PUBLICATION

Identifying the activation motif in the N-terminal of rainbow trout and zebrafish melanocortin-2 receptor accessory protein 1 (MRAP1) orthologs

Authors
Dores, R.M., Liang, L., Hollmann, R.E., Sandhu, N., Vijayan, M.M.
ID
ZDB-PUB-160113-10
Date
2016
Source
General and comparative endocrinology   234: 117-22 (Journal)
Registered Authors
Keywords
MC2R, MRAP1, Rainbow Trout, Zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Humans
  • Membrane Proteins/metabolism*
  • Molecular Sequence Data
  • Oncorhynchus mykiss
  • Receptor, Melanocortin, Type 2/metabolism*
  • Zebrafish
PubMed
26752246 Full text @ Gen. Comp. Endocrinol.
Abstract
The activation of mammalian melanocortin-2 receptor (MC2R) orthologs is dependent on a four-amino acid activation motif (LDYL/I) located in the N-terminal of mammalian MRAP1 (melanocortin-2 receptor accessory protein). Previous alanine substitution analysis had shown that the Y residue in this motif appears to be the most important for mediating the activation of mammalian MC2R orthologs. Similar, but not identical amino acid motifs were detected in rainbow trout MRAP1 (YDYL) and zebrafish MRAP1 (YDYV). To determine the importance of these residues in the putative activation motifs, rainbow trout and zebrfish MRAP1 orthologs were individually co-expressed in CHO cells with rainbow trout MC2R, and the activation of this receptor with either the wild-type MRAP1 ortholog or alanine-substituted analogs of the two teleost MRAP1s was analyzed. Alanine substitutions at all four amino acid positions in rainbow trout MRAP1 blocked activation of the rainbow trout MC2R. Single alanine substitutions of the D and Y residues in rainbow trout and zebrafish MRAP1 indicate that these two residues play a significant role in the activation of rainbow trout MC2R. These observations indicate that there are subtle differences in the way that teleost and mammalian MRAPs are involved in the activation of their corresponding MC2R orthologs.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping