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0  structures 628  species 0  interactions 3456  sequences 39  architectures

Family: Tim17 (PF02466)

Summary: Tim17/Tim22/Tim23/Pmp24 family

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This is the Wikipedia entry entitled "NADH dehydrogenase (ubiquinone)". More...

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This is the Wikipedia entry entitled "Translocase of the inner membrane". More...

Translocase of the inner membrane Edit Wikipedia article

Tim17/Tim22/Tim23 family
Symbol Tim17
Pfam PF02466
InterPro IPR003397
TCDB 3.A.8
OPM superfamily 303
OPM protein 3awr

The translocase of the inner membrane (TIM) is a complex of proteins found in the inner mitochondrial membrane of the mitochondria. Components of the TIM complex facilitate the translocation of proteins across the inner membrane and into the mitochondrial matrix. They also facilitate the insertion of proteins into the inner mitochondrial membrane, where they must reside in order to function, these mainly include members of the mitochondrial carrier family of proteins.

The TIM complex

The TIM complex facilitates translocation of matrix-targeted proteins into the mitochondrial matrix.[1] These proteins contain a cleavable presequence. The TIM23 complex is made up of the subunits Tim17, Tim21 and Tim23, which are thought to contribute to the structural formation of the translocation channel that spans the inner membrane, and Tim44, which is a peripheral membrane protein.[2] Tim44 is only weakly associated with Tim23 and is located on the matrix side of the inner membrane. At the opening of the TIM17-23 complex, Tim44 recruits mitochondrial heat shock protein 70, which further mediates translocation of the precursor through ATP hydrolysis.[3] Following protein entry into the matrix, the presequence is cleaved off by the matrix processing peptidase and the protein undergoes folding into an active conformation,[4] facilitated by HSP60.

The TIM22 complex

The TIM22 complex is responsible for mediating the integration of carrier preproteins into the inner membrane. Tim22, a subunit of the TIM22 complex, forms a channel within the inner membrane and is referred to as the carrier translocase. Tim54 and the small Tim proteins, Tim9, Tim10 and Tim12 also contribute to the TIM22 complex[5] as well as Tim18. The function of Tim18 is not yet clear; however it is believed to play a role in assembly and stabilisation of the TIM22 complex, although is not involved in protein insertion into the membrane. Tim54, although it does not associate directly with Tim22, is also believed to assist in the stability of Tim22.[6] Unlike cleavable preproteins, following translocation across the outer membrane via the translocase of the outer membrane, carrier preproteins are bound by the soluble Tim9-Tim10 complex of which the majority of this complex (~95%) is free floating within the intermembrane space.[7] It is possible that this small Tim complex is able to stabilise precursor carrier proteins by acting as a chaperone and preventing the hydrophobic precursors from aggregating in the aqueous environment of the intermembrane space.[8] A small portion of Tim9 and Tim10 (~5%) assembles into a modified complex containing Tim12, on the outer surface of the TIM22 complex.[9] Tim12 is membrane bound and thus may act as a linker molecule docking Tim9 and Tim10 to the face of the TIM22 complex.[7] The carrier preprotein is then inserted into the inner mitochondrial membrane in a potential-dependent fashion.[10] The membrane potential is necessary for both insertion of the precursor into the carrier translocase and lateral release of the protein into the lipid phase of the inner mitochondrial membrane, which completes protein translocation. However this membrane potential-dependent process takes place in absence of ATP-driven machinery.[8]


Human proteins containing this domain


See Also


  1. ^ Sirrenberg C, Bauer MF, Guiard B, Neupert W, Brunner M (December 1996). "Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22". Nature 384 (6609): 582–5. doi:10.1038/384582a0. PMID 8955274. 
  2. ^ Dekker PJ, Martin F, Maarse AC, Bömer U, Müller H, Guiard B, Meijer M, Rassow J, Pfanner N (September 1997). "The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44". EMBO J. 16 (17): 5408–19. doi:10.1093/emboj/16.17.5408. PMC 1170172. PMID 9312000. 
  3. ^ Gabriel K, Egan B, Lithgow T (May 2003). "Tom40, the import channel of the mitochondrial outer membrane, plays an active role in sorting imported proteins". EMBO J. 22 (10): 2380–6. doi:10.1093/emboj/cdg229. PMC 155987. PMID 12743032. 
  4. ^ Liu Q, Krzewska J, Liberek K, Craig EA (March 2001). "Mitochondrial Hsp70 Ssc1: role in protein folding". J. Biol. Chem. 276 (9): 6112–8. doi:10.1074/jbc.M009519200. PMID 11096111. 
  5. ^ Paschen SA, Rothbauer U, Káldi K, Bauer MF, Neupert W, Brunner M (December 2000). "The role of the TIM8-13 complex in the import of Tim23 into mitochondria". EMBO J. 19 (23): 6392–400. doi:10.1093/emboj/19.23.6392. PMC 305865. PMID 11101512. 
  6. ^ Mühlenbein N, Hofmann S, Rothbauer U, Bauer MF (April 2004). "Organization and function of the small Tim complexes acting along the import pathway of metabolite carriers into mammalian mitochondria". J. Biol. Chem. 279 (14): 13540–6. doi:10.1074/jbc.M312485200. PMID 14726512. 
  7. ^ a b Gebert N, Chacinska A, Wagner K, Guiard B, Koehler CM, Rehling P, Pfanner N, Wiedemann N (June 2008). "Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase". EMBO Rep. 9 (6): 548–54. doi:10.1038/embor.2008.49. PMC 2427372. PMID 18421298. 
  8. ^ a b Wiedemann N, Frazier AE, Pfanner N (April 2004). "The protein import machinery of mitochondria". J. Biol. Chem. 279 (15): 14473–6. doi:10.1074/jbc.R400003200. PMID 14973134. 
  9. ^ Bolender N, Sickmann A, Wagner R, Meisinger C, Pfanner N (January 2008). "Multiple pathways for sorting mitochondrial precursor proteins". EMBO Rep. 9 (1): 42–9. doi:10.1038/sj.embor.7401126. PMC 2246611. PMID 18174896. 
  10. ^ Endres M, Neupert W, Brunner M (June 1999). "Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex". EMBO J. 18 (12): 3214–21. doi:10.1093/emboj/18.12.3214. PMC 1171402. PMID 10369662. 

See also

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Tim17/Tim22/Tim23/Pmp24 family Provide feedback

The pre-protein translocase of the mitochondrial outer membrane (Tom) allows the import of pre-proteins from the cytoplasm. Tom forms a complex with a number of proteins, including Tim17. Tim17 and Tim23 are thought to form the translocation channel of the inner membrane. This family includes Tim17, Tim22 and Tim23. This family also includes Pmp24 a peroxisomal protein. The involvement of this domain in the targeting of PMP24 remains to be proved. PMP24 was known as Pmp27 in [3].

Literature references

  1. Bomer U, Rassow J, Zufall N, Pfanner N, Meijer M, Maarse AC; , J Mol Biol 1996;262:389-395.: The preprotein translocase of the inner mitochondrial membrane: evolutionary conservation of targeting and assembly of Tim17. PUBMED:8893850 EPMC:8893850

  2. Reguenga C, Oliveira ME, Gouveia AM, Eckerskorn C, Sa-Miranda C, Azevedo JE; , Biochim Biophys Acta. 1999;1445:337-341.: Identification of a 24 kDa intrinsic membrane protein from mammalian peroxisomes. PUBMED:10366717 EPMC:10366717

  3. Marshall PA, Krimkevich YI, Lark RH, Dyer JM, Veenhuis M, Goodman JM; , J Cell Biol. 1995;129:345-355.: Pmp27 promotes peroxisomal proliferation. PUBMED:7721939 EPMC:7721939

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003397

The membrane-embedded multi-protein complexes of mitochondria mediate the transport of nuclear-encoded proteins across and into the outer or inner mitochondrial membranes [PUBMED:15232570]. The TOM (translocase of the outer mitochondrial membrane) complex consists of cytosol-exposed receptors and a pore-forming core, and mediates the transport of proteins from the cytosol across and into the outer mitochondrial membrane. A novel protein complex in the outer membrane of mitochondria, called the SAM complex (sorting and assembly machinery), is involved in the biogenesis of beta-barrel proteins of the outer membrane. Two translocases of the inner mitochondrial membrane (TIM22 and TIM23 complexes) mediate protein transport at the inner membrane.

The TIM23 complex (a presequence translocase) mediates the transport of presequence-containing proteins across and into the inner membrane. Tim23 and Tim17 form part of this complex. Tim23 forms a pore in the inner membrane. The role of Tim17 is not yet fully understood. The TIM22 complex (a twin-pore carrier translocase) catalyses the insertion of multi-spanning proteins that have internal targeting signals into the inner membrane. The TIM22 complex mediates the membrane insertion of multi-spanning inner-membrane proteins that have internal targeting signals, and it uses the membrane potential as an external driving force. The Tim22 subunit of the mitochondrial import inner membrane translocase is included in this family.

This family also includes Pmp24, a peroxisomal membrane protein, and NADH ubiquinone dehydrogenase 1 alpha subunit 11. Pmp24 was previously known as Pmp27 [PUBMED:7721939].

Domain organisation

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Seed source: Pfam-B_2241 (release 5.4) & Pfam-B_7792 (Release 8.0)
Previous IDs: none
Type: Family
Author: Mian N, Bateman A
Number in seed: 460
Number in full: 3456
Average length of the domain: 120.90 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 58.46 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.7 29.7
Trusted cut-off 29.7 29.7
Noise cut-off 29.6 29.6
Model length: 113
Family (HMM) version: 15
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