TY - JOUR
T1 - EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of EH domain-containing proteins
AU - Pohl, Ute
AU - Smith, Justin S.
AU - Tachibana, Issei
AU - Ueki, Keisuke
AU - Lee, Hyun K.
AU - Ramaswamy, Shivapriya
AU - Wu, Qiang
AU - Mohrenweiser, Harvey W.
AU - Jenkins, Robert B.
AU - Louis, David N.
N1 - Funding Information:
The authors are grateful to Stephanie Billings, Jonathan Silver, and Lisa Blazejewski for expert technical assistance, to Catherine Dulac and Georgy Koentges for helpful discussions, and to Elspeth Bruford (HUGO/GDB Nomenclature Committee, University College London) for advice on naming EHD2, EHD3, and EHD4. U. Pohl is a fellow of the Deutsche Forschungsgemeinschaft. J. S. Smith is supported by the Sydney Luckman Endowed Physician Scientist Scholarship. I. Tachibana is supported by the Lindsey Bock Foundation Fellowship. Work by the Lawrence Livermore National Laboratory was performed under the auspices of the U.S. Department of Energy under Contract W-7405-Eng-48. The work in this study was supported by NIH CA 69285 (D. N. Louis) and in part by CA 50905 (R. B. Jenkins).
PY - 2000/1/15
Y1 - 2000/1/15
N2 - Exon trapping from a bacterial artificial chromosome (BAC 78138) mapping to the 19q13.3 glioma tumor suppressor candidate region yielded two exons that recognized a 3.6-kb transcript on Northern blot. Screening of a human fetal brain cDNA library with these exons identified three novel genes, designated EHD2, EHD3, and EHD4, which are homologous to the recently characterized human EHD1 (testilin/HPAST) and its mouse homolog Ehd1, as well as to homologs in Drosophila (Past1) and Caenorhabditis elegans. Alignment of the predicted peptide sequences revealed striking similarities, with multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal, and an eps15 homology (EH) protein-binding domain with an EF-hand motif at the C- terminus. The genes are specifically expressed, with EHD2 highly expressed in heart, EHD3 in brain and heart, and EHD4 in heart and pancreas. EHD2 was confirmed to originate from BAC 78138 at 19q13.3; radiation hybrid mapping localized EHD3 and EHD4 to 2p21 and 15q11.1, respectively; EHD1 has been previously mapped to 11q13. The three EHD1 paralogs therefore represent novel members of a family of human EH domain-containing proteins that may play a role in endocytosis and signaling. Mutation analysis of the five coding exons of EHD2 in gliomas failed to detect any tumor-specific alterations, thus indicating that EHD2 is an unlikely candidate for the 19q tumor suppressor gene. (C) 2000 Academic Press.
AB - Exon trapping from a bacterial artificial chromosome (BAC 78138) mapping to the 19q13.3 glioma tumor suppressor candidate region yielded two exons that recognized a 3.6-kb transcript on Northern blot. Screening of a human fetal brain cDNA library with these exons identified three novel genes, designated EHD2, EHD3, and EHD4, which are homologous to the recently characterized human EHD1 (testilin/HPAST) and its mouse homolog Ehd1, as well as to homologs in Drosophila (Past1) and Caenorhabditis elegans. Alignment of the predicted peptide sequences revealed striking similarities, with multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal, and an eps15 homology (EH) protein-binding domain with an EF-hand motif at the C- terminus. The genes are specifically expressed, with EHD2 highly expressed in heart, EHD3 in brain and heart, and EHD4 in heart and pancreas. EHD2 was confirmed to originate from BAC 78138 at 19q13.3; radiation hybrid mapping localized EHD3 and EHD4 to 2p21 and 15q11.1, respectively; EHD1 has been previously mapped to 11q13. The three EHD1 paralogs therefore represent novel members of a family of human EH domain-containing proteins that may play a role in endocytosis and signaling. Mutation analysis of the five coding exons of EHD2 in gliomas failed to detect any tumor-specific alterations, thus indicating that EHD2 is an unlikely candidate for the 19q tumor suppressor gene. (C) 2000 Academic Press.
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U2 - 10.1006/geno.1999.6087
DO - 10.1006/geno.1999.6087
M3 - Article
C2 - 10673336
AN - SCOPUS:0034104215
VL - 63
SP - 255
EP - 262
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 2
ER -