[F-actin]-monooxygenase MICAL3 (MICAL3)
The protein contains 2002 amino acids for an estimated molecular weight of 224295 Da.
Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs11913706 | |
| dbSNP:rs2289719 | |
| dbSNP:rs5992128 |
No binding partner found
Biological Process
Actin cytoskeleton organization
Actin filament depolymerization
Cell cycle
Cell division
Cytoskeleton organization
Exocytosis
Oxidation-reduction process
The reference OMIM entry for this protein is 608882
Microtubule-associated monooxygenase, calponin and lim domains-containing, 3; mical3
Flavoprotein oxidoreductase mical3
Kiaa1364
CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned MICAL3, which they designated KIAA1364. The transcript contains several C-terminal repetitive elements. RT-PCR ELISA detected intermediate expression in adult brain, lung, liver, kidney, testis, ovary, fetal liver, and most specific brain regions examined. Lower levels were detected in heart and fetal brain, and little to no expression was detected in skeletal muscle, pancreas, and spleen. Terman et al. (2002) reported that all members of the evolutionarily conserved MICAL family of proteins have an N-terminal monooxygenase domain containing flavin adenine dinucleotide (FAD)-binding motifs, followed by a calponin (see 600806) homology domain, a LIM domain, and an ERM alpha domain (see 123900)-like coiled-coil motif. In situ hybridization of rat brain detected Mical3 expression in spinal cord, dorsal root ganglia, and sympathetic ganglia at embryonic days 15 and 18. The expression patterns of Mical1 (607129), Mical2 (608881), and Mical3 appeared to overlap but were distinct. By database analysis, Li et al. (2015) identified at least 19 possible MICAL3 transcripts, not all of which encode proteins.GENE FUNCTION
Li et al. (2015) identified 7 putative PAX5 (167414)-binding sites upstream of the distal promoter (P1) of MICAL3. Using reporter gene assays and chromatin immunoprecipitation analysis, they found that PAX5 directly upregulated expression of an MICAL3 reporter via binding to the 3 binding sites nearest to the MICAL3 transcriptional start site. In human endothelial cells, PAX5 also upregulated expression of the precursor for microRNA-648 (MIR648; 616205), which arises from intron 1 of the MICAL3 gene. Placental growth factor (PGF; 601121) downregulated expression of both MICAL3 and the MIR648 precursor in endothelial cells by downregulating PAX5.GENE STRUCTURE
Li et al. (2015) determined that the MICAL3 upstream region contains at least 3 putative promoters and that intron 1 is host to MIR648. They identified binding sites for several transcription factors, including PAX5, SMAD3 (603109), HNF3A (FOXA1; 602294), and HNF4A (600281), upstream of the distal promoter (P1).MAPPING
By radiation hybrid analysis, Nagase et al. (2000) mapped the MICAL3 gene to chromosome 22. Hartz (2015) mapped the MICAL3 gene to chromosome 22q11.21 based on an alignment of the MICAL3 sequence (GenBank GENBANK AB037785) with the genomic sequence (GRCh38). ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 608882 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).