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 517057344  13 LLQTGPGGQSRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEALLQTASLKAGD 91
Cdd:cd00060    2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-GGGVYLEDLGsTNGTFVNGKRITPPVPLQDGD 80

                         90
                 ....*....|...
gi 517057344  92 SFRLGkDVEFQFV 104
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 517057344  13 LLQTGPGGQSRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEALLQTASLKAGD 91
Cdd:cd00060    2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-GGGVYLEDLGsTNGTFVNGKRITPPVPLQDGD 80

                         90
                 ....*....|...
gi 517057344  92 SFRLGkDVEFQFV 104
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 517057344   33 SIGRASNADIVVDDPFLAPIHARIERQSDGGFIIRRMG-LNPIMLRGEALL-QTASLKAGDSFRL 95
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 517057344  13 LLQTGPGGQSRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERQsDGGFIIRRMG-LNPIMLRGEALLQTASLKAGD 91
Cdd:cd00060    2 LIVLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-GGGVYLEDLGsTNGTFVNGKRITPPVPLQDGD 80

                         90
                 ....*....|...
gi 517057344  92 SFRLGkDVEFQFV 104
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 517057344   33 SIGRASNADIVVDDPFLAPIHARIERQSDGGFIIRRMG-LNPIMLRGEALL-QTASLKAGDSFRL 95
Cdd:pfam00498   2 TIGRSPDCDIVLDDPSVSRRHAEIRYDGGGRFYLEDLGsTNGTFVNGQRLGpEPVRLKDGDVIRL 66

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 517057344  19 GGQSRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERQSDGGFIIRRMG-LNPIMLRGEALLQTASLKAGDSFRLGk 97
Cdd:cd22673   10 GTDGSRFPLTKKSCTFGRDLSCDIRIQLPGVSREHCRIEVDENGKAYLENLStTNPTLVNGKAIEKSAELKDGDVITIG- 88

                 ....*.
gi 517057344  98 DVEFQF 103
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 517057344   21 QSRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERQSDGGFIIRRMGLNPIMLRGEALLQ-TASLKAGDSFRLGKdV 99
Cdd:pfam16697   8 AGAEFPLEGGRYRIGSDPDCDIVLSDKEVSRVHLKLEVDDEGWRLDDLGSGNGTLVNGQRVTElGIALRPGDRIELGQ-T 86

                  ....*
gi 517057344  100 EFQFV 104
Cdd:pfam16697  87 EFCLV 91

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 517057344  13 LLQTGPGGQSRSHVLdrPEMSIGRASNADIVVDDPFLAPIHARIERQSDGGFIIRRMGLNPIMLRGEAlLQTASLKAGDS 92
Cdd:cd22694    1 LTIRIPGGELRFDPG--SSVRIGRDPDADVRLDDPRVSRRHALLEFDGDGWVYTDLGSRNGTYLNGRR-VQQVKLSDGTR 77

                         90
                 ....*....|....*.
gi 517057344  93 FRLGK---DVEFQFVV 105
Cdd:cd22694   78 VRLGDptdGPALTVVV 93

forkhead associated (FHA) domain found in Saccharomyces cerevisiae DNA damage response protein kinase DUN1 and similar proteins; DUN1 is a protein kinase that controls the DNA damage response in yeast. It phosphorylates SML1 on serine residues and cooperates with the PAN deadenylation complex in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress. It contains an FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 517057344  26 VLDRPEMSIGRASNADIVVDDPFLAPIHARIERQSDGGFIIRRMGLNPIMLRGEALL-QTASLKAGDSFRLGKdVEFQFV 104
Cdd:cd22683   17 ITNRNVTTIGRSRSCDLVLSDPSISRFHAELRLEQNGINVIDNNSANGTFINGKRIKgKTYILKNGDIIVFGK-CSFLIK 95

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 517057344  11 PSLLQTGPGGQSRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERqSDGGFIIRRMG-LNPIMLRGeALLQTASLKA 89
Cdd:cd22737    2 PMMKITRPDGDTLTFELPPQAVRIGRASDNDIVIPEGSVSRHHATLVP-TPGGTQIRDLRsTNGTFVNG-LRVDAALLHD 79

                         90
                 ....*....|....
gi 517057344  90 GDSFRLGkDVEFQF 103
Cdd:cd22737   80 GDVVTIG-DIDFVF 92

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 517057344    33 SIGRASN-ADIVVDDPFLAPIHARIERQSDGGFIIRRMG-LNPIMLRGEAL 81
Cdd:smart00240   2 TIGRSSEdCDIQLDGPSISRRHAVIVYDGGGRFYLIDLGsTNGTFVNGKRI 52

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 517057344  26 VLDRPEMSIGRASNADIVVDDPFLAPIHARIeRQSDGGFIIRRMG-LN-PIMLRGEALLQTASLKAGDSFRLGKDVEFQF 103
Cdd:cd22680   17 PFDFSSVSIGRDPENVIVIPDPFVSRNHARI-TVDSNEIYIEDLGsTNgTFVNDFKRIKGPAKLHPNDIIKLGRTTVLKV 95

                 .
gi 517057344 104 V 104
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 517057344  22 SRSHVLDRPEMSIGRASNADIVVDDPFLAPIHARIERQSDG-GFIIRRMG-LNPIMLRGEAL--LQTASLKAGDSFRLG 96
Cdd:cd22691   21 KFSKSEEEDILVVGRHPDCDIVLDHPSISRFHLEIRIIPSRrKITLTDLSsVHGTWVNGQRIepGVPVELEEGDTVRLG 99