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Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, in response to endoplasmic reticulum stress. Negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation. Probable tumor suppressor initially identified as a CDK5R1 interactor controlling cell proliferation. Also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint. Through its interaction with CDKN2A/ARF and MDM2 may induce MDM2-dependent p53/TP53 ubiquitination, stabilization and activation in the nucleus, thereby promoting G1 cell cycle arrest and inhibition of cell proliferation. May also play a role in the rupture of the nuclear envelope during apoptosis. May regulate MAPK14 activity by regulating its dephosphorylation by PPM1D/WIP1. Required for liver development.; (Microbial infection) May be negatively regulated by hepatitis B virus large envelope protein mutant pre-s2 to promote mitotic entry.
Gene References into Functions
CDK5RAP3 negatively regulates the beta-catenin signaling pathway by repressing GSK-3beta phosphorylation in gastric neoplasms. PMID: 27793695
C53/LZAP protein bound indirectly to the microtubule (MT), and expression of the C53/LZAP cleavage product caused abnormal MT bundling and NE rupture. PMID: 23478299
our findings provide the new evidence that overexpression of CDK5RAP3 promotes HCC metastasis via downregulation of p14(ARF). PMID: 22860085
LZAP may play an important role in hepatocellular carcinoma progression PMID: 22028922
our results strongly suggest that the binding of hepatitis viral pre-S2 LHBs with C53 is a novel negative regulator of the checkpoint response PMID: 21971960
Data indicate that IC53 is a positive mediator for colon cancer progression, and IC53-rs2737 may serve as protection from the onset of colorectal cancer. PMID: 21394385
Nuclear gamma-tubulin interacts with tumor suppressor protein C53 that is involved in regulation of DNA damage PMID: 21465471
the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1 PMID: 21283629
Findings reveal that CDK5RAP3 is widely overexpressed in hepatocellular carcinoma and that overexpression of CDK5RAP3 promotes HCC metastasis through PAK4 activation. PMID: 21385901
IC53 is a novel gene, mainly expressed in vascular endothelial cells and mediates cell proliferation PMID: 12054757
results strongly indicate that in response to genotoxic stress, Cdk5 activator-binding protein C53(C53) serves as an important regulatory component of DNA damage checkpoint through modulating cyclin dependent kinase 1-cyclin B1 function PMID: 15790566
It is suggested that LZAP can regulate ARF biochemical and biological activity; additionally, LZAP has p53-dependent cell-cycle effects that are independent of ARF. PMID: 16173922
it is concluded that CDK5RAP3, CCNB2, and RAGE genes may be used as a very reliable biomarkers of lung adenocarcinoma PMID: 17549666
LZAP has a role in NF-kappaB regulation and tumor suppression. PMID: 17785205
CDK5 regulatory subunit associated protein 3 promotes checkpoint kinase 1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response. PMID: 19223857
Endothelium-specific overexpression of human IC53 downregulates endothelial nitric oxide synthase activity and elevates systolic blood pressure in mice. PMID: 19541669
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Subcellular Location
Nucleus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.
Protein Families
CDK5RAP3 family
Tissue Specificity
Ubiquitously expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform 3 is expressed in kidney, liver, skeletal muscle and placenta.