ZFYVE19
Domain
The FYVE-type zinc finger mediates binding to phosphatidylinositol-3-phosphate (PtdIns(3)P).
The MIM1-B motif mediates interaction with VPS4A.
Function
Key regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. Together with CHMP4C, required to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ZFYVE19/ANCHR and VPS4 and subsequent abscission.
Involvement in disease
A chromosomal aberration involving ZFYVE19 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A/MLL1 (PubMed:12618766).
Cholestasis, progressive familial intrahepatic, 9
PFIC9
An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC9 onset is in infancy or early childhood.
None
The disease is caused by variants affecting the gene represented in this entry. Some evidences point to Met-76 as the main translation initiation site. In this context, PFIC9-associated variant p.M76V can disrupt translation initiation.
Post-translational modifications
Phosphorylated in vitro at Ser-22 by AURKB; however, phosphorylation at this site could not be confirmed in vivo.
Tissue Specificity
Detected in brain, heart, skeletal muscle and kidney (PubMed:12618766). Expressed in the liver (at protein level) (PubMed:12618766, PubMed:32737136).
Cellular localization
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cleavage furrow
- Midbody
- Midbody ring
- Localizes mainly on centrosomes in interphase and early mitosis. Localizes at the cleavage furrow and midbody ring in late mitosis and cytokinesis.
Alternative names
ANCHR, MPFYVE, ZFYVE19, Abscission/NoCut checkpoint regulator, MLL partner containing FYVE domain, Zinc finger FYVE domain-containing protein 19