InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MICU1

Summary

InnateDB Protein

IDBP-379535.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MICU1

Protein Name

mitochondrial calcium uptake 1

Synonyms

CALC; CBARA1; EFHA3; MPXPS;

Species

Homo sapiens

Ensembl Protein

ENSP00000402470

InnateDB Gene

IDBG-77896 (MICU1)

Protein Structure

UniProt Annotation

Function

Key regulator of mitochondrial calcium uniporter (MCU) required to increase calcium uptake by MCU when cytoplasmic calcium is high. MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, respectively. MICU1 acts as a stimulator of MCU that senses calcium level via its EF-hand domains: enhances MCU opening at high Ca(2+) concentration, allowing a rapid response of mitochondria to Ca(2+) signals generated in the cytoplasm. Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake. Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG. {ECO:0000269PubMed:16002733, ECO:0000269PubMed:20693986, ECO:0000269PubMed:22904319, ECO:0000269PubMed:23101630, ECO:0000269PubMed:23747253, ECO:0000269PubMed:24313810, ECO:0000269PubMed:24332854, ECO:0000269PubMed:24503055, ECO:0000269PubMed:24560927}.

Subcellular Localization

Mitochondrion inner membrane; Peripheral membrane protein. Mitochondrion intermembrane space. Note=Localizes at the outer surface of the mitochondrion inner membrane.

Disease Associations

Myopathy with extrapyramidal signs (MPXPS) [MIM:615673]: An autosomal recessive disorder characterized by early-onset proximal muscle weakness with a static course and moderately to grossly elevated serum creatine kinase levels accompanied by learning difficulties. Most patients develop subtle extrapyramidal motor signs that progress to a debilitating disorder of involuntary movement with variable features, including chorea, tremor, dystonic posturing and orofacial dyskinesia. Additional variable features include ataxia, microcephaly, ophthalmoplegia, ptosis, optic atrophy and axonal peripheral neuropathy. {ECO:0000269PubMed:24336167}. Note=The disease is caused by mutations affecting the gene represented in this entry. The complex phenotype is due to alterations in mitochondrial calcium signaling characterized by increased mitochondrial Ca(2+) load (PubMed:24336167). {ECO:0000269PubMed:24336167}.

Tissue Specificity

Expressed in epithelial cell lines. Strongly expressed in epidermal keratinocytes and dermal endothelial cells. {ECO:0000269PubMed:16002733, ECO:0000269PubMed:9806765}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.

Experimentally validated
Total	6 [view]
Protein-Protein	5 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0046982	protein heterodimerization activity

Biological Process

GO:0006851	mitochondrial calcium ion transport
GO:0006952	defense response
GO:0036444	calcium ion import into mitochondrion
GO:0051260	protein homooligomerization
GO:0051560	mitochondrial calcium ion homeostasis
GO:0051561	positive regulation of mitochondrial calcium ion concentration
GO:0070509	calcium ion import

Cellular Component

GO:0005622	intracellular
GO:0005743	mitochondrial inner membrane
GO:0005758	mitochondrial intermembrane space
GO:0032592	integral component of mitochondrial membrane
GO:0034704	calcium channel complex
GO:1990246	uniplex complex