ATPIF1
Template:PBB ATPase inhibitor, mitochondrial is an enzyme that in humans is encoded by the ATPIF1 gene.[1][2]
It prevents ATPase from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation [3] 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.[4] 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.[3]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Abnormal[5] |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal[6] |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Brain histopathology | Abnormal |
| Salmonella infection | Normal[7] |
| Citrobacter infection | Normal[8] |
| All tests and analysis from[9][10] |
Model organisms have been used in the study of ATPIF1 function. A conditional knockout mouse line, called Atpif1tm1a(EUCOMM)Wtsi[11][12] 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.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty three tests were carried out on mutant mice and three significant abnormalities were observed.[9] Homozygous mutant animals displayed hyperactivity and brain dysmorphology, while males also had decreased circulating alkaline phosphatase levels.[9]
| Mitochondrial ATPase inhibitor, IATP | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 c-terminal coiled-coil domain from bovine if1 | |||||||||
| Identifiers | |||||||||
| Symbol | IATP | ||||||||
| Pfam | PF04568 | ||||||||
| InterPro | IPR007648 | ||||||||
| SCOP2 | 1hf9 / SCOPe / SUPFAM | ||||||||
| |||||||||
References
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: ATPIF1 ATPase inhibitory factor 1".
- ^ a b 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Anxiety data for Atpif1". Wellcome Trust Sanger Institute.
- ^ "Clinical chemistry data for Atpif1". Wellcome Trust Sanger Institute.
- ^ "Salmonella infection data for Atpif1". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Atpif1". Wellcome Trust Sanger Institute.
- ^ a b c d 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".
- ^ "Mouse Genome Informatics".
- ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; 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. PMC 3572410. 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)