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Alternative titles; symbolsCYTOPLASMIC LINKER PROTEIN 170-RELATED PROTEIN, 59-KD; CLIPR59HGNC Approved Gene Symbol: CLIP3Cytogenetic location: 19q13.12 Genom...

Alternative titles; symbols


HGNC Approved Gene Symbol: CLIP3

Cytogenetic location: 19q13.12 Genomic coordinates (GRCh38): 19:36,014,659-36,032,872 (from NCBI)

▼ Description
CLIP3 is a membrane-associated protein that contains several protein-protein interaction domains. It associates with the plasma membrane and trans-Golgi membrane and appears to play an important role in myoblast fusion (summary by Sun et al., 2015).

▼ Cloning and Expression
Using the microtubule-binding motif of CLIP170 (RSN; 179838) as query in a database search, followed by RT-PCR, Perez et al. (2002) cloned CLIPR59. The deduced 547-amino acid, 59.5-kD protein has a 4-domain structure containing an N-terminal acidic region rich in glutamic acid and proline; 3 ankyrin (see 600465)-like repeats; 2 microtubule-binding motifs separated by a serine-rich region; and a unique C terminus. Northern blot analysis revealed expression in various tissues, with highest expression in brain. Western blot analysis of HeLa cells indicated that the endogenous protein has an apparent molecular mass of about 60 kD. Immunolocalization of CLIPR59 in HeLa cells revealed colocalization with galactosyltransferase (137060) in Golgi stacks, suggesting that it localizes to the trans-Golgi or trans-Golgi network (TGN).

▼ Gene Function
Perez et al. (2002) determined that the 60-amino acid C-terminal domain of CLIPR59 is necessary and sufficient for Golgi targeting. The isolated microtubule-binding domain of CLIPR59 localized to microtubules when expressed in HeLa cells. However, the authors suggested that this domain is normally inhibited by the presence of adjacent domains, because neither full-length CLIPR59 nor a mutant missing the membrane-targeting region localized to microtubules. Overexpression of full-length CLIPR59 did not affect the microtubule network, but it perturbed endosome-TGN dynamics.

Sun et al. (2015) found that knockdown of Clipr59 in a mouse muscle cell line suppressed myoblast fusion. Yeast 2-hybrid screening of a mouse embryonic fibroblast cDNA library with Clipr59 as bait identified Elmo2 (606421) as a Clipr59-associated protein. Protein pull-down assays showed that interaction between Clipr59 and Elmo2 was mediated by the atypical pleckstrin (PLEK; 173570) homology domain of Elmo2 and the glu-pro-rich domain of Clipr59. The Clipr59-Elmo2 interaction was regulated by RhoG (179505), and interaction of Clipr59 with Elmo2 enhanced Rac1 (602048) activation. Sun et al. (2015) concluded that the CLIPR59-ELMO2 complex is required for myoblast fusion.

▼ Gene Structure
Perez et al. (2002) stated that the CLIPR59 gene contains 14 exons and spans 17 kb.

▼ Mapping
Perez et al. (2002) stated that the CLIPR59 gene maps to chromosome 19q13.

Tags: 19q13.12