Characterization of a Second Human Pulmonary Surfactant-associated Protein SP-A Gene

Abstract

Pulmonary surfactant is a lipid-protein complex involved in maintaining alveolar stability. SP-A is the major surfactant-associated protein of 26 to 38 kD. A human SP-A gene (SP-A I) and two distinct SP-A cDNAs, MPSAP 1A and MPSAP 6A, have been reported previously. We have isolated and characterized a second human SP-A gene (SP-A II), which appears to code for the mRNA corresponding to the previously described MPSAP-1A cDNA. Both genes consist of five exons, a consensus recognition sequence for initiation, TATAAA, and a polyadenylation signal sequence. Significant divergence in the two genes is observed throughout. The divergence is highest in the upstream region, intron I, exon III, and noncoding portion of exon V. The coding regions of all other exons and the introns show much lower divergence. Transcripts from both genes were found in adult human lung, using gene-specific oligonucleotide probes in Northern blot analysis.

Collectins — soluble proteins containing collagenous regions and lectin domains — and their roles in innate immunity

“…The human MBP gene (Fig. 4) is 7 kb long and contains 4 exons: exon 1 encodes the leader peptide, N-terminal region and part of the collagen-like region; exon 2 encodes the remainder of the collagen-like region; and exon 3 encodes the sequences White et al, 1985;Floros et al, 1986;Katyal et al, 1992). The human SP-A structural gene (gene symbol SFTP 1) is 4.5 kb long and contains 5 exons, with exon 2 encoding the signal peptide, the amino-terminal region, and the first 10 Gly-Xaa-Yaa triplets, and exon 3 encoding the remaining 13 Gly-Xaa-Yaa triplets.…”

“…Exon 4 and part of exon 5 encode a putative amphipathic a-helical region, whereas the remainder of exon 5 encodes the C-type lectin domain. The 2 SP-A genes that are expressed encode for polypeptides differing at only 6 amino acid positions (White et al, 1985;Katyal et al, 1992). SP-A has been cloned at the cDNA level in a variety of other species, such as dog, rabbit, rat, and mouse (Korfhagen et al, 1991).…”

“…The human MBP gene (gene symbol -MBL) has been localized to lOqll.2-q21 (Sastry et ai., 1989), and the human SP-A gene(s) (gene symbol SFTP 1) have been localized to lOq21-q24 (Fisher et al, 1987). There appear to be at least 2 SP-A genes (SP-AI and SP-AII; White et al, 1985;Floros et al, 1986;Katyal et al, 1992) and 1 SP-A pseudogene (Korfhagen et al, 1991) It has been established that, in humans, a low serum concentration of MBP correlates with a common opsonic defect (Super et al,, 1989) and that deficiency of MBP is associated with recurrent infections in the very young (Turner, 1991). It is considered that low serum levels or lack of MBP results in an inability to activate the classical pathway of complement (via MASP or Clr2Clsz), by an antibody-independent route, and this prevents efficient coating of pathogenic organisms with the activated C4 and C3 fragments that are required for efficient opsonization by cells carrying C4b and/or C3b receptors.…”

Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

“…Human SP-A is encoded by two very similar but non-identical genes, SP-A1 [4] and SP-A2 [5]. The two genes are 94 % identical at the nucleotide level and encode proteins with about 96 % identity.…”

Role of CBP/p300 and SRC-1 in Transcriptional Regulation of the Pulmonary Surfactant Protein-A (SP-A) Gene by Thyroid Transcription Factor-1 (TTF-1)

“…Transcription of the SP-A gene is initiated in fetal lung after ϳ70% of gestation is completed and reaches maximum levels just prior to birth (6). In humans and baboons, SP-A is encoded by two highly similar genes, SP-A1 and SP-A2 (7,8), whereas, in rabbits (9), rats (10) and mice (11), SP-A is encoded by a single-copy gene.…”