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6  structures 1080  species 0  interactions 5813  sequences 71  architectures

Family: Tim17 (PF02466)

Summary: Tim17/Tim22/Tim23/Pmp24 family

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

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Tim17/Tim22/Tim23 family
Identifiers
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 TIM23 complex

The TIM23 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]

Subfamilies

Human proteins containing this domain

TIM17A; TIMM17A; TIMM17B; TIMM22; TIMM23;

See also

References

  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 1170172Freely accessible. 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 155987Freely accessible. 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 305865Freely accessible. 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 2427372Freely accessible. 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 2246611Freely accessible. 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 1171402Freely accessible. PMID 10369662. 

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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 [1, 2, 3]. Tim17, Tim22, and Tim23, are the central components of the widely conserved multi-subunit protein translocases, TIM23 and TIM22, which mediate protein transport across and into the inner mitochondrial membrane, respectively [4]. In addition, several Tim17 family proteins occupy the inner and outer membranes of plastids. 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 [3]. Family members are suggested to be exclusive to eukaryotes, where the distribution in the eukaryotic subgroups of the mitochondrial Tim17, Tim22 and Tim23 proteins, as well as the peroxisomal Tim17 family proteins, suggests that they all likely to be present in the last eukaryotic common ancestor (LECA) [4].

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

  4. Zarsky V, Dolezal P;, Biol Direct. 2016;11:54.: Evolution of the Tim17 protein family. PUBMED:27760563 EPMC:27760563


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Domain organisation

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  Seed
(439)
Full
(5813)
Representative proteomes UniProt
(8108)
NCBI
(9122)
Meta
(12)
RP15
(1503)
RP35
(3228)
RP55
(4675)
RP75
(5726)
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  Seed
(439)
Full
(5813)
Representative proteomes UniProt
(8108)
NCBI
(9122)
Meta
(12)
RP15
(1503)
RP35
(3228)
RP55
(4675)
RP75
(5726)
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  Seed
(439)
Full
(5813)
Representative proteomes UniProt
(8108)
NCBI
(9122)
Meta
(12)
RP15
(1503)
RP35
(3228)
RP55
(4675)
RP75
(5726)
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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_2241 (release 5.4) & Pfam-B_7792 (Release 8.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mian N , Bateman A , El-Gebali S
Number in seed: 439
Number in full: 5813
Average length of the domain: 114.80 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 54.14 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 32.7 32.7
Trusted cut-off 32.7 32.7
Noise cut-off 32.6 32.6
Model length: 111
Family (HMM) version: 19
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Tim17 domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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