CELF2 (CUGBP, Elav-like family member 2)

	Figure 1. RRM position of CELF2 protein variants.
Description	This is an evolutionarily conserved protein. The members of the CELF protein family contain two N-terminal RNA recognition motif (RRM) domains and one C-terminal RRM domain, and a divergent segment of 160-230 amino acids between second and third RRM domains. This divergent domain is unique to CELF2 proteins and has been shown to contain one or more activation molecules required for splicing activity (figure 1).
Expression	CELF2 is a ubiquitously expressed protein. According to the NCBI Entrez GEO profiles the CELF2 is expressed in brain, heart, thymus, spleen, bone, tongue, stomach, intestine, pancreas, liver, breast, lung, kidney, testis, ovary, prostate, placenta and skin. In addition, according to expression atlas brain, bone marrow, heart, spleen, lymph node, ovary and adipose tissue has more expression of CELF2.
Localisation	CELF2 variant 1 is predominantly nuclear, while variants 2 and 3 are predominantly cytoplasmic (Ramalingam et al., 2008). CELF2 variant 1 accumulates in the cytoplasm following radiation exposure (Mukhopadhyay et al., 2003a). The C terminus of CELF2 transcript variant 1 is rich in arginine and lysine residues 13 amino acids (KRLKVQLKRSKND) 467 - 480, which is common for NLS elements recognized by importin proteins. Ladd and Cooper, has reported that the C-terminus of CELF2 contains a strong nuclear localization signal overlapping the third RRM (Ladd and Cooper, 2004). However, our unpublished data suggests that nuclear localization signal extends to the RNA recognition motif 1 and 2 domains. Finally, CELF2 has several leucine-rich motifs that resembles nuclear export signals recognized by the export protein CRM1.
Function	CELF2 is an RNA-binding protein implicated in the regulation of several post-transcriptional events. It has been shown to regulate pre-mRNA splicing (Faustino and Cooper, 2005), mRNA editing (Anant et al., 2001), mRNA translation and stability. CELF2 has been shown to be involved in alternative splicing of muscle specific genes including exon 5 of cardiac troponin T (Ladd et al., 2001), exon 11 of insulin receptor, intron 2 of chloride channel 1, exons 5 and 21 of NMDAR-1, and the muscle-specific exon of α-actinin (Gromak et al., 2003). Another function for CELF2 relates to its ability to bind to AU-rich sequences in 3' untranslated region (3' UTR) of the target mRNAs. Upon binding to the AU-rich sequences in cyclooxygenase-2 (COX-2) 3' UTR, CELF2 enhances the stability of COX-2 mRNA. However, CUGBP2 binding also results in the inhibition of its translation (Murmu et al., 2004). In our earlier studies we have demonstrated that CELF2 can interact with HuR, a key inducer of RNA stability and translation, and competitively inhibit HuR function (Sureban et al., 2007). Recently, platelet derived growth factor was shown to enhance CELF2 binding to COX-2 mRNA through increased phosphorylation of a tyrosine residue at position 39 in the protein (Xu et al., 2007). These data suggest that posttranscriptional control mechanisms are in place to modulate the CELF2 function as a regulator of stability and translation of AU-rich transcripts.
Homology	According to GeneCards, the CELF2 has orthologs in 72 species including much lower organisms such as Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus tropicalis and Oryza sativa. Furthermore, in humans it has 6 paralogs from CELF1 to CELF6.

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