SATB2

SATB2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases SATB2, GLSS, SATB homeobox 2
External IDs MGI: 2679336 HomoloGene: 32249 GeneCards: SATB2
Genetically Related Diseases
ulcerative colitis[1]
Orthologs
Species Human Mouse
Entrez

23314

212712

Ensembl

ENSG00000119042

ENSMUSG00000038331

UniProt

Q9UPW6

Q8VI24

RefSeq (mRNA)

NM_001172509
NM_001172517
NM_015265

NM_139146

RefSeq (protein)

NP_001165980.1
NP_001165988.1
NP_056080.1

NP_631885.1

Location (UCSC) Chr 2: 199.27 – 199.47 Mb Chr 1: 56.79 – 56.98 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

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.[4] SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling.[5] SATB2 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.[6]

Function

With an average worldwide prevalence of 1/800 live births, oral clefts are one of the most common birth defects.[7] 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.[8]
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.[8]

Mutations in the SATB2 gene have been found to cause isolated cleft palates.[9] 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.[6]

Structure

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

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.[10]
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.[6]

References

  1. ↑ "Diseases that are genetically associated with SATB2 view/edit references on wikidata".
  2. ↑ "Human PubMed Reference:".
  3. ↑ "Mouse PubMed Reference:".
  4. ↑ 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 Research. 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID 10470851.
  5. ↑ "Entrez Gene: SATB homeobox 2".
  6. 1 2 3 Rosenfeld JA, Ballif BC, Lucas A, Spence EJ, Powell C, Aylsworth AS, Torchia BA, Shaffer LG (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 2719055Freely accessible. PMID 19668335.
  7. ↑ Jugessur A, Shi M, Gjessing HK, Lie RT, Wilcox AJ, Weinberg CR, Christensen K, Boyles AL, Daack-Hirsch S, Nguyen TT, Christiansen L, Lidral AC, Murray JC (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 2901336Freely accessible. PMID 20634891.
  8. 1 2 Beaty TH, Hetmanski JB, Fallin MD, Park JW, Sull JW, McIntosh I, Liang KY, Vanderkolk CA, Redett RJ, Boyadjiev SA, Jabs EW, Chong SS, Cheah FS, Wu-Chou YH, Chen PK, Chiu YF, Yeow V, Ng IS, Cheng J, Huang S, Ye X, Wang H, Ingersoll R, Scott AF (November 2006). "Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations". Human Genetics. 120 (4): 501–18. doi:10.1007/s00439-006-0235-9. PMID 16953426.
  9. ↑ Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews. Genetics. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810Freely accessible. PMID 21331089.
  10. ↑ 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". Human Molecular Genetics. 12 (19): 2491–501. doi:10.1093/hmg/ddg248. PMID 12915443.

Further reading

Registry of SATB2 cases http://satb2gene.com

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

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