Gene: [20p1/ENKB] prodynorphin (preproenkephalin B); [PDYN ]
GEN | [1] The
structural organization of preproenkephalin B gene resembles those of the
genes encoding the other opioid peptide precursors, that is,
preproenkephalin A (Noda-1982a) and the corticotropin-beta-lipotropin
precursor (Nakanishi-1980; Nakanishi-1981; Takahashi-1981; Cochet-1982;
Whitfeld-1982; Notake-1983) (ACTH-beta-LPH precursor). [2] Human preproenkephalin B gene contains three introns (intron A, intron B and intron C in the 5' to 3' direction) and four exons. Intron A (~1.2 kb) and intron B (~9.9 kb) are inserted within the segment encoding the 5'-untranslated region of the mRNA, 77 bp and 17 bp upstream from the translational initiation site, respectively. Intron C (~1.7kb) interrupts the protein-coding sequence between the triplets encoding amino acid residues 43 and 44 of preproenkephalin B. [3] The 5'-flanking region of the human preproenkephalin B gene contains triple tandem-repeated sequences of 68 bp (81-148 bp, 149-216 bp and 217-284 bp upstream from the putative capping site); one of the three repeats has one mismatch. It is tempting to hypothesize that the tandem-repeated sequence proceding this cellular gene is involved in the modulation of gene expression. The translational initiation site assigned is supported by the presence of a nonsense codon (TGA) found in frame 7-9 nucleotides upstream from this site in the human sequence. Human preproenkephalin B is composed of 254 amino acids including a putative signal peptide (Blobel-1975; Steiner-1980) of 20 aminoacids." |
FUN | Preproenkephalin B gene contains the determinants for neoendorphin, dynorphin, and leumorphin (containing rimorphin in its amino-terminus). This opioid peptides, each with a leucine-enkephalin structure, act on kappa-receptor." |
EVO | [1] The primary
structure of porcine preproenkephalin B has been elucidated by cloning and
sequencing cDNA (Kakidani-1982): it contains neoendorphin (Minamino-1981;
Kangawa-1981), dynorphin (Goldstein-1981; Tachibana-1982) and leumorphin
(Kakidani-1982; Yamamoto-1983; Suda-1983) (containing rimorphin as its
amino-terminus) (Kilpatrick-1982; Fischli-1982). These opioid peptides,
each having a leucine-enkephalin structure (Hughes-1975), act on the
k-receptor (Suda-1983; Chavkin-1982; Oka-1982; Corbett-1982;
Paterson-1983). [2] Comparison of the nucleotide sequences of the human and porcine preproenkephalin B cDNAs shows that the 60-bp human DNA sequence corresponding to exon 2 is totally absent from the porcine cDNA. Either the exon has been deleted from the porcine gene or the exonic sequence has been eliminated by RNA splicing. However, the possible existence of a human mRNA species devoid of this exonic sequence cannot be excluded. [3] Human preproenkephalin B exhibits two amino acid deletions (Asp-Lys between residues 197 and 198) in comparison with its porcine counterpart. The deduced sequence of the carboxy-terminal portion of human leumorphin differs in three amino acid substitutions from porcine leumorphin: that is, Ser (residue 248) instead of Tyr, Gly (residue 249) instead of Glu, and Ala (residue 254) instead of Val. [4] The amino acid sequences of porcine and human preproenkephalin B were aligned with those of human and bovine preproenkephalin A. Sequence homology extends over the entire molecules. Of the positions aligned, pairs of identical or chemically similar amino acids occupy 55% of porcine preproenkephalin B/human preproenkephalin A, 58% of porcine preproenkephalin B/bovine preproenkephalin A, 52% of human preproenkephalin B/human preproenkephalin A and 54% of human preproenkephalin B/bovine preproenkephalin A; gaps have been counted as one substitution regardless of their length. The observed extents of similarity are statistically significant. This, together with the similarity found between the structural organizations of the genes encoding the two precursors, suggests that the preproenkephalin A and preproenkephalin B genes originated from a common ancestor by gene duplication. [5] There is striking similarity among the structural organizations of the mammalian genes encoding preproenkephalin B, preproenkephalin A and the ACTH-beta-LPH precursor, which all represent a multi-hormone precursor. All three genes contain an intron in the protein-coding sequence near the signal peptide region and another intron in the segment encoding the 5-untranslated sequence near the translational initiation site; the protein-coding sequences of the preproenkephalin A and preproenkephalin B genes are split at an equivalent position. Thus, all of the repeated enkephalin or melanotropin sequences contained in these precursors are encoded by a single large exon. A second small exon of similar size encodes the signal peptide. The observed resemblance in structural organization suggests that the preproenkephalin A and preproenkephalin B genes and the ACTH-beta-LPH precursor gene may have evolved by an analogous mechanism." |
FAG | On other functionally related opioid peptides, see GEM:02p233/POMC and GEM:08q2/ENKA." |
REF | GEN
"Benoist, Chambon: Nature, 290, 304-310, 1981 GEN "Blobel, Dobberstein: J Cell Biol, 67, 852-862, 1975 EAG "Chavkin &: Science, 215, 413-415, 1982 GEN "Cochet M &: Nature, 297, 335-339, 1982 EAG "Corbett &: Nature, 299, 79-81, 1982 EAG "Fischli &: PNAS, 79, 5435-5437, 1982 GEN "Fromm, Berg: J Mol Appl Genet, 1, 457-481, 1982 EAG "Goldstein &: PNAS, 78, 7219-7223, 1981 GEN "Gruss &: PNAS, 78, 943-947, 1981 LIN,MAP "Hazan &: CCG, 58, (HGM11), 2029, 1991 CLO,GEN,EXP,EAG "Horikawa S &: Nature, 306, 611-614, 1983 EAG "Hughes &: Nature, 258, 577-579, 1975 EAG "Kakidani &: Nature, 298, 245-249, 1982 EAG "Kangawa &: BBRC, 99, 871-878, 1981 EAG "Kilpatrick &: PNAS, 79, 6480-6483, 1982 GEN "Levinson &: Nature, 295, 568-572, 1982 LOC,POL,MOL "Litt M &: AJHG, 42, 327-334, 1988 LOC,MOL,FAG "Litt M &: CCG, 46, (HGM9), 651, 1987 EAG "Minamino &: BBRC, 99, 864-870, 1981 GEN "Mount SM: NAR, 10, 459-472, 1982 GEN "Nakanishi &: Eur J Biochem, 115, 429-438, 1981 GEN "Nakanishi &: Nature, 287, 752-755, 1980 GEN "Noda M &: Nature, 297, 431-434, 1982a EAG "Noda M &: Nature, 295, 202-206, 1982b GEN "Notake &: FEBS Lett, 156, 67-71, 1983 EAG "Oka &: Eur J Pharmacol, 79, 301-305, 1982 EAG "Paterson &: Brit Med Bull, 39, 31-36, 1983 LOC,MAP "Simpson NE: J Med Genet, 25, 794-894, 1988 GEN "Steiner &: Ann NY Acad Sci, 343, 1-16, 1980 EAG "Suda &: Life Sci, 32, 2769-2775, 1983 LIN,MAP "Summar ML &: Mol Endocrinol, 4, 947-950, 1990 EAG "Tachibana &: Nature, 295, 339-340, 1982 GEN "Takahashi H &: FEBS Lett, 135, 97-102, 1981 GEN "Whitfeld PL &: DNA, 1, 133-143, 1982 EAG "Yamamoto &: Regul Pept, 6, 163-168, 1983 |
SWI | SWISSPROT: P01213 |
KEY | neu, horm |
CLA | coding, basic |
LOC | 20 pt-12 |
MIM | MIM: 131340 |
SYN | PDYN |
