The CD137 Gene

Accession numbers: human (AL009183, AY438976) and mouse (U02567)

The CD137 cDNA was initially isolated from activated murine T cells by a modified differential screening procedure (Kwon and Weissman, 1989). Its deduced amino acid sequence and its transcript expression profile indicated that it was an inducible T cell surface molecule (Kwon and Weissman, 1989; Pollok etal., 1993). CD137 was categorized as an early activation gene because the protein synthesis inhibitor, cyclohexamide, blocked formation of its transcripts (Kwon et al., 1987).

The nucleotide sequence of CD137 contains a single long open-reading frame, starting with the ATG codon at positions 1-3. This reading frame encodes a polypeptide of 256 amino acids with a Mr of 27,587. The assigned ATG is preceded by an in-frame termination codon TGA (nucleotide residues -5 contains to 4) with eight out of nine residues similar to the consensus sequence (CCRC-CATGG, where "R" represents guanosine or adenine). The codon for the carboxy terminal leucine is followed by the translation termination codon TGA (nucleotide residues 769-771). The CD137 transcript contains an unusually long 3'-untranslated sequence that does not extend as far as the poly(A)+ tail. A potential polyadeny-lation signal is located at nucleotides 1158-1163. This signal may sometimes be functional because CD137 transcripts are of at least two different sizes.

CD137 (Figure 1.2A and 1.2B) (accession number: U02567) is made up of eight exons and seven introns, in which there are two exons for the 5'UTR and eight for the coding region. Two kinds of UTR sequences were detected in the DNA sequence and found to be separated by an intron of ~2.5 kb in length. The cysteine-rich extracellular domain is constructed from six exons, but most of the putative functional domains are encoded by separate exons. The signal sequence, transmembrane region, and serine, threonine, proline (STP)-rich region immediately proximal to the transmembrane domain are located in separate ex-ons. The cytoplasmic domain that contains the p56lck-binding site is located in the last exon of the gene. Exon/intron boundaries were assigned by comparing the CD137 cDNA sequence with the genomic sequence. No TATA box-related elements were found in the flanking sequence of the type 15' UTR. Instead, there were very good matches to the consensus TPA-responsive element (AP-1) at nt -18 to -10, and of the NF-KB-binding sequence at nt -49 to -39. Upstream of these elements, this region contains a potential ets-binding site at nt -169 to -162, an activator protein 2 (AP-2)-binding site at nt -498 to -494, and an SP-1 binding site at nt -522 to -516. The 5' flanking region of the type II 5'UTR contains a TATA-related element at nt -28 to -23. Two potential ets-binding sites appear at nt -15 to -8 and -139 to -132, two potential AP-2-binding sites at nt -89 to -82 and -331, and a very good match to an AP-1-binding site at nt -311 to -302.

Figure 1.2. Genomic organization of the human (A) and murine (B) CD137 receptors. Exons are shown as boxes; untranslated regions (UTR) are represented by black shading, and protein coding regions by no shading; they are labeled with Roman numerals. Lengths of introns and exons are shown in Arabic numerals (base pairs).

Figure 1.2. Genomic organization of the human (A) and murine (B) CD137 receptors. Exons are shown as boxes; untranslated regions (UTR) are represented by black shading, and protein coding regions by no shading; they are labeled with Roman numerals. Lengths of introns and exons are shown in Arabic numerals (base pairs).

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