The midkine (MK) family of growth/differentiation factors: structure of an MK-related sequence in a pseudogene and evolutionary relationships among members of the MK family.
Midkine (MK) is a novel heparin-binding growth/differentiation factor coded by a retinoic acid-responsive gene. MK cDNA probe reacts with two bands, a 4 kb one and a 3 kb one, upon Southern blot analysis of Hin dIII fragments of mouse genomic DNA: the midkine gene (Mdk) is on the 4 kb fragment. Sequence analysis of the 3 kb fragment revealed that it has an Mdk-related sequence (Mdk-rs) highly homologous to MK cDNA, three mouse Aluequivalent repeats and seven A+T-rich segments. The Mdk-rs carried an inserted microsatellite DNA, is flanked by imperfect direct repeats observed in many retroposons, and lacks introns. Interspecific hybrid analysis revealed that Mdk-rs is located on chromosome 11, while Mdk is known to be on chromosome 2. The evolutional velocity of Mdk-rs was calculated to be 11 times higher than that of mouse Mdk. These features suggest that Mdk-rs is a processed pseudogene generated in the mouse genome. The 3 kb fragment with Mdk-rs, which is rich in inserted DNA sequences probably due to the presence of A+T-rich segments, may be a hot spot for amplification and evolution of genomic DNA. Mdk-rs was estimated to have been generated about 19.1 million years ago. A chicken protein retinoic acid-induced, heparin-binding protein (RIHB), is highly homologous to MK, and its divergence from human MK was estimated to have occurred about 250 million years ago, suggesting that RIHB is the chicken homology of MK. Thus, so far there are only two established protein members, MK and heparin-binding, growth-associated molecule (HB-GAM)/pleiotrophin (PTN) in the MK family.
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Department of Biochemistry, Faculty of Medicine, Kagoshima University.
Matsubara
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Guénet
J L
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Muramatsu
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D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry; D006801:Humans; D051379:Mice; D000078792:Midkine; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011544:Pseudogenes / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D016207:Cytokines; D018076:DNA, Complementary; D018168:Receptors, Retinoic Acid; C066845:pleiotrophin; D000078792:Midkine