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 7, 13, 15). 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 (20), but Tim17p is required in vivo for maintenance of the twin-pore architecture and for normal function of the pore (21). Tim17p also has a role in sorting incoming proteins to the mitochondrial matrix or the inner membrane (23). Tim50p interacts with precursor proteins and with Tim23p to guide precursors from the TOM complex to the TIM23 complex (25, 27). Two additional non-essential components, Tim21p and Pam17p, interact with the core of the TIM23 complex and may modulate its activity (23, 14, 18).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 (5, 10). Other components include Tim44p, an essential subunit that mediates the association of the core TIM23 complex with the PAM complex (16, 18); 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 (4). Pam17p mediates the association between Pam16p and Pam18p (22). 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 (26). 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 (7, 14).About PAM16, PAM17, and PAM18 Pam16p and Pam18p are both related to J-proteins, which act as cochaperones for chaperone proteins belonging to the Hsp70 family. Pam18p is considered a J-protein because it has all of the characteristic sequence elements, while Pam16p is \"J-like\" because it lacks the conserved HPD motif (6, 11, 1). Both proteins are constituents of the import motor (PAM) complex, and interact with each other to form a heterodimer (19, 4). Pam18p stimulates the ATPase activity of Ssc1p, which is the catalytic component of the import motor, while Pam16p inhibits the stimulatory activity of Pam18p (24, 19). The localization and role of Pam17p are currently unclear. It is a conserved protein that was identified as a component of the import motor complex (22), but other studies have detected interactions between Pam17p and components of the TIM23 core complex, and not between Pam17p and the import motor subunits (14). It has been proposed that Pam17p mediates association of the Pam16p-Pam18p heterodimer with the TIM23 complex, and alternatively that its role is to modulate the function of the core complex by affecting its conformation (14, 22). In keeping with their proposed roles in the import motor, mutations in all three of the PAM genes affect the ability of the TIM23 complex to import proteins into the mitochondrial matrix, but not its ability to insert proteins into the inner membrane (6, 11, 28, 22). PAM16 and PAM18 are essential genes (19, 4), while a pam17 null mutant is viable but displays a slow respiratory growth phenotype (22).", "date_edited": "2009-08-06"}, "literature_overview": {"primary_count": 36, "additional_count": 38, "review_count": 38, "go_count": 6, "phenotype_count": 6, "disease_count": 0, "interaction_count": 74, "regulation_count": 1, "ptm_count": 2, "funComplement_count": 0, "htp_count": 10, "total_count": 166}, "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": 3, "target_count": 0}, "reference_mapping": {"548660": 1, "548663": 2, "547045": 3, "508413": 4, "636958": 5, "545204": 6, "469940": 7, "484329": 8, "513495": 9, "552329": 10, "545201": 11, "632880": 12, "475882": 13, "475867": 14, "477306": 15, "536105": 16, "542872": 17, "489586": 18, "523437": 19, "564516": 20, "471021": 21, "523434": 22, "533004": 23, "536449": 24, "475888": 25, "628239": 26, "475885": 27, "502091": 28}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: PAM18", "date_created": "2003-07-02", "references": [{"id": 548660, "display_name": "Truscott KN, et al. (2003)", "citation": "Truscott KN, et al. (2003) A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria. J Cell Biol 163(4):707-13", "pubmed_id": 14638855, "link": "/reference/S000074354", "year": 2003, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1083/jcb.200308004"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173675/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/14638855"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: TIM14", "date_created": "2010-02-16", "references": [{"id": 548663, "display_name": "Mokranjac D, et al. (2003)", "citation": "Mokranjac D, et al. (2003) Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria. EMBO J 22(19):4945-56", "pubmed_id": 14517234, "link": "/reference/S000074353", "year": 2003, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1093/emboj/cdg485"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC204468/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/14517234"}]}]}], "complexes": [{"format_name": "CPX-539", "display_name": "TIM23 mitochondrial inner membrane pre-sequence translocase complex, motor variant"}]},
tabs: {"id": 1313236, "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}
};
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.
BLASTN |
BLASTP |
Design Primers |
Restriction Fragment Map |
Restriction Fragment Sizes |
Six-Frame Translation
BLASTN vs. fungi |
BLASTP at NCBI |
BLASTP vs. fungi
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.
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 PAM18 alleles in SGD search
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.
View computational annotations
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 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 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.
362 total interactions for 218 unique genes
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.
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.
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
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.
PAM18 / YLR008C Overview
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S288C vs. other strains
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