| IMMT | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | IMMT, HMP, MINOS2, P87, P87/89, P89, PIG52, Mic60, PIG4, inner membrane mitochondrial protein, MICOS60, mitofilin | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 600378 MGI: 1923864 HomoloGene: 38234 GeneCards: IMMT | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Mitochondrial inner membrane protein is a protein that in humans is encoded by the IMMT gene.[5][6][7])
IMMT encodes an inner mitochondrial membrane (IMM) protein in the nucleus. It is posttranslational transported to the IMM. Mic60/Mitofilin (encoded by the IMMT gene) is a core subunit of the MICOS-complex, directly located next to cristae junctions (CJ). Human Mic60 exists in two isoforms of different size, anchored to the IMM via its N-terminus, while most of the protein is located to the inner mitochondrial space (IMS).
Function
Mic60 is evolutionary one of the oldest MICOS subunits as homologous were found in anaerobic prokaryotes. It is mainly present in two isoforms (ca. 88 and 90 kDa). In the brain, four isoforms are known, which differ in their isoelectric point due to different post-translational modifications. The amino terminus of Mic60 is anchored in the IM, while most of the protein is extended to the IMS. C-terminal Mic60 has a conserved mitofilin domain which is crucial for building the MICOS-complex. A central coiled-coil domain is required to enable protein-protein interactions.
Interactions
Mic60 indirectly interacts with all known MICOS-complex and SAM complex components. It directly interacts with Mic25, Mic19 and SAM50. Together with Mic25 and Mic19, Mic60 forms the Mic60-Mic19-Mic25 subcomplex. This subcomplex, especially Mic60, is crucial for the physical contact between the IMM and the outer mitochondrial membrane (OMM) via its interaction with SAM50. Mic60 also interacts with the translocase of the OMM (TOM) and the translocase of the IMM (TIM) to ensure the localization of Mic60 near to CJs. Through its interaction with TOM and TIM, Mic60 additionally influences the import of precursor proteins.
Localisation/Import
Mic60 is translated in the cytosol and translocated into the IMS via TOMM40. TIMM23 transports Mic60 into the IM, where a mitochondrial processing peptidase (MPP) cleaves of the N-terminal mitochondrial targeting signal (MTS). Mic60 is anchored in the IMM through its transmembrane (TM) domain.
Interactions
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000132305 - Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000052337 - Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Gieffers C, Korioth F, Heimann P, Ungermann C, Frey J (May 1997). "Mitofilin is a transmembrane protein of the inner mitochondrial membrane expressed as two isoforms". Experimental Cell Research. 232 (2): 395–399. doi:10.1006/excr.1997.3539. PMID 9168817.
- ↑ Icho T, Ikeda T, Matsumoto Y, Hanaoka F, Kaji K, Tsuchida N (July 1994). "A novel human gene that is preferentially transcribed in heart muscle". Gene. 144 (2): 301–306. doi:10.1016/0378-1119(94)90394-8. PMID 8039717.
- ↑ "Entrez Gene: IMMT inner membrane protein, mitochondrial (mitofilin)".
- ↑ Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (January 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–167. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
Further reading
- Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–320. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (September 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–828. doi:10.1101/gr.6.9.807. PMID 8889549.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Liu J, Akoulitchev S, Weber A, Ge H, Chuikov S, Libutti D, et al. (February 2001). "Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum". Cell. 104 (3): 353–363. doi:10.1016/S0092-8674(01)00223-9. PMID 11239393. S2CID 16066683.
- Bernert G, Fountoulakis M, Lubec G (December 2002). "Manifold decreased protein levels of matrin 3, reduced motor protein HMP and hlark in fetal Down's syndrome brain". Proteomics. 2 (12): 1752–1757. doi:10.1002/1615-9861(200212)2:12<1752::AID-PROT1752>3.0.CO;2-Y. PMID 12469345. S2CID 32160196.
- Millar JK, Christie S, Porteous DJ (November 2003). "Yeast two-hybrid screens implicate DISC1 in brain development and function". Biochemical and Biophysical Research Communications. 311 (4): 1019–1025. doi:10.1016/j.bbrc.2003.10.101. PMID 14623284.
- Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (January 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–167. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
- Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, et al. (September 2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease". Molecular Cell. 15 (6): 853–865. doi:10.1016/j.molcel.2004.09.016. PMID 15383276.
- John GB, Shang Y, Li L, Renken C, Mannella CA, Selker JM, et al. (March 2005). "The mitochondrial inner membrane protein mitofilin controls cristae morphology". Molecular Biology of the Cell. 16 (3): 1543–1554. doi:10.1091/mbc.E04-08-0697. PMC 551514. PMID 15647377.
- Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, et al. (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–968. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
- Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–814. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
- Camargo LM, Collura V, Rain JC, Mizuguchi K, Hermjakob H, Kerrien S, et al. (January 2007). "Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia". Molecular Psychiatry. 12 (1): 74–86. doi:10.1038/sj.mp.4001880. PMID 17043677.
- Xie J, Marusich MF, Souda P, Whitelegge J, Capaldi RA (July 2007). "The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11". FEBS Letters. 581 (18): 3545–3549. doi:10.1016/j.febslet.2007.06.052. PMID 17624330. S2CID 726629.