Reaction: VRK1/VRK2 phosphorylate BANF1
- in pathway: Nuclear Envelope Breakdown
In mitotic prophase, chromatin detaches from the nuclear envelope, and this contributes to the nuclear envelope breakdown. VRK1 (and possibly VRK2) mediated phosphorylation of BANF1 (BAF), a protein that simultaneously interacts with DNA, LEM-domain inner nuclear membrane proteins, and lamins (Zheng et al. 2000, Shumaker et al. 2001, Haraguchi et al. 2001, Mansharamani and Wilson 2005, Brachner et al. 2005) is considered to be one of the key steps in the detachment of the nuclear envelope from chromatin (Bengtsson and Wilson 2006, Nichols et al. 2006, Gorjanacz et al. 2007).
BANF1 (BAF i.e. barrier-to-autointegration factor) is a DNA-binding protein that was initially discovered as a regulator of retroviral integration (Lee and Craigie 1994, Lee and Craigie 1998). BANF1 (BAF) binds DNA non-specifically as a homodimer (Zheng et al. 2000). Proteins of the inner nuclear membrane that possess a LEM domain, TMPO (LAP2beta), EMD (emerin), LEMD3 (MAN1) and LEMD2 (LEM2), form three-way complexes with BANF1 and lamins - intermediary filaments of the nucleoplasm (Shumaker et al. 2001, Holaska et al. 2003, Mansharamani and Wilson 2005, Brachner et al. 2005). These complexes are thought to be important for the structure of the nuclear lamina and also enable attachment of chromatin to the nuclear envelope (Haraguchi et al. 2001, Dechat et al. 2004).
In mitosis, VRK1 (and to a lesser extent VRK2) serine/threonine kinase phosphorylates BANF1 (BAF) on serine residue S4 and threonine residues T2 and T3 (Nichols et al. 2006, Gorjanacz et al. 2007, Asencio et al. 2012). Only VRK2 isoform VRK2-2 which can localize to the nucleus (Blanco et al. 2006) is annotated as BANF1 kinase. Phosphorylated BANF1 (BAF) dissociates from chromatin and the inner nuclear membrane proteins (Bengtsson and Wilson 2006), allowing chromatin to detach from the nuclear envelope.
VRK1 and VRK2 are autophosphorylated but not all autophosphorylation sites have been mapped and the impact of autophosphorylation on catalytic activity has not been determined.
BANF1 (BAF i.e. barrier-to-autointegration factor) is a DNA-binding protein that was initially discovered as a regulator of retroviral integration (Lee and Craigie 1994, Lee and Craigie 1998). BANF1 (BAF) binds DNA non-specifically as a homodimer (Zheng et al. 2000). Proteins of the inner nuclear membrane that possess a LEM domain, TMPO (LAP2beta), EMD (emerin), LEMD3 (MAN1) and LEMD2 (LEM2), form three-way complexes with BANF1 and lamins - intermediary filaments of the nucleoplasm (Shumaker et al. 2001, Holaska et al. 2003, Mansharamani and Wilson 2005, Brachner et al. 2005). These complexes are thought to be important for the structure of the nuclear lamina and also enable attachment of chromatin to the nuclear envelope (Haraguchi et al. 2001, Dechat et al. 2004).
In mitosis, VRK1 (and to a lesser extent VRK2) serine/threonine kinase phosphorylates BANF1 (BAF) on serine residue S4 and threonine residues T2 and T3 (Nichols et al. 2006, Gorjanacz et al. 2007, Asencio et al. 2012). Only VRK2 isoform VRK2-2 which can localize to the nucleus (Blanco et al. 2006) is annotated as BANF1 kinase. Phosphorylated BANF1 (BAF) dissociates from chromatin and the inner nuclear membrane proteins (Bengtsson and Wilson 2006), allowing chromatin to detach from the nuclear envelope.
VRK1 and VRK2 are autophosphorylated but not all autophosphorylation sites have been mapped and the impact of autophosphorylation on catalytic activity has not been determined.
Reaction - small molecule participants:
ADP [nucleoplasm]
ATP [nucleoplasm]
Reactome.org reaction link: R-HSA-2993898
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
ADP(3-)
Reactome.org link: R-HSA-2993898