TIMMDC1

TIMMDC1
Identifiers
Aliases	TIMMDC1, C3orf1, translocase of inner mitochondrial membrane domain containing 1, MC1DN31
External IDs	OMIM: 615534; MGI: 1922139; HomoloGene: 9578; GeneCards: TIMMDC1; OMA:TIMMDC1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q13.33 Start 119,498,547 bp[1] End 119,525,090 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B4 Start 38,318,709 bp[2] End 38,343,025 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in myocardium of left ventricle cardiac muscle tissue of right atrium deltoid muscle tibialis anterior muscle quadriceps femoris muscle vastus lateralis muscle right ventricle skin of arm apex of heart biceps brachii Top expressed in gastrula muscle of thigh Gonadal ridge skeletal muscle tissue medullary collecting duct cumulus cell soleus muscle myocardium of ventricle intercostal muscle renal corpuscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component integral component of membrane mitochondrial inner membrane membrane mitochondrion mitochondrial membranes nucleoplasm nucleus Biological process mitochondrial respiratory chain complex I assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51300 76916 Ensembl ENSG00000113845 ENSMUSG00000002846 UniProt Q9NPL8 Q8BUY5 RefSeq (mRNA) NM_016589 NM_024273 RefSeq (protein) NP_057673 NP_077235 Location (UCSC) Chr 3: 119.5 – 119.53 Mb Chr 16: 38.32 – 38.34 Mb PubMed search [3] [4]
Wikidata
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TIMMDC1 is a protein that in humans is encoded by the TIMMDC1 gene.^[5][6] It is a chaperone protein involved in constructing the membrane arm of mitochondrial Complex I.^[7] A frameshift mutation in an intron of this gene has been shown to cause failure to thrive, retardation of psychomotor development, infantile-onset hypotonia, and severe neurologic dysfunction.^[8] High expression of this gene has been associated with migration of lung cancer cells while depletion of the protein has been shown to affect regulation of apoptosis, the cell cycle, and cell migration.^[9]

Structure

The TIMMDC1 gene is located on the q arm of chromosome 3 in position 13.33 and spans 25,760 base pairs, with 7 exons.^[6] The gene produces a 32.2 kDa protein composed of 285 amino acids.^[10][11] The TIMMDC1 protein has 4 transmembrane domains, with the N-terminal and C-terminal extensions localized in the mitochondrial matrix. TIMMDC1 is a multipass mitochondrial inner membrane protein, predicted to be a member of the 4-pass transmembrane protein family of TIM17-TIM22-TIM23. Its topology is predicted to be analogous to TIMM23.^[12]

Function

TIMMDC1 is a chaperone protein involved in the assembly of the mitochondrial Complex I (NADH-ubiquinone oxidoreductase), participating in the construction of the membrane arm of complex I.^[7]

Clinical Significance

A frameshift mutation in intron 5 of the TIMMDC1 gene has been shown to cause severe neurologic dysfunction, infantile-onset hypotonia, retardation of psychomotor development, and failure to thrive.^[8] Additionally, high expression of TIMMDC1 has been associated with metastasis of lung carcinoma cells, with depletion of the protein inhibiting growth and migration of 95D lung carcinoma cells. Depletion of TIMMDC1 has also been shown to alter expression of genes involved in the regulation of apoptosis, cell-cycle arrest, and cell migration, including CCNG2, PTEN, TIMP3, and COL3A1.^[9]

Interactions

The TIMMDC1 protein interacts with the intermediate 315 kDa subcomplex of incompletely assembled complex I and has interactions with FATE1, in addition to about 60 other proteins.^[13][7] TIMMDC1 associates reciprocally with multiple components of the ECSIT-TMEM126B-ACAD9-NDUFAF1 assembly factor complex (MCIA complex).^[12]

References

External links

• Human TIMMDC1 genome location and TIMMDC1 gene details page in the UCSC Genome Browser.

Further reading