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PR01029

Identifier
PENKAPRCRSR  [View Relations]  [View Alignment]  
Accession
PR01029
No. of Motifs
10
Creation Date
02-DEC-1998  (UPDATE 22-JUN-1999)
Title
Proenkephalin A precursor signature
Database References
PRINTS; PR01028 OPIOIDPRCRSR
INTERPRO; IPR000703
Literature References
1. MOLLEREAU, C., SIMONS, M.-J., SOULARUE, P., LINERS, F., VASSART, G.,
MEUNIER, J.-C. AND PARMENTIER, M.
Structure, tissue distribution, and chromosomal localization of the
prepronociceptin gene.
PROC.NATL.ACAD.SCI.U.S.A. 93 8666-8670 (1996).
 
2. SAITO, Y., MARUYAMA, K., SAIDO, T.C. AND KAWASHIMA, S.
N23K, a gene transiently up-regulated during neural differentiation,
encodes a precursor protein for a newly identified neuropeptide nociceptin.
BIOCHEM.BIOPHYS.RES.COMMUN. 217 539-545 (1995). 
 
3. YOSHIKAWA, K., WILLIAMS, C. AND SABOL, S.L.
Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and
distribution in the central nervous system.
J.BIOL.CHEM. 259 14301-14308 (1984). 
 
4. HOWELLS, R.D., KILPATRICK, D.L., BHATT, R., MONAHAN, J.J., POONIAN, M.
AND UDENFRIEND, S.
Molecular cloning and sequence determination of rat preproenkephalin cDNA:
sensitive probe for studying transcriptional changes in rat tissues.
PROC.NATL.ACAD.SCI.U.S.A. 81 7651-7655 (1984). 

Documentation
Vertebrate endogenous opioid neuropeptides are released by post-transla-
tional proteolytic cleavage of precursor proteins. The precursors consist of
the following components: a signal sequence that precedes a conserved region
of about 50 residues; a variable-length region; and the sequence of the 
neuropeptide itself. Three types of precursor are known: preproenkephalin A 
(gene PENK), which is processed to produce 6 copies of Met-enkephalin, plus
Leu-enkephalin; preproenkephalin B (gene PDYN), which is processed to
produce neoendorphin, dynorphin, leumorphin, rimorphin and Leu-enkephalin;
and prepronocipeptin (gene PNOC), whose processing produces nociceptin
(orphanin FQ) and two other potential neuropeptides.
 
Sequence analysis reveals that the conserved N-terminal region of the
precursors contains 6 cysteines, which are probably involved in disulphide
bond formation. It is speculated that this region might be important for 
neuropeptide processing [1].
 
The primary structure of rat preproenkephalin is highly similar to those of
bovine and human preproenkephalins, and contains four copies of Met-
enkephalin, one of Leu-enkephalin, one of Met-enkephalin-Arg6-Gly7-Leu8,
and one of Met-enkephalin-Arg6-Phe7 [3,4]. Rat preproenkephalin contains
269 amino acid residues, making it larger than the human (267 residues) 
and bovine (263 residues) precursors [3,4]. 
 
PENKAPRCRSR is a 10-element fingerprint that provides a signature for the
proenkephalin A precursor. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from short conserved regions 
spanning the full alignment length, focusing on those regions that 
characterise the proenkephalin A precursors but distinguish them from the
rest of the opioid neuropeptide precursor family - motif 1 spans the signal
sequence; motifs 2 and 3 reside within the N-terminal Cys-rich region 
encoded by PROSITE pattern OPIOIDS_PRECURSOR (PS01252), falling between the
third and fourth, and fifth and sixth conserved Cys residues respectively;
motifs 4 and 5 lie within the variable region, motif 5 lying immediately 
N-terminal to the first Met-enkephalin; motif 6 spans an acidic region that
precedes the third Met-enkephalin; motif 8 includes the C-terminal residues 
of Met-enkephalin-Arg-Gly-Leu; motif 9 spans the region just preceding the
Leu-enkephalin peptide; and motif 10 spans an acidic region that lies
N-terminal to Met-enkephalin-Arg-Phe. Two iterations on OWL30.2 were 
required to reach convergence, at which point a true set comprising 6
sequences was identified. Several partial matches were also found, all of
which are family members and fragments that fail to match one or more motifs.
 
An update on SPTR37_9f identified a true set of 6 sequences, and 1
partial match.
Summary Information
   6 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
1 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
106666666666
90000000000
80000000000
70000000000
60010011111
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
PENK_BOVIN    PENK_CAVPO    PENK_HUMAN    PENK_MESAU    
PENK_MOUSE PENK_RAT
True Positive Partials
Codes involving 6 elements
PENK_XENLA
Sequence Titles
PENK_BOVIN  PROENKEPHALIN A PRECURSOR - BOS TAURUS (BOVINE). 
PENK_CAVPO PROENKEPHALIN A PRECURSOR - CAVIA PORCELLUS (GUINEA PIG).
PENK_HUMAN PROENKEPHALIN A PRECURSOR - HOMO SAPIENS (HUMAN).
PENK_MESAU PROENKEPHALIN A PRECURSOR - MESOCRICETUS AURATUS (GOLDEN HAMSTER).
PENK_MOUSE PROENKEPHALIN A PRECURSOR - MUS MUSCULUS (MOUSE).
PENK_RAT PROENKEPHALIN A PRECURSOR - RATTUS NORVEGICUS (RAT).

PENK_XENLA PROENKEPHALIN A1 PRECURSOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
OWL30_2    2  100  NSINGLE    
SPTR37_9f 1 75 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
LCIWLLALGSCLLATVQAD PENK_RAT 7 7 -
LCTWLLALGSCLLATVQAE PENK_MOUSE 7 7 -
LCTWLVALGPGLLATVQAE PENK_CAVPO 7 7 -
LCTWLLLLGPGLLATVRAE PENK_HUMAN 7 7 -

Motif 2 width=14
Element Seqn Id St Int Rpt
SYRLVRPGDINFLA PENK_RAT 34 8 -
TYRLVRPGDINFLA PENK_MOUSE 34 8 -
SYRLVRPGDLNFLA PENK_CAVPO 34 8 -
SYRLVRPADINFLA PENK_HUMAN 34 8 -

Motif 3 width=12
Element Seqn Id St Int Rpt
EGQLPSFKIWET PENK_RAT 53 5 -
EGQLPSFKIWET PENK_MOUSE 53 5 -
EGQLPSLKIWET PENK_CAVPO 53 5 -
EGKLPSLKIWET PENK_HUMAN 53 5 -

Motif 4 width=12
Element Seqn Id St Int Rpt
KDLLQVSKPEFP PENK_RAT 66 1 -
KDLLQVSRPEFP PENK_MOUSE 66 1 -
KDLLQVSKQELP PENK_CAVPO 66 1 -
KELLQLSKPELP PENK_HUMAN 66 1 -

Motif 5 width=17
Element Seqn Id St Int Rpt
KDSSKQDESHLLAKKYG PENK_RAT 85 7 -
KDSSKQDESHLLAKKYG PENK_MOUSE 85 7 -
RESGKQDESHLLSKKYG PENK_CAVPO 85 7 -
RENSKPEESHLLAKRYG PENK_HUMAN 85 7 -

Motif 6 width=18
Element Seqn Id St Int Rpt
DELYPVEPEEEANGGEIL PENK_RAT 115 13 -
DELYPMEPEEEANGGEIL PENK_MOUSE 115 13 -
DELYPVEPEEEANGGEIL PENK_CAVPO 115 13 -
DELYPMEPEEEANGSEIL PENK_HUMAN 115 13 -

Motif 7 width=16
Element Seqn Id St Int Rpt
DTLANSSDLLKELLGT PENK_RAT 148 15 -
DTLANSSDLLKELLGT PENK_MOUSE 148 15 -
DALANSSDLLKELLGT PENK_CAVPO 148 15 -
DSLANSSDLLKELLET PENK_HUMAN 148 15 -

Motif 8 width=18
Element Seqn Id St Int Rpt
MRGLKRSPQLEDEAKELQ PENK_RAT 192 28 -
MRSLKRSPQLEDEAKELQ PENK_MOUSE 192 28 -
MRGLKRSPQVEDEAKELQ PENK_CAVPO 191 27 -
MRGLKRSPQLEDEAKELQ PENK_HUMAN 190 26 -

Motif 9 width=15
Element Seqn Id St Int Rpt
MRRVGRPEWWMDYQK PENK_RAT 216 6 -
MRRVGRPEWWMDYQK PENK_MOUSE 216 6 -
MRRVGRPEWWMDYQK PENK_CAVPO 215 6 -
MRRVGRPEWWMDYQK PENK_HUMAN 214 6 -

Motif 10 width=20
Element Seqn Id St Int Rpt
LPSDEEGESYSKEVPEMEKR PENK_RAT 243 12 -
LPSDEEGENYSKEVPEIEKR PENK_MOUSE 243 12 -
LPSDEEGESYSKEVPEMEKR PENK_CAVPO 242 12 -
LPSDEEGESYSKEVPEMEKR PENK_HUMAN 241 12 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
LCIWLLALGSCLLATVQAD PENK_RAT 7 7 -
LCTWLLALGSCLLATVQAE PENK_MOUSE 7 7 -
LCTWLVALGPGLLATVQAE PENK_CAVPO 7 7 -
LCTWLLVLGSCLLATVQAE PENK_MESAU 7 7 -
LCTWLLLLGPGLLATVRAE PENK_HUMAN 7 7 -
LCTWLLALGPGLLATVRAE PENK_BOVIN 7 7 -

Motif 2 width=14
Element Seqn Id St Int Rpt
SYRLVRPGDINFLA PENK_RAT 34 8 -
TYRLVRPGDINFLA PENK_MOUSE 34 8 -
SYRLVRPGDLNFLA PENK_CAVPO 34 8 -
SYHLVSPGDINFLA PENK_MESAU 34 8 -
SYRLVRPADINFLA PENK_HUMAN 34 8 -
SYRLARPTDLNPLA PENK_BOVIN 34 8 -

Motif 3 width=12
Element Seqn Id St Int Rpt
EGQLPSFKIWET PENK_RAT 53 5 -
EGQLPSFKIWET PENK_MOUSE 53 5 -
EGQLPSLKIWET PENK_CAVPO 53 5 -
EGQMPSHKIWET PENK_MESAU 53 5 -
EGKLPSLKIWET PENK_HUMAN 53 5 -
EGKLPSLKTWET PENK_BOVIN 53 5 -

Motif 4 width=12
Element Seqn Id St Int Rpt
KDLLQVSKPEFP PENK_RAT 66 1 -
KDLLQVSRPEFP PENK_MOUSE 66 1 -
KDLLQVSKQELP PENK_CAVPO 66 1 -
KDLLQVSKPEFP PENK_MESAU 66 1 -
KELLQLSKPELP PENK_HUMAN 66 1 -
KELLQLTKLELP PENK_BOVIN 66 1 -

Motif 5 width=17
Element Seqn Id St Int Rpt
KDSSKQDESHLLAKKYG PENK_RAT 85 7 -
KDSSKQDESHLLAKKYG PENK_MOUSE 85 7 -
RESGKQDESHLLSKKYG PENK_CAVPO 85 7 -
KDSNKQDESHLLAKKYG PENK_MESAU 85 7 -
RENSKPEESHLLAKRYG PENK_HUMAN 85 7 -
SALSKQEESHLLAKKYG PENK_BOVIN 82 4 -

Motif 6 width=18
Element Seqn Id St Int Rpt
DELYPVEPEEEANGGEIL PENK_RAT 115 13 -
DELYPMEPEEEANGGEIL PENK_MOUSE 115 13 -
DELYPVEPEEEANGGEIL PENK_CAVPO 115 13 -
DELYPVEPEEEANGGEIL PENK_MESAU 115 13 -
DELYPMEPEEEANGSEIL PENK_HUMAN 115 13 -
DELYPLEVEEEANGGEVL PENK_BOVIN 112 13 -

Motif 7 width=16
Element Seqn Id St Int Rpt
DTLANSSDLLKELLGT PENK_RAT 148 15 -
DTLANSSDLLKELLGT PENK_MOUSE 148 15 -
DALANSSDLLKELLGT PENK_CAVPO 148 15 -
DTLANSSDLLKELLGT PENK_MESAU 148 15 -
DSLANSSDLLKELLET PENK_HUMAN 148 15 -
DGLGNSSNLLKELLGA PENK_BOVIN 145 15 -

Motif 8 width=18
Element Seqn Id St Int Rpt
MRGLKRSPQLEDEAKELQ PENK_RAT 192 28 -
MRSLKRSPQLEDEAKELQ PENK_MOUSE 192 28 -
MRGLKRSPQVEDEAKELQ PENK_CAVPO 191 27 -
MRGLKRSPQVEDEAKELQ PENK_MESAU 191 27 -
MRGLKRSPQLEDEAKELQ PENK_HUMAN 190 26 -
MRGLKRSPHLEDETKELQ PENK_BOVIN 186 25 -

Motif 9 width=15
Element Seqn Id St Int Rpt
MRRVGRPEWWMDYQK PENK_RAT 216 6 -
MRRVGRPEWWMDYQK PENK_MOUSE 216 6 -
MRRVGRPEWWMDYQK PENK_CAVPO 215 6 -
MRRVGRPEWWMDYQK PENK_MESAU 215 6 -
MRRVGRPEWWMDYQK PENK_HUMAN 214 6 -
MRRVGRPEWWMDYQK PENK_BOVIN 210 6 -

Motif 10 width=20
Element Seqn Id St Int Rpt
LPSDEEGESYSKEVPEMEKR PENK_RAT 243 12 -
LPSDEEGENYSKEVPEIEKR PENK_MOUSE 243 12 -
LPSDEEGESYSKEVPEMEKR PENK_CAVPO 242 12 -
LPSDEEAESYSKEVPEIEKR PENK_MESAU 242 12 -
LPSDEEGESYSKEVPEMEKR PENK_HUMAN 241 12 -
LPSEEEGESYSKEVPEMEKR PENK_BOVIN 237 12 -