Atlas of Genetics and Cytogenetics in Oncology and Haematology
HOXA11 (homeobox A11)
| Identity |
| Other names | HOX1I (HOMEOBOX 1I) |
| HGNC | HOXA11 |
| Location | 7p15-7p14.2 |
| DNA/RNA |
 | |
| Description | spans a 3,7 kb genomic region containing 2 exons |
| Transcription | mRNA 2295 bp |
| Protein |
 | |
| homeobox containing protein with C terminal localisation of the homedomain. N terminal several repeat regions: 1: Poly-Ser; 2: Poly-Arg; 3 :Poly-Ala; 4: Poly-Gly; 5: Poly-Ala. | |
| Description | 313 amino acids, 34.5 kDa, contains a homeodomain with helix-turn-helix (HTH) motif. The HTH motif consists of approximately 20 residues and is characterised by 2 alpha-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix of the HTH motif binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure. |
| Expression | in lung, bone, uterus, placenta, testis, prostate, liver, hematopoietic precursor cells, endometrium |
| Localisation | nucleus |
| Function | Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. HOXA11 is involved in the regulation of uterine development and is required for female fertility. Expression of HOXA11 is detected at all differentiation stages of normal T cells in the thymus, suggesting a role in normal T cell development. |
| Homology | homolog to murine Hox-1.9; ABD-B homeobox family |
| Mutations |
| Germinal | Mutation of HOXA11 in radio-ulnar synostosis with amegakaryotic thrombocytopenia; autosomal dominant inheritance; 1-bp deletion in exon 2 of the HOXA11 gene. Deletion of an adenine converted AAC (asparagine) to ACA (threonine), resulting in a premature termination codon and truncation of the remaining 22 amino acids of the HOXA11 protein. |
| Implicated in |
| Entity | inv(7)(p15q34), t(7;7)(p15;q34) |
| Disease | T-cell acute lymphoblastic leukemia |
| Cytogenetics | inv(7)(p15q34) or t(7;7)(p15;q34) places 5'HOXA cluster genes (7p15) under the influence of strong enhancers within the TCRB locus (7q34) resulting in ectopic expression of especially HOXA10 and HOXA11 |
| Abnormal Protein | no fusion protein but ectopic expression of HOXA10 and HOXA11 |
| Entity | t(7;11)(p15;p15) |
| Disease | CML, only once reported |
| Prognosis | unknown |
| Cytogenetics | this rearrangement fuses the 5' NUP98 gene in frame to the 3' HOXA11 gene generation a chimeric fusion transcript |
| Hybrid/Mutated Gene | 5' NUP98-3'HOXA11 |
| External links |
| Bibliography |
| Homeotic transformations and limb defects in Hox A11 mutant mice. |
| Small KM, Potter SS |
| Genes & development. 1993 ; 7 (12A) : 2318-2328. |
| PMID 7902826 |
| Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. |
| Davis AP, Witte DP, Hsieh-Li HM, Potter SS, Capecchi MR |
| Nature. 1995 ; 375 (6534) : 791-795. |
| PMID 7596412 |
| Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. |
| Hsieh-Li HM, Witte DP, Weinstein M, Branford W, Li H, Small K, Potter SS |
| Development (Cambridge, England). 1995 ; 121 (5) : 1373-1385. |
| PMID 7789268 |
| Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice. |
| Gendron RL, Paradis H, Hsieh-Li HM, Lee DW, Potter SS, Markoff E |
| Biology of reproduction. 1997 ; 56 (5) : 1097-1105. |
| PMID 9160706 |
| Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional redundancy and regulatory interactions. |
| Branford WW, Benson GV, Ma L, Maas RL, Potter SS |
| Developmental biology. 2000 ; 224 (2) : 373-387. |
| PMID 10926774 |
| Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. |
| Thompson AA, Nguyen LT |
| Nature genetics. 2000 ; 26 (4) : 397-398. |
| PMID 11101832 |
| Single-translocation and double-chimeric transcripts: detection of NUP98-HOXA9 in myeloid leukemias with HOXA11 or HOXA13 breaks of the chromosomal translocation t(7;11)(p15;p15). |
| Fujino T, Suzuki A, Ito Y, Ohyashiki K, Hatano Y, Miura I, Nakamura T |
| Blood. 2002 ; 99 (4) : 1428-1433. |
| PMID 11830496 |
| Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development. |
| Taghon T, Thys K, De Smedt M, Weerkamp F, Staal FJ, Plum J, Leclercq G |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (6) : 1157-1163. |
| PMID 12764384 |
| Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. |
| Wellik DM, Capecchi MR |
| Science (New York, N.Y.). 2003 ; 301 (5631) : 363-367. |
| PMID 12869760 |
| HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). |
| Soulier J, Clappier E, Cayuela JM, Regnault A, Garcˆ‚a-Peydrˆ„ M, Dombret H, Baruchel A, Toribio ML, Sigaux F |
| Blood. 2005 ; 106 (1) : 274-286. |
| PMID 15774621 |
| A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. |
| Speleman F, Cauwelier B, Dastugue N, Cools J, Verhasselt B, Poppe B, Van Roy N, Vandesompele J, Graux C, Uyttebroeck A, Boogaerts M, De Moerloose B, Benoit Y, Selleslag D, Billiet J, Robert A, Huguet F, Vandenberghe P, De Paepe A, Marynen P, Hagemeijer A |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (3) : 358-366. |
| PMID 15674412 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 06-2006 | Barbara Cauwelier, Frank Speleman |
| Centrum Medische Genetica Gent (CMGG), Medical Research Building (MRB), 2 nd floor, room 120.024, De Pintelaan 185, B-9000 Ghent, Belgium |
| Citation |
| This paper should be referenced as such : |
| Cauwelier B, Speleman F . HOXA11 (homeobox A11). Atlas Genet Cytogenet Oncol Haematol. June 2006 . URL : http://AtlasGeneticsOncology.org/Genes/HOXA11ID40847ch7p15.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Aug 11 21:14:23 2008 |
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