Alternative titles; symbols
HGNC Approved Gene Symbol: COL26A1
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38): 7:101,362,388-101,559,024 (from NCBI)
Sato et al. (2002) cloned mouse Emid2, which they called Col26a1, by yeast 2-hybrid analysis using Hsp47 (600943) as bait. The deduced 438-amino acid protein contains an N-terminal signal sequence, followed by 3 noncollagenous domains separated by 2 collagenous domains. Emid2 has 13 cysteine residues in the N-terminal portion of the first noncollagenous region and 2 clusters of gly-X-Y collagen-like repeats. Northern blot analysis detected highest expression in neonatal testis and ovary, with lower expression in adult testis and ovary. Immunohistochemical analysis detected mouse Emid2 in the extracellular matrix of testis and ovary.
By searching a database for sequences similar to EMID1 (608926), Leimeister et al. (2002) identified 2 splice variants encoding EMID2, which they designated EMU2. The deduced proteins contain 441 and 439 amino acids. EMID2 contains an N-terminal signal peptide, followed by an emilin (EMI) domain, 2 collagen stretches, and a novel C-terminal domain. The EMI domain contains 7 conserved cysteines that may mediate dimerization. In situ hybridization of mouse embryos detected Emid2 expression in somites and in mesenchymal cells of the head and branchial arches at embryonic day 9.5. At later developmental stages, Emid2 was expressed in mesenchyme of the salivary gland, the inner ear, and the developing kidney nephrons adjacent to Emid1-positive epithelium. Emid2 was also expressed in spinal nerves and ganglia, in the head mesenchyme, and in skeletal muscle.
Sato et al. (2002) determined that mouse Emid2 shows collagen-like characteristics, including hydroxylation and N-glycosylation. The N-glycans were found to be modified to more complex forms in the Golgi apparatus before secretion. In addition, Emid2 formed trimers that were secreted into the culture medium of transfected human embryonic kidney cells. Pulse-chase experiments revealed that posttranslational modification was required for secretion.
Leimeister et al. (2002) determined that mouse Emid2 and Emid1 are N-glycosylated proteins that exist as monomers, but they can form homodimers, homotrimers, or larger complexes. Emid2 and Emid1 could also form heteromeric complexes via their EMI domains. Both proteins were secreted by transfected human embryonic kidney cells and deposited in the extracellular matrix.
Leimeister et al. (2002) determined that the EMID2 gene contains 13 exons and spans 196 kb.
Lettice et al. (2011) identified a highly conserved noncoding element, which they called HCNE2, within an intron of EMID2. They found that HCNE2 functions as a limb bud enhancer in mouse embryos. In a child with a de novo 7q inversion and features of holoprosencephaly as well as severe upper limb syndactyly and lower limb synpolydactyly, Lettice et al. (2011) found that the limb phenotype in this child was due to the increased proximity of Sonic hedgehog (SHH; 600725) to HCNE2 and the resulting ectopic expression of SHH. Lettice et al. (2011) termed this mechanism of disease 'enhancer adoption.'
By genomic sequence analysis, Leimeister et al. (2002) mapped the EMID2 gene to chromosome 7q22.1.
Leimeister, C., Steidl, C., Schumacher, N., Erhard, S., Gessler, M. Developmental expression and biochemical characterization of Emu family members. Dev. Biol. 249: 204-218, 2002. [PubMed: 12221002] [Full Text: https://doi.org/10.1006/dbio.2002.0764]
Lettice, L. A., Daniels, S., Sweeney, E., Venkataraman, S., Devenney, P. S., Gautier, P., Morrison, H., Fantes, J., Hill, R. E., FitzPatrick, D. R. Enhancer-adoption as a mechanism of human developmental disease. Hum. Mutat. 32: 1492-1499, 2011. [PubMed: 21948517] [Full Text: https://doi.org/10.1002/humu.21615]
Sato, K., Yomogida, K., Wada, T., Yorihuzi, T., Nishimune, Y., Hosokawa, N., Nagata, K. Type XXVI collagen, a new member of the collagen family, is specifically expressed in the testis and ovary. J. Biol. Chem. 277: 37678-37684, 2002. [PubMed: 12145293] [Full Text: https://doi.org/10.1074/jbc.M205347200]