SOX11 (SRY (sex determining region Y)-box 11)

2010-01-01   Xiao Wang , Birgitta Sander 

Department of Pathology, F46, Karolinska Institutet, SE 141 86 Stockholm, Sweden (XW); Department of Pathology, F46, Karolinska University Hospital, Karolinska Institutet, SE 141 86 Stockholm, Sweden (BS)

Identity

HGNC
LOCATION
2p25.2
LOCUSID
ALIAS
CSS9,MRD27
FUSION GENES

DNA/RNA

Atlas Image
The human SOX11 gene. The only exon is indicated by the red box. The number above the box shows the size of the exon.

Description

The intronless gene encompasses 8718 base pairs and is located at 2p25.2.

Transcription

The mRNA SOX11 transcript contains one exon with 8718 base pairs.

Proteins

Atlas Image
The human SOX11 protein and functional domains. Numbers indicate the amino acid positions at the beginning and the end of each domain. The grey bar shows the High-Mobility-Group (HMG) box DNA-binding domain; and the dark blue bar shows the TransActivation Domain (TAD).

Description

The human SOX11 protein has 441 amino acids and 46.7 KDa molecular weight. It contains two functional domains: a Sry-related high-mobility group (HMG) box (Sox) DNA-binding domain, located in the N-terminal third (47-122), and a transactivation domain (TAD), located at the C-terminus (408-441) (Dy et al., 2008; Penzo-Méndez, 2009).

Expression

SOX11 is widely expressed during organogenesis in the embryo and is highly expressed in the central and peripheral nervous system of the human fetus (Jay et al., 1995; Sock et al., 2004). SOX11 expression is more restricted by birth, and low transcript levels of SOX11 were detected in adult colon, small intestine, heart and brain (Weigle et al., 2005). High level of SOX11 mRNA is only present in normal prostate tissue (Brennan et al., 2009).

Localisation

Nucleus.

Function

SOX11 contains domains that may function as transcriptional activators or repressors and is a member of the group C SOX transcription factor family. It appears to have critical roles in embryonic neurogenesis and development of many organ systems including heart, palate and eyelids (Sock et al., 2004). SOX11 can, together with SOX4, regulate the differentiation of neuronal progenitors (Bergsland et al., 2006). SOX11 is involved in the transcriptional regulation of specific gene expression programs in adult neurogenesis at the stage of the immature neuron (Haslinger et al., 2009). SOX11 controls morphological maturation such as neurite growth (Jankowski et al., 2006) and modulates the regeneration following peripheral nerve injury (Jankowski et al., 2009). The class-III beta-tubulin gene TUBB3 is the first and still the unique gene to be identified as a direct target of SOX11 (Dy et al., 2008). SOX11 has been suggested to bind and regulate LINE retrotransposons (Tchénio, 2000).

Homology

The two domains are highly conserved regions between species (from human to fly). In the SOX C group, consisting of SOX4, SOX11 and SOX12, the HMG box and C33 domains are more highly conserved among Sox4 orthologues and SOX11 orthologues than among SOX12.

Implicated in

Entity name
Malignant glioma
Note
SOX11 was identified by screening an expression database for genes highly expressed in glioblastoma multiforme (Weigle et al., 2005). Overexpression of SOX11 can prevent tumorigenesis of glioma-initiating cells by inducing their neuronal differentiation (Hide et al., 2009).
Disease
Malignant glioma comprises of the majority of primary brain tumors with 16800 new cases reported each year in USA.
Prognosis
SOX11 can serve as a target antigen for glioma-directed cytotoxic T lymphocytes (CTLs), and this novel CTL epitope may serve as a suitable candidate for a T cell-based immunotherapy of glioma patients (Schmitz et al., 2007).
Entity name
Medulloblastoma
Note
SOX11 has been shown to be overexpressed in most classical medulloblastomas (Lee et al., 2002).
Disease
Medulloblastomas are brain tumors occurred in the cerebellum.
Entity name
Haematological malignancies
Note
Overexpression of SOX11 was first described as a unique marker for a specific malignant B cell lymphoma, mantle cell lymphoma (Ek et al., 2008; Wang et al., 2008).
Subsequent studies have demonstrated that Sox11 is also present in:
- 2/3 cases of T-cell prolymphocytic leukemia (Dictor et al., 2009; Mozos et al., 2009). - Almost all of B-cell lymphoblastic leukemia/lymphomas and T-cell lymphoblastic leukemia/lymphomas;
Prognosis
Expression of SOX11 in mantle cell lymphoma is not only a new diagnostic marker but may also carry information related to the clinical and biological behaviour (Wang et al., 2008).
Entity name
Ovarian cancer
Note
SOX11 is overexpressed in many epithelial ovarian cancers, and loss of Sox11 is associated with a decreased recurrence-free survival and a more aggressive phenotype (Brennan et al., 2009).
Prognosis
SOX11 is differently expressed in epithelial ovarian cancer and is a prognostic marker.

Bibliography

Pubmed IDLast YearTitleAuthors
171828722006The establishment of neuronal properties is controlled by Sox4 and Sox11.Bergsland M et al
192727682009The transcription factor Sox11 is a prognostic factor for improved recurrence-free survival in epithelial ovarian cancer.Brennan DJ et al
198019692010Nuclear expression of sox11 is highly associated with mantle cell lymphoma but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms.Chen YH et al
198807792009Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma.Dictor M et al
184034182008The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping expression patterns and molecular properties.Dy P et al
179340692008Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma.Ek S et al
194900902009Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesis.Haslinger A et al
198089592009Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.Hide T et al
191332452009Sox11 transcription factor modulates peripheral nerve regeneration in adult mice.Jankowski MP et al
86664061995The human SOX11 gene: cloning, chromosomal assignment and tissue expression.Jay P et al
121259832002Differential expression of SOX4 and SOX11 in medulloblastoma.Lee CJ et al
198807782009SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype.Mozos A et al
196512332010Critical roles for SoxC transcription factors in development and cancer.Penzo-Méndez AI et al
165043792007Identification of a naturally processed T cell epitope derived from the glioma-associated protein SOX11.Schmitz M et al
152542312004Gene targeting reveals a widespread role for the high-mobility-group transcription factor Sox11 in tissue remodeling.Sock E et al
106066372000Members of the SRY family regulate the human LINE retrotransposons.Tchénio T et al
187298572008The subcellular Sox11 distribution pattern identifies subsets of mantle cell lymphoma: correlation to overall survival.Wang X et al
155838152005Highly specific overexpression of the transcription factor SOX11 in human malignant gliomas.Weigle B et al

Other Information

Locus ID:

NCBI: 6664
MIM: 600898
HGNC: 11191
Ensembl: ENSG00000176887

Variants:

dbSNP: 6664
ClinVar: 6664
TCGA: ENSG00000176887
COSMIC: SOX11

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000176887ENST00000322002P35716

Expression (GTEx)

0
1
2
3

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
201244762010Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.89
198807782009SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype.67
229157602012Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features.54
179340692008Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma.47
198807792009Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma.35
198089592009Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.32
233212502013SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma.31
206243182010SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies.28
248868742014De novo SOX11 mutations cause Coffin-Siris syndrome.26
126375432003Identification of novel domains within Sox-2 and Sox-11 involved in autoinhibition of DNA binding and partnership specificity.25

Citation

Xiao Wang ; Birgitta Sander

SOX11 (SRY (sex determining region Y)-box 11)

Atlas Genet Cytogenet Oncol Haematol. 2010-01-01

Online version: http://atlasgeneticsoncology.org/gene/42357/sox11