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1 Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907-2026, USA
2 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
(RECEIVED June 1, 2004; FINAL REVISION June 1, 2004; ACCEPTED July 11, 2004)
The C terminus of the nuclear protein NuMA, NuMA-CT, has a well-known function in mitosis via its proximal segment, but it seems also involved in the control of differentiation. To further investigate the structure and function of NuMA, we exploited established computational techniques and tools to collate and characterize proteins with regions similar to the distal portion of NuMA-CT (NuMA-CTDP). The phylogenetic distribution of NuMA-CTDP was examined by PSI-BLAST- and TBLASTN-based analysis of genome and protein sequence databases. Proteins and open reading frames with a NuMA-CTDP-like region were found in a diverse set of vertebrate species including mammals, birds, amphibia, and early teleost fish. The potential structure of NuMA-CTDP was investigated by searching a database of protein sequences of known three-dimensional structure with a hidden Markov model (HMM) estimated using representative (human, frog, chicken, and pufferfish) sequences. The two highest scoring sequences that aligned to the HMM were the extracellular domains of
3-integrin and Her2, suggesting that NuMA-CTDP may have a primarily
fold structure. These data indicate that NuMA-CTDP may represent an important functional sequence conserved in vertebrates, where it may act as a receptor to coordinate cellular events.
Keywords: nuclear mitotic apparatus protein;
3-integrin; chordate; mammary epithelial cells; differentiation
Abbreviations: ESTs, expressed sequence tags HMM, hidden Markov model NCBI, National Center for Biotechnology Information NuMA, nuclear mitotic apparatus protein NuMA-CT, NuMA C terminus NuMA-CTDP, distal portion of NuMA CT NuMA-NT, NuMA N terminus RAR, retinoic acid receptor RCSB, Research Collaboratory for Structural Biology SAM, Sequence Alignment and Modeling.
Article and publication are at http://www.proteinscience.org/cgi/doi/10.1110/ps.04906804.
Reprint requests to: Sophie A. Lelièvre, Department of Basic Medical Sciences, Purdue University, 625 Harrison Street, LYNN, West Lafayette, IN 47907-2026, USA; e-mail: lelievre{at}purdue.edu; fax: (765) 494-0781.
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