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Mitochondrial dynamics protein MID49

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Protein-coding gene in the species Homo sapiens
MIEF2
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

4WOY

Identifiers
AliasesMIEF2, SMCR7, mitochondrial elongation factor 2, MID49, COXPD49
External IDsOMIM: 615498; MGI: 2144199; HomoloGene: 27354; GeneCards: MIEF2; OMA:MIEF2 - orthologs
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)
Chromosome 17 (human)Genomic location for MIEF2Genomic location for MIEF2
Band17p11.2Start18,260,597 bp
End18,266,552 bp
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)
Chromosome 11 (mouse)Genomic location for MIEF2Genomic location for MIEF2
Band11|11 B2Start60,619,224 bp
End60,623,777 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • muscle of thigh

  • apex of heart

  • gastrocnemius muscle

  • left ventricle

  • skeletal muscle tissue

  • gonad

  • prefrontal cortex

  • human kidney

  • left adrenal gland

  • right adrenal gland
Top expressed in
  • knee joint

  • muscle of thigh

  • skeletal muscle tissue

  • quadriceps femoris muscle

  • gastrocnemius muscle

  • tibialis anterior muscle

  • ankle

  • temporal muscle

  • sternocleidomastoid muscle

  • medial head of gastrocnemius muscle
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

125170

237781

Ensembl

ENSG00000284495
ENSG00000177427

ENSMUSG00000018599

UniProt

Q96C03

Q5NCS9

RefSeq (mRNA)

NM_148886
NM_001144900
NM_139162

NM_001009927

RefSeq (protein)

NP_001138372
NP_631901
NP_683684

NP_001009927

Location (UCSC)Chr 17: 18.26 – 18.27 MbChr 11: 60.62 – 60.62 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Mitochondrial elongation factor 2 is a protein that in humans is encoded by the MIEF2 gene.

MID49 Protein Structure

The MID49 protein is used to assist in mitochondrial binary fission. It is a dynamic peripheral protein receptor found on the surface of the mitochondrial membrane. MID51 is a very similar protein and studies have shown that it has a variant nucleotidyl transferase structure which allows it to move phosphates as a co-factor. This structure and ability is essential because it allows it to interact with ADP which will activate the Drp1 protein. Further studies have shown that MID49 and MID51 are homologous in sequence and MID49 also has a nucleotidyl transferase domain but it is still unknown if MID49 can also bind a co-factor. Instead of a co-factor ligand, it was found that MID49 has a loop structure on its surface that allows it to physically interact with the Drp1 protein. To recap, the MID51 and MID49 are both similar proteins that recruit Drp1 protein to induce mitochondrial binary fission but they have small differences in structure which allows them to bind Drp1 in different ways.

MID49 Protein's Role in Mitochondrial Binary Fission

The MID49 peripheral protein will attract the Drp1 to the surface of the mitochondrial membrane which then induces endoplasmic reticulum contact. The ER then releases Ca2+ into the mitochondria once there is physical contact at the membrane. The influx of calcium induces a constriction response in the mitochondria. With this constriction in the middle, the MID49 keeps recruiting more and more Drp1 proteins to make a sort of chain structure to wrap around that narrowed area called the oligomeric ring. The Drp1 proteins will eventually disassociate with the MID49 proteins through hydrolysis which causes a much tighter constriction around the mitochondria. There are still studies being done to confirm if this constriction alone will then split the mitochondria in the middle to complete a binary fission event.

Function

This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. .

References

  1. ^ ENSG00000177427 GRCh38: Ensembl release 89: ENSG00000284495, ENSG00000177427Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000018599Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: Mitochondrial elongation factor 2". Retrieved 2018-04-01.
  6. Losón, Oliver C; Meng, Shuxia; Ngo, Huu; Liu, Raymond; Kaiser, Jens T; Chan, David C (March 2015). "Crystal structure and functional analysis of MiD49, a receptor for the mitochondrial fission protein Drp1". Protein Science. 24 (3): 386–394. doi:10.1002/pro.2629. ISSN 0961-8368. PMC 4353364. PMID 25581164.
  7. Fenton, Adam R.; Jongens, Thomas A.; Holzbaur, Erika L. F. (2021-02-01). "Mitochondrial dynamics: Shaping and remodeling an organelle network". Current Opinion in Cell Biology. Cell Architecture. 68: 28–36. doi:10.1016/j.ceb.2020.08.014. ISSN 0955-0674. PMC 7925334. PMID 32961383.

(Updated 2 and 3 reference list)

2. Losón, Oliver C; Meng, Shuxia; Ngo, Huu; Liu, Raymond; Kaiser, Jens T; Chan, David C (2015–3). "Crystal structure and functional analysis of MiD49, a receptor for the mitochondrial fission protein Drp1". Protein Science.

3. Fenton, Adam R.; Jongens, Thomas A.; Holzbaur, Erika L. F. (2021-02-01). "Mitochondrial dynamics: Shaping and remodeling an organelle network". Current Opinion in Cell Biology. Cell Architecture. 68: 28–36.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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