nuclear-interacting partner of ALK; nuclear-interacting partner of anaplastic lymphoma kinase; hNIPA; zinc finger C3HC-type protein 1 (ZC3HC1, NIPA, HSPC216)
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Function
- ubiquitin conjugation, 3rd step
- component of SCF(NIPA) E3 ubiquitin-protein ligase complex (unless phosphorylated on Ser-354)
- its cell-cycle-dependent phosphorylation regulates assembly of the SCF(NIPA) complex, restricting CCNB1 (cyclin B1) ubiquitinationactivity to interphase
- its inactivation results in nuclear accumulation of CCNB1 in interphase & premature mitotic entry
- may have an antiapoptotic role in NPM-ALK-mediated signaling events
- protein modification; protein ubiquitination
- phosphorylated on Ser at G2/M phase,
- not phosphorylated on Ser during S phase & G0 phases
- may be weakly phosphorylated on Tyr
- Ser-354 phosphorylation results in its dissociation from the SCF(NIPA) complex, thus preventing CCNB1 degradation, leading to mitotic entry
- interacts with the NPM-ALK fusion protein (phospho-Tyr dependent)
- interacts with SKP1, CCNB1
Structure
- the F-box-like region is required for the interaction with SKP1 (does not contain F-box domain)
- contains 1 C3HC-type Zn+2 finger
Compartment
Alternative splicing
named isoforms=3
Expression
- widely expressed
- highly expressed in heart, skeletal muscle & testis
- expressed in brain, placenta, lung, kidney, liver, pancreas, spleen, thymus, prostate, ovary small intestine & colon
- weakly or not expressed in leukocytes
- weakly expressed in G0/G1 phases
- abundant during S phase & G2/M phases
- decreases after G2/M phase