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While the mitochondrial genome encodes a handful of proteins, most of the hundreds of proteins that reside in the mitochondrion are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria via a series of complex molecular machines (see 5, 8 for review). Many of the proteins imported into mitochondria are involved in respiration, which is not an essential process: S. cerevisiae is able to carry out either fermentative growth on carbon sources such as glucose, or respiratory growth on nonfermentable carbon sources such as glycerol and ethanol. However, since maintenance of the mitochondrial compartment is essential to life, mutations that completely disrupt mitochondrial import are lethal.About the TIM23 complex

The Translocase of the Inner Mitochondrial membrane (TIM23 complex) receives proteins from the Translocase of the Outer Mitochondrial membrane (TOM complex) and either directs them into the mitochondrial matrix or facilitates their integration into the mitochondrial inner membrane (reviewed in 6, 8, 10). The membrane-embedded core of the complex is composed of three essential proteins: Tim23p, Tim17p, and Tim50p. Tim23p and Tim17p, which share sequence similarity, comprise the twin-pore structure through which precursor proteins translocate. Tim23p alone has the ability to form a voltage-sensitive channel (13), but Tim17p is required in vivo for maintenance of the twin-pore architecture and for normal function of the pore (15). Tim17p also has a role in sorting incoming proteins to the mitochondrial matrix or the inner membrane (1). Tim50p interacts with precursor proteins and with Tim23p to guide precursors from the TOM complex to the TIM23 complex (19, 20). Two additional non-essential components, Tim21p and Pam17p, interact with the core of the TIM23 complex and may modulate its activity (1, 2, 14).Proteins destined for the mitochondrial matrix require the action of a sub-complex of the TIM23 complex, known as the import motor or presequence translocase-associated motor (PAM) complex. Its catalytic component is Ssc1p, a member of the heat shock 70 protein family commonly referred to as mtHsp70, which undergoes cycles of binding and release of the precursor, hydrolyzing ATP and changing conformation in the process. The nucleotide release factor Mge1p promotes this cycle by facilitating the dissociation of ADP from Ssc1p (7, 9). Other components include Tim44p, an essential subunit that mediates the association of the core TIM23 complex with the PAM complex (11, 14); Pam18p (Tim14p), a J-protein cochaperone that stimulates the ATPase activity of Ssc1p; and Pam16p (Tim16p), a J-like protein that binds to Pam18p and regulates its activity (16). Pam17p mediates the association between Pam16p and Pam18p (17). Once imported proteins reach the mitochondrial matrix, their correct folding is facilitated by a soluble complex consisting of Ssc1p and its cochaperones Mdj1p and Mge1p (18). A subset of proteins destined for insertion into the mitochondrial inner membrane is translocated via the TIM23 complex but then inserted laterally into the inner membrane rather than entering the mitochondrial matrix. This mechanism is currently not understood in detail. The TIM23 complex adopts different conformations during the two kinds of import, but it is unclear whether this inner membrane import is accomplished by the core complex alone (Tim23p, Tim17p, and Tim50p), or by the entire TIM23 complex including the import motor subunits (6, 2).About TIM21

TIM21 encodes a conserved but nonessential subunit of the TIM23 complex. The tim21 null mutant is viable and does not display any growth defects under normal conditions, but respiratory growth defects are apparent at high temperatures, and both respiratory and fermentative growth are slower under conditions of reduced mitochondrial membrane potential (3, 1, 4). Tim21p is an integral protein of the mitochondrial inner membrane, with a small N-terminal domain extending into the matrix and a C-terminal domain in the intermembrane space (3, 1). It interacts with the TIM23 complex core subunits, with TOM complex subunits, and with respiratory chain enzymes (3, 1, 12). The role of Tim21p in import is not clear. One model proposes that the TIM23 complex exists either in an inner membrane import-competent form containing Tim21p but not the PAM complex, or in a matrix import-competent form lacking Tim21p and associated with the PAM complex, suggesting that Tim21p binding facilitates the inner membrane import pathway (12). An alternative model suggests that Tim21p and the PAM complex are both associated with the TIM23 core complex at all times, and that Tim21p and Pam17p may have opposing regulatory effects on import (2).", "date_edited": "2009-08-06"}, "literature_overview": {"primary_count": 19, "additional_count": 40, "review_count": 31, "go_count": 6, "phenotype_count": 3, "disease_count": 0, "interaction_count": 50, "regulation_count": 5, "ptm_count": 0, "funComplement_count": 0, "htp_count": 15, "total_count": 139}, "disease_overview": {"manual_disease_terms": [], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": null}, "ecnumbers": [], "URS_ID": null, "main_strain": "S288C", "regulation_overview": {"regulator_count": 5, "target_count": 0}, "reference_mapping": {"533004": 1, "475867": 2, "501897": 3, "498341": 4, "484329": 5, "469940": 6, "636958": 7, "475882": 8, "552329": 9, "477306": 10, "536105": 11, "488662": 12, "564516": 13, "489586": 14, "471021": 15, "508413": 16, "523434": 17, "628239": 18, "475888": 19, "475885": 20}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: TIM21", "date_created": "2005-04-04", "references": [{"id": 533004, "display_name": "Chacinska A, et al. (2005)", "citation": "Chacinska A, et al. (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120(6):817-29", "pubmed_id": 15797382, "link": "/reference/S000081217", "year": 2005, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/j.cell.2005.01.011"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/15797382"}]}]}, {"category": "Nomenclature history", "history_type": "LSP", "note": "Nomenclature history: FMP17 was a reserved name for YGR033C from September 2003 to April 2005. The reservation was removed at the request of the author, and the FMP17 gene name has been retired.", "date_created": "2005-04-04", "references": []}], "complexes": [{"format_name": "CPX-6127", "display_name": "TIM23 mitochondrial inner membrane pre-sequence translocase complex, sort variant"}]}, tabs: {"id": 1269489, "protein_tab": true, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": true, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": true, "disease_tab": false} }; TIM21 | SGD

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TIM21 / YGR033C Overview

Standard Name
TIM21 1
Systematic Name
YGR033C
SGD ID
SGD:S000003265
Feature Type
ORF , Verified
Description
Nonessential component of the TIM23 complex; interacts with the Translocase of the Outer Mitochondrial membrane (TOM complex) and with respiratory enzymes; may regulate the Translocase of the Inner Mitochondrial membrane (TIM23 complex) activity 1 2 3 4
Name Description
Translocase of the Inner Mitochondrial membrane 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.

Analyze Sequence

S288C only

BLASTN | BLASTP | Design Primers | Restriction Fragment Map | Restriction Fragment Sizes | Six-Frame Translation

S288C vs. other species

BLASTN vs. fungi | BLASTP at NCBI | BLASTP vs. fungi

S288C vs. other strains

Strain Alignment | Variant Viewer

Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.

Length (a.a.)
239
Mol. Weight (Da)
27228.0
Isoelectric Point
10.78
Median Abundance (molecules/cell)
2644 +/- 1005
Half-life (hr)
7.3

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.

View all TIM21 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.

Summary
Subunit of TIM23 mitochondrial import inner membrane translocase complex which imports proteins that possess a matrix-targeting N-terminal presequence into the mitochondrial matrix

View computational annotations

Molecular Function

Manually Curated

Biological Process

Manually Curated

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.

Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.

Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.

263 total interactions for 184 unique genes

Physical Interactions

  • Affinity Capture-MS: 16
  • Affinity Capture-RNA: 8
  • Affinity Capture-Western: 63
  • Co-crystal Structure: 1
  • Co-fractionation: 1
  • Co-localization: 1
  • Co-purification: 8
  • Reconstituted Complex: 9

Genetic Interactions

  • Dosage Growth Defect: 2
  • Dosage Rescue: 1
  • Negative Genetic: 134
  • Phenotypic Suppression: 1
  • Positive Genetic: 17
  • Synthetic Lethality: 1
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.

Regulators
5
Targets
0
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.

Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.

Last Updated: 2009-08-06

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.

Primary
19
Additional
40
Reviews
31

Resources

AlphaFold Protein Structure | Entrez Gene | Entrez RefSeq Protein | FungiDB | Search all NCBI | UniParc | UniProtKB