Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene

Abstract

CD26 is a lymphocyte cell surface antigen which is increased during T-cell activation and is also expressed in other tissues. It is an atypical serine protease belonging to the prolyl oligopeptidase family. CD26 has been implicated in a variety of biological functions including T-cell activation, cell-to-cell adhesion, and recently in HIV infection. This paper describes, through the isolation and partial sequencing of eight human CD26 genomic clones, the first information on the genomic organization of the prolyl oligopeptidase family. We have established that the human CD26 gene spans approximately 70 kilobases (kb) and contains 26 exons, ranging in size from 45 base pairs (bp) to 1.4 kb. The nucleotides that encode the serine recognition site (G-W-S-Y-G) are split between two exons. This clearly distinguishes the genomic organization of the prolyl oligopeptidase family from that of the classical serine protease family. The 5' flanking domain of the CD26 gene contains neither a TATA box nor a CAAT box, but a 300 bp region extremely rich in C and G (72%) contains potential binding sites for several transcriptional factors. The human CD26 gene encodes two messages sized at about 4.2 and 2.8 kb. These are both expressed at high levels in the placenta and kidney and at moderate levels in the lung and liver. Only the 4.2 kb mRNA was expressed at low levels in skeletal muscle, heart, brain, and pancreas. Fluorescence in situ hybridization on metaphase chromosome spreads located the human CD26 gene to the long arm of chromosome 2(2q24.3).

Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter

“…The structure presented here for the first two exons and introns is consistent with the structure of the DPP IV gene deduced by Abbott et al [27]. The 5'-flanking region of the DPP IV gene contained potential binding sites for many transcription factors, as indicated in Figure 2.…”

“…While this study was in progress, Abbott et al [27] published a description of the structure of the human DPP IV structural gene. It was shown to contain 26 exons.…”

Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia

“…A 0.5 µg total RNA was reverse transcribed with 0.2 µg random hexamers (Boehringer, Vienna, Austria) in the presence of 200 U Moloney murine leukaemia reverse trancriptase (RT; BRL, Meylan, France). CD26 cDNA was amplified using the sense primer 5′-ATG GAC GGG GAA AGA AGA TA-3′ corresponding to bases 568Ð587 of the human cDNA sequence (Abbott et al, 1994) and the antisense primer 5′-TTT ACA GTT GGA TTC ACA GCT C-3′ corresponding to bases 789Ð810, to generate a 223-bp product. β2-microglobulin cDNA was amplified using the sense primer 5′-CAT CCA GCG TAC TCC AAA GA-3′ and antisense 5′-GAC AAG TCT GAA TGC TCC AC-3′ to generate a 165-bp product.…”

Tyrosine 547 Constitutes an Essential Part of the Catalytic Mechanism of Dipeptidyl Peptidase IV

“…Furthermore, the catalytically essential Ser 630 is located in a so-called "nucleophile elbow" consisting of the sequence Gly 628 -Trp 629 -Ser 630 -Tyr 631 -Gly 632 , a consensus sequence characteristic for all serine peptidases in the SC clan, i.e. GX1SX2G (12,13). Furthermore, the crystal structure determinations have suggested detailed information of the catalytic mechanism of DPP-IV.…”