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PR01280

Identifier
CRFRECEPTOR1  [View Relations]  [View Alignment]  
Accession
PR01280
No. of Motifs
4
Creation Date
18-MAR-2000
Title
Corticotropin releasing factor type 1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN
PRINTS; PR01279 CRFRECEPTOR
GCRDB; GCR_0679; GCR_0680; GCR_0846; GCR_2030
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. YU, J., XIE, L.Y. AND ABOU-SAMRA, A.B.
Molecular cloning of a type A chicken corticotropin-releasing factor
receptor with high affinity for urotensin I.
ENDOCRINOLOGY 137 192-197 (1996). 

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 (CRF-R) has been found in human
cortex tissue, pituitary, brainstem and testis [7]. The protein comprises
~420 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]. The human CRF-R1 includes an insertion of 29
amino acids in the first putative cytoplasmic domain. This form of the
receptor couples poorly to stimulation of adenylate cyclase by comparison
with its shorter variant.
 
The sequence of the CRF-R is highly conserved from avian to mammalian
species, the majority of the sequence divergence occuring in the putative
signal peptide and extracellular N-terminal domain [8]. Five additional
amino acids are inserted in the N-terminus of the avian receptor, and 
despite its overall similarity to the type 1 mammalian CRF-R, its ligand 
binding properties are similar to those of the type 2 receptor (i.e., it 
has a higher affinity for urotensin I than for CRF) [8]. 
 
CRFRECEPTOR1 is a 4-element fingerprint that provides a signature for type 1 
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 1 CRF receptors but distinguish them
from the rest of the CRF receptor family - motifs 1-3 span the C-terminus
of the putative signal sequence and the N-terminal extracellular domain; 
and motif 4 encodes the first extracellular loop. Two iterations on 
SPTR37_10f were required to reach convergence, at which point a true set 
comprising 6 sequences was identified. 
Summary Information
6 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
46666
30000
20000
1234
True Positives
CRFR_CHICK    CRFR_HUMAN    CRFR_MOUSE    CRFR_RAT      
CRFR_SHEEP CRFR_XENLA
Sequence Titles
CRFR_CHICK  CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 PRECURSOR (CRF-R) (CRF1) - GALLUS GALLUS (CHICKEN). 
CRFR_HUMAN CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 PRECURSOR (CRF-R) (CRF1) - HOMO SAPIENS (HUMAN).
CRFR_MOUSE CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 PRECURSOR (CRF-R) (CRF1) - MUS MUSCULUS (MOUSE).
CRFR_RAT CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 PRECURSOR (CRF-R) (CRF1) - RATTUS NORVEGICUS (RAT).
CRFR_SHEEP CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 PRECURSOR (CRF-R) (CRF1) - OVIS ARIES (SHEEP).
CRFR_XENLA CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 PRECURSOR (CRF-R) (CRF1) - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
SPTR37_10f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
LGLNPVSTSLQDQ CRFR_MOUSE 16 16 -
LGLNPVSTSLQDQ CRFR_RAT 16 16 -
LGLNPVSASLQDQ CRFR_HUMAN 16 16 -
LWDSPVAASIQEQ CRFR_CHICK 21 21 -
AGISFALTSLQDQ CRFR_XENLA 17 17 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CESLSLASNVSGLQC CRFR_MOUSE 30 1 -
CENLSLTSNVSGLQC CRFR_RAT 30 1 -
CESLSLASNISGLQC CRFR_HUMAN 30 1 -
CESLLPTTNHTGPQC CRFR_CHICK 35 1 -
CETLQHNSNFTGLAC CRFR_XENLA 30 0 -

Motif 3 width=12
Element Seqn Id St Int Rpt
QEILNEEKKSKV CRFR_MOUSE 103 58 -
QEILNEEKKSKV CRFR_RAT 103 58 -
QEILNEEKKSKV CRFR_HUMAN 103 58 -
QEILSEEKRSKL CRFR_CHICK 108 58 -
QEILKQEKKTKV CRFR_XENLA 103 58 -

Motif 4 width=15
Element Seqn Id St Int Rpt
VVQLTVSPEVHQSNV CRFR_MOUSE 171 56 -
VVQLTVSPEVHQSNV CRFR_RAT 171 56 -
VVQLTMSPEVHQSNV CRFR_HUMAN 200 85 -
VVQLTMNPEVHESNV CRFR_CHICK 176 56 -
VMQLTLSHEAHDSNV CRFR_XENLA 171 56 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
LGLNPVSTSLQDQ CRFR_MOUSE 16 16 -
LGLNPVSTSLQDQ CRFR_RAT 16 16 -
LGLNPVSASLQDQ CRFR_HUMAN 16 16 -
LWDSPVAASIQEQ CRFR_CHICK 21 21 -
LGLNSISASLQDQ CRFR_SHEEP 16 16 -
AGISFALTSLQDQ CRFR_XENLA 17 17 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CESLSLASNVSGLQC CRFR_MOUSE 30 1 -
CENLSLTSNVSGLQC CRFR_RAT 30 1 -
CESLSLASNISGLQC CRFR_HUMAN 30 1 -
CESLLPTTNHTGPQC CRFR_CHICK 35 1 -
CESLSLASNVSGLQC CRFR_SHEEP 30 1 -
CETLQHNSNFTGLAC CRFR_XENLA 30 0 -

Motif 3 width=12
Element Seqn Id St Int Rpt
QEILNEEKKSKV CRFR_MOUSE 103 58 -
QEILNEEKKSKV CRFR_RAT 103 58 -
QEILNEEKKSKV CRFR_HUMAN 103 58 -
QEILSEEKRSKL CRFR_CHICK 108 58 -
QEILSEGEKSKA CRFR_SHEEP 103 58 -
QEILKQEKKTKV CRFR_XENLA 103 58 -

Motif 4 width=15
Element Seqn Id St Int Rpt
VVQLTVSPEVHQSNV CRFR_MOUSE 171 56 -
VVQLTVSPEVHQSNV CRFR_RAT 171 56 -
VVQLTMSPEVHQSNV CRFR_HUMAN 200 85 -
VVQLTMNPEVHESNV CRFR_CHICK 176 56 -
VVQLTMSPEVHQSNV CRFR_SHEEP 171 56 -
VMQLTLSHEAHDSNV CRFR_XENLA 171 56 -