SATB2

SATB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WI3, 1WIZ, 2CSF
Identifiers
Aliases	SATB2, GLSS, SATB homeobox 2
External IDs	OMIM: 608148; MGI: 2679336; HomoloGene: 32249; GeneCards: SATB2; OMA:SATB2 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q33.1 Start 199,269,500 bp End 199,471,266 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 C1.3 Start 56,833,140 bp End 57,017,809 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in periodontal fiber mucosa of sigmoid colon tibia rectum mucosa of ileum mucosa of transverse colon middle temporal gyrus Brodmann area 46 superior frontal gyrus postcentral gyrus Top expressed in facial skeleton Dermatocranium membranous bone mandible maxilla rib body of femur barrel cortex left colon molar More reference expression data BioGPS n/a
Gene ontology Molecular function sequence-specific DNA binding DNA binding chromatin binding protein binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component histone deacetylase complex transcription regulator complex nuclear matrix nucleus nucleoplasm Biological process commitment of neuronal cell to specific neuron type in forebrain embryonic skeletal system morphogenesis cellular response to organic substance chromatin remodeling roof of mouth development regulation of transcription, DNA-templated embryonic pattern specification regulation of transcription by RNA polymerase II neuron migration negative regulation of transcription by RNA polymerase II transcription, DNA-templated multicellular organism development cartilage development regulation of gene expression osteoblast development positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II chromatin organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23314 212712 Ensembl ENSG00000119042 ENSMUSG00000038331 UniProt Q9UPW6 Q8VI24 RefSeq (mRNA) NM_001172509 NM_001172517 NM_015265 NM_139146 NM_001358580 NM_001358581 RefSeq (protein) NP_001165980 NP_001165988 NP_056080 NP_631885 NP_001345509 NP_001345510 Location (UCSC) Chr 2: 199.27 – 199.47 Mb Chr 1: 56.83 – 57.02 Mb PubMed search
Wikidata
View/Edit Human View/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. SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling. SATB2 shows a restricted mode of expression [1] and is expressed in certain cell nuclei [2]. The SATB2 protein is mainly expressed in the epithelial cells of the colon and rectum, followed by the nuclei of neurons in the brain.

Function

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

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 unaffected parent or other relatives may also carry the mutation), combined they may account for up to 5% of non-syndromic oral cleft.

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

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 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.

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.

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 intellectual disabilities 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.

SATB2 expression is highly specific for cancer in the lower GI-tract and has been implicated as a cancer biomarker for colorectal cancer.

Further reading

• Dobreva G, Dambacher J, Grosschedl R (December 2003). "SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression". Genes & Development. 17 (24): 3048–3061. doi:10.1101/gad.1153003. PMC 305257. PMID 14701874.
• Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Fariñas I, et al. (June 2006). "SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation". Cell. 125 (5): 971–986. doi:10.1016/j.cell.2006.05.012. PMID 16751105. S2CID 2882724.
• Alcamo EA, Chirivella L, Dautzenberg M, Dobreva G, Fariñas I, Grosschedl R, et al. (February 2008). "Satb2 regulates callosal projection neuron identity in the developing cerebral cortex". Neuron. 57 (3): 364–377. doi:10.1016/j.neuron.2007.12.012. PMID 18255030. S2CID 6716396.
• Beaty TH, Hetmanski JB, Fallin MD, Park JW, Sull JW, McIntosh I, et al. (November 2006). "Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations". Human Genetics. 120 (4): 501–518. doi:10.1007/s00439-006-0235-9. PMID 16953426. S2CID 7836461.
• Machado RD, Pauciulo MW, Fretwell N, Veal C, Thomson JR, Vilariño Güell C, et al. (September 2000). "A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium". Genomics. 68 (2): 220–228. doi:10.1006/geno.2000.6291. PMID 10964520.
• Jugessur A, Shi M, Gjessing HK, Lie RT, Wilcox AJ, Weinberg CR, et al. (July 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. Bibcode:2010PLoSO...511493J. doi:10.1371/journal.pone.0011493. PMC 2901336. PMID 20634891.
• Carter TC, Molloy AM, Pangilinan F, Troendle JF, Kirke PN, Conley MR, et al. (February 2010). "Testing reported associations of genetic risk factors for oral clefts in a large Irish study population". Birth Defects Research. Part A, Clinical and Molecular Teratology. 88 (2): 84–93. doi:10.1002/bdra.20639. PMC 3503531. PMID 19937600.
• Rosenfeld JA, Ballif BC, Lucas A, Spence EJ, Powell C, Aylsworth AS, et al. (August 2009). "Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome". PLOS ONE. 4 (8): e6568. Bibcode:2009PLoSO...4.6568R. doi:10.1371/journal.pone.0006568. PMC 2719055. PMID 19668335.
• Vieira AR, Avila JR, Daack-Hirsch S, Dragan E, Félix TM, Rahimov F, et al. (December 2005). "Medical sequencing of candidate genes for nonsyndromic cleft lip and palate". PLOS Genetics. 1 (6): e64. doi:10.1371/journal.pgen.0010064. PMC 1298935. PMID 16327884.

External links

• SATB2 human gene location in the UCSC Genome Browser.
• SATB2 human gene details in the UCSC Genome Browser.

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.