Geminin (GMNN)

Gem; Geminin,DNA Replication Inhibitor

SPN	U340
HGNC	17493
MGI	1927344
PubMed	16847348
RGD	1308137
UniProt	O75496
Wiki	Geminin

Geminin is a nuclear protein made up of about 200 amino acids, with a molecular weight of approximately 25 kDa. Geminin is a protein with a potential dual role during the metazoan cell cycle. Geminin was originally identified as an inhibitor of DNA replication and substrate of the anaphase promoting complex (APC). However, geminin also appears to play important roles in the progression of the cell cycle and cell proliferation, and is overexpressed in many cancerous tumors.

Geminin is absent during G₁ phase and accumulates through S, G₂ phase and M phases of the cell cycle. Geminin levels drop at the metaphase / anaphase transition of mitosis when it is degraded by the Anaphase Promoting Complex (APC).Recently, geminin has been found to be overexpressed in several malignancies and cancer cell lines.

Reference

"Geminin, an inhibitor of DNA replication, is degraded during mitosis."
Cell 93:1043-1053(1998) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and analysis of human chromosome 6."
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding."
J. Biol. Chem. 279:19691-19697(2004) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression."
J. Biol. Chem. 286:23234-23246(2011) [PubMed] [Europe PMC] [Abstract]

"Dynamic association of ORCA with prereplicative complex components regulates DNA replication initiation."
Mol. Cell. Biol. 32:3107-3120(2012) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation."
J. Mol. Biol. 342:275-287(2004) [PubMed] [Europe PMC] [Abstract]

"A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition."
Mol. Cell 15:245-258(2004) [PubMed] [Europe PMC] [Abstract]

"Molecular structure of human geminin."
Nat. Struct. Mol. Biol. 11:1021-1022(2004) [PubMed] [Europe PMC] [Abstract]

"Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing."
Proc. Natl. Acad. Sci. U.S.A. 106:19807-19812(2009) [PubMed] [Europe PMC] [Abstract]

"Structural basis for homeodomain recognition by the cell-cycle regulator Geminin."
Proc. Natl. Acad. Sci. U.S.A. 109:8931-8936(2012) [PubMed] [Europe PMC] [Abstract]

"The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing."
J. Biol. Chem. 288:31624-31634(2013) [PubMed] [Europe PMC] [Abstract]