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FLASH GENE

Symbol

MICU1

contributors: mct - updated : 26-05-2016

HGNC name	mitochondrial calcium uptake 1
HGNC id	1530

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive liver         Lymphoid/Immune spleen       highly Nervous brain       highly Reproductive female system breast       Respiratory lung         Urinary kidney       highly

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

two canonical EF hands that are essential for its activity, indicating a role in calcium sensing , and are located in the mitochondrial matrix

mono polymer

hexamer

HOMOLOGY

intraspecies

paralog to MICU2

Homologene

FAMILY

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,membrane
text	associated with the mitochondrial inner membrane
	localizes to the mitochondrial matrix side of the inner mitochondrial membrane

basic FUNCTION	required for high-capacity mitochondrial calcium uptake
	could act as a Ca2+ sensor via its two canonical EF hands, and gate the activity of a partner channel
	not involved in LETM1- and UCP2/3-dependent mitochondrial Ca2+ transport in the endothelial cell
	EF-hand-containing protein that serves as a putative regulator of the uniporter
	diminution of MICU1 or MCU reduced mitochondrial Ca(2+) uptake in response to d-glucose, whereas d-glucose-triggered cytosolic Ca(2+) oscillations remained unaffected
	crucial role of MICU1 and MCU in mitochondrial Ca(2+) uptake in pancreatic beta-cells and their involvement in the positive feedback required for sustained insulin secretion
	is a gatekeeper of MCU-mediated Ca(2+)(m) uptake that is essential to prevent [Ca(2+)](m) overload and associated stress
	essential role of MICU1 to control Ca2+m uptake and protect cells against deleterious consequences associated with Ca2+m overload
	is likely a marker for undifferentiated human embryonic stem cells (hESCs) that plays a role in maintaining stemness, cell cycle progression, and proliferation
	MICU1 physically associates with and is co-expressed with a paralog, MICU2
	upon Ca(2+) binding, MICU1 undergoes large conformational changes, resulting in the formation of multiple oligomers to activate MCU
	at higher [Ca(2+)], the stimulatory effect of MICU1 allows the prompt response of mitochondria to Ca(2+) signals generated in the cytoplasm
	key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (SMDT1) forms the mitochondrial Ca(2+) channel
	MICU1 is endowed with a specific inhibitory effect on MCU at low [Ca(2+)]c, separate and kinetically different from that of MICU2
	MICU1 has a double role in MCU regulation, inhibitory at low [Ca(2+)]c and activatory at high [Ca(2+)]c
	is vital for adaptation to postnatal life and for tissue repair after injury

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

Ca(2+)-free MICU1 forms a hexamer that binds and inhibits MCU

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	MCU forms oligomers in the mitochondrial inner membrane, physically interacts with CBARA1, and resides within a large molecular weight complex
	MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca2+ threshold for Ca2+m uptake without affecting the kinetic properties of MCU-mediated Ca2+ uptake
	MICU1 inhibits the mitochondrial Ca2+ channel MCU under resting conditions
	SMDT1 was required for the interaction of MCU with MICU1 and MICU2
	MICU1 interacts with MCU to establish the Ca(2+) threshold for mitochondrial Ca(2+) uptake and MCU activity
	among the interaction partners of CHDCHD4 is MICU1-the regulator of the mitochondrial Ca(2+) uniporter (MCU), which transfers Ca(2+) across the inner membrane
	SMDT1-dependent regulation of MCU channel activity requires intermembrane space-localized MICU1, MICU2, and cytoplasmic Ca(2+)
	SMDT1 second function is to maintain tight MICU1, MICU2 regulation of the MCU pore, a role that requires SMDT1 to bind MICU1 using its conserved C-terminal polyaspartate tail

cell & other

REGULATION

Other

both MICU1 and MICU2 are regulated by calcium through their EF-hand domains, thus accounting for the sigmoidal response of MCU to [Ca(2+)] in situ and allowing tight physiological control

ASSOCIATED DISORDERS

corresponding disease(s)

MICU1D

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   results in mitochondrial Ca2+ overload

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS