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 392891661   8 IKNSSGEEVYVLKEKgsVVNFGREKKVCHITFDPHaarVSRIHASIEWGDEGLFFTD-KSKEGTEINGTRLKQsSQELHE 86
Cdd:cd00060    5 LDGDGGGREFPLTKG--VVTIGRSPDCDIVLDDPS---VSRRHARIEVDGGGVYLEDlGSTNGTFVNGKRITP-PVPLQD 78

                         90
                 ....*....|....*
gi 392891661  87 GvYQLAIGGISMTLE 101
Cdd:cd00060   79 G-DVIRLGDTTFRFE 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 392891661   8 IKNSSGEEVYVLKEKgsVVNFGREKKVCHITFDPHaarVSRIHASIEWGDEGLFFTD-KSKEGTEINGTRLKQsSQELHE 86
Cdd:cd00060    5 LDGDGGGREFPLTKG--VVTIGRSPDCDIVLDDPS---VSRRHARIEVDGGGVYLEDlGSTNGTFVNGKRITP-PVPLQD 78

                         90
                 ....*....|....*
gi 392891661  87 GvYQLAIGGISMTLE 101
Cdd:cd00060   79 G-DVIRLGDTTFRFE 92

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392891661   26 VNFGREKKvCHITFDphAARVSRIHASIEWGDEGLFF-TD-KSKEGTEINGTRLKQSSQELHEG 87
Cdd:pfam00498   1 VTIGRSPD-CDIVLD--DPSVSRRHAEIRYDGGGRFYlEDlGSTNGTFVNGQRLGPEPVRLKDG 61

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 392891661    28 FGREKKVCHITFDPHaaRVSRIHASIEWGDEGLFFT--DKSKEGTEINGTRL 77
Cdd:smart00240   3 IGRSSEDCDIQLDGP--SISRRHAVIVYDGGGRFYLidLGSTNGTFVNGKRI 52

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 392891661   8 IKNSSGEEVYVLKEKgsVVNFGREKKVCHITFDPHaarVSRIHASIEWGDEGLFFTD-KSKEGTEINGTRLKQsSQELHE 86
Cdd:cd00060    5 LDGDGGGREFPLTKG--VVTIGRSPDCDIVLDDPS---VSRRHARIEVDGGGVYLEDlGSTNGTFVNGKRITP-PVPLQD 78

                         90
                 ....*....|....*
gi 392891661  87 GvYQLAIGGISMTLE 101
Cdd:cd00060   79 G-DVIRLGDTTFRFE 92

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392891661   26 VNFGREKKvCHITFDphAARVSRIHASIEWGDEGLFF-TD-KSKEGTEINGTRLKQSSQELHEG 87
Cdd:pfam00498   1 VTIGRSPD-CDIVLD--DPSVSRRHAEIRYDGGGRFYlEDlGSTNGTFVNGQRLGPEPVRLKDG 61

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392891661   4 NGIKIKNSSGEEVYVLKEKGSVVNFGREKKVCHITFDP--HAARVSRIHASI-----EWGDEGLFFTDKSKEGTEINGTR 76
Cdd:cd22685    8 IGLSASRSEPRDLYTFRPDLCEYRIGRNPEVCDVFLCSsqHPNLISREHAEIhaerdGNGNWKVLIEDRSTNGTYVNDVR 87

                         90
                 ....*....|..
gi 392891661  77 LKQ-SSQELHEG 87
Cdd:cd22685   88 LQDgQRRELSDG 99

forkhead associated (FHA) domain found in the family of TRAF-interacting protein with FHA domain-containing protein A (TIFA); The TIFA family includes TIFA and TIFA-like protein, TIFAB. TIFA, also called putative MAPK-activating protein PM14, putative NF-kappa-B-activating protein 20, or TRAF2-binding protein (T2BP), is an adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs). It promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism. TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling. TIFAB, also called TIFA-like protein, inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA. It regulates USP15-mediated p53 signaling during stressed and malignant hematopoiesis. Both TIFA and TIFAB harbor a conserved FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392891661  25 VVNFGREKKVCHITFdpHAARVSRIHASIE----WGDEGLFFTDK--SKEGT-EINGTRLKQSSQ-ELHeGVYQLAIGGI 96
Cdd:cd22664   34 VLKFGRDSNCCHYTL--QDKRVSRIQFSLQpfkeFNSSVLCFEIKnlSKKTKlWVNGLELGYLNKvELP-AKCTVRFGEF 110

                         90
                 ....*....|
gi 392891661  97 SMTLEVDGDE 106
Cdd:cd22664  111 QFLLEKEDGE 120

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 392891661    28 FGREKKVCHITFDPHaaRVSRIHASIEWGDEGLFFT--DKSKEGTEINGTRL 77
Cdd:smart00240   3 IGRSSEDCDIQLDGP--SISRRHAVIVYDGGGRFYLidLGSTNGTFVNGKRI 52

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 392891661  21 EKGSVVNFGREKKVCHITF-DPhaaRVSRIHASIEWGDEGLFFTD--KSKEGTEINGTRLkqSSQELHEGvyQLAIG-GI 96
Cdd:cd22696   18 ESGKTYFIGKDPTVCDIVLqDP---SISRQHARLSIDQDNRVFIEdlSSKNGVLVNGKPI--EGKEEISG--SDVISlGT 90

                 ....*..
gi 392891661  97 SMTLEVD 103
Cdd:cd22696   91 TSFLLVD 97

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 392891661  23 GSVVNFGREKKvCHITFDPhaARVSRIHASIEWGDEGLFFTDK-SKEGTEINGTRLKQ 79
Cdd:cd22694   15 GSSVRIGRDPD-ADVRLDD--PRVSRRHALLEFDGDGWVYTDLgSRNGTYLNGRRVQQ 69

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392891661  29 GREKKVCHITFDPHAArVSRIHASIE-WGDEGLFF-TD-KSKEGTEINGTRLKQSSQELHE 86
Cdd:cd22686   31 GREKDHGHTIRIPELG-VSKFHAEIYyDDDEQSYTiVDlGSQNGTYLNGVRISQPKEKSDP 90