The reference OMIM entry for this protein is 610243

Zinc finger fyve domain-containing protein 27; zfyve27
Protrudin

DESCRIPTION

ZFYVE27 is involved in the regulation of endoplasmic reticulum (ER) morphology and the formation of ER tubules and networks (Chang et al., 2013).

CLONING

Mannan et al. (2006) identified ZFYVE27 as a potential spastin (604277)-interacting protein in a yeast 2-hybrid assay. They described 4 splice variants of ZFYVE27. The deduced 403-amino acid ZFYVE27a protein has 3 transmembrane (TM) domains in its N-terminal half and a C-terminal domain containing the zinc finger FYVE domain. ZFYVE27b and ZFYVE27c contain 342 and 317 amino acids, respectively, and are N-terminally truncated compared with ZFYVE27a, such that ZFYVE27b lacks TM1 and ZFYVE27c lacks TM1 and TM2. The deduced 285-amino acid ZFYVE27d protein has TM2 and TM3, but it differs at the C terminus compared with the other isoforms and lacks the zinc finger FYVE domain. RT-PCR of human brain RNA amplified a single transcript corresponding to ZFYVE27c. Transient transfection of HeLa cells with epitope-tagged ZFYVE27c constructs revealed that ZFYVE27c was predominantly expressed in punctate vesicles, although a tubular pattern of expression was observed in a small proportion of cells. Colocalization studies detected overlapping expression with the endosomal marker EEA1 (605070) and the endoplasmic reticulum marker RTN1 (600865). Chang et al. (2013) reported that protrudin exists in multiple splice forms, all of which encode proteins with 3 hydrophobic segments. The 411-amino acid isoform (GenBank GENBANK NP_653189) contains a RAB-binding domain near its N terminus, followed by 2 closely spaced hydrophobic segments, a third elongated hydrophobic segment, 2 phenylalanines in an acidic tract (FFAT), a coiled-coil domain, and a C-terminal FYVE domain with a zinc-binding motif. The first 2 hydrophobic segments form TM domains, whereas the third hydrophobic segment contains a proline residue (pro200) that bends the segment into an intramembrane hairpin that does not span the bilayer. When expressed within the ER membrane, the RAB-binding, FFAT, coiled-coil, and FYVE domains of protrudin were detected on the cytoplasmic side, with only the short segment between TM1 and TM2 on the luminal side. Protrudin formed oligomers via its N-terminal 92 residues. In transfected HeLa cells, protrudin localized to tubular ER structures, but not to sheet-like ER structures.

GENE STRUCTURE

Mannan et al. (2006) determined that the ZFYVE27 gene consists of 13 exons.

MAPPING

Mannan et al. (2006) noted that the ZFYVE27 gene maps to chromosome 10q24.2.

GENE FUNCTION

Using coimmunoprecipitation studies in NIH3T3 cells, Mannan et al. (2006) found that ZFYVE27c interacted with the N-terminal domain of spastin, which consists of an MIT (microtubule-interacting and trafficking) motif. An immunoprecipitation assay confirmed interaction of endogenous spastin with transfected ZFYVE27c. Shirane and Nakayama (2006) identified protrudin as a mammalian protein that promoted neurite formation through interaction with the guanosine diphosphate (GDP)-bound form of Rab11 (see 605570). Phosphorylation of protrudin by extracellular signal-regulated kinase (ERK; 600997) in response to nerve growth factor (NGFB; 162030) promoted protrudin association with Rab11-GDP. Downregulation of protrudin by RNA interference induced membrane extension in all directions and inhibited neurite formation. Thus, Shirane and Nakayama (2006) concluded that protrudin regulates Rab11-depen ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 610243 was added.

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