forkhead-associated domain-containing protein / FHA domain-containing protein [Arabidopsis thaliana]
Protein Classification
FHA domain-containing protein( domain architecture ID 10044597)
FHA (forkhead-associated) domain-containing protein participates in signal transduction pathways via protein-protein interactions involving recognition of pThr and pTyr phosphopeptides
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||
| PLDc_Tdp1_1 | cd09122 | Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of ... |
385-551 | 1.83e-45 | ||||
Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. : Pssm-ID: 197221 Cd Length: 145 Bit Score: 160.11 E-value: 1.83e-45
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| PLDc_SF super family | cl15239 | Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D ... |
772-877 | 2.40e-18 | ||||
Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D (PLD) superfamily proteins. The PLD superfamily is composed of a large and diverse group of proteins including plant, mammalian and bacterial PLDs, bacterial cardiolipin (CL) synthases, bacterial phosphatidylserine synthases (PSS), eukaryotic phosphatidylglycerophosphate (PGP) synthase, eukaryotic tyrosyl-DNA phosphodiesterase 1 (Tdp1), and some bacterial endonucleases (Nuc and BfiI), among others. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze the transphosphatidylation of phospholipids to acceptor alcohols. The majority of members in this superfamily contain a short conserved sequence motif (H-x-K-x(4)-D, where x represents any amino acid residue), called the HKD signature motif. There are varying expanded forms of this motif in different family members. Some members contain variant HKD motifs. Most PLD enzymes are monomeric proteins with two HKD motif-containing domains. Two HKD motifs from two domains form a single active site. Some PLD enzymes have only one copy of the HKD motif per subunit but form a functionally active dimer, which has a single active site at the dimer interface containing the two HKD motifs from both subunits. Different PLD enzymes may have evolved through domain fusion of a common catalytic core with separate substrate recognition domains. Despite their various catalytic functions and a very broad range of substrate specificities, the diverse group of PLD enzymes can bind to a phosphodiester moiety. Most of them are active as bi-lobed monomers or dimers, and may possess similar core structures for catalytic activity. They are generally thought to utilize a common two-step ping-pong catalytic mechanism, involving an enzyme-substrate intermediate, to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group. The actual alignment was detected with superfamily member cd09123: Pssm-ID: 472788 Cd Length: 182 Bit Score: 83.55 E-value: 2.40e-18
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| HIRAN | pfam08797 | HIRAN domain; The HIRAN domain (HIP116, Rad5p N-terminal) is found in the N-terminal regions ... |
611-737 | 2.28e-15 | ||||
HIRAN domain; The HIRAN domain (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p. The HIRAN domain is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. It has been predicted that this domain functions as a DNA-binding domain that probably recognizes features associated with damaged DNA or stalled replication forks : Pssm-ID: 400928 [Multi-domain] Cd Length: 96 Bit Score: 72.36 E-value: 2.28e-15
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| FHA | cd00060 | forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small ... |
20-142 | 8.68e-11 | ||||
forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function. : Pssm-ID: 438714 [Multi-domain] Cd Length: 92 Bit Score: 59.21 E-value: 8.68e-11
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| Name | Accession | Description | Interval | E-value | ||||
| PLDc_Tdp1_1 | cd09122 | Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of ... |
385-551 | 1.83e-45 | ||||
Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Pssm-ID: 197221 Cd Length: 145 Bit Score: 160.11 E-value: 1.83e-45
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| PLDc_Tdp1_2 | cd09123 | Catalytic domain, repeat 2, of tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of ... |
772-877 | 2.40e-18 | ||||
Catalytic domain, repeat 2, of tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Pssm-ID: 197222 Cd Length: 182 Bit Score: 83.55 E-value: 2.40e-18
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| Tyr-DNA_phospho | pfam06087 | Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can ... |
366-590 | 4.56e-17 | ||||
Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Tyrosyl-DNA phosphodiesterase can hydrolyse the bond between topoisomerase I and DNA. Pssm-ID: 461824 [Multi-domain] Cd Length: 442 Bit Score: 84.63 E-value: 4.56e-17
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| HIRAN | pfam08797 | HIRAN domain; The HIRAN domain (HIP116, Rad5p N-terminal) is found in the N-terminal regions ... |
611-737 | 2.28e-15 | ||||
HIRAN domain; The HIRAN domain (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p. The HIRAN domain is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. It has been predicted that this domain functions as a DNA-binding domain that probably recognizes features associated with damaged DNA or stalled replication forks Pssm-ID: 400928 [Multi-domain] Cd Length: 96 Bit Score: 72.36 E-value: 2.28e-15
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| HIRAN | smart00910 | The HIRAN protein (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2 ... |
618-734 | 1.16e-11 | ||||
The HIRAN protein (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p; HIRAN is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. It has been predicted that this protein functions as a DNA-binding domain that probably recognises features associated with damaged DNA or stalled replication forks. Pssm-ID: 214906 [Multi-domain] Cd Length: 90 Bit Score: 61.53 E-value: 1.16e-11
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| FHA | cd00060 | forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small ... |
20-142 | 8.68e-11 | ||||
forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function. Pssm-ID: 438714 [Multi-domain] Cd Length: 92 Bit Score: 59.21 E-value: 8.68e-11
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| FHA | COG1716 | Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]; |
20-142 | 1.23e-10 | ||||
Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]; Pssm-ID: 441322 [Multi-domain] Cd Length: 96 Bit Score: 58.82 E-value: 1.23e-10
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| FHA | pfam00498 | FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif. |
40-142 | 5.34e-09 | ||||
FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif. Pssm-ID: 459831 [Multi-domain] Cd Length: 66 Bit Score: 53.35 E-value: 5.34e-09
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| FHA | smart00240 | Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear ... |
40-126 | 6.18e-08 | ||||
Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. Pssm-ID: 214578 [Multi-domain] Cd Length: 52 Bit Score: 49.87 E-value: 6.18e-08
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| Name | Accession | Description | Interval | E-value | ||||
| PLDc_Tdp1_1 | cd09122 | Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of ... |
385-551 | 1.83e-45 | ||||
Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Pssm-ID: 197221 Cd Length: 145 Bit Score: 160.11 E-value: 1.83e-45
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| PLDc_Tdp1_2 | cd09123 | Catalytic domain, repeat 2, of tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of ... |
772-877 | 2.40e-18 | ||||
Catalytic domain, repeat 2, of tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 2, of Tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-), which exists in eukaryotes but not in prokaryotes. Tdp1 acts as an important DNA repair enzyme that removes stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is a monomeric protein that contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Thus, this family represents a distinct class within the PLD superfamily. Like other PLD enzymes, Tdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Pssm-ID: 197222 Cd Length: 182 Bit Score: 83.55 E-value: 2.40e-18
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| Tyr-DNA_phospho | pfam06087 | Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can ... |
366-590 | 4.56e-17 | ||||
Tyrosyl-DNA phosphodiesterase; Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Tyrosyl-DNA phosphodiesterase can hydrolyse the bond between topoisomerase I and DNA. Pssm-ID: 461824 [Multi-domain] Cd Length: 442 Bit Score: 84.63 E-value: 4.56e-17
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| HIRAN | pfam08797 | HIRAN domain; The HIRAN domain (HIP116, Rad5p N-terminal) is found in the N-terminal regions ... |
611-737 | 2.28e-15 | ||||
HIRAN domain; The HIRAN domain (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p. The HIRAN domain is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. It has been predicted that this domain functions as a DNA-binding domain that probably recognizes features associated with damaged DNA or stalled replication forks Pssm-ID: 400928 [Multi-domain] Cd Length: 96 Bit Score: 72.36 E-value: 2.28e-15
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| HIRAN | smart00910 | The HIRAN protein (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2 ... |
618-734 | 1.16e-11 | ||||
The HIRAN protein (HIP116, Rad5p N-terminal) is found in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p; HIRAN is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. It has been predicted that this protein functions as a DNA-binding domain that probably recognises features associated with damaged DNA or stalled replication forks. Pssm-ID: 214906 [Multi-domain] Cd Length: 90 Bit Score: 61.53 E-value: 1.16e-11
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| PLDc_mTdp1_1 | cd09193 | Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, ... |
385-522 | 7.74e-11 | ||||
Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase (Tdp1, EC 3.1.4.-). Human Tdp1 (hTdp1) acts as an important DNA repair enzyme with a preference for single-stranded or blunt-ended duplex oligonucleotides. It can remove stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of a phosphodiester bond between a tyrosine side chain and a DNA 3'-phosphate. It is therefore a potential molecular target for new anti-cancer drugs. hTdp1 has been shown to associate with additional proteins, such as XRCC1, to form a multi-enzyme complex. These additional proteins may be involved in recognizing 3'-phoshotyrosyl DNA in vivo. hTdp1 is a monomeric protein containing two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, hTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Pssm-ID: 197289 [Multi-domain] Cd Length: 169 Bit Score: 61.55 E-value: 7.74e-11
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| FHA | cd00060 | forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small ... |
20-142 | 8.68e-11 | ||||
forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function. Pssm-ID: 438714 [Multi-domain] Cd Length: 92 Bit Score: 59.21 E-value: 8.68e-11
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| FHA | COG1716 | Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]; |
20-142 | 1.23e-10 | ||||
Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]; Pssm-ID: 441322 [Multi-domain] Cd Length: 96 Bit Score: 58.82 E-value: 1.23e-10
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| PLDc_yTdp1_1 | cd09194 | Catalytic domain, repeat 1, of yeast tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, ... |
366-513 | 4.47e-09 | ||||
Catalytic domain, repeat 1, of yeast tyrosyl-DNA phosphodiesterase; Catalytic domain, repeat 1, of yeast tyrosyl-DNA phosphodiesterase (yTdp1, EC 3.1.4.-). yTdp1 is involved in the repair of topoisomerase I DNA lesions by hydrolyzing the topoisomerase from the 3'-end of the DNA during double-strand break repair. Unlike human Tdp1 whose substrate-binding pocket can accommodate a fairly large topoisomerase I peptide fragment, yTdp1 has a preference for substrates containing one to four amino acid residues. The monomeric yTdp1 contains two copies of a variant HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which consists of the highly conserved histidine and lysine residues, but lacks the aspartate residue that is well conserved in other phospholipase D (PLD, EC 3.1.4.4) enzymes. Like other PLD enzymes, yTdp1 may utilize a common two-step general acid/base catalytic mechanism, involving a DNA-enzyme intermediate to cleave phosphodiester bonds. A single active site involved in phosphatidyl group transfer would be formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Pssm-ID: 197290 Cd Length: 166 Bit Score: 56.53 E-value: 4.47e-09
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| FHA | pfam00498 | FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif. |
40-142 | 5.34e-09 | ||||
FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif. Pssm-ID: 459831 [Multi-domain] Cd Length: 66 Bit Score: 53.35 E-value: 5.34e-09
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| FHA_PPP1R8 | cd22674 | forkhead associated (FHA) domain found in protein phosphatase 1 regulatory inhibitor subunit 8 ... |
29-142 | 7.47e-09 | ||||
forkhead associated (FHA) domain found in protein phosphatase 1 regulatory inhibitor subunit 8 (PPP1R8) and similar proteins; PPP1R8, also called nuclear inhibitor of protein phosphatase 1 (NIPP-1), is an inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. It may also be involved in pre-mRNA splicing and binds DNA and might act as a transcriptional repressor. PPP1R8 seems to be required for cell proliferation. PPP1R8 contains an FHA domain that mediates interactions with threonine-phosphorylated maternal embryonic leucine zipper kinase (MELK). The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438726 [Multi-domain] Cd Length: 108 Bit Score: 54.19 E-value: 7.47e-09
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| FHA | smart00240 | Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear ... |
40-126 | 6.18e-08 | ||||
Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. Pssm-ID: 214578 [Multi-domain] Cd Length: 52 Bit Score: 49.87 E-value: 6.18e-08
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| FHA_MEK1-like | cd22670 | forkhead associated (FHA) domain found in Saccharomyces cerevisiae meiosis-specific serine ... |
34-128 | 5.34e-07 | ||||
forkhead associated (FHA) domain found in Saccharomyces cerevisiae meiosis-specific serine/threonine-protein kinase MEK1 and similar proteins; MEK1 (EC 2.7.11.1), also known as MRE4, is a meiosis-specific protein kinase required for chromosome synapsis and meiotic recombination. The recruitment and activation of MEK1 require the phosphorylation of the chromosome axis protein Hop1 at Thr318 (pT318), which is necessary for recognition by the MEK1 FHA domain. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438722 [Multi-domain] Cd Length: 105 Bit Score: 48.76 E-value: 5.34e-07
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| FHA_NBN | cd22667 | forkhead associated (FHA) domain found in nibrin and similar proteins; Nibrin (NBN), also ... |
32-142 | 2.94e-05 | ||||
forkhead associated (FHA) domain found in nibrin and similar proteins; Nibrin (NBN), also called cell cycle regulatory protein p95, or Nijmegen breakage syndrome protein 1 (NBS1), is a novel DNA double-strand break repair protein that is mutated in Nijmegen breakage syndrome. It is a component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. Nibrin modulates the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. Nibrin also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. Nibrin is a major player in the control of intra-S-phase checkpoint. This subfamily also includes Schizosaccharomyces pombe DNA repair and telomere maintenance protein Nbs1 and Arabidopsis thaliana AtNbs1. SpNbs1 is an FHA domain-containing protein required for DNA damage repair and S-phase DNA damage checkpoint. It is involved in telomere length maintenance and maintenance of chromatin structure. AtNbs1 is a component of MRN complex. It also functions in the very early stages of meiosis. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438719 [Multi-domain] Cd Length: 108 Bit Score: 43.85 E-value: 2.94e-05
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| FHA_MDC1 | cd22665 | forkhead associated (FHA) domain found in mediator of DNA damage checkpoint protein 1 (MDC1) ... |
41-80 | 7.54e-05 | ||||
forkhead associated (FHA) domain found in mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins; MDC1, also called nuclear factor with BRCT domains 1 (NFBD1), is a nuclear chromatin-associated protein that is required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S and G2/M phases of the cell cycle. It directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. MDC1 contains a forkhead-associated (FHA) domain and two BRCT domains, as well as an internal 41-amino acid repeat sequence. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438717 [Multi-domain] Cd Length: 97 Bit Score: 42.22 E-value: 7.54e-05
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| FHA_Kanadaptin | cd22677 | forkhead associated (FHA) domain found in kanadaptin and similar proteins; Kanadaptin, also ... |
36-80 | 9.57e-05 | ||||
forkhead associated (FHA) domain found in kanadaptin and similar proteins; Kanadaptin, also called human lung cancer oncogene 3 protein (HLC-3), kidney anion exchanger adapter protein, or solute carrier family 4 anion exchanger member 1 adapter protein (SLC4A1AP), is a nuclear protein widely expressed in mammalian tissues. It was originally isolated as a kidney Cl-/HCO3- anion exchanger 1 (kAE1)-binding protein. It is a highly mobile nucleocytoplasmic shuttling and multilocalizing protein. Its role in mammalian cells remains unclear. It contains an FHA domain, which is a small phosphopeptide recognition module. Pssm-ID: 438729 [Multi-domain] Cd Length: 106 Bit Score: 42.16 E-value: 9.57e-05
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| FHA_PML1-like | cd22681 | forkhead associated (FHA) domain found in Saccharomyces cerevisiae pre-mRNA leakage protein 1 ... |
24-80 | 1.80e-04 | ||||
forkhead associated (FHA) domain found in Saccharomyces cerevisiae pre-mRNA leakage protein 1 (PML1) and similar proteins; PML1 is an FHA domain-containing protein required for efficient splicing and pre-mRNA nuclear retention. It is a component of the pre-mRNA retention and splicing (RES) complex composed of at least BUD13, IST3, and PML1. It contains an FHA domain, which is a small phosphopeptide recognition module. Pssm-ID: 438733 [Multi-domain] Cd Length: 129 Bit Score: 42.04 E-value: 1.80e-04
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| FHA_SNIP1_DDL-like | cd22676 | forkhead associated (FHA) domain found in Smad nuclear-interacting protein 1 (SNIP1), FHA ... |
28-142 | 2.99e-04 | ||||
forkhead associated (FHA) domain found in Smad nuclear-interacting protein 1 (SNIP1), FHA domain-containing protein DDL, and similar proteins; SNIP1 is an FHA domain-containing protein required for pre-mRNA splicing as a component of the spliceosome. It inhibits NF-kappaB signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional co-activators. It is involved in microRNA (miRNA) biogenesis. SNIP1 is a regulator of the cell cycle and cyclin D1 expression and may be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. This family also includes Arabidopsis thaliana FHA domain-containing protein DDL and similar proteins. DDL, also called protein DAWDLE, is involved in the microRNA (miRNA) and short interfering RNA (siRNA) biogenesis. It may facilitate DCL1 to access or recognize primary miRNAs. DDL binds RNA non-specifically. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438728 [Multi-domain] Cd Length: 111 Bit Score: 41.13 E-value: 2.99e-04
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| FHA_FOXK | cd22688 | forkhead associated (FHA) domain found in the Forkhead box protein K (FOXK) subfamily; The ... |
41-84 | 5.39e-04 | ||||
forkhead associated (FHA) domain found in the Forkhead box protein K (FOXK) subfamily; The FOXK subfamily includes two-winged helix transcription factors, FOXK1 and FOXK2. FOXK1, also called myocyte nuclear factor (MNF), acts as a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of myoglobin genes. It positively regulates Wnt/beta-catenin signaling by translocating dishevelled (DVL) proteins into the nucleus. It also reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression. In addition, FOXK1 plays important roles in multiple human cancers. FOXK2, also called cellular transcription factor ILF-1 or interleukin enhancer-binding factor 1, is a transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. It binds to NFAT-like motifs (purine-rich) in the IL2 promoter. It also binds to the HIV-1 long terminal repeat. FOXK2 may be involved in both positive and negative regulation of important viral and cellular promoter elements. In addition, FOXK2 plays a critical role in suppressing tumorigenesis. The Forkhead (FH) domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438740 [Multi-domain] Cd Length: 100 Bit Score: 39.95 E-value: 5.39e-04
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| FHA_CHK2 | cd22666 | forkhead associated (FHA) domain found in checkpoint kinase 2 (Chk2) and similar proteins; ... |
19-140 | 6.08e-04 | ||||
forkhead associated (FHA) domain found in checkpoint kinase 2 (Chk2) and similar proteins; Chk2, also called Hucds1, Cds1 homolog, or serine/threonine-protein kinase Chk2, plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438718 [Multi-domain] Cd Length: 112 Bit Score: 40.30 E-value: 6.08e-04
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| FHA_Ct664-like | cd22696 | forkhead associated (FHA) domain found in Chlamydia trachomatis Ct664 protein and similar ... |
32-80 | 1.24e-03 | ||||
forkhead associated (FHA) domain found in Chlamydia trachomatis Ct664 protein and similar proteins; This subfamily corresponds to a group of uncharacterized FHA domain-containing proteins which show high sequence similarity with Chlamydia trachomatis Ct664 protein. Ct664 situates within the type III secretion system cluster that also encodes an STPK (CT673 in C. trachomatis), suggesting a role of CT664 in the chlamydial type III secretion system by mediating phosphorylation-dependent protein-protein interactions. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438748 [Multi-domain] Cd Length: 97 Bit Score: 39.01 E-value: 1.24e-03
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| FHA_Ki67 | cd22673 | forkhead associated (FHA) domain found in proliferation marker protein Ki-67 and similar ... |
32-79 | 6.35e-03 | ||||
forkhead associated (FHA) domain found in proliferation marker protein Ki-67 and similar proteins; Ki-67, also called antigen identified by monoclonal antibody Ki-67, antigen KI-67, or antigen Ki67, acts as a biological surfactant to disperse mitotic chromosomes. It is required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly. Ki-67 binds DNA with a preference for supercoiled DNA and AT-rich DNA. It may also play a role in chromatin organization. Ki-67 contains an FHA domain at its N-terminus. The FHA domain is a small phosphopeptide recognition module. Pssm-ID: 438725 [Multi-domain] Cd Length: 95 Bit Score: 36.81 E-value: 6.35e-03
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