forkhead associated (FHA) domain found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. Specially, RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       10 WCLRRVGMS--AGWLLLEDGCEVTVGRGFGVTYQLVSkICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPL 87
Cdd:cd22663   1 WCLRRVGHGidPLVLLLEDGKEVTVGRGLGVTYQLVS-TCPLMISRNHCVLKKNDEGQWTIKDNKSLNGVWVNGERIEPL 79

                        90       100       110
                ....*....|....*....|....*....|.
2PIE_A       88 RVYSIHQGDYIQLGVPLENKENAEYEYEVTE 118
Cdd:cd22663  80 KPYPLNEGDLIQLGVPPENKEPAEYVFNLIK 110

forkhead associated (FHA) domain found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. Specially, RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       10 WCLRRVGMS--AGWLLLEDGCEVTVGRGFGVTYQLVSkICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPL 87
Cdd:cd22663   1 WCLRRVGHGidPLVLLLEDGKEVTVGRGLGVTYQLVS-TCPLMISRNHCVLKKNDEGQWTIKDNKSLNGVWVNGERIEPL 79

                        90       100       110
                ....*....|....*....|....*....|.
2PIE_A       88 RVYSIHQGDYIQLGVPLENKENAEYEYEVTE 118
Cdd:cd22663  80 KPYPLNEGDLIQLGVPPENKEPAEYVFNLIK 110

Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
2PIE_A       26 DGCEVTVGRGFGVTYQLVSKicplMISRNHCVLKQNPeGQWTIMDNKSLNGVWLNRARLEplRVYSIHQGDYIQLG 101
Cdd:COG1716  19 DGGPLTIGRAPDNDIVLDDP----TVSRRHARIRRDG-GGWVLEDLGSTNGTFVNGQRVT--EPAPLRDGDVIRLG 87

forkhead associated (FHA) domain found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. Specially, RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       10 WCLRRVGMS--AGWLLLEDGCEVTVGRGFGVTYQLVSkICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPL 87
Cdd:cd22663   1 WCLRRVGHGidPLVLLLEDGKEVTVGRGLGVTYQLVS-TCPLMISRNHCVLKKNDEGQWTIKDNKSLNGVWVNGERIEPL 79

                        90       100       110
                ....*....|....*....|....*....|.
2PIE_A       88 RVYSIHQGDYIQLGVPLENKENAEYEYEVTE 118
Cdd:cd22663  80 KPYPLNEGDLIQLGVPPENKEPAEYVFNLIK 110

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
2PIE_A       26 DGCEVTVGRGFGVTYQLVSKicplMISRNHCVLKQNpEGQWTIMDNKSLNGVWLNRARLEPLRVysIHQGDYIQLG 101
Cdd:cd00060  17 TKGVVTIGRSPDCDIVLDDP----SVSRRHARIEVD-GGGVYLEDLGSTNGTFVNGKRITPPVP--LQDGDVIRLG 85

forkhead associated (FHA) domain found in Saccharomyces cerevisiae defective in mitotic arrest protein 1 (DMA1), 2 (DMA2) and similar proteins; DMA1 (also known as checkpoint forkhead associated with RING domains-containing protein 1, or CHF1) and DMA2 (also known as checkpoint forkhead associated with RING domains-containing protein 2, or CHF2) are E3 ubiquitin-protein ligases which function in cell cycle retarding in conjunction with the UBC4 and UBC13/MMS2 complex, two E2 ubiquitin conjugating enzymes. They are involved in nutritional control of the cell cycle and required for proper spindle positioning, likely regulating septin ring deposition at the bud neck. DMA1 targets the degradation of G1 cyclin PCL1. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
2PIE_A       50 MISRNHCVLKQNpEGQWTIMDNKSLNGVWLNRARLEPL----RVYSIHQGDYIQLG 101
Cdd:cd22692  62 VVSRTHGCIKVD-EGNWYIKDVKSSSGTFLNHQRLSPAsrtsKPYPLRDGDILQLG 116

forkhead associated (FHA) domain found in transcription factor 19 (TCF-19) and similar proteins; TCF-19, also called transcription factor SC1, was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It also functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. TCF-19 contains an N-terminal fork head association domain (FHA), a proline rich region, and a C-terminal plant homeodomain (PHD) finger. The FHA domain may serve as a nuclear signaling domain or as a phosphoprotein binding domain. The proline rich region is a common characteristic of trans-activating factors. The PHD finger may allow TCF-19 to interact with chromatin via methylated histone H3.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       12 LRRVGMSAGWL-------LLEDGCEVTVGRGF---GVTyqLVSKICPLMISRNHCVLKQNPE--GQWTIM--DNkSLNGV 77
Cdd:cd22685   5 LLRIGLSASRSeprdlytFRPDLCEYRIGRNPevcDVF--LCSSQHPNLISREHAEIHAERDgnGNWKVLieDR-STNGT 81

                        90       100
                ....*....|....*....|....
2PIE_A       78 WLNRARLEPLRVYSIHQGDYIQLG 101
Cdd:cd22685  82 YVNDVRLQDGQRRELSDGDTITFG 105

Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain.

                           10        20        30
                   ....*....|....*....|....*....|....
2PIE_A          51 ISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARL 84
Cdd:smart00240  19 ISRRHAVIVYDGGGRFYLIDLGSTNGTFVNGKRI 52

forkhead associated (FHA) domain found in sarcolemmal membrane-associated protein (SLMAP) and similar proteins; SLMAP, also called sarcolemmal-associated protein (SLAP), is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. It is a cardiac membrane protein that plays an important role in E-C coupling and the adrenergic response of the heart. Overexpression of the SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. SLMAP contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       51 ISRNHCVLKQNPeGQWTIMDNKSLNGVWLNRARL----EPLRVYSIHQGDYIQLGVplenkenaeyeyEVTEEDWETIYP 126
Cdd:cd22679  49 LSRNHALLWYDD-GKFYLQDTKSSNGTFVNNQRLskgsEESEPRELHSGDIVQFGV------------DVVENSRKVTHG 115

                .
2PIE_A      127 C 127
Cdd:cd22679 116 C 116

forkhead associated (FHA) domain found in Myxococcus xanthus EspA and similar proteins; EspA is a histidine protein kinase with a fork head-associated (FHA) domain at the N-terminus and a receiver domain at the C-terminus. It functions as an inhibitor of sporulation during early fruiting body development while cells are aggregating into raised mounds. EspA is part of a two-component signal transduction system that regulates the timing of sporulation initiation. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
2PIE_A       29 EVTVGRGFGVTYqlvsKICPLMISRNHC-VLKQNpeGQWTIMDNKSLNGVWLNRARLEPlrvYSIHQGDYIQLG 101
Cdd:cd22698  22 EFTIGRSSNNDI----RLNDHSVSRHHArIVRQG--DKCNLTDLGSTNGTFLNGIRVGT---HELKHGDRIQLG 86

forkhead associated (FHA) domain found in Synechocystis sp. Slr1951 protein and similar proteins; This subfamily corresponds to a group of uncharacterized FHA domain-containing proteins which show high sequence similarity with Synechocystis sp. protein Slr1951 and protein Sll1895. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       30 VTVGRGFGVTYQLVSKicplMISRNHCVL--KQNPEGQ---WTIMD----NKSLNGVWLNRARLEplrVYSIHQGDYIQL 100
Cdd:cd22697  20 YTIGRHPGNDIQIPSQ----QISRRHATLrrKINPNLDisfWIIDGdlegAESLNGLWVNGERIL---QHELVNGDEIAL 92

                        90
                ....*....|....
2PIE_A      101 GvpleNKENAEYEY 114
Cdd:cd22697  93 G----PKIVLRYQA 102

forkhead associated (FHA) domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 64 (VPS64) and similar proteins; This subfamily includes VPS64 (also called factor arrest protein 9 or FAR9) and factor arrest protein 10 (FAR10), which participate in the control of the re-entry into the cell cycle following pheromone treatment. VPS64 is also involved in vacuolar protein sorting. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
2PIE_A       51 ISRNHCVLKQNPE-GQWTIMDNKSLNGVWLNRARLEPLRVySIHQGDYIQLGVPLENK 107
Cdd:cd22695  65 LSRNHACLSCDPTtGKVYIRDLKSSNGTFVNGQKIRQNDV-ELKVGDEVDLGTDIDSK 121

forkhead associated (FHA) domain found in Arabidopsis thaliana Protein PARALLEL SPINDLE 1 (PS1) and similar proteins; PS1 is an FHA domain-containing protein required for normal spindle orientation at male meiosis II and normal formation of tetrad of microspores. It is not involved in female meiosis. Mutations in PS1 lead to the production of diploid pollen grains. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
2PIE_A       51 ISRNHCVLKQNPEGQ-WTIMDNKSLNGVWLNRARLEPLRVYSIHQGDYIQLG 101
Cdd:cd22691  48 ISRFHLEIRIIPSRRkITLTDLSSVHGTWVNGQRIEPGVPVELEEGDTVRLG 99

forkhead associated (FHA) domain found in aprataxin, bifunctional polynucleotide phosphatase/kinase (PNKP), aprataxin and PNK-like factor (APLF), and similar proteins; The family includes aprataxin, PNKP, and APLF. Aprataxin (EC 3.6.1.71/EC 3.6.1.72), also called forkhead-associated domain histidine triad-like protein (FHA-HIT), is a DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair, and base excision repair. It catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. It can also hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity. Likewise, it catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA but has higher specific activity with 5'-linked adenosine (AppDNA). PNKP (EC 3.1.3.32/EC 2.7.1.78), also called DNA 5'-kinase/3'-phosphatase, or polynucleotide kinase-3'-phosphatase, plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNKP ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone. APLF, also called apurinic-apyrimidinic endonuclease APLF, PNK and APTX-like FHA domain-containing protein, or XRCC1-interacting protein 1 (XIP1), is a novel apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease with conserved zinc-finger-like motifs involved in single-strand and double-strand DNA break repair. It is recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. It can introduce nicks at hydroxyuracil and other types of pyrimidine base damage. Together with PARP3, APLF promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). Members of this family contain an FHA domain at their N-terminus. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2PIE_A       22 LLLEDGCEVTVGRG--FGVTYQLVskicplmiSRNHCVLK-QNPEGQWTIMdNKSLNGVWLNRARLEPLRV-----YSIH 93
Cdd:cd22671  13 IELKEGGPTVLGRGplLGIRDKRV--------SRKQAEITvDDDTGSVTVT-QLGTNPSFVNRADGEGKVLkkgesVELK 83

                        90       100
                ....*....|....*....|....
2PIE_A       94 QGDYIQLgvpLENKenaeYEYEVT 117
Cdd:cd22671  84 DGDVISL---LPGK----YPFRVE 100

forkhead associated (FHA) domain found in Corynebacterium glutamicum oxoglutarate dehydrogenase inhibitor (OdhI) and similar proteins; OdhI is an essential component of the PknG signaling pathway. It regulates glutamate production under biotin non-limiting conditions. It can inhibit the activity of 2-oxoglutarate dehydrogenase only when it is unphosphorylated. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
2PIE_A       49 LMISRNHCVLKQNpEGQWTIMDNKSLNGVWLNRarlEPLRVYSIHQGDYIQLG 101
Cdd:cd22721  46 VTVSRRHAEFRIN-EGEFEVVDVGSLNGTYVNR---EPRNAQVMQTGDEIQIG 94

first forkhead associated (FHA) domain found in Saccharomyces cerevisiae Serine/threonine-protein kinase RAD53 and similar proteins; RAD53, also called CHEK2 homolog, or serine-protein kinase 1 (Spk1), is a nuclear protein kinase that phosphorylates proteins on serine, threonine, and tyrosine. It controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints and prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. It may be involved in the phosphorylation of RPH1. RAD53 contains two FHA domains. This model corresponds to the first one. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
2PIE_A       31 TVGRGFGVTYQLVSkicpLMISRNHCVLKQ---NPEGQWTIMDNKSLNGVWLNRARLEPLRVYSIHQGDYIQLGV 102
Cdd:cd22689  48 TFGRHPACDYHLGN----SRLSNKHFQILLgesDPSDGNVLLNDISSNGTWLNGQRLEKNSNQLLSQGDEITIGV 118

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
2PIE_A       51 ISRNHCVLK-QNPEGQWT--IMDNKSLNGVWLNRARLEPLRVYSIHQGDYIQL 100
Cdd:cd22681  66 CSKQHCVIQfRNVKGILKpyIMDLDSSNGTCLNDNVIPSSRYVELRSGDVITF 118

forkhead associated (FHA) domain found in Arabidopsis thaliana protein phosphatase 2C 70 (AtPP2C70) and similar proteins; AtPP2C70, also called kinase-associated protein phosphatase, or protein ROOT ATTENUATED GROWTH 1, dephosphorylates the serine/threonine receptor-like kinase RLK5. It may function as a signaling component in a pathway involving RLK5. It acts as a negative regulator of the CLAVATA1 signaling in plant development by binding and dephosphorylating CLAVATA1. It is also a component of a signaling pathway which mediates adaptation to NaCl stress. It contains an FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
2PIE_A       26 DGCEVTVGRGFGVTYQLVSKICplmiSRNHCVLKQN-PEGQWTIMDNKSLNGVWLNRARLEP-LRVYSIHQGDYIQLG 101
Cdd:cd22678  21 TRLPLTIGRIQRGDIALKDDEV----SGKHARIEWNsTGSKWELVDLGSLNGTLVNGESISPnGRPVVLSSGDVITLG 94