PPEF2

protein phosphatase with EF-hand domain 2

Tier: Gold Standard Ciliary Genes

Ensembl:
ENSG00000156194
UniProt:
O14830
OMIM:
602256
Synonyms:
PPP7CB

Cilia effects upon perturbation of PPEF2

Cilia number / % ciliated:
Decreased cilia number
Loss-of-function effect:
Shorter cilia

Ciliogenesis screen results (4 screens)

  • Kim2016: Not Reported
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.65) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Ciliopathy associations

  • Nonsyndromic Tetralogy of Fallot

References: PMID:41071877

Subcellular localization

cilia

References: PMID:39550471, PMID:41071877

Functional category

  • Ciliary assembly/disassembly
  • Actin & cytoskeleton regulation
  • Protein processing & maturation
  • Signaling (Hedgehog, GPCRs, ion channels)

Function

In C. elegans, the PEF-1 protein (ortholog of human PPEF1/PPEF2) localizes inside cilia, and pef-1 mutants show structural cilia defects (microtubule degeneration) and functional cilia defects (impaired chemosensation, thermosensation, light, and CO₂ response) (PMID: 39550471). We first examined the subcellular localization of these ciliary genes in both mouse embryonic fibroblasts (MEFs) and E10.5 mouse OFTs. Immunofluorescence staining analysis revealed that Mlf1 and Pkhd1l1 colocalized with acetylated α-tubulin and specifically accumulated in cilia axonemes, Sptbn5 colocalized with both acetylated α-tubulin and γ-tubulin along the entire cilia, Ppef2 and Tekt3 were localized to basal bodies of cilia, and Agbl2 was located at the base of cilia and overlapped with Nek2, a marker of centriole (Fig. 5A and fig. S16). ). Ultrastructural analysis using TEM further revealed that Pkhd1l1−/− mouse OFT tissues displayed severely disorganized ciliary axonemes, with microtubule loss and irregular ciliary distribution and orientation, compared to the typical 9+0 microtubule arrangement in wild-type Pkhd1l1+/+ mice (Fig. 3, I and J). Thus, these findings highlight the critical role of ciliary genes in ciliogenesis and their essential function located in cardiac OFT development. (41071877)