Atlas of Genetics and Cytogenetics in Oncology and Haematology
DLX5 (distal-less homeobox 5)
| Identity |
| Other names | SHFM1D |
| HGNC (Hugo) | DLX5 |
| LocusID (NCBI) | 1749 |
| Location | 7q21.3 |
| Location_base_pair | Starts at 96649702 and ends at 96654143 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| Local_order | -DLX6-DLX5-ACN9- |
 | |
| Local order of DLX5 and flanking genes DLX6 and ACN9 is shown, with centromere at left and telomere (qter) at right. Arrows indicate transcriptional orientation of individual genes. DLX6 gene range: 96635290 - 96640352; DLX5 gene range: 96649702 - 96654143; ACN9 gene range: 96745905 - 96811075 (Hillier et al., 2003). | |
| DNA/RNA |
 | |
| Exon 1: 1 - 563; exon 2: 2463 - 2647; exon 3: 3767 - 4442. | |
| Description | The DLX5 gene is composed of 3 exons spanning a genomic region of 4442 bp. |
| Transcription | The DLX5 coding sequence consists of 870 bp from the start of the first codon to the stop codon (Simeone et al., 1994). |
| Pseudogene | None known. |
| Protein |
 | |
| DLL_N: homeobox protein distal-less-like N terminal; Homeodomain: homeobox DNA binding domain. | |
| Description | The DLX5 protein consists of 289 amino acids with a calculated molecular weight of 31,5 kDa. The protein contains two motifs, one dubbed homeobox protein distal-less-like N terminal and a second known as a homeodomain. |
| Localisation | Nucleus. |
| Function | Transcription factor important in the control of bone formation in embryonic development (Hassan et al., 2004). |
| Homology | None reported to date. |
| Mutations |
| Germinal | A novel DLX5 mutation (c.A533C: p.Q178P) was identified in a family with autosomal recessive split hand and foot malformation (Shamseldin et al., 2012). |
| Somatic | A DLX5 mutation (c.C119G: p.S40C) was observed in an ovarian carcinoma (Cancer Genome Atlas Research Network, 2011). Overexpression of DLX5 has been reported in several types of human malignancy including lung cancer (Kato et al., 2008; Xu and Testa, 2009), T-cell lymphoma (Tan et al., 2008), and ovarian cancer (Tan et al., 2010), etc. |
| Implicated in |
| Entity | Lung cancer |
| Note | The DLX5 gene was reported to be overexpressed in the great majority of human non-small cell lung cancers examined by Kato et al., 2008. Furthermore, immunohistochemical studies revealed that positive immunostaining for DLX5 correlated with tumor size and poorer prognosis. |
| Entity | Lymphoma |
| Note | DLX5 was found to be highly expressed in 3 of 7 (42%) patient-derived T-cell lymphomas compared with that observed in nonmalignant lymph node samples (Tan et al., 2008). In addition, these investigators found repeated upregulation of Dlx5 in T-cell lymphomas from transgenic mice in which the Lck promoter was used to drive expression of a constitutively active form of Akt2 in the thymus. Dlx5 was overexpressed due to a novel chromosome inversion that placed the T-cell receptor beta (Tcrb) enhancer region near the Dlx5 locus. |
| Entity | Breast cancer |
| Note | Both DLX5 and DLX6 were found to be upregulated during metastasis formation after intravenous injection of MDA-MB-231 breast cancer cells. The in vitro treatment of MDA-MB-231 cells with endothelin 1, a peptide associated with breast cancer invasive phenotype, resulted in a switch from DLX2 to DLX5 expression. Mutually exclusive expression of DLX2 and DLX5 was found in both MDA-MB-231 cells and human breast cancer specimens. This evidence suggested that DLX genes are involved in human breast cancer progression, and that expression of DLX2 and DLX5 genes might serve as prognostic markers (Morini et al., 2010). |
| Entity | Various cancers |
| Note | DLX5 mRNA is abundantly expressed in many cancer cell lines derived from malignant tissues of breast, brain, lung, skin, and ovarian cancer patients, whereas expression of DLX5 was low or undetectable in tumor cells from patients with leukemia or with colorectal, prostate, and kidney cancers (Tan et al., 2010). |
| External links |
| Bibliography |
| Cloning and characterization of two members of the vertebrate Dlx gene family. |
| Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K, et al. |
| Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2250-4. |
| PMID 7907794 |
| The DNA sequence of human chromosome 7. |
| Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK. |
| Nature. 2003 Jul 10;424(6945):157-64. |
| PMID 12853948 |
| Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene. |
| Hassan MQ, Javed A, Morasso MI, Karlin J, Montecino M, van Wijnen AJ, Stein GS, Stein JL, Lian JB. |
| Mol Cell Biol. 2004 Oct;24(20):9248-61. |
| PMID 15456894 |
| Activation of placenta-specific transcription factor distal-less homeobox 5 predicts clinical outcome in primary lung cancer patients. |
| Kato T, Sato N, Takano A, Miyamoto M, Nishimura H, Tsuchiya E, Kondo S, Nakamura Y, Daigo Y. |
| Clin Cancer Res. 2008 Apr 15;14(8):2363-70. |
| PMID 18413826 |
| A novel recurrent chromosomal inversion implicates the homeobox gene Dlx5 in T-cell lymphomas from Lck-Akt2 transgenic mice. |
| Tan Y, Timakhov RA, Rao M, Altomare DA, Xu J, Liu Z, Gao Q, Jhanwar SC, Di Cristofano A, Wiest DL, Knepper JE, Testa JR. |
| Cancer Res. 2008 Mar 1;68(5):1296-302. |
| PMID 18316591 |
| DLX5 (distal-less homeobox 5) promotes tumor cell proliferation by transcriptionally regulating MYC. |
| Xu J, Testa JR. |
| J Biol Chem. 2009 Jul 31;284(31):20593-601. Epub 2009 Jun 4. |
| PMID 19497851 |
| Mutually exclusive expression of DLX2 and DLX5/6 is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231. |
| Morini M, Astigiano S, Gitton Y, Emionite L, Mirisola V, Levi G, Barbieri O. |
| BMC Cancer. 2010 Nov 25;10:649. |
| PMID 21108812 |
| Upregulation of DLX5 promotes ovarian cancer cell proliferation by enhancing IRS-2-AKT signaling. |
| Tan Y, Cheung M, Pei J, Menges CW, Godwin AK, Testa JR. |
| Cancer Res. 2010 Nov 15;70(22):9197-206. Epub 2010 Nov 2. |
| PMID 21045156 |
| Integrated genomic analyses of ovarian carcinoma. |
| Cancer Genome Atlas Research Network. |
| Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166. |
| PMID 21720365 |
| Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation. |
| Shamseldin HE, Faden MA, Alashram W, Alkuraya FS. |
| J Med Genet. 2012 Jan;49(1):16-20. Epub 2011 Nov 25. |
| PMID 22121204 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 03-2012 | Jinfei Xu, Joseph R Testa |
| Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA |
| Citation |
| This paper should be referenced as such : |
| Xu J, Testa JR . DLX5 (distal-less homeobox 5). Atlas Genet Cytogenet Oncol Haematol. March 2012 . URL : http://AtlasGeneticsOncology.org/Genes/DLX5ID44295ch7q21.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/handle/2042/47484/03-2012-DLX5ID44295ch7q21.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 13:00:59 CEST 2013 |
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