Identifier
HISTAMINEH4R  [View Relations]  [View Alignment]  
Accession
PR01726
No. of Motifs
6
Creation Date
15-APR-2002
Title
Histamine H4 receptor signature
Database References
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. ODA, T., MORIKAWA, N., SAITO, Y., MASUHO, Y. AND MATSUMOTO, S.
Molecular cloning and characterization of a novel type of histamine receptor
preferentially expressed in leukocytes.
J.BIOL.CHEM. 275(47) 36781-36786 (2000).
 
8. NAKAMURA, T., ITADANI, H., HIDAKA, Y., OHTA, M. AND TANAKA, K.
Molecular cloning and characterization of a new human histamine receptor,
HH4R.
BIOCHEM.BIOPHYS.RES.COMMUN. 279(2) 615-620 (2000).
 
9. LIU, C., MA, X., JIANG, X., WILSON, S.J., HOFSTRA, C.L., BLEVITT, J., 
PYATI, J., LI, X., CHAI, W., CARRUTHERS, N. AND LOVENBERG, T.W.
Cloning and pharmacological characterization of a fourth histamine
receptor (H(4)) expressed in bone marrow.
MOL.PHARMACOL. 59(3) 420-426 (2001).
 
10. MORSE, K.L., BEHAN, J., LAZ, T.M., WEST, R.E.JR., GREENFEDER, S.A.,
ANTHES, J.C., UMLAND, S., WAN, Y., HIPKIN, R.W., GONSIOREK, W., SHIN, N., 
GUSTAFSON, E.L., QIAO, X., WANG, S., HEDRICK, J.A., GREENE, J., BAYNE, M.
AND MONSMA, F.J.JR.
Cloning and characterization of a novel human histamine receptor.
J.PHARMACOL.EXP.THER. 296(3) 1058-1066 (2001).
 
11. ZHU, Y., MICHALOVICH, D., WU, H., TAN, K.B., DYTKO, G.M., MANNAN, I.J., 
BOYCE, R., ALSTON, J., TIERNEY, L.A., LI, X., HERRITY, N.C., VAWTER, L., 
SARAU, H.M., AMES, R.S., DAVENPORT, C.M., HIEBLE, J.P., WILSON, S., 
BERGSMA, D.J. AND FITZGERALD, L.R.
Cloning, expression, and pharmacological characterization of a novel human
histamine receptor.
MOL.PHARMACOL. 59(3) 434-441 (2001).

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]. 
 
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.
A fourth member of the histamine receptor family, HH4R, has been identified
that is expressed primarily in cells and tissues of the immune system, 
including: peripheral blood leukocytes, bone marrow, spleen and thymus 
[7,9-11]. This expression pattern suggests that the receptor may represent a
novel therapeutic target for the regulation of immune function, particularly
in allergy and asthma [9]. Binding of histamine to HH4R appears to result in
inhibition of forskolin-stimulated cAMP accumulation through coupling to Gi
proteins [8,10]. The receptor has also been found to have a relatively high 
level of constitutive activity [10].
 
HISTAMINEH4R is a 6-element fingerprint that provides a signature for the 
histamine H4 receptors. The fingerprint was derived from an initial 
alignment of 5 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
that characterise the H4 receptors but distinguish them from the rest of 
the histamine receptor family - motif 1 spans the first cytoplasmic loop;
motif 2 is located in the second external loop; motifs 3-5 lie in the third
cytoplasmic loop; and motif 6 lies at the C-terminus. Two iterations on 
SPTR40_20f 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
HH4R_HUMAN    Q8WNV9        Q91ZY1        Q91ZY2        
Q91ZY3 Q96LD9
Sequence Titles
HH4R_HUMAN  Histamine H4 receptor (HH4R) (GPRv53) - Homo sapiens (Human). 
Q8WNV9 HISTAMINE H4 RECEPTOR - Sus scrofa (Pig).
Q91ZY1 HISTAMINE H4 RECEPTOR - Rattus norvegicus (Rat).
Q91ZY2 HISTAMINE H4 RECEPTOR - Mus musculus (Mouse).
Q91ZY3 HISTAMINE H4 RECEPTOR - Cavia porcellus (Guinea pig).
Q96LD9 HISTAMINE RECEPTOR H4 - Homo sapiens (Human).
Scan History
SPTR40_20f 2  280  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
DKNLRHRSSY HH4R_HUMAN 43 43 -
DKNLRHRSSY Q96LD9 43 43 -
DRNLRHRSNY Q91ZY1 43 43 -
DRNLRHRSNY Q91ZY3 42 42 -
DRNLRHRSNY Q91ZY2 43 43 -

Motif 2 width=11
Element Seqn Id St Int Rpt
ECEPGFFSEWY HH4R_HUMAN 163 110 -
ECEPGFFSEWY Q96LD9 163 110 -
ECEPGFVTEWY Q91ZY1 165 112 -
ECEPGFLKKWY Q91ZY3 162 110 -
DCEPGFVTEWY Q91ZY2 165 112 -

Motif 3 width=15
Element Seqn Id St Int Rpt
WSLWKRDHLSRCQSH HH4R_HUMAN 199 25 -
WSLWKRDHLSRCQSH Q96LD9 199 25 -
WSLWKRGSLSRCPSH Q91ZY1 201 25 -
WSLWKREKLSRCLSH Q91ZY3 198 25 -
WSLWKRRALSRCPSH Q91ZY2 201 25 -

Motif 4 width=15
Element Seqn Id St Int Rpt
SERQRRKSSLMFSSR HH4R_HUMAN 250 36 -
SERQRRKSSLMFSSR Q96LD9 250 36 -
SESPRGKSSLLVSLR Q91ZY1 252 36 -
SDKSRRKSSLLFSIR Q91ZY3 250 37 -
SESPRRKSSILVSLR Q91ZY2 252 36 -

Motif 5 width=20
Element Seqn Id St Int Rpt
SDSVALHQREHVELLRARRL HH4R_HUMAN 282 17 -
SDSVALHQREHVELLRARRL Q96LD9 282 17 -
SESPVLHQREHVELLRGRKL Q91ZY1 284 17 -
SDSLALQQREHIELFRARKL Q91ZY3 282 17 -
SESAALRQREYAELLRGRKL Q91ZY2 284 17 -

Motif 6 width=11
Element Seqn Id St Int Rpt
HKRFQKAFLKI HH4R_HUMAN 362 60 -
HKRFQKAFLKI Q96LD9 362 60 -
HRRFQKAFWKI Q91ZY1 364 60 -
HKRFQKAFLKI Q91ZY3 362 60 -
HRRFQKAFWKI Q91ZY2 364 60 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
DKNLRHRSSY HH4R_HUMAN 43 43 -
DKNLRHRSSY Q96LD9 43 43 -
DKNLRHRSNY Q8WNV9 45 45 -
DRNLRHRSNY Q91ZY1 43 43 -
DRNLRHRSNY Q91ZY3 42 42 -
DRNLRHRSNY Q91ZY2 43 43 -

Motif 2 width=11
Element Seqn Id St Int Rpt
ECEPGFFSEWY HH4R_HUMAN 163 110 -
ECEPGFFSEWY Q96LD9 163 110 -
DCEPGFLKEWY Q8WNV9 165 110 -
ECEPGFVTEWY Q91ZY1 165 112 -
ECEPGFLKKWY Q91ZY3 162 110 -
DCEPGFVTEWY Q91ZY2 165 112 -

Motif 3 width=15
Element Seqn Id St Int Rpt
WSLWKRDHLSRCQSH HH4R_HUMAN 199 25 -
WSLWKRDHLSRCQSH Q96LD9 199 25 -
WSLWKRGHLSRCQSH Q8WNV9 201 25 -
WSLWKRGSLSRCPSH Q91ZY1 201 25 -
WSLWKREKLSRCLSH Q91ZY3 198 25 -
WSLWKRRALSRCPSH Q91ZY2 201 25 -

Motif 4 width=15
Element Seqn Id St Int Rpt
SERQRRKSSLMFSSR HH4R_HUMAN 250 36 -
SERQRRKSSLMFSSR Q96LD9 250 36 -
SERPRRKSTLWFSLR Q8WNV9 252 36 -
SESPRGKSSLLVSLR Q91ZY1 252 36 -
SDKSRRKSSLLFSIR Q91ZY3 250 37 -
SESPRRKSSILVSLR Q91ZY2 252 36 -

Motif 5 width=20
Element Seqn Id St Int Rpt
SDSVALHQREHVELLRARRL HH4R_HUMAN 282 17 -
SDSVALHQREHVELLRARRL Q96LD9 282 17 -
SDSLALHQKEHLELLRARKL Q8WNV9 283 16 -
SESPVLHQREHVELLRGRKL Q91ZY1 284 17 -
SDSLALQQREHIELFRARKL Q91ZY3 282 17 -
SESAALRQREYAELLRGRKL Q91ZY2 284 17 -

Motif 6 width=11
Element Seqn Id St Int Rpt
HKRFQKAFLKI HH4R_HUMAN 362 60 -
HKRFQKAFLKI Q96LD9 362 60 -
HKRFQKAFLKI Q8WNV9 363 60 -
HRRFQKAFWKI Q91ZY1 364 60 -
HKRFQKAFLKI Q91ZY3 362 60 -
HRRFQKAFWKI Q91ZY2 364 60 -