The human PD-1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors.
We report the complete cDNA sequence and the genomic structure of the human PD-1 homologue. An analysis of the expression pattern of the human PD-1 gene (hPD-1) and the murine PD-1 gene (mPD-1) in developing bone marrow B-lineage cells was also undertaken. The full length hPD-1 cDNA is 2106 nucleotides long and encodes a predicted protein of 288 amino acid residues. The hPD-1 and mPD-1 genes share 70% homology at the nucleotide level and 60% homology at the amino acid level. Four potential sites for N-linked glycosylation are conserved, as are a stretch of amino acids between two cysteine residues resembling a V-set immunoglobulin domain, and another region containing a motif similar to an immunoreceptor tyrosine-based inhibitory motif. Isolation of the genomic locus of the hPD-1 gene reveals that the gene is composed of five exons located on human chromosome 2 at band q37. The 5' flanking region lacks TATA and CAAT cis-acting elements, but includes a number of potential transcription factor binding sites and a dominant transcription start site. The mPD-1 gene was preferentially expressed in pro-B cells from murine adult bone marrow. Although hPD-1 was not preferentially expressed in pro-B cells from human fetal bone marrow, treatment of isolated pro-B cells with interleukin-7 resulted in a dramatic increase in expression. These data suggest that PD-1 may play a role in B-cell differentiation during the pro-B cell stage.
Finger
L R
LR
Department of Medicine, New York Medical College, Elmsford 10523, USA.
Pu
J
J
Wasserman
R
R
Vibhakar
R
R
Louie
E
E
Hardy
R R
RR
Burrows
P D
PD
Billips
L G
LG
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D002478:Cells, Cultured; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000276:immunology; D005796:Genes / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D015851:Interleukin-7; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins; D012333:RNA, Messenger