Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes?

Abstract

To date five human mucin cDNAs (MUC2, 5A, 5B, 5C and 6) mapped to 11p15.3-15.5, so it appears that this chromosome region might contain several distinct gene loci for mucins. Three of these cDNAs, MUC5A, B and C, were cloned in our laboratory and previously published. A common number, 5, was recommended by the Human Gene Mapping Nomenclature Committee to designate them because of their common provenance from human tracheobronchial mucosa. In order to define whether they are products of the same gene locus or distinct loci, we describe in this paper physical mapping of these cDNAs using the strategy of analysis of CpG islands by pulse-field gel electrophoresis. The data suggest that MUC5A and MUC5C are part of the same gene (called MUC5AC) which is distinct from MUC5B. In the second part of this work, complete sequences of the inserts corresponding to previously described (JER47, JER58) and novel (JER62, JUL32, MAR2, MAR10 and MAR11) cDNAs of the so-called MUC5AC gene are presented and analysed. The data show that in this mucin gene, the tandem repeat domain is interrupted several times with a subdomain encoding a 130 amino acid cysteine-rich peptide in which the TR3A and TR3B peptides previously isolated by Rose et al. [Rose, Kaufman and Martin (1989) J. Biol. Chem., 264, 8193-8199] from airway mucins are found. A consensus peptide sequence for these subdomains involving invariant positions of most of the cysteines is proposed. The consensus nucleotide sequence of this subdomain is also found in the MUC2 gene and in the MUC5B gene, two other mucin genes mapped to 11p15. The functional significance for secreted mucins of these cysteine-rich subdomains and the modular organization of mucin peptides are discussed.

Cloning of the Amino-terminal and 5′-Flanking Region of the Human MUC5AC Mucin Gene and Transcriptional Up-regulation by Bacterial Exoproducts

“…Terminus-Based on the 99% sequence identity between MUC5AC clone JUL 32 (19) and HGM-1 nucleotides 1947-2278 (1), we hypothesized that HGM-1 is a part of MUC5AC. Based on Ͼ60% similarity between HGM-1 and the amino-terminal cysteine-rich domain of MUC2 (D-domain 3), we hypothesized that HGM-1 is an amino-terminal sequence.…”

“…Northern Blot Analysis of Tissue Distribution of RNA Corresponding to Newly Cloned Sequence-Our interpretation that the 5Ј extension of HGM-1 (MUC5AC-5ЈRP) is at the 5Ј-end of MUC5AC rests primarily on the 99% similarity between a portion of HGM-1 and the MUC5AC cDNA JUL 32 (19). Further confirmation of the identity between our new sequence and MUC5AC was provided by Northern blot analysis in which we observed that a probe from our new sequence showed tissuespecific hybridization identical to that obtained using a probe from the previously described MUC5AC C-terminal cDNA NP3a (8) (Fig.…”

“…This cDNA likely derives from MUC5AC as nucleotides 1942-2281 are 99% similar to the MUC5AC clone JUL 32 (19) and nucleotides 2190 -2541 are 92% similar to the 5Ј-end of MUC5AC clone NP3a (1). As noted by Klomp et al (1), the ϳ8% discrepancy between HGM-1 and NP3a suggests that portions of HGM-1 are repeated twice in MUC5AC.…”

Postnatal Changes and Effects of Glucocorticoid on MUC5AC mRNA Expression in the Rat Stomach

“…Adult rats (8 weeks after birth) served as controls. Five doses of hydrocortisone (1,5,10,25, 50 mg/kg) and vehicle (olive oil) were subcutaneously injected into the 5-d-old rats. After 2 d (7-d-old), the animals were sacrificed under ether anesthesia.…”

“…The cDNAs of the human mucin core peptides have been partially or fully cloned, and MUC1-8 has been detected in various organs. [1][2][3][4][5][6][7][8][9] Mucins are classified according to their biochemical characteristics as membrane-associated and secreted types. The secreted mucins are further classified as gel-forming and soluble types.…”