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 1582722977  14 LLQTGPGGQSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEALLQTASLKAGD 92
Cdd:cd00060     2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-GGGVYLEDLGsTNGTFVNGKRITPPVPLQDGD 80

                          90
                  ....*....|...
gi 1582722977  93 SFRLGkDVEFQFV 105
Cdd:cd00060    81 VIRLG-DTTFRFE 92

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 1582722977  14 LLQTGPGGQSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEALLQTASLKAGD 92
Cdd:cd00060     2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-GGGVYLEDLGsTNGTFVNGKRITPPVPLQDGD 80

                          90
                  ....*....|...
gi 1582722977  93 SFRLGkDVEFQFV 105
Cdd:cd00060    81 VIRLG-DTTFRFE 92

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1582722977  34 SIGRAANADIVVDDPFLAPIHARIERQSDGGFIIRRMG-LNPIMLRGEALLQT-ASLKAGDSFRL 96
Cdd:pfam00498   2 TIGRSPDCDIVLDDPSVSRRHAEIRYDGGGRFYLEDLGsTNGTFVNGQRLGPEpVRLKDGDVIRL 66

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 1582722977  14 LLQTGPGGQSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEALLQTASLKAGD 92
Cdd:cd00060     2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-GGGVYLEDLGsTNGTFVNGKRITPPVPLQDGD 80

                          90
                  ....*....|...
gi 1582722977  93 SFRLGkDVEFQFV 105
Cdd:cd00060    81 VIRLG-DTTFRFE 92

Predicted component of the type VI protein secretion system, contains a FHA domain [Signal transduction mechanisms, Intracellular trafficking, secretion, and vesicular transport];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  19 PGGQSRSHVLDRPEMSIGRAANADIVVDDP--FLAPIHARIERQsDGGFIIRRMGLNPIMLRGEAL----LQTASLKAGD 92
Cdd:COG3456    14 ESGSAASATFGRGGGTIGRSADCDWVLPDPdrSVSRRHAEIRFR-DGAFCLTDLSTNGTFLNGSDHplgpGRPVRLRDGD 92

                          90
                  ....*....|....
gi 1582722977  93 SFRLGkdvEFQFVV 106
Cdd:COG3456    93 RLRIG---DYEIRV 103

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 1582722977  20 GGQSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQSDGGFIIRRMG-LNPIMLRGEALLQTASLKAGDSFRLGk 98
Cdd:cd22673    10 GTDGSRFPLTKKSCTFGRDLSCDIRIQLPGVSREHCRIEVDENGKAYLENLStTNPTLVNGKAIEKSAELKDGDVITIG- 88

                  ....*.
gi 1582722977  99 DVEFQF 104
Cdd:cd22673    89 GRSFRF 94

Inner membrane component of T3SS, cytoplasmic domain; Yop-YscD-cpl is the cytoplasmic domain of Yop proteins like YscD from Proteobacteria. YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  22 QSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQSDGGFIIRRMGLNPIMLRGEALLQ-TASLKAGDSFRLGKdV 100
Cdd:pfam16697   8 AGAEFPLEGGRYRIGSDPDCDIVLSDKEVSRVHLKLEVDDEGWRLDDLGSGNGTLVNGQRVTElGIALRPGDRIELGQ-T 86

                  ....*
gi 1582722977 101 EFQFV 105
Cdd:pfam16697  87 EFCLV 91

forkhead associated (FHA) domain found in Mycobacterium tuberculosis GarA, Corynebacterium glutamicum OdhI and similar proteins; This family includes Mycobacterium tuberculosis glycogen accumulation regulator GarA and Corynebacterium glutamicum oxoglutarate dehydrogenase inhibitor (OdhI). GarA is involved in the regulation of glutamate metabolism. It acts as a phosphorylation-dependent molecular switch that modulates the activities of Kgd, Gdh and GltB. GarA binds to Kgd, Gdh, GltB, PknB, and the N-terminal region of PknG via its FHA domain. OdhI is an essential component of the PknG signaling pathway. 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  14 LLQTGPGGQSRsHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEaLLQTASLKAGD 92
Cdd:cd22684     5 VVRRGPNAGAR-FLLDQDVTTAGRHPESDIFLDDVTVSRRHAEFRRA-EGGFVVRDVGsLNGTYVNRE-RIDSAVLRNGD 81

                  ....*.
gi 1582722977  93 SFRLGK 98
Cdd:cd22684    82 EVQIGK 87

forkhead associated (FHA) domain found in Mycobacterium tuberculosis FHA domain-containing protein FhaB and similar proteins; FhaB, also called FtsZ-interacting protein A (FipA), is a putative virulence factor involved in regulating cell shape. It can interact with polyketide-associated protein PapA5, a putative membrane protein involved in the biosynthesis of virulence enhancing lipids. FhaB regulates growth and cell division. It is probably required for divisomal protein assembly under oxidative stress. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  17 TGPGGQSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQSDGGFIIRRMGLNPIMLRGEALLQTASLKAGDSFRL 96
Cdd:cd22693     4 IEGTLQGQTFPIDKSGITIGRADDNDLVLSDDFVSSRHARIYLQGSSWYLEDLGSTNGTFVNGNRVTQPVVVQPGDTIRI 83

                  ....
gi 1582722977  97 GKDV 100
Cdd:cd22693    84 GATV 87

second forkhead associated (FHA) domain found in Mycobacterium tuberculosis ABC transporter ATP-binding/permease protein Rv1747 and similar proteins; Rv1747 is a putative ATP-binding cassette (ABC) transporter involved in the translocation of an unknown substrate across the membrane. It is required for normal virulent infection by M. tuberculosis. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). Recruitment and phosphorylation of Rv1747 depend on the interaction between its two non-redundant FHA domains and the autophosphorylated form of serine/threonine protein kinase PknF. This model corresponds to the second FHA domain, which has a circularly permuted FHA domain fold with a conserved pThr-binding interface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  12 PSLLQTGPGGQSRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERqSDGGFIIRRMG-LNPIMLRGeALLQTASLKA 90
Cdd:cd22737     2 PMMKITRPDGDTLTFELPPQAVRIGRASDNDIVIPEGSVSRHHATLVP-TPGGTQIRDLRsTNGTFVNG-LRVDAALLHD 79

                          90
                  ....*....|....
gi 1582722977  91 GDSFRLGkDVEFQF 104
Cdd:cd22737    80 GDVVTIG-DIDFVF 92

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  32 EMSIGRAANADIVVDDPFLAPIHARI---------------ERQSDGGFII--RRMGLNPIMLrgeallqtasLKAGDSF 94
Cdd:cd22670    23 VITIGRSPSCDIVINDPFVSRTHCRIysvqfdessaplvyvEDLSSNGTYLngKLIGRNNTVL----------LSDGDVI 92

                          90
                  ....*....|.
gi 1582722977  95 RLGKDVEFQFV 105
Cdd:cd22670    93 EIAHSATFVYV 103

forkhead associated (FHA) domain found in Sulfolobus Acidocaldarius FHA domain-containing protein ArnA and similar proteins; ArnA is an FHA domain-containing protein from Sulfolobus acidocaldarius that was shown to strongly interact with ArnB, a von Willebrand domain-containing protein. They act synergistically and negatively to modulate motility. ArnA is involved in regulating archaella expression in S. acidocaldarius. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1582722977  27 VLDRPEMSIGRAANADIVVDDPFLAPIHARIeRQSDGGFIIRRMG-LN-PIMLRGEALLQTASLKAGDSFRLGKDVEFQF 104
Cdd:cd22680    17 PFDFSSVSIGRDPENVIVIPDPFVSRNHARI-TVDSNEIYIEDLGsTNgTFVNDFKRIKGPAKLHPNDIIKLGRTTVLKV 95

                  .
gi 1582722977 105 V 105
Cdd:cd22680    96 T 96

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1582722977  23 SRSHVLDRPEMSIGRAANADIVVDDPFLAPIHARIERQSDG-GFIIRRMG-LNPIMLRGEAL--LQTASLKAGDSFRLG 97
Cdd:cd22691    21 KFSKSEEEDILVVGRHPDCDIVLDHPSISRFHLEIRIIPSRrKITLTDLSsVHGTWVNGQRIepGVPVELEEGDTVRLG 99