The reference OMIM entry for this protein is 609078

Lysine-specific demethylase 2b; kdm2b
F-box and leucine-rich repeat protein 10; fbxl10
Fbl10
Cxxc finger protein 2; cxxc2
Jumonji c domain-containing histone demethylase 1b; jhdm1b

DESCRIPTION

Members of the F-box protein family, such as FBXL10, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (601434), cullin (see CUL1; 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (summary by Jin et al., 2004).

CLONING

Winston et al. (1999) cloned a partial cDNA encoding mouse Fbl10. The deduced protein contains an F box, followed by 8 tandem leucine-rich repeats. Jin et al. (2004) reported that the human FBXL10 protein contains an N-terminal JmjC domain, which is found in cupin metalloenzymes, central zinc finger and PHD domains, and a C-terminal F box that is followed by 8 leucine-rich repeats. Boulard et al. (2015) reported that mouse Fbxl10 encodes 2 protein isoforms. Fbxl10-1 contains 1,309 amino acids and has a JmjC histone demethylase domain in its N-terminal half, followed by a central CxxC motif, a PHD domain, an F-box domain, and a C-terminal leucine-rich repeat region. Fbxl10-2 contains 776 amino acids and is translated from an mRNA initiated from an internal promoter. Fbxl10-2 lacks the N-terminal half of Fbxl10-1 and begins with the CxxC motif. Boulard et al. (2015) reported that Fbxl10-2 is the predominant form in mouse embryos and in most adult mouse tissues.

GENE FUNCTION

Using insertional mutagenesis with Blm (RECQL3; 604610)-deficient mice, Suzuki et al. (2006) identified Fbxl10 as a putative tumor suppressor. Fbxl10 knockdown by RNA interference increased the mutation rate in mouse fibroblasts, but it did not increase their tolerance to the DNA methylating agent MNNG, suggesting that Fbxl10 functions in a DNA repair process other than mismatch repair. Frescas et al. (2007) identified human JHDM1B as a nucleolar protein and showed that JHDM1B preferentially binds the transcribed region of ribosomal DNA to repress the transcription of ribosomal RNA genes. Frescas et al. (2007) also showed that repression of ribosomal RNA genes by JHDM1B is dependent on its JmjC domain, which is necessary for the specific demethylation of trimethylated lysine-4 on histone H3 (see 602810) in the nucleolus. In agreement with the notion that ribosomal RNA synthesis and cell growth are coupled processes, Frescas et al. (2007) showed a JmjC-domain-dependent negative effect of JHDM1B on cell size and cell proliferation. Because aberrant ribosome biogenesis and the disruption of epigenetic control mechanisms contribute to cellular transformation, these results, together with the low levels of JHDM1B expression found in aggressive brain tumors, suggested a role for JHDM1B in cancer development. JUN (165160) is a component of the heterodimeric transcription factor AP1 that is rapidly activated in response to ultraviolet (UV) light. In unstressed cells, JUN activity is negatively regulated by transcriptional repressor complexes. Koyama-Nasu et al. (2007) showed that FBL10 interacted with JUN and repressed JUN-mediated transcription in human cell lines. Chromatin immunoprecipitation assays demonstrated that FBL10 was present at the JUN promoter and that JUN was required for recruitment of FBL10. FBL10 bound unmethylated CpG sequences in the JUN promoter through its CxxC zinc finger and tethered transcriptional repressor complexes. Suppression of FBL10 expression by RNA interference induced transcription of J ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 609078 was added.

May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).