Summary: Mitochondrial ATPase inhibitor, IATP
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ATPIF1 Edit Wikipedia article
|This article is an orphan, as no other articles link to it. (December 2008)|
|ATPase inhibitory factor 1|
|RNA expression pattern|
This gene encodes a mitochondrial ATPase inhibitor. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified.
It prevents ATPase from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation  ATP synthase inhibitor forms a one to one complex with the F1 ATPase, possibly by binding at the alpha-beta interface. It is thought to inhibit ATP synthesis by preventing the release of ATP. The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH, the inhibitor forms a dimer via antiparallel coiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity.
 Model organisms
|Glucose tolerance test||Normal|
|Auditory brainstem response||Normal|
|Peripheral blood lymphocytes||Normal|
|All tests and analysis from|
Model organisms have been used in the study of ATPIF1 function. A conditional knockout mouse line, called Atpif1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice and three significant abnormalities were observed. Homozygous mutant animals displayed hyperactivity and brain dysmorphology, while males also had decreased circulating alkaline phosphatase levels.
|c-terminal coiled-coil domain from bovine if1|
- Ichikawa N, Ushida S, Kawabata M, Masazumi Y (Mar 2000). "Nucleotide sequence of cDNA coding the mitochondrial precursor protein of the ATPase inhibitor from humans". Biosci Biotechnol Biochem 63 (12): 2225–2227. DOI:10.1271/bbb.63.2225. PMID 10664857.
- "Entrez Gene: ATPIF1 ATPase inhibitory factor 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=93974.
- Cabezon E, Butler PJ, Runswick MJ, Carbajo RJ, Walker JE (November 2002). "Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F-ATPases". J. Biol. Chem. 277 (44): 41334–41. DOI:10.1074/jbc.M207169200. PMID 12186878.
- van Raaij MJ, Orriss GL, Montgomery MG, Runswick MJ, Fearnley IM, Skehel JM, Walker JE (December 1996). "The ATPase inhibitor protein from bovine heart mitochondria: the minimal inhibitory sequence". Biochemistry 35 (49): 15618–25. DOI:10.1021/bi960628f. PMID 8961923.
- "Anxiety data for Atpif1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MCEQ/open-field/.
- "Clinical chemistry data for Atpif1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MCEQ/plasma-chemistry/.
- "Salmonella infection data for Atpif1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MCEQ/salmonella-challenge/.
- "Citrobacter infection data for Atpif1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MCEQ/citrobacter-challenge/.
- Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. DOI:10.1111/j.1755-3768.2010.4142.x.
- Mouse Resources Portal, Wellcome Trust Sanger Institute.
- "International Knockout Mouse Consortium". http://www.knockoutmouse.org/martsearch/search?query=Atpif1.
- "Mouse Genome Informatics". http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4433166.
- Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. DOI:10.1038/nature10163. PMID 21677750.
- Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. DOI:10.1038/474262a. PMID 21677718.
- Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. DOI:10.1016/j.cell.2006.12.018. PMID 17218247.
- van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. DOI:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3218837.
 Further reading
- Cabezón E, Runswick MJ, Leslie AG, Walker JE (2002). "The structure of bovine IF(1), the regulatory subunit of mitochondrial F-ATPase". EMBO J. 20 (24): 6990–6996. DOI:10.1093/emboj/20.24.6990. PMC 125800. PMID 11742976. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125800.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. DOI:10.1038/ng1285. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Burwick NR, Wahl ML, Fang J et al. (2005). "An Inhibitor of the F1 subunit of ATP synthase (IF1) modulates the activity of angiostatin on the endothelial cell surface". J. Biol. Chem. 280 (3): 1740–1745. DOI:10.1074/jbc.M405947200. PMC 1201548. PMID 15528193. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1201548.
- Andersen JS, Lam YW, Leung AK et al. (2005). "Nucleolar proteome dynamics". Nature 433 (7021): 77–83. DOI:10.1038/nature03207. PMID 15635413.
- Cortés-Hernández P, Domínguez-Ramírez L, Estrada-Bernal A et al. (2005). "The inhibitor protein of the F1F0-ATP synthase is associated to the external surface of endothelial cells". Biochem. Biophys. Res. Commun. 330 (3): 844–849. DOI:10.1016/j.bbrc.2005.03.064. PMID 15809073.
- Lim J, Hao T, Shaw C et al. (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.
- Ma J, Dempsey AA, Stamatiou D et al. (2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis 191 (1): 63–72. DOI:10.1016/j.atherosclerosis.2006.05.032. PMID 16806233.
- Contessi S, Comelli M, Cmet S et al. (2008). "IF(1) distribution in HepG2 cells in relation to ecto-F(0)F (1)ATPsynthase and calmodulin". J. Bioenerg. Biomembr. 39 (4): 291–300. DOI:10.1007/s10863-007-9091-0. PMID 17851741.
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Mitochondrial ATPase inhibitor, IATP Provide feedback
ATP synthase inhibitor prevents the enzyme from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation  ATP synthase inhibitor forms a one to one complex with the F1 ATPase, possibly by binding at the alpha-beta interface. It is thought to inhibit ATP synthesis by preventing the release of ATP . The minimum inhibitory region for bovine inhibitor (P01096) is from residues 39 to 72 . The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH , the inhibitor forms a dimer via antiparallel coiled coil interactions between the C terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity .
Cabezon E, Butler PJ, Runswick MJ, Carbajo RJ, Walker JE; , J Biol Chem 2002;277:41334-41341.: Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F-ATPases. PUBMED:12186878 EPMC:12186878
van Raaij MJ, Orriss GL, Montgomery MG, Runswick MJ, Fearnley IM, Skehel JM, Walker JE; , Biochemistry 1996;35:15618-15625.: The ATPase inhibitor protein from bovine heart mitochondria: the minimal inhibitory sequence. PUBMED:8961923 EPMC:8961923
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR007648
ATP synthase inhibitor prevents the enzyme from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation [PUBMED:12186878] ATP synthase inhibitor forms a one to one complex with the F1 ATPase, possibly by binding at the alpha-beta interface. It is thought to inhibit ATP synthesis by preventing the release of ATP [PUBMED:8961923]. The minimum inhibitory region for bovine inhibitor (SWISSPROT) is from residues 39 to 72 [PUBMED:8961923]. The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH , the inhibitor forms a dimer via antiparallel coiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity [PUBMED:12186878].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||mitochondrion (GO:0005739)|
|Molecular function||enzyme inhibitor activity (GO:0004857)|
|Biological process||negative regulation of nucleotide metabolic process (GO:0045980)|
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Number in seed:||34|
|Number in full:||329|
|Average length of the domain:||83.00 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||76.51 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||7|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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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 IATP domain has been found. There are 8 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 seqence.
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