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 78187977   3 PCFQLLRI----GGGRGGDLYTFHPPSksgCTYRLGCRADLCDVALRPQQEPGLISGVHAELHAELQG-DDWRVSLEDHS 77
Cdd:cd22685   1 PCFQLLRIglsaSRSEPRDLYTFRPDL---CEYRIGRNPEVCDVFLCSSQHPNLISREHAEIHAERDGnGNWKVLIEDRS 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 78187977  78 SQGTLVNNVRLPRGHRLELSDGDLLTFGPEG------QAGTSSSEFYFMFQQV 124
Cdd:cd22685  78 TNGTYVNDVRLQDGQRRELSDGDTITFGHKNgrrvkqWPYQKSSEFYFLFQKV 130

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 78187977   3 PCFQLLRI----GGGRGGDLYTFHPPSksgCTYRLGCRADLCDVALRPQQEPGLISGVHAELHAELQG-DDWRVSLEDHS 77
Cdd:cd22685   1 PCFQLLRIglsaSRSEPRDLYTFRPDL---CEYRIGRNPEVCDVFLCSSQHPNLISREHAEIHAERDGnGNWKVLIEDRS 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 78187977  78 SQGTLVNNVRLPRGHRLELSDGDLLTFGPEG------QAGTSSSEFYFMFQQV 124
Cdd:cd22685  78 TNGTYVNDVRLQDGQRRELSDGDTITFGHKNgrrvkqWPYQKSSEFYFLFQKV 130

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 78187977    31 YRLGcRADLCDVALRPQQepglISGVHAELHAElqgDDWRVSLEDH-SSQGTLVNNVRLPRgHRLELSDGDLLTF 104
Cdd:pfam00498   1 VTIG-RSPDCDIVLDDPS----VSRRHAEIRYD---GGGRFYLEDLgSTNGTFVNGQRLGP-EPVRLKDGDVIRL 66

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 78187977     31 YRLGCRADLCDVALRPQQepglISGVHAELHAELQGddwRVSLEDHSS-QGTLVNNVRL 88
Cdd:smart00240   1 VTIGRSSEDCDIQLDGPS----ISRRHAVIVYDGGG---RFYLIDLGStNGTFVNGKRI 52

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 78187977   3 PCFQLLRI----GGGRGGDLYTFHPPSksgCTYRLGCRADLCDVALRPQQEPGLISGVHAELHAELQG-DDWRVSLEDHS 77
Cdd:cd22685   1 PCFQLLRIglsaSRSEPRDLYTFRPDL---CEYRIGRNPEVCDVFLCSSQHPNLISREHAEIHAERDGnGNWKVLIEDRS 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 78187977  78 SQGTLVNNVRLPRGHRLELSDGDLLTFGPEG------QAGTSSSEFYFMFQQV 124
Cdd:cd22685  78 TNGTYVNDVRLQDGQRRELSDGDTITFGHKNgrrvkqWPYQKSSEFYFLFQKV 130

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 78187977  27 SGCTYRLGcRADLCDVALRPQQepglISGVHAELHAelqgDDWRVSLEDHSSQ-GTLVNNVRLPRGHRLElsDGDLLTFG 105
Cdd:cd00060  17 TKGVVTIG-RSPDCDIVLDDPS----VSRRHARIEV----DGGGVYLEDLGSTnGTFVNGKRITPPVPLQ--DGDVIRLG 85

                .
gi 78187977 106 P 106
Cdd:cd00060  86 D 86

forkhead associated (FHA) domain found in nibrin and similar proteins; Nibrin (NBN), also called cell cycle regulatory protein p95, or Nijmegen breakage syndrome protein 1 (NBS1), is a novel DNA double-strand break repair protein that is mutated in Nijmegen breakage syndrome. It is a component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. Nibrin modulates the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. Nibrin also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. Nibrin is a major player in the control of intra-S-phase checkpoint. This subfamily also includes Schizosaccharomyces pombe DNA repair and telomere maintenance protein Nbs1 and Arabidopsis thaliana AtNbs1. SpNbs1 is an FHA domain-containing protein required for DNA damage repair and S-phase DNA damage checkpoint. It is involved in telomere length maintenance and maintenance of chromatin structure. AtNbs1 is a component of MRN complex. It also functions in the very early stages of meiosis. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 78187977  30 TYRLGcRADlCDVALRPQQEpglISGVHAEL---HAELQGDDW----RVSLEDHSSQGTLVNNVRLPRGHRLELSDGDLL 102
Cdd:cd22667  21 EYTVG-RKD-CDIIIVDDSS---ISRKHATLtvlHPEANLSDPdtrpELTLKDLSKYGTFVNGEKLKGGSEVTLKDGDVI 95

                ...
gi 78187977 103 TFG 105
Cdd:cd22667  96 TFG 98

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 78187977  36 RADLCDVALRPQQepGLISGvhaeLHAELQGDDWRVSLEDHSSQGTLVNN--VRLPRGHRLELSDGDLLTFGP 106
Cdd:COG3456  32 RSADCDWVLPDPD--RSVSR----RHAEIRFRDGAFCLTDLSTNGTFLNGsdHPLGPGRPVRLRDGDRLRIGD 98

forkhead associated (FHA) domain found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also called RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22 and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated-(FHA) domain and a RING-HC finger. The CHFR FHA domain has been crystallized as a segment-swapped dimer. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 78187977  36 RADLCDVALrpqqePG--LISGVHAELhaeLQGDDWRVSLEDHSSQGTLVNNVRLPRGHRLELSDGDLLTF 104
Cdd:cd22672  27 RAKDCDLSF-----PGnkLVSGDHCKI---IRDEKGQVWLEDTSTNGTLVNKVKVVKGQKVELKHGDVIYL 89

forkhead associated (FHA) domain found in sarcolemmal membrane-associated protein (SLMAP) and similar proteins; SLMAP, also called sarcolemmal-associated protein (SLAP), is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. It is a cardiac membrane protein that plays an important role in E-C coupling and the adrenergic response of the heart. Overexpression of the SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. SLMAP contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 78187977  61 HAELQGDDWRVSLED-HSSQGTLVNNVRLPRGHRL----ELSDGDLLTFG 105
Cdd:cd22679  53 HALLWYDDGKFYLQDtKSSNGTFVNNQRLSKGSEEseprELHSGDIVQFG 102

forkhead associated (FHA) domain found in mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins; MDC1, also called nuclear factor with BRCT domains 1 (NFBD1), is a nuclear chromatin-associated protein that is required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S and G2/M phases of the cell cycle. It directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. MDC1 contains a forkhead-associated (FHA) domain and two BRCT domains, as well as an internal 41-amino acid repeat sequence. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 78187977  35 CRADLCDVALrPQQEpglISGVHAELhaELQGDDWrvSLED-HSSQGTLVNN-VRLPRGHRLELSDGDLLTFG 105
Cdd:cd22665  26 GRDPSCSVVL-PDKS---VSKQHACI--EVDGGTH--LIEDlGSTNGTRIGNkVRLKPNVRYELIDGDLLLFG 90

forkhead associated (FHA) domain found in checkpoint kinase 2 (Chk2) and similar proteins; Chk2, also called Hucds1, Cds1 homolog, or serine/threonine-protein kinase Chk2, plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 78187977  31 YRLGcRADLCD-----VALRPQQEPGLISGVHAELHAE-LQGDDWRVSLEDHSSQGTLVNNVRLPRGHRLELSDGD 100
Cdd:cd22666  21 YTFG-RDKSCDycfdsPALKKTSYYRTYSKKHFRIFREkGSKNTYPVFLEDHSSNGTFVNGEKIGKGKKRPLNNND 95

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 78187977  36 RADLCDVALrpqQEPGlISGVHAELHAELQGddwRVSLEDHSS-QGTLVNNVRLPrgHRLELSDGDLLTFG 105
Cdd:cd22673  27 RDLSCDIRI---QLPG-VSREHCRIEVDENG---KAYLENLSTtNPTLVNGKAIE--KSAELKDGDVITIG 88

forkhead associated (FHA) domain found in Smad nuclear-interacting protein 1 (SNIP1), FHA domain-containing protein DDL, and similar proteins; SNIP1 is an FHA domain-containing protein required for pre-mRNA splicing as a component of the spliceosome. It inhibits NF-kappaB signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional co-activators. It is involved in microRNA (miRNA) biogenesis. SNIP1 is a regulator of the cell cycle and cyclin D1 expression and may be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. This family also includes Arabidopsis thaliana FHA domain-containing protein DDL and similar proteins. DDL, also called protein DAWDLE, is involved in the microRNA (miRNA) and short interfering RNA (siRNA) biogenesis. It may facilitate DCL1 to access or recognize primary miRNAs. DDL binds RNA non-specifically. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 78187977  20 TFHPPSKSgcTYRLGCRADLCDVALRpqqEPGlISGVHA-----ELHAELQGDDWRV------SLEdhSSQGTLVNNVRL 88
Cdd:cd22676  14 TIDIHRQS--AYLIGRDRRVADIPLD---HPS-CSKQHAviqfrEVEKRNEGDVIENirpyiiDLG--STNGTFLNGEKI 85

                        90       100
                ....*....|....*....|....*....
gi 78187977  89 PRGHRLELSDGDLLTFgpegqaGTSSSEF 117
Cdd:cd22676  86 EPRRYYELREKDVLKF------GLSTREY 108