Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.1.1 (
hexokinase
)
5,274
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
Ran-binding protein 2
(
RanBP2
) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of
RanBP2
have been identified. Yet, the significance of these interactions with
RanBP2
and the genetic and physiological role(s) of
RanBP2
in a whole-animal model remain elusive. Here, we report the identification of two novel partners of
RanBP2
and a novel physiological role of
RanBP2
in a mouse model.
RanBP2
associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis,
hexokinase
type I (HKI) via its leucine-rich domain. The leucine-rich domain of
RanBP2
also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of
RanBP2
in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and
RanBP2
suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of
RanBP2
and its role in HKI function, a mouse model harboring a genetically disrupted
RanBP2
locus was generated.
RanBP2
(-/-) are embryonically lethal, and haploinsufficiency of
RanBP2
in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred
RanBP2
(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence,
RanBP2
and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.
...
PMID:RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism. 1706 63
