The three heavy-chain precursors for the inter-alpha-inhibitor family in mouse: new members of the multicopper oxidase protein group with differential transcription in liver and brain.
The inter-alpha-inhibitor (I alpha I) family is comprised of the plasma protease inhibitors I alpha I, inter-alpha-like inhibitor (I alpha LI), pre-alpha-inhibitor (P alpha I) and bikunin. I alpha I, I alpha LI and P alpha I are distinct assemblies of bikunin with one of three heavy (H) chains designated H1, H2 and H3. These H chains and bikunin are respectively encoded by a set of three H genes and an alpha 1-microglobulin/bikunin precursor (AMBP) gene. All four gene products undergo maturation steps from precursor polypeptides. The full-length cDNAs for the H1-, H2- and H3-chain precursors were cloned from a mouse liver cDNA library and sequenced. Extensive searches of amino acid sequence similarities to other proteins in databanks revealed (i) a highly significant similarity of the C-terminal sequence in the three H-chain precursors to the multicopper-binding domain in the group of multicopper oxidase proteins and (ii) the presence of von Willebrand type-A domains in the mature H chains. Amino acid sequence comparisons between the three mouse H1-, H2- and H3-chain precursors and their human counterparts allowed us to appraise the timing and order of occurrence of the three H-chain genes from a shared ancestor during mammalian evolution. Owing to a multiple alignment of the six mouse and human nucleotide sequences for these H-chain precursors, a reverse transcriptase PCR assay with degenerate oligonucleotides was designed, allowing us to (i) present evidence that no mRNAs for further H genes exist in mouse liver and (ii) demonstrate a previously undescribed transcription of the H2- and H3-chain mRNAs in mouse brain, which contrasts with the expression of all four, H1, H2, H3 and AMBP, mRNAs in liver.
Chan
P
P
Institut National de la Santé et la Recherche Médicale, Unit 78, Boisguillaume, France.
Risler
J L
JL
Raguenez
G
G
Salier
J P
JP
D000510:Alpha-Globulins / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D018076:DNA, Complementary / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D017385:Sequence Homology; D014158:Transcription, Genetic; D014841:von Willebrand Factor / Q000737:chemistry
D000510:Alpha-Globulins; D018076:DNA, Complementary; D011498:Protein Precursors; D012333:RNA, Messenger; D014841:von Willebrand Factor; C011877:inter-alpha-inhibitor; D010088:Oxidoreductases; C024748:copper oxidase; D012194:RNA-Directed DNA Polymerase