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 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTPIPAGVP 146
Cdd:cd22693    1 LVIIEGTLQGQTFPIDKSGITIGRADDNDLVLSDDFVSSRHARIYLQGSSWYLEDLGSTNGTFVNGNRVTQPVVVQPGDT 80

                         90
                 ....*....|.
gi 290573126 147 IRIGRTSIELR 157
Cdd:cd22693   81 IRIGATVFEVR 91

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 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTPIPAGVP 146
Cdd:cd22693    1 LVIIEGTLQGQTFPIDKSGITIGRADDNDLVLSDDFVSSRHARIYLQGSSWYLEDLGSTNGTFVNGNRVTQPVVVQPGDT 80

                         90
                 ....*....|.
gi 290573126 147 IRIGRTSIELR 157
Cdd:cd22693   81 IRIGATVFEVR 91

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 290573126   86 IRIGRAPDSTLVITDDYASGRHAQLVPRGD-QWLVEDLGSTNGTYLGRAKVSG-PTPIPAGVPIRI 149
Cdd:pfam00498   1 VTIGRSPDCDIVLDDPSVSRRHAEIRYDGGgRFYLEDLGSTNGTFVNGQRLGPePVRLKDGDVIRL 66

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 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTPIPAGVP 146
Cdd:cd22693    1 LVIIEGTLQGQTFPIDKSGITIGRADDNDLVLSDDFVSSRHARIYLQGSSWYLEDLGSTNGTFVNGNRVTQPVVVQPGDT 80

                         90
                 ....*....|.
gi 290573126 147 IRIGRTSIELR 157
Cdd:cd22693   81 IRIGATVFEVR 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 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTPIPAGVP 146
Cdd:cd00060    2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVDGGGVYLEDLGSTNGTFVNGKRITPPVPLQDGDV 81

                         90
                 ....*....|.
gi 290573126 147 IRIGRTSIELR 157
Cdd:cd00060   82 IRLGDTTFRFE 92

forkhead associated (FHA) domain found in Mycobacterium tuberculosis FHA domain-containing protein FhaA and similar proteins; FhaA regulates cell growth and peptidoglycan synthesis by binding to MviN. It may inhibit the late stages of peptidoglycan synthesis. It contains an FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 290573126  79 LPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTPIPAGVPIRIGRTSIELR 157
Cdd:cd22668   13 YQLREGSNIIGRGSDADFRLPDTGVSRRHAEIRWDGQVAHLTDLGSTNGTTVNNAPVTPEWRLADGDVITLGHSEIIVR 91

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVsGPTPIPAGVP 146
Cdd:cd22698    4 LIEQKGSEEGKDYELDQDEFTIGRSSNNDIRLNDHSVSRHHARIVRQGDKCNLTDLGSTNGTFLNGIRV-GTHELKHGDR 82

                 ....*.
gi 290573126 147 IRIGRT 152
Cdd:cd22698   83 IQLGET 88

first 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 first FHA domain. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 290573126  85 PIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSgPTPIPAGVPIRIGR 151
Cdd:cd22694   17 SVRIGRDPDADVRLDDPRVSRRHALLEFDGDGWVYTDLGSRNGTYLNGRRVQ-QVKLSDGTRVRLGD 82

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 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGpTPIPAGVP 146
Cdd:cd22684    4 LVVRRGPNAGARFLLDQDVTTAGRHPESDIFLDDVTVSRRHAEFRRAEGGFVVRDVGSLNGTYVNRERIDS-AVLRNGDE 82

                 ....*
gi 290573126 147 IRIGR 151
Cdd:cd22684   83 VQIGK 87

forkhead associated (FHA) domain found in Bdellovibrio bacteriovorus GGDEF domain protein DgcB and similar proteins; DgcB is a GGDEF enzyme that produces cyclic-di-GMP in response to an unknown stimulus. It appends the C-terminal GGDEF enzymatic domain with an N-terminal forkhead-associated (FHA) domain that acts as a consensus phosphopeptide sensor. The GGDEF and sensory FHA domains form an asymmetrical dimer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  67 LVVTEGE-LAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTP--IPA 143
Cdd:cd22682    2 LLMIIGPpGVGKQFPITESTIVIGRSVESQVQIDDDSVSRYHAKLAVNPSAVSIIDLGSTNGTIVNGKKIPKLAScdLQN 81

                         90
                 ....*....|
gi 290573126 144 GVPIRIGRTS 153
Cdd:cd22682   82 GDQIKIGNTI 91

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 290573126    86 IRIGRAP-DSTLVITDDYASGRHAQLVPRGD-QWLVEDLGSTNGTYLGRAKV 135
Cdd:smart00240   1 VTIGRSSeDCDIQLDGPSISRRHAVIVYDGGgRFYLIDLGSTNGTFVNGKRI 52

forkhead associated (FHA) domain found in Mycobacterium tuberculosis glycogen accumulation regulator GarA and similar proteins; GarA is an FHA domain-containing protein involved in the regulation of glutamate metabolism. It acts as a phosphorylation-dependent ON/OFF molecular switch that modulates the activities of KGD, GDH and GltB. Its FHA domain has dual specificity. It binds to both phosphorylated upstream partners, such as the kinases PknB and PknG, and nonphosphorylated downstream partners, such as the 2-oxoglutarate decarboxylase KGD. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  67 LVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTpIPAGVP 146
Cdd:cd22720    7 LVVKRGPNAGSRFLLDQAITSAGRHPDSDIFLDDVTVSRRHAEFRLENNEFNVVDVGSLNGTYVNREPVDSAV-LANGDE 85

                 ....*
gi 290573126 147 IRIGR 151
Cdd:cd22720   86 VQIGK 90

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  56 GITSGPRPPRQLVVTEGELAGTQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKV 135
Cdd:cd22721    1 GAENLPAGSALLVVKRGPNAGARFLLDQPTTTAGRHPESDIFLDDVTVSRRHAEFRINEGEFEVVDVGSLNGTYVNREPR 80

                         90
                 ....*....|....*.
gi 290573126 136 SGPTpIPAGVPIRIGR 151
Cdd:cd22721   81 NAQV-MQTGDEIQIGK 95

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  83 NAPIRIGRAPDSTLVITDDYASGRHAQLvprgdqWLV------------EDLgSTNGTYL 130
Cdd:cd22670   21 NQVITIGRSPSCDIVINDPFVSRTHCRI------YSVqfdessaplvyvEDL-SSNGTYL 73

second 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 second one. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 290573126  85 PIRIGRAPDSTLVITDDYASGRH------AQLVPRGDQWlVEDLgSTNGTYLGRAKV 135
Cdd:cd22690   20 TTFIGRSKDCDEEITDPRISKHHciitrkRSGKGLDDVY-VTDT-STNGTFINNNRL 74

forkhead associated (FHA) domain found in Mycobacterium tuberculosis transcriptional regulatory protein EmbR and similar proteins; EmbR is a transcriptional regulator of the embCAB operon encoding cell wall arabinosyltransferases (EmbC, -A, and -B), and is phosphorylated by the cognate mycobacterial serine/threonine protein kinase PknH. It interacts with RNA polymerase and possesses a phosphorylation-dependent ATPase activity. EmbR contains a regulatory C-terminal forkhead-associated (FHA) domain, which mediates binding to a threonine-phosphorylated site in PknH. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  65 RQLVVTEGELagtqLPLGNAPIRIGRAPDSTLVITDDYASGRHAQLVPRGDQWLVEDLGSTNGTYLGRAKVSGPTPIPAG 144
Cdd:cd22669    1 YLHDIASGRG----YPLQAAATRIGRLHDNDIVLDSANVSRHHAVIVDTGTNYVINDLRSSNGVHVQHERIRSAVTLNDG 76

                 ....*.
gi 290573126 145 VPIRIG 150
Cdd:cd22669   77 DHIRIC 82

forkhead associated (FHA) domain found in Trypanosoma brucei Parvulin 42 (TbPar42) and similar proteins; TbPar42 is a nuclear protein that plays a key role in parasite cell proliferation. It exhibits an N-terminal forkhead associated (FHA)-domain and a peptidyl-prolyl-cis/trans-isomerase (PPIase) domain, both connected by a linker. Its PPIase domain adopts a parvulin fold and reflects structural elements of Pin1-type proteins but is catalytically inactive. Its FHA domain may be involved in the binding of phosphorylated target proteins. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  88 IGRAPDSTLVITDDYASGRHAQLVPRGDQ--WLVEDLGSTNGTYLGRAKVSG--PTPIPAGVPIRIGRTS 153
Cdd:cd22675   33 FGRSPVCDYVLEHPSISSVHAVLVFHGEQkcFVLMDLGSTNGVKLNGKRIEKgrPLPLPVGSVIQFGFSA 102

forkhead associated (FHA) domain found in angiogenic factor with G patch and FHA domains 1 (AGGF1) and similar proteins; AGGF1, also called angiogenic factor VG5Q, or G patch domain-containing protein 7 (GPATC7), or vasculogenesis gene on 5q protein, is an angiogenic factor involved in vascular development, angiogenesis, specification of hemangioblasts, and differentiation of veins. It promotes angiogenesis and the proliferation of endothelial cells. It inhibits inflammatory effect and preserve vascular integrity in non-nervous system diseases. Mutated AGGF1 causes susceptibility to Klippel-Trenaunay syndrome, a vascular disorder. Increased AGGF1 expression is associated with tumor angiogenesis. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290573126  88 IGRAPD--STLVITDDYASGRHAQLV---PRGDQWLVeDLGSTNGTYLG------RAKVSGPTPIPAGVPIRIGRTSIEL 156
Cdd:cd22686   30 IGREKDhgHTIRIPELGVSKFHAEIYyddDEQSYTIV-DLGSQNGTYLNgvrisqPKEKSDPYPLTHGDELKIGETTLLF 108

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 290573126  77 TQLPLGNAPIRIGRAPDSTLVITDDYASGRHAQL--VPRGDQWLVEDLGSTNGTYL--GRAKVSGPTPIPAGVPIRIG 150
Cdd:cd22691   22 FSKSEEEDILVVGRHPDCDIVLDHPSISRFHLEIriIPSRRKITLTDLSSVHGTWVngQRIEPGVPVELEEGDTVRLG 99