CD137 Protein

Accession numbers: human (BC006196. L12964, U03397) and mouse (AK019885, BC028507, J04492, NM011612)

The deduced sequence of the first 23 amino acids of CD137 cDNA has characteristics of the signal peptide of secretory and membrane-associated proteins (Blobel and Dobberstein, 1975) and fits the -1, -3 rule (von Heijne, 1983). The nucleotide sequence of murine CD137 has a single open reading frame which encodes a deduced polypeptide of 256 amino acids with a calculated mass of 27,587 Da. The first 23 amino acids appear to constitute a signal peptide, although the presence of lysine at -4 and glutamic acid at -5 is somewhat unusual.

Two potential asparagine-linked glycosylation signals are located at positions 128 and 138. Thus the protein backbone ofprocessedCD137wouldhave amass of 25,167 Da. Its residues are arranged with spacing reminiscent of that seen in several groups of proteins including zinc finger DNA-binding proteins, the epidermal growth factor receptor, Drosophila Notch, and certain translation factors. The predicted protein contained an unusually large number (23) of cysteines in a region with four potential TNFR motifs, of which the first is partial and the third different from those of the TNFR.

Following this ligand-binding domain is a stretch of amino acids (residues 140-185), in which almost 30% of the amino acids are serines and threonines, and potential sites of O -linked glycosylation reminiscent of those seen, for example, in the low-density lipoprotein receptor. Amino acids 186-211 constitute the hydrophobic transmembrane domain followed by a stop-transfer sequence containing several basic residues. This region may serve as a membrane-spanning anchor domain. The C-terminal part of the cytoplasmic domain contains two short runs of three and four acidic residues, respectively, and a sequence of five glycines followed by a tyrosine. The extracellular domain contains four potential C6 (CXn CXX CXn CXnC) motifs, of which the first is partial, and the third distinct from those of the nerve growth factor receptor and the TNF receptor.

The amino acids flanking certain of the cysteine groups also resemble sequences found in other proteins. For example, if leucine is isomerized to isoleucine, there is an exact match to seven of the eight amino acids of a putative zinc finger structure in the yeast Elf-2|3 protein. These residues may represent metal binding sites but their role can not be accurately predicted.

The human homologue of CD137 (huCD137) contains 255 amino acids with two potential N-linked glycosylation sites, and the molecular weight of its protein backbone is calculated to be 27 kD (Kwon et al., 1989). HuCD137 has features, such as a signal sequence and transmembrane domain, indicating that it is a receptor protein. It has 60% amino acid identity to mouse CD137. In the cytoplasmic domain, five regions are conserved between mouse and human, indicating that they may be important for CD137 function.

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