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PR01281

Identifier
CRFRECEPTOR2  [View Relations]  [View Alignment]  
Accession
PR01281
No. of Motifs
5
Creation Date
18-MAR-2000
Title
Corticotropin releasing factor type 2 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN
PRINTS; PR01279 CRFRECEPTOR
GCRDB; GCR_1963; GCR_2555; GCR_2562
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994). 
 
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.
Molecular cloning and expression of a cDNA encoding the secretin receptor
EMBO J. 10 1635-1641 (1991).
 
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H., 
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor
SCIENCE 254 1022-1024 (1991).
 
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F., 
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
 
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
 
6. CHEN, R., LEWIS, K.A., PERRIN, M.H. AND VALE, W.W.
Expression cloning of a human corticotropin-releasing-factor receptor.
PROC.NATL.ACAD.SCI.U.S.A. 90 8967-8971 (1993). 
7. VITA, N., LAURENT, P., LEFORT, S., CHALON, P., LELIAS, J.M., KAGHAD, M.,
LE FUR, G., CAPUT, D. AND FERRARA, P.
Primary structure and functional expression of mouse pituitary and human
brain corticotrophin releasing factor receptors.
FEBS LETT. 335 1-5 (1993). 
 
8. LIAW, C.W., LOVENBERG, T.W., BARRY, G., OLTERSDORF, T., GRIGORIADIS, D.E.
AND DE SOUZA, E.B.
Cloning and characterization of the human corticotropin-releasing factor-2 
receptor complementary deoxyribonucleic acid.
ENDOCRINOLOGY 137 72-77 (1996). 
 
9. LOVENBERG, T.W., LIAW, C.W., GRIGORIADIS, D.E., CLEVENGER, W.,
CHALMERS, D.T., DE SOUZA, E.B. AND OLTERSDORF, T.
Cloning and characterization of a functionally distinct corticotropin- 
releasing factor receptor subtype from rat brain.
PROC.NATL.ACAD.SCI.U.S.A. 92 836-840 (1995). 

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 secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a
manner reminiscent of the rhodopsins and other receptors believed to inter-
act with G proteins. However, while a similar 3D framework has been
proposed to account for this, there is no significant sequence similarity
between these families: the secretin-like receptors thus bear their own
unique `7TM' signature.
 
Corticotropin-releasing factor (CRF) is the principal neuroregulator of the
hypothalamic-pituitary-adrenocortical axis, playing an important role in
coordinating the endocrine, autonomic and behavioral responses to stress
and immune challenge [6]. The CRF receptor has been found in human cortex
tissue, pituitary, brainstem and testis [7]. The protein comprises 415 
amino acid residues with the characterstic 7TM architecture of the
secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2
and CRF-R3) are produced as a result of alternative splicing of the same
gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to
CRF with a high affinity [6]. For the CRF-R2 receptor, at least 2 splice 
forms with different 5'-coding sequences (CRF2 alpha and CRF2 beta) have 
been identified in rat [8].
 
The sequence of the CRF-R is highly conserved between species, the majority 
of the sequence divergence occuring in the putative signal peptide and 
extracellular N-terminal domain. The relative abundance of CRF-R2 messenger
RNA appears to be lower in humans than in rats for the heart and skeletal
tissues studied to date [8]. CRF-R2 stimulates cAMP production in response
to CRF and known CRF-like agonists [9]. CRF and the non-mammalian 
CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclase
activity in a dose-dependent manner, with a rank order of potency that
differs from that of the CRF1 receptor (sauvagine>urotensin>=rat/human 
CRF>ovine CRF) [9]. The differences in the pharmacological profiles and 
tissue distributions of CRF-R1 and CRF-R2 suggests important functional
differences between the two receptors [9].   
 
CRFRECEPTOR is a 5-element fingerprint that provides a signature for type 2 
corticotropin releasing factor receptors. The fingerprint was derived from
an initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise the type 2 CRF receptors but distinguish them
from the rest of the CRF receptor family - motifs 1-3 span the putative
N-terminal extracellular domain; motif 4 spans the first extracellular 
loop; and motif 5 resides within the second extracellular loop. A single
iteration on SPTR37_10f was required to reach convergence, no further
sequences being identified beyond the starting set. Two partial matches
were found, O43461 and Q99431, both of which are type 2 CRF receptors that
fail to match the first motif. 
Summary Information
   4 codes involving  5 elements
2 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
544444
402222
300000
200000
12345
True Positives
CRF2_HUMAN    CRF2_MOUSE    CRF2_RAT      CRF2_XENLA    
True Positive Partials
Codes involving 4 elements
O43461 Q99431
Sequence Titles
CRF2_HUMAN  CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 PRECURSOR (CRF-R) (CRF2) - HOMO SAPIENS (HUMAN). 
CRF2_MOUSE CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 PRECURSOR (CRF-R) (CRF2) (CRF-RB) (CRH-R2) - MUS MUSCULUS (MOUSE).
CRF2_RAT CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 PRECURSOR (CRF-R) (CRF2) - RATTUS NORVEGICUS (RAT).
CRF2_XENLA CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 PRECURSOR (CRF-R) (CRF2) - XENOPUS LAEVIS (AFRICAN CLAWED FROG).

O43461 CORTICOTROPIN RELEASING HORMONE RECEPTOR TYPE 2 GAMMA ISOFORM - HOMO SAPIENS (HUMAN).
Q99431 CORTICOTROPIN RELEASING HORMONE RECEPTOR TYPE 2 BETA ISOFORM (CRF2 RECEPTOR, BETA ISOFORM) - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_10f 1  75   NSINGLE    
Initial Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
EPPDPEGPY CRF2_RAT 29 29 -
PPLDPEGPY CRF2_HUMAN 29 29 -
TIGNFSGPY CRF2_MOUSE 49 49 -
SFFGFEGPY CRF2_XENLA 34 34 -

Motif 2 width=9
Element Seqn Id St Int Rpt
QSAPGALVE CRF2_RAT 53 15 -
RSAAGALVE CRF2_HUMAN 53 15 -
QSAPGALVE CRF2_MOUSE 73 15 -
RSLAGELVE CRF2_XENLA 56 13 -

Motif 3 width=10
Element Seqn Id St Int Rpt
HCEPILDDKQ CRF2_RAT 97 35 -
QCEPILDDKQ CRF2_HUMAN 97 35 -
HCEPILDDKQ CRF2_MOUSE 117 35 -
QCVPILDNKR CRF2_XENLA 100 35 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LLQLIDHEVHEGNEVW CRF2_RAT 168 61 -
LLQLVDHEVHESNEVW CRF2_HUMAN 168 61 -
LLQLIDHEVHEGNEVW CRF2_MOUSE 188 61 -
LLQMIDHNIHESNEVW CRF2_XENLA 170 60 -

Motif 5 width=8
Element Seqn Id St Int Rpt
KEPGDLVD CRF2_RAT 258 74 -
KEPGDLVD CRF2_HUMAN 258 74 -
KEAGDLVD CRF2_MOUSE 278 74 -
KEPGKYID CRF2_XENLA 260 74 -
Final Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
EPPDPEGPY CRF2_RAT 29 29 -
PPLDPEGPY CRF2_HUMAN 29 29 -
TIGNFSGPY CRF2_MOUSE 49 49 -
SFFGFEGPY CRF2_XENLA 34 34 -

Motif 2 width=9
Element Seqn Id St Int Rpt
QSAPGALVE CRF2_RAT 53 15 -
RSAAGALVE CRF2_HUMAN 53 15 -
QSAPGALVE CRF2_MOUSE 73 15 -
RSLAGELVE CRF2_XENLA 56 13 -

Motif 3 width=10
Element Seqn Id St Int Rpt
HCEPILDDKQ CRF2_RAT 97 35 -
QCEPILDDKQ CRF2_HUMAN 97 35 -
HCEPILDDKQ CRF2_MOUSE 117 35 -
QCVPILDNKR CRF2_XENLA 100 35 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LLQLIDHEVHEGNEVW CRF2_RAT 168 61 -
LLQLVDHEVHESNEVW CRF2_HUMAN 168 61 -
LLQLIDHEVHEGNEVW CRF2_MOUSE 188 61 -
LLQMIDHNIHESNEVW CRF2_XENLA 170 60 -

Motif 5 width=8
Element Seqn Id St Int Rpt
KEPGDLVD CRF2_RAT 258 74 -
KEPGDLVD CRF2_HUMAN 258 74 -
KEAGDLVD CRF2_MOUSE 278 74 -
KEPGKYID CRF2_XENLA 260 74 -