| 简介 | This gene encodes a protein that plays a critical role in cell cycle regulation. The encoded protein inhibits DNA replication by binding to DNA replication factor Cdt1, preventing the incorporation of minichromosome maintenance proteins into the pre-replication complex. The encoded protein is expressed during the S and G2 phases of the cell cycle and is degraded by the anaphase-promoting complex during the metaphase-anaphase transition. Increased expression of this gene may play a role in several malignancies including colon, rectal and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and two pseudogenes of this gene are located on the short arm of chromosome 16. [provided by RefSeq, Oct 2011]
Diseases associated with GMNN include Meier-Gorlin Syndrome 6 and Meier-Gorlin Syndrome 1. Among its related pathways are Assembly of the pre-replicative complex and Regulation of activated PAK-2p34 by proteasome mediated degradation. Gene Ontology (GO) annotations related to this gene include transcription corepressor activity and DNA-binding transcription factor binding. An important paralog of this gene is MCIDAS.
Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:14993212, 20129055, 24064211, 9635433).
It is degraded during the mitotic phase of the cell cycle (PubMed:14993212, 24064211, 9635433).
Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle (PubMed:14993212, 24064211, 9635433).
Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055).
Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (PubMed:22615398).
Cytoplasm {ECO:0000269 PubMed:21543332}
Nucleus {ECO:0000269 PubMed:21543332}
Note: Mainly cytoplasmic but can be relocalized to the nucleus {ECO:0000269 PubMed:21543332}
Quaternary structure:
Homotetramer (PubMed:15260975, 15313623, 15378034, 19906994).
Interacts with CDT1; this inhibits binding of the MCM complex to origins of replication (PubMed:14993212, 15260975, 19906994, 21543332).
The complex with CDT1 exists in two forms, a 'permissive' heterotrimer and an 'inhibitory' heterohexamer (PubMed:14993212, 15260975, 19906994).
Interacts (via coiled-coil domain) with IDAS (via coiled-coil domain); this targets GMNN to the nucleus (PubMed:21543332).
The heterodimer formed by GMNN and MCIDAS has much lower affinity for CDT1 than the GMNN homodimer (PubMed:24064211).
Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10 (PubMed:22615398).
Interacts with LRWD1 from G1/S to mitosis (PubMed:22645314). |
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