SATB2

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SATB homeobox 2
PDB 1wi3 EBI.jpg
PDB rendering based on 1wi3.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SATB2 ; FLJ21474; FLJ32076; KIAA1034; MGC119474; MGC119477
External IDs OMIM608148 MGI2679336 HomoloGene32249 GeneCards: SATB2 Gene
Orthologs
Species Human Mouse
Entrez 23314 212712
Ensembl ENSG00000119042 ENSMUSG00000038331
UniProt Q9UPW6 Q8VI24
RefSeq (mRNA) NM_001172509 NM_139146
RefSeq (protein) NP_001165980 NP_631885
Location (UCSC) Chr 2:
200.13 – 200.34 Mb
Chr 1:
56.79 – 56.98 Mb
PubMed search [1] [2]

Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene.[1] SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling.[2] SATB2 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.[3]

Function[edit]

With an average worldwide prevalence of 1/800 live births, oral clefts are one of the most common birth defects.[4] Although over 300 malformation syndromes can include an oral cleft, non-syndromic forms represent about 70% of cases with cleft lip with or without cleft palate (CL/P) and roughly 50% of cases with cleft palate (CP) only. Non-syndromic oral clefts are considered ‘complex’ or ‘multifactorial’ in that both genes and environmental factors contribute to the etiology. Current research suggests that several genes are likely to control risk, as well as environmental factors such as maternal smoking.[5]
Re-sequencing studies to identify specific mutations suggest several different genes may control risk to oral clefts, and many distinct variants or mutations in apparently causal genes have been found reflecting a high degree of allelic heterogeneity. Although most of these mutations are extremely rare and often show incomplete penetrance (i.e., an unaVected parent or other relative may also carry the mutation), combined they may account for up to 5% of non-syndromic oral cleft.[5]

Mutations in the SATB2 gene have been found to cause isolated cleft palates.[6] SATB2 also likely influences brain development. This is consistent with mouse studies that show SATB2 is necessary for proper establishment of cortical neuron connections across the corpus callosum, despite the apparently normal corpus callosum in heterozygous knockout mice.[3]

Structure[edit]

SATB2 is a 733 amino-acid homeodomain-containing human protein with a molecular weight of 82.5 kDa encoded by the SATB2 gene on 2q33. The protein contains two degenerate homeodomain regions known as CUT domains (amino acid 352–437 and 482–560) and a classical homeodomain (amino acid 614–677). There is an extraordinarily high degree of sequence conservation, with only three predicted amino-acid substitutions in the 733 residue protein with I481V, A590T and I730T being amino acid differences between the human and the mouse protein.

Clinical significance[edit]

SATB2 was found to be disrupted in two unrelated cases with de novo apparently balanced chromosome translocations associated with cleft palate and Pierre Robin Sequence.[7]
The role of SATB2 in tooth and jaw development is supported by the identification of a de novo SATB2 mutation in a male with profound mental retardation and jaw and tooth abnormalities and a translocation interrupting SATB2 in an individual with Robin sequence. In addition, mouse models have demonstrated haploinsufficiency of SATB2 results in craniofacial defects that phenocopy those caused by 2q32q33 deletion in humans; moreover, full functional loss of SATB2 amplifies these defects.[3]

References[edit]

  1. ^ Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (June 1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID 10470851. 
  2. ^ "Entrez Gene: SATB homeobox 2". 
  3. ^ a b c Rosenfeld JA, Ballif BC, Lucas A, et al. (2009). "Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome.". PLoS ONE 4 (8): e6568. doi:10.1371/journal.pone.0006568. PMC 2719055. PMID 19668335. 
  4. ^ Jugessur A, Shi M, Gjessing HK, et al. (2010). "Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.". PLoS ONE 5 (7): e11493. doi:10.1371/journal.pone.0011493. PMC 2901336. PMID 20634891. 
  5. ^ a b Beaty TH, Hetmanski JB, Fallin MD, et al. (2006). "Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations.". Hum. Genet. 120 (4): 501–18. doi:10.1007/s00439-006-0235-9. PMID 16953426. 
  6. ^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nat. Rev. Genet. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089. 
  7. ^ FitzPatrick DR, Carr IM, McLaren L, Leek JP, Wightman P, Williamson K, Gautier P, McGill N, Hayward C, Firth H, Markham AF, Fantes JA, Bonthron DT (October 2003). "Identification of SATB2 as the cleft palate gene on 2q32-q33". Hum. Mol. Genet. 12 (19): 2491–501. doi:10.1093/hmg/ddg248. PMID 12915443. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.