title: Isoform cloning, actin binding, and chromosomal localization of human erythroid dematin, a member of the villin superfamily.
abstract: Dematin is an actin-bundling protein of the erythroid membrane skeleton and is abundantly expressed in human brain, heart, skeletal, muscle, kidney, and lung. The 48-kDa subunit of dematin contains a headpiece domain which was originally identified in villin, and actin-binding protein of the brush-border cytoskeleton. The head-piece domain of villin is essential for its morphogenic function in vivo. Here we report the primary structure of 52-kDa subunit of dematin which differs from the 48-kDa subunit by a 22-amino-acid insertion within its headpiece domain. A unique feature of the insertion sequence of the 52-kDa subunit is its homology to erythrocyte protein 4.2. The insertion sequence also includes a cysteine residue which may explain the formation of sulfhydryl-linked trimers of dematin. Actin binding measurements using recombinant fusion proteins revealed that each monomer of dematin contains two F-actin binding sites: one in the headpiece domain and the other in the undefined N-terminal domain. Although the actin bundling activity of intact dematin was abolished by phosphorylation, no effect of phosphorylation was observed on the actin binding activity of fusion proteins. Using somatic cell hybrid panels and fluorescence in situ hybridization, the dematin gene was localized on the short arm of chromosome 8. The dematin locus, 8p21.1, is distal to the known locus of human erythroid ankyrin (8p11.2) and may contribute to the etiology of hemolytic anemia in a subset of patients with severe hereditary spherocytosis.
authors.affiliation: Department of Biomedical Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Azim
authors.forename: J H
authors.initials: JH
authors.lastname: Knoll
authors.forename: A H
authors.initials: AH
authors.lastname: Beggs
authors.forename: A H
authors.initials: AH
authors.lastname: Chishti
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D001798:Blood Proteins; D002352:Carrier Proteins; C044805:DMTN protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C026615:villin; D017868:Cyclic AMP-Dependent Protein Kinases