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Gene Review

A1cf  -  APOBEC1 complementation factor

Rattus norvegicus

Synonyms: A1cft, APOBEC1-stimulating protein, Acf, Apobec-1, Asp
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Disease relevance of Acf

  • Modification of the carboxylate functions of Asp, Asp, and of the COOH-terminal Gln with glycine ethyl ester in the presence of a soluble carbodiimide completely abolished the toxicity but left the affinity for the sea anemone toxin receptor unchanged [1].
  • Tumor mitochondrial transfer ribonucleic acids: the nucleotide sequence of Morris hepatoma 5123D mitochondrial tRNA GUC Asp [2].
  • Changing Glu-1025 to Asp in Fujinami sarcoma virus P130gag-fps made the protein temperature sensitive for transformation and protein-tyrosine kinase activity [3].
  • To show this, Arg-116 in alphaA-crystallin was mutated to Lys (R116K), Cys (R116C), Gly (R116G), and Asp (R116D) and expressed in Escherichia coli cells [4].
  • In male rats, many lumbar and sacral dorsal root ganglion cells and their associated glia show high levels of Glu or Asp immunoreactivity, and fewer than half of these also express substance P or calcitonin gene-related peptide [5].

Psychiatry related information on Acf

  • Here the purification and characterization of a protease from Alzheimer's disease brain capable of cleaving a 10 amino acid synthetic substrate flanking the N terminus of A beta at the Met-Asp bond are described [6].
  • A range of agonists and antagonists active at different glutamate/aspartate (Glu/Asp) receptor subtypes were injected into rat ventral tegmental (VTA) sites downstream from self-stimulation electrodes in the medial forebrain bundle [7].

High impact information on Acf

  • A highly conserved residue, Asp 87, positioned within a putative nucleotide-binding pocket in the top of the equatorial domain, is essential for ATP hydrolysis and polypeptide release [8].
  • More interestingly, it also reveals the substitution of an Asp residue always found in the serine protease active site triad (Asp, His, Ser) by a Leu residue [9].
  • The synthetic peptide stimulated the 2-oxoglutarate decarboxylation in contrast to synthetic, modified epidermal growth factor (Met-21 and His-22 deleted and Glu-24 replaced by Asp) and synthetic peptides corresponding to residues 60-71 in human factor IX [10].
  • We show here, by yeast two-hybrid screenings and biochemical assays, that a region at the amino terminus of the human nuclear pore complex protein Nup96 interacts with the WD (Trp-Asp) repeat region of human Sec13 [11].
  • These include two putative transmembrane domains, two sequences rich in Pro, Glu, Asp, Ser, and Thr (PEST sequences), and two polyproline-rich domains [12].

Chemical compound and disease context of Acf

  • In contrast to the effects in nonkindled rats, i.p. injection of Asp 20 mmol/kg in 15% DMSO in amygdala-kindled rats precipitated electroclinical generalized seizures identical to kindled ones [13].
  • (1) Forebrain ischemia by 4-vessel occlusion generated significant correlations between the Glu and Asp levels and the DA, NE and 5-HT levels (r = 0.922-0.967, P < 0.01, n = 6) [14].
  • The ability of neonatal capsaicin to inhibit, and dorsal rhizotomy to potentiate Asp release correlates well with their distinct effects on hyperalgesia and suggests that these manipulations do not produce identical lesions [15].
  • In SHE rats, ketamine anesthesia produced a similar degree of cerebral edema, however, it did not alter Asp and Glu concentrations in the microdialysates [16].
  • The effects of aspartate (Asp) and 2-oxoglutarate (2-OG) on metabolism and function of isolated rat heart during hypoxia and reoxygenation were studied [17].

Biological context of Acf

  • Metabolic regulation of apoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor [18].
  • Two novel mRNA transcripts have been identified that result from species- and tissue-specific, alternative polyadenylation and splicing of the pre-mRNA encoding the apolipoprotein B (apoB) editing catalytic subunit 1 (APOBEC-1) complementation factor (ACF) family of related proteins [19].
  • Caspases, Asp-specific cysteine protease, cleave proteins upon apoptosis [20].
  • These results indicate that tachykinins (SP and NKA) and CGRP are capable of modulating the basal and electrically evoked release of endogenous Glu and Asp, and these actions may provide an important mechanism by which the peptides contribute to the regulation of the primary afferent synaptic transmission [21].
  • Although the deduced amino acid sequence is not largely similar to those of bacterial and parasite sialidases, it contains two Asp blocks, the conserved sequence of the sialidases from these microorganisms [22].

Anatomical context of Acf

  • Ethanol stimulated apoB mRNA editing was associated with a 2- to 3-fold increase in ACF phosphorylation relative to that in control primary hepatocytes [18].
  • We have previously demonstrated that nociceptive stimulation (metatarsal injection of formalin) caused a tetrodotoxin (TTX)-sensitive release of Asp and a TTX-insensitive release of Glu from the dorsal spinal cord [23].
  • High-intensity repetitive electrical stimulation of a lumbar dorsal root produced a Ca2(+)-dependent increase in the basal release of Asp, Glu, glycine (Gly), serine (Ser), and threonine (Thr) [21].
  • Calcium and magnesium ions also enhanced the binding (Glu greater than Asp) in the order, whole particulate membranes greater than or equal to P2 greater than or equal to SPM greater than SJ [24].
  • The binding of the putative excitatory transmitters glutamate (Glu) and aspartate (Asp) was measured in various subcellular fractions in order to assess their degree of localization in synaptic junctions (SJs) [24].

Associations of Acf with chemical compounds

  • Significantly increased release of glutamate (Glu; 110%) and aspartate (Asp; 112%) was only observed in the 0-10 min sample [25].
  • Intradiaylsate infusion of SP(5-11) increased the release of Asp, Glu, asparagine (Asn), glycine (Gly), and taurine (Tau) [23].
  • Neonatal capsaicin treatment did not significantly alter the basal efflux of 9 endogenous amino acids from the spinal slices, but it prevented the dorsal root stimulation-evoked release of Asp, Glu, Gly, and Thr and the SP-induced increase in the basal release of Glu [21].
  • Intrathecal delivery of 10 micrograms, but not 1 microgram, S(+)-ibuprofen also suppressed formalin-induced behavior, PGE2-LI, Glu, and Asp release [25].
  • From the sequence, we deduced that the DSP cDNA coded for 366 amino acids, predominantly Asp, Ser, Glu, and Gly [26].

Physical interactions of Acf

  • Moreover, alkaline phosphatase treatment of nuclear extracts reduced the amount of APOBEC-1 co-immunoprecipitated with ACF and inhibited in vitro editing activity [18].

Other interactions of Acf

  • Identification of novel alternative splice variants of APOBEC-1 complementation factor with different capacities to support apolipoprotein B mRNA editing [19].
  • These data, together with the finding that all ACF variants were co-expressed in rat liver nuclei (the site of apoB mRNA editing), suggested that ACF variants might compete with one another for APOBEC-1 and apoB mRNA binding and thereby contribute to the regulation of apoB mRNA editing [19].

Analytical, diagnostic and therapeutic context of Acf


  1. Structure-function relationships of sea anemone toxin II from Anemonia sulcata. Barhanin, J., Hugues, M., Schweitz, H., Vincent, J.P., Lazdunski, M. J. Biol. Chem. (1981) [Pubmed]
  2. Tumor mitochondrial transfer ribonucleic acids: the nucleotide sequence of Morris hepatoma 5123D mitochondrial tRNA GUC Asp. Agrawal, H.P., Randerath, K., Randerath, E. Nucleic Acids Res. (1981) [Pubmed]
  3. Investigation of the role of P130gag-fps in transformation: generation and use of a temperature-sensitive mutant P130gag-fps. Weinmaster, G.A., Hunter, T. J. Virol. (1988) [Pubmed]
  4. A positive charge preservation at position 116 of alpha A-crystallin is critical for its structural and functional integrity. Bera, S., Thampi, P., Cho, W.J., Abraham, E.C. Biochemistry (2002) [Pubmed]
  5. Glutamate and aspartate immunoreactivity in dorsal root ganglion cells supplying visceral and somatic targets and evidence for peripheral axonal transport. Keast, J.R., Stephensen, T.M. J. Comp. Neurol. (2000) [Pubmed]
  6. Identification of a metalloprotease from Alzheimer's disease brain able to degrade the beta-amyloid precursor protein and generate amyloidogenic fragments. Papastoitsis, G., Siman, R., Scott, R., Abraham, C.R. Biochemistry (1994) [Pubmed]
  7. Excitatory amino acid pathways in brain-stimulation reward. Herberg, L.J., Rose, I.C. Behav. Brain Res. (1990) [Pubmed]
  8. Residues in chaperonin GroEL required for polypeptide binding and release. Fenton, W.A., Kashi, Y., Furtak, K., Horwich, A.L. Nature (1994) [Pubmed]
  9. Amino acid sequence of rat submaxillary tonin reveals similarities to serine proteases. Lazure, C., Leduc, R., Seidah, N.G., Thibault, G., Genest, J., Chrétien, M. Nature (1984) [Pubmed]
  10. Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase. Stenflo, J., Holme, E., Lindstedt, S., Chandramouli, N., Huang, L.H., Tam, J.P., Merrifield, R.B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  11. Sec13 shuttles between the nucleus and the cytoplasm and stably interacts with Nup96 at the nuclear pore complex. Enninga, J., Levay, A., Fontoura, B.M. Mol. Cell. Biol. (2003) [Pubmed]
  12. STEP61: a member of a family of brain-enriched PTPs is localized to the endoplasmic reticulum. Bult, A., Zhao, F., Dirkx, R., Sharma, E., Lukacsi, E., Solimena, M., Naegele, J.R., Lombroso, P.J. J. Neurosci. (1996) [Pubmed]
  13. Important roles of N-methyl-D-aspartate receptors in expression of amygdaloid-kindled seizure demonstrated by intraperitoneal administration of L-aspartate in dimethyl sulfoxide. Mori, N., Wada, J.A., Sato, T., Saito, H., Kumashiro, H. Epilepsia (1992) [Pubmed]
  14. Presynaptic glutamate receptors facilitate release of norepinephrine and 5-hydroxytryptamine as well as dopamine in the normal and ischemic striatum. Ohta, K., Fukuuchi, Y., Shimazu, K., Komatsumoto, S., Ichijo, M., Araki, N., Shibata, M. J. Auton. Nerv. Syst. (1994) [Pubmed]
  15. Capsaicin inhibits whereas rhizotomy potentiates substance P-induced release of excitatory amino acids in the rat spinal cord in vivo. Skilling, S.R., Larson, A.A. Neurosci. Lett. (1993) [Pubmed]
  16. Extracellular concentrations of taurine, glutamate, and aspartate in the cerebral cortex of rats at the asymptomatic stage of thioacetamide-induced hepatic failure: modulation by ketamine anesthesia. Albrecht, J., Hilgier, W., Zielińska, M., Januszewski, S., Hesselink, M., Quack, G. Neurochem. Res. (2000) [Pubmed]
  17. Substrate accessibility to cytosolic aspartate aminotransferase improves posthypoxic recovery of isolated rat heart. Pisarenko, O.I., Studneva, I.M., Shulzhenko, V.S., Korchazhkina, O.V., Kapelko, V.I. Biochem. Mol. Med. (1995) [Pubmed]
  18. Metabolic regulation of apoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor. Lehmann, D.M., Galloway, C.A., Sowden, M.P., Smith, H.C. Nucleic Acids Res. (2006) [Pubmed]
  19. Identification of novel alternative splice variants of APOBEC-1 complementation factor with different capacities to support apolipoprotein B mRNA editing. Sowden, M.P., Lehmann, D.M., Lin, X., Smith, C.O., Smith, H.C. J. Biol. Chem. (2004) [Pubmed]
  20. Biochemical characterization of apoptotic cleavage of KH-type splicing regulatory protein (KSRP)/far upstream element-binding protein 2 (FBP2). Seok, H., Cho, J., Cheon, M., Park, I.S. Protein Pept. Lett. (2002) [Pubmed]
  21. Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice. Kangrga, I., Randic, M. J. Neurosci. (1990) [Pubmed]
  22. Molecular cloning and expression of cDNA encoding rat skeletal muscle cytosolic sialidase. Miyagi, T., Konno, K., Emori, Y., Kawasaki, H., Suzuki, K., Yasui, A., Tsuik, S. J. Biol. Chem. (1993) [Pubmed]
  23. Differential effects of C- and N-terminal substance P metabolites on the release of amino acid neurotransmitters from the spinal cord: potential role in nociception. Skilling, S.R., Smullin, D.H., Larson, A.A. J. Neurosci. (1990) [Pubmed]
  24. Glutamate and aspartate binding sites are enriched in synaptic junctions isolated from rat brain. Foster, A.C., Mena, E.E., Fagg, G.E., Cotman, C.W. J. Neurosci. (1981) [Pubmed]
  25. Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: a microdialysis study in unanesthetized rats. Malmberg, A.B., Yaksh, T.L. J. Neurosci. (1995) [Pubmed]
  26. Cloning and sequence determination of rat dentin sialoprotein, a novel dentin protein. Ritchie, H.H., Hou, H., Veis, A., Butler, W.T. J. Biol. Chem. (1994) [Pubmed]
  27. cAMP-dependent phosphorylation stimulates water permeability of aquaporin-collecting duct water channel protein expressed in Xenopus oocytes. Kuwahara, M., Fushimi, K., Terada, Y., Bai, L., Marumo, F., Sasaki, S. J. Biol. Chem. (1995) [Pubmed]
  28. Tissue kallikrein-binding protein is a serpin. I. Purification, characterization, and distribution in normotensive and spontaneously hypertensive rats. Chao, J., Chai, K.X., Chen, L.M., Xiong, W., Chao, S., Woodley-Miller, C., Wang, L.X., Lu, H.S., Chao, L. J. Biol. Chem. (1990) [Pubmed]
  29. Neuronal nitric-oxide synthase mutant (Ser-1412 --> Asp) demonstrates surprising connections between heme reduction, NO complex formation, and catalysis. Adak, S., Santolini, J., Tikunova, S., Wang, Q., Johnson, J.D., Stuehr, D.J. J. Biol. Chem. (2001) [Pubmed]
  30. On the release of glutamate and aspartate in the basal ganglia of the rat: interactions with monoamines and neuropeptides. Herrera-Marschitz, M., Goiny, M., You, Z.B., Meana, J.J., Pettersson, E., Rodriguez-Puertas, R., Xu, Z.Q., Terenius, L., Hökfelt, T., Ungerstedt, U. Neuroscience and biobehavioral reviews. (1997) [Pubmed]
  31. On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis. Herrera-Marschitz, M., You, Z.B., Goiny, M., Meana, J.J., Silveira, R., Godukhin, O.V., Chen, Y., Espinoza, S., Pettersson, E., Loidl, C.F., Lubec, G., Andersson, K., Nylander, I., Terenius, L., Ungerstedt, U. J. Neurochem. (1996) [Pubmed]
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