This entry represents the RNA recognition motif 1 (RRM1) of ACF. ACF (APOBEC-1-stimulating protein, also known as ASP) is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing [, ]. It may also act as an apoB mRNA recognition factor and chaperone, and play a key role in cell growth and differentiation. ACF shuttles between the cytoplasm and nucleus []. ACF contains three RNA recognition motifs (RRMs), which display high affinity for an 11 nucleotide AU-rich mooring sequence 3' of the edited cytidine in apoB mRNA. All three RRMs may be required for complementation of editing activity in living cells. RRM2/3 are implicated in ACF interaction with APOBEC-1 [].
This entry represents the RNA recognition motif 3 (RRM3) of ACF.ACF (APOBEC-1-stimulating protein, also known as ASP) is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing [, ]. It may also act as an apoB mRNA recognition factor and chaperone, and play a key role in cell growth and differentiation. ACF shuttles between the cytoplasm and nucleus []. ACF contains three RNA recognition motifs (RRMs), which display high affinity for an 11 nucleotide AU-rich mooring sequence 3' of the edited cytidine in apoB mRNA. All three RRMs may be required for complementation of editing activity in living cells. RRM2/3 are implicated in ACF interaction with APOBEC-1 [].
APOBEC1 complementation factor (A1CF or ACF) and APOBEC1 (an RNA-binding cytidine deaminase) form the apolipoprotein B (apoB) mRNA editing enzyme complex, which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in apoB mRNA [, ]. APOBEC1 alone induces nonsense-mediated decay (NMD), while the APOBEC1-ACF complex edits and remains associated with the edited RNA to protect it from NMD []. ACF has been shown to bind with high affinity to single-stranded but not double-stranded apoB mRNA [].
APOBEC1 complementation factor (A1CF or ACF) and APOBEC1 (an RNA-binding cytidine deaminase) form the apolipoprotein B (apoB) mRNA editing enzyme complex, which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in apoB mRNA [, ]. APOBEC1 alone induces nonsense-mediated decay (NMD), while the APOBEC1-ACF complex edits and remains associated with the edited RNA to protect it from NMD []. ACF has been shown to bind with high affinity to single-stranded but not double-stranded apoB mRNA [].A1CF contains three RNA recognition motifs (RRMs) and a C-terminal double-stranded RNA binding motif (DSRM). This entry represents the DSRM of A1CF.
This entry includes APOBEC1 from animals. APOBEC1 is a catalytic component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the APOB mRNA [].
This entry represents the RNA recognition motif 1 (RRM1) of hnRNP A/B, which is a RNA-binding protein that is involved in mRNA processing [, ]. hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing []. hnRNP A/B contains two RNA recognition motifs (RRMs), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.
Cytidine deaminase () (cytidine aminohydrolase) catalyzes the hydrolysis of cytidine into uridine and ammonia while deoxycytidylate deaminase () (dCMP deaminase) hydrolyzes dCMP into dUMP. Both enzymes are known to bind zinc and to require it for their catalytic activity [, ]. These two enzymes do not share any sequence similarity with the exception of a region that contains three conserved histidine and cysteine residues which are thought to be involved in the binding of the catalytic zinc ion.Such a region is also found in other proteins [, ]:Yeast cytosine deaminase () (gene FCY1) which transforms cytosine into uracil.Mammalian apolipoprotein B mRNA editing protein, responsible for the postranscriptional editing of a CAA codon into a UAA (stop) codon in the APOB mRNA.Riboflavin biosynthesis protein ribG, which converts 2,5-diamino-6-(ribosylamino)-4(3H)-pyrimidinone 5'-phosphate into 5-amino-6-(ribosylamino)-2,4(1H,3H)-pyrimidinedione 5'-phosphate.Bacillus cereus blasticidin-S deaminase (), which catalyzes the deamination of the cytosine moiety of the antibiotics blasticidin S, cytomycin and acetylblasticidin S.Bacillus subtilis protein comEB. This protein is required for the binding and uptake of transforming DNA.B. subtilis hypothetical protein yaaJ.Escherichia coli hypothetical protein yfhC.Yeast hypothetical protein YJL035c.
Betaine-homocysteine methyltransferase (BHMT) is involved in the regulation of homocysteine metabolism. It converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline. BHMT requires a thiol reducing agent for its activity. The catalytic zinc of BHMT is bound by three thiolates and one hydroxyl group. A disulphide bond is formed between two of the three zinc-binding ligands when BHMT is inactive [].BHMT regulates homocysteine levels in the liver. The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury, but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. It also has a generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine []. However, the peripheral metabolism of homocysteine protects the liver without the direct action of BHMT in the liver [].The human betaine-homocysteine methyltransferase-2 is also a zinc metalloenzyme that uses S-methylmethionine (SMM) as a methyl donor for the methylation of homocysteine. Unlike the highly homologous BHMT, BHMT-2 cannot use betaine as a substrate [].This entry also includes homocysteine S-methyltransferase (), which converts S-adenosylmethionine to methionine []; selenocysteine methyltransferase (), which methylates DL- and L-selenocysteine, DL-homocysteine, and DL- and L-cysteine []; and S-methylmethionine--homocysteine S-methyltransferase BHMT2 (also ), which converts converts homocysteine to methionine [].
The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 2 (RRM2) of CELF-1 and CELF-2 protein. CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) [].The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase []. It preferentially targets UGU-rich mRNA elements []. CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene [, ]. CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein. The Xenopus homologue of CELF-1 is EDEN-BP (embryo deadenylation element-binding protein), which mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression []. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding []. CELF-2 (also known as CUGBP2 or ETR-3) shares high sequence identity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing []. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C terminus, within RRM3 [].
The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 3 (RRM3) of CELF-1 andCELF-2 protein. CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) [].The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase []. It preferentially targets UGU-rich mRNA elements []. CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene [, ]. CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein. The Xenopus homologue of CELF-1 is EDEN-BP (embryo deadenylation element-binding protein), which mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression []. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding []. CELF-2 (also known as CUGBP2 or ETR-3) shares high sequenceidentity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing []. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C terminus, within RRM3 [].
The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 1 (RRM1) of CELF-1 and CELF-2 protein. CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) [].The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase []. It preferentially targets UGU-rich mRNA elements []. CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene [, ]. CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein. The Xenopus homologue of CELF-1 is EDEN-BP (embryo deadenylation element-binding protein), which mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression []. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding []. CELF-2 (also known as CUGBP2 or ETR-3) shares high sequence identity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing []. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C terminus, within RRM3 [].Proteins containing this motif also include Drosophila melanogaster Bruno protein, which plays a central role in regulation ofOskar (Osk) expression in flies. It mediates repression by binding to regulatory Bruno response elements (BREs) in the Osk mRNA 3' UTR []. The full-length Bruno protein contains three RRMs, two located in the N-terminal half of the protein and the third near the C terminus, separated by a linker region.
