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ATPase inhibitory factor 1
External IDs OMIM614981 MGI1196457 HomoloGene40581 GeneCards: ATPIF1 Gene
RNA expression pattern
PBB GE ATPIF1 218671 s at tn.png
More reference expression data
Species Human Mouse
Entrez 93974 11983
Ensembl ENSG00000130770 ENSMUSG00000054428
UniProt Q9UII2 O35143
RefSeq (mRNA) NM_016311 NM_007512
RefSeq (protein) NP_057395 NP_031538
Location (UCSC) Chr 1:
28.56 – 28.57 Mb
Chr 4:
132.53 – 132.53 Mb
PubMed search [1] [2]

ATPase inhibitor, mitochondrial is an enzyme that in humans is encoded by the ATPIF1 gene.[1][2]

This gene encodes a mitochondrial ATPase inhibitor. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified.[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[edit]

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
PDB 1hf9 EBI.jpg
c-terminal coiled-coil domain from bovine if1
Symbol IATP
Pfam PF04568
InterPro IPR007648
SCOP 1hf9


  1. ^ 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. 
  2. ^ a b "Entrez Gene: ATPIF1 ATPase inhibitory factor 1". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ "Anxiety data for Atpif1". Wellcome Trust Sanger Institute. 
  6. ^ "Clinical chemistry data for Atpif1". Wellcome Trust Sanger Institute. 
  7. ^ "Salmonella infection data for Atpif1". Wellcome Trust Sanger Institute. 
  8. ^ "Citrobacter infection data for Atpif1". Wellcome Trust Sanger Institute. 
  9. ^ 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. 
  10. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ^ "International Knockout Mouse Consortium". 
  12. ^ "Mouse Genome Informatics". 
  13. ^ 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.  edit
  14. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  15. ^ 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. 
  16. ^ 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. 

Further reading[edit]

This article incorporates text from the public domain Pfam and InterPro IPR007648