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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6642639   32 IILGRNSkksTVDVDLSSLGggmnISRNHARIFYDftRRRFSLEVLG-KNGCFVEGVlhlPGNPNVKLDSQDLLQIGDKE 110
Cdd:COG1716  23 LTIGRAP---DNDIVLDDPT----VSRRHARIRRD--GGGWVLEDLGsTNGTFVNGQ---RVTEPAPLRDGDVIRLGKTE 90

                ....*.
gi 6642639  111 FYFLLP 116
Cdd:COG1716  91 LRFRLS 96

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 6642639      32 IILGRNSKKSTVDVDLSSlgggmnISRNHARIFYDFTRRRFSLEVLGKNGCFVEGV 87
Cdd:smart00240   1 VTIGRSSEDCDIQLDGPS------ISRRHAVIVYDGGGRFYLIDLGSTNGTFVNGK 50

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6642639   16 AKLQGEDFEYYMQSYSIILGRNSKKSTVDVDL--SSLgggmnISRNHARIFYDftRRRFSLEVLGKNGCFVEGVLHLPGN 93
Cdd:cd22688   5 ARLEGREFEYLMRKSRVVIGRNSSRGPVDVNMghSSF-----ISRKHLEIFYE--GGRFFLLCNGKNGIFVDGVFQRRGA 77

                ....*...
gi 6642639   94 PNVKLDSQ 101
Cdd:cd22688  78 PPLQLPKT 85

forkhead associated (FHA) domain found in forkhead box protein K2 (FOXK2) and similar proteins; 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 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 FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6642639   16 AKLQGEDFEYYMQSYSIILGRNSKKSTVDVdlsSLGGGMNISRNHARIF-------YDFTRRRFSLEVLGKNGCFVEGVL 88
Cdd:cd22723   5 ARLEGREFEYLMKKRSVTIGRNSSQGSVDV---SMGHSSFISRRHLEIFtagedggDGGGGGDFYLRCLGKNGVFVDGVF 81

                        90
                ....*....|
gi 6642639   89 HLPGNPNVKL 98
Cdd:cd22723  82 QRRGAPPLQL 91

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6642639   24 EYYMQSYSIILGRNSKKSTVDVDLSslgggmnISRNHARIFYDftRRRFSLEVLG-KNGCFVEGVlhlPGNPNVKLDSQD 102
Cdd:cd00060  13 EFPLTKGVVTIGRSPDCDIVLDDPS-------VSRRHARIEVD--GGGVYLEDLGsTNGTFVNGK---RITPPVPLQDGD 80

                        90
                ....*....|.
gi 6642639  103 LLQIGDKEFYF 113
Cdd:cd00060  81 VIRLGDTTFRF 91

forkhead associated (FHA) domain found in Saccharomyces cerevisiae plasmid maintenance protein 2 (PLM2) and similar proteins; This subfamily includes two homologs PLM2 and TOS4 (also called target of SBF protein 4), which are predicted to be chromatin-associated proteins. They bind to the promoters of genes with functions important for the G1/S (start) transition. PLM2 targets primarily genes involved in DNA synthesis and repair, chromosome segregation, nuclear division, and transcription. TOS4 targets primarily genes involved in pheromone response, polarized growth, and transcription. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 6642639   32 IILGRNSKKSTVdvdlsSLGGGMNISRNHARIFYDFTRRRFSLEVLGKNGCFV 84
Cdd:cd22699  23 VTIGRSSQSCDY-----ISRKNKQISRVHATIQYDPDRNELEITCLGWNGVTV 70

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 6642639   31 SIILGRNSKksTVDVDLSslgggmnISRNHARIFYDFTRRRFSLEVLGKNGCFV 84
Cdd:cd22671  20 PTVLGRGPL--LGIRDKR-------VSRKQAEITVDDDTGSVTVTQLGTNPSFV 64

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6642639   20 GEDFEYYMQSYSIILGRNSkksTVDVDLSSlgggMNISRNHARIFYDFTRRrFSLEVLGK-NGCFVEGVlhlPGNPNVKL 98
Cdd:cd22673  11 TDGSRFPLTKKSCTFGRDL---SCDIRIQL----PGVSREHCRIEVDENGK-AYLENLSTtNPTLVNGK---AIEKSAEL 79

                        90
                ....*....|....*
gi 6642639   99 DSQDLLQIGDKEFYF 113
Cdd:cd22673  80 KDGDVITIGGRSFRF 94

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6642639   24 EYYMQS-YSIILGRNSKksTVDVDLSSlgggMNISRNHARIFYDFTRRRFSLEVLGKNGCFVEGVlhlPGNPNVKLDSQD 102
Cdd:cd22696  14 EFFLESgKTYFIGKDPT--VCDIVLQD----PSISRQHARLSIDQDNRVFIEDLSSKNGVLVNGK---PIEGKEEISGSD 84

                ....*....
gi 6642639  103 LLQIGDKEF 111
Cdd:cd22696  85 VISLGTTSF 93