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PR00520

Identifier
ACTROPHINR  [View Relations]  [View Alignment]  
Accession
PR00520
No. of Motifs
6
Creation Date
20-MAY-1996  (UPDATE 28-JUL-1999)
Title
Adrenocorticotrophin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00534 MCRFAMILY
INTERPRO; IPR001168
GCRDB; GCR_0445
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.
Melanocortins.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.180-191.

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]. 
 
Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones and beta-
endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH 
regulates synthesis and release of glucocorticoids and aldosterone in
the adrenal cortex; it also has a trophic action on these cells [6]. 
ACTH and beta-endorphin are synthesised and released in response to 
corticotrophin-releasing factor at times of stress (heat, cold, infections,
etc.) - their release leads to increased metabolism and analgesia res..
The ACTH receptor is found in high levels in the adrenal cortex - binding
sites are present in lower levels in the CNS. 
 
ACTROPHINR is a 6-element fingerprint that provides a signature for the
adrenocorticotrophin receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections   
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the ACTH receptors but distinguish them
from the rest of the melanocortin receptors - motifs 1 and 2 were drawn
from the N-terminal region preceding TM domain 1; motif 3 spans the first
external loop; motif 4 spans the C-terminus of TM domain 4 and the second
external loop; motif 5 lies in the third cytoplasmic loop; and motif 6
resides in the C-terminal region following TM domain 7. A single iteration
on OWL27.1 was required to reach convergence, no further sequences being
identfied beyond the starting set. 
 
An update on SPTR37_9f identified a true set of 4 sequences, and 1
partial match.
Summary Information
   4 codes involving  6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6444444
5000000
4011110
3000000
2000000
123456
True Positives
ACTR_BOVIN    ACTR_HUMAN    ACTR_MESAU    ACTR_MOUSE    
True Positive Partials
Codes involving 4 elements
O57317
Sequence Titles
ACTR_BOVIN  ADRENOCORTICOTROPIC HORMONE RECEPTOR (ACTH-R) (MELANOCORTIN-2 RECEPTOR) (MC2-R) (ADRENOCORTICOTROPIN RECEPTOR) - BOS TAURUS (BOVINE). 
ACTR_HUMAN ADRENOCORTICOTROPIC HORMONE RECEPTOR (ACTH-R) (MELANOCORTIN-2 RECEPTOR) (MC2-R) (ADRENOCORTICOTROPIN RECEPTOR) - HOMO SAPIENS (HUMAN).
ACTR_MESAU ADRENOCORTICOTROPIC HORMONE RECEPTOR (ACTH-R) (MELANOCORTIN-2 RECEPTOR) (MC2-R) (ADRENOCORTICOTROPIN RECEPTOR) - MESOCRICETUS AURATUS (GOLDEN HAMSTER).
ACTR_MOUSE ADRENOCORTICOTROPIC HORMONE RECEPTOR (ACTH-R) (MELANOCORTIN-2 RECEPTOR) (MC2-R) (ADRENOCORTICOTROPIN RECEPTOR) - MUS MUSCULUS (MOUSE).

O57317 MELANOCORTIN 2-RECEPTOR - GALLUS GALLUS (CHICKEN).
Scan History
OWL27_1    1  50   NSINGLE    
SPTR37_9f 2 150 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
HILNLYENINSTARNNS ACTR_BOVIN 3 3 -
HIINSYENINNTARNNS ACTR_HUMAN 3 3 -
HIINSYEHTNDTARNNS JC4046 3 3 -

Motif 2 width=11
Element Seqn Id St Int Rpt
DCPAVILPEEI ACTR_BOVIN 20 0 -
DCPDVVLPEEI JC4046 20 0 -
DCPRVVLPEEI ACTR_HUMAN 20 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
NMGYLKPRGSFESTA JC4046 88 57 -
NMGYLKPRGSFETTA ACTR_HUMAN 88 57 -
NMGYLEPRGSFESTA ACTR_BOVIN 88 57 -

Motif 4 width=14
Element Seqn Id St Int Rpt
CTGTGITMVIFSHH ACTR_HUMAN 158 55 -
CTGSGITMVIFSHH JC4046 158 55 -
CTGSGITIVTFSHH ACTR_BOVIN 158 55 -

Motif 5 width=15
Element Seqn Id St Int Rpt
SHARKISTLPRTNMK JC4046 202 30 -
SHTRKISTLPRANMK ACTR_HUMAN 202 30 -
SHTRRTPSLPKANMR ACTR_BOVIN 202 30 -

Motif 6 width=9
Element Seqn Id St Int Rpt
RDAFKRMLF JC4046 284 67 -
RVAFKKMVI ACTR_BOVIN 284 67 -
RDAFKKMIF ACTR_HUMAN 284 67 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
HIINSYEHTNDTARNNS ACTR_MOUSE 3 3 -
HIINSYENINNTARNNS ACTR_HUMAN 3 3 -
HIITPYEHTNDTARNNS ACTR_MESAU 3 3 -
HILNLYENINSTARNNS ACTR_BOVIN 3 3 -

Motif 2 width=11
Element Seqn Id St Int Rpt
DCPDVVLPEEI ACTR_MOUSE 20 0 -
DCPRVVLPEEI ACTR_HUMAN 20 0 -
DCPDVVLPEEI ACTR_MESAU 20 0 -
DCPAVILPEEI ACTR_BOVIN 20 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
NMGYLKPRGSFESTA ACTR_MOUSE 88 57 -
NMGYLKPRGSFETTA ACTR_HUMAN 88 57 -
NRGYLQPRGNFESTA ACTR_MESAU 88 57 -
NMGYLEPRGSFESTA ACTR_BOVIN 88 57 -

Motif 4 width=14
Element Seqn Id St Int Rpt
CTGSGITMVIFSHH ACTR_MOUSE 158 55 -
CTGTGITMVIFSHH ACTR_HUMAN 158 55 -
CTGSGIAMVIFSHH ACTR_MESAU 158 55 -
CTGSGITIVTFSHH ACTR_BOVIN 158 55 -

Motif 5 width=15
Element Seqn Id St Int Rpt
SHARKISTLPRTNMK ACTR_MOUSE 202 30 -
SHTRKISTLPRANMK ACTR_HUMAN 202 30 -
SHARKISTLPRANMK ACTR_MESAU 202 30 -
SHTRRTPSLPKANMR ACTR_BOVIN 202 30 -

Motif 6 width=9
Element Seqn Id St Int Rpt
RDAFKRMLF ACTR_MOUSE 284 67 -
RDAFKKMIF ACTR_HUMAN 284 67 -
RDAFKKMFS ACTR_MESAU 284 67 -
RVAFKKMVI ACTR_BOVIN 284 67 -