Alternative titles; symbols
HGNC Approved Gene Symbol: TTC3
Cytogenetic location: 21q22.13 Genomic coordinates (GRCh38) : 21:37,073,254-37,203,118 (from NCBI)
The Down syndrome (DS; 190685) region on chromosome 21, which is responsible for the main features of DS, has been defined by analysis of DS patients with partial trisomy 21. Within the DS region, Ohira et al. (1996) constructed a 1.6-Mb P1 contig map on 21q22.2 and performed cDNA library screening and exon trapping using these P1 clones and a human fetal brain cDNA library. They obtained 67 cDNA fragments and 52 possible exons. Among them, 23 cDNA fragments and 4 exons were derived from a single gene by localization on P1 clones and by Northern analysis. To obtain the full-length cDNA sequence, longer cDNA clones were further screened from another human cDNA library that was enriched with longer cDNA species. These clones were assembled to a sequence of 9,045 bp. The cDNA encodes a 2,025-amino acid protein containing 3 tetratricopeptide repeat (TPR) motifs (amino acid residues 231-264, 265-298, and 299-332). The authors symbolized the gene TPRD for a gene containing the TPR motifs on the Down syndrome region. The TPR domain has been found in protein phosphatases and in other proteins involved in the regulation of RNA synthesis or mitosis.
Independently, Tsukahara et al. (1996) identified and cloned a 9,078-bp cDNA, which they designated TPRDI, from the Down syndrome critical region by exon trapping. The cDNA encodes a putative protein (TPRDI) of 2,025 amino acid residues. Two isoforms, TPRDII (8,992 bp) and TPRDIII (7,416 bp), were also isolated. TPRDII, which is probably an alternative splicing product from the TPRD gene transcript, encodes 2 large open reading frames of 200 and 1,792 amino acid residues, respectively. TPRDIII, which is probably generated by transcription from an alternative start site of the TPRD gene, encodes a putative protein of 1,715 amino acid residues. Northern blot analysis revealed that TPRDI and its isoforms are present in 7- to 17-day mouse embryos and in all the human adult and fetal tissues examined. TPRDI has 3 units of the 34-amino acid TPR motif, which may mediate interaction with various proteins. A larger open reading frame encoded by TPRDII also has 3 units of the TPR motif, but TPRDIII has only two-thirds of this motif unit. Thus, the TPRD gene may belong to the TPR gene family. Near-central and C-terminal regions of TPRDs showed some homology to several matrix proteins such as trichohyalin and bullous pemphigoid antigen. The authors speculated that overexpression of the TPRD gene may cause several morphologic anomalies observed in Down syndrome.
By EST database analysis, screening a hippocampus cDNA library, and 5-prime and 3-prime RACE, Eki et al. (1997) cloned TTC3, which they called DCRR1. The deduced protein contains 1,941 amino acids and has a calculated molecular mass of 220.2 kD. An N-terminal domain shares similarity with several protein phosphatases, and a C-terminal region shares similarity with myosin heavy chains (see 160730) or proteins involved in microtubule and cytoskeleton dynamics, including CENPE (117143). DCRR1 contains a cytochrome c family (see 516030) heme-binding motif, a profilin (see 176610) signature sequence, a transmembrane domain, sites for N-glycosylation, phosphorylation, and glycosaminoglycan attachment, and 3 nuclear localization signals. Northern blot analysis detected 7.9- and 9.0-kb transcripts in several tissues, including spleen, thymus, prostate, and ovary. Testis expressed only the 7.9-kb transcript, and no expression was detected in placenta, lung, and liver.
The TTC3 gene maps to chromosome 21q22.2 (Ohira et al., 1996).
Eki, T., Abe, M., Naitou, M., Sasanuma, S.-I., Nohata, J., Kawashima, K., Ahmad, I., Hanaoka, F., Murakami, Y. Cloning and characterization of novel gene, DCRR1, expressed from Down's syndrome critical region of human chromosome 21q22.2. DNA Seq. 7: 153-164, 1997. [PubMed: 9254009] [Full Text: https://doi.org/10.3109/10425179709034031]
Ohira, M., Ootsuyama A., Suzuki, E., Ichikawa, H., Seki, N., Nagase, T., Monura, N., Ohki, M. Identification of a novel human gene containing the tetratricopeptide repeat domain from the Down syndrome region of chromosome 21. DNA Res. 3: 9-16, 1996. [PubMed: 8724848] [Full Text: https://doi.org/10.1093/dnares/3.1.9]
Tsukahara, F., Hattori, M., Muraki, T., Sakaki, Y. Identification and cloning of a novel cDNA belonging to tetratricopeptide repeat gene family from Down syndrome-critical region 21q22.2. J. Biochem. 120: 820-827, 1996. [PubMed: 8947847] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a021485]