forkhead associated (FHA) domain found in microspherule protein 1 (MCRS1) and similar proteins; MCRS1, also called 58 kDa microspherule protein (MSP58), cell cycle-regulated factor p78, or INO80 complex subunit J, is a nuclear RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal ribonucleoparticles (mRNPs) from neurons. It is a cell-cycle-dependent protein that acts as an inhibitor of TERT telomerase activity. It associates with LPTS/PinX1 and reduces the telomere length. It modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. As part of the NSL complex, MCRS1 may be involved in acetylation of nucleosomal histone H4 on several lysine residues. MCRS1 is also a putative regulatory component of the chromatin remodeling INO80 complex, which is involved in transcriptional regulation, DNA replication, and probably DNA repair. MCRS1 contains an FHA domain at its C-terminus. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410049 583 ASRGAFAVLYGRYSKHYIKKPEVLVGRSTEDLAVDIDLGREKRGSKISRRQAIIRLGDDGSFHIKNLGKYSISVNEKEVD 662
Cdd:cd22687   1 FDSGALAVLRGRLVRYLMRSREVTIGRSTKDNQVDIDLSLEGPAWKISRRQAVIKLKNDGDFYIKNEGKRPIYVNGKPVP 80

                        90       100
                ....*....|....*....|....*
gi 18410049 663 PGQSLILKSDCLVEIRGMPFIFETN 687
Cdd:cd22687  81 TGEKAILNNNSLIEIGGLRFVFLIN 105

forkhead associated (FHA) domain found in microspherule protein 1 (MCRS1) and similar proteins; MCRS1, also called 58 kDa microspherule protein (MSP58), cell cycle-regulated factor p78, or INO80 complex subunit J, is a nuclear RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal ribonucleoparticles (mRNPs) from neurons. It is a cell-cycle-dependent protein that acts as an inhibitor of TERT telomerase activity. It associates with LPTS/PinX1 and reduces the telomere length. It modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. As part of the NSL complex, MCRS1 may be involved in acetylation of nucleosomal histone H4 on several lysine residues. MCRS1 is also a putative regulatory component of the chromatin remodeling INO80 complex, which is involved in transcriptional regulation, DNA replication, and probably DNA repair. MCRS1 contains an FHA domain at its C-terminus. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410049 583 ASRGAFAVLYGRYSKHYIKKPEVLVGRSTEDLAVDIDLGREKRGSKISRRQAIIRLGDDGSFHIKNLGKYSISVNEKEVD 662
Cdd:cd22687   1 FDSGALAVLRGRLVRYLMRSREVTIGRSTKDNQVDIDLSLEGPAWKISRRQAVIKLKNDGDFYIKNEGKRPIYVNGKPVP 80

                        90       100
                ....*....|....*....|....*
gi 18410049 663 PGQSLILKSDCLVEIRGMPFIFETN 687
Cdd:cd22687  81 TGEKAILNNNSLIEIGGLRFVFLIN 105

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18410049   605 VLVGRSTEdlaVDIDLGrekrGSKISRRQAIIRLGDDGSFHIKNLG-KYSISVNEKEVDPgQSLILKSDCLVEI 677
Cdd:pfam00498   1 VTIGRSPD---CDIVLD----DPSVSRRHAEIRYDGGGRFYLEDLGsTNGTFVNGQRLGP-EPVRLKDGDVIRL 66

forkhead associated (FHA) domain found in microspherule protein 1 (MCRS1) and similar proteins; MCRS1, also called 58 kDa microspherule protein (MSP58), cell cycle-regulated factor p78, or INO80 complex subunit J, is a nuclear RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal ribonucleoparticles (mRNPs) from neurons. It is a cell-cycle-dependent protein that acts as an inhibitor of TERT telomerase activity. It associates with LPTS/PinX1 and reduces the telomere length. It modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. As part of the NSL complex, MCRS1 may be involved in acetylation of nucleosomal histone H4 on several lysine residues. MCRS1 is also a putative regulatory component of the chromatin remodeling INO80 complex, which is involved in transcriptional regulation, DNA replication, and probably DNA repair. MCRS1 contains an FHA domain at its C-terminus. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410049 583 ASRGAFAVLYGRYSKHYIKKPEVLVGRSTEDLAVDIDLGREKRGSKISRRQAIIRLGDDGSFHIKNLGKYSISVNEKEVD 662
Cdd:cd22687   1 FDSGALAVLRGRLVRYLMRSREVTIGRSTKDNQVDIDLSLEGPAWKISRRQAVIKLKNDGDFYIKNEGKRPIYVNGKPVP 80

                        90       100
                ....*....|....*....|....*
gi 18410049 663 PGQSLILKSDCLVEIRGMPFIFETN 687
Cdd:cd22687  81 TGEKAILNNNSLIEIGGLRFVFLIN 105

forkhead associated (FHA) domain found in Saccharomyces cerevisiae fork head protein homolog 1 (FKH1), 2 (FKH2) and similar proteins; This family includes FKH1 and FKH2, as well as pre-rRNA-processing protein FHL1. FKH1 and FKH2 are forkhead transcription factors that regulate the expression of the CLB2 cluster of genes during the G2/M phase of the mitotic cell cycle. The CLB2 cluster of genes includes mitotic regulators such as CLB1, CLB2, CDC5 and CDC20, as well as SWI5 and ACE2. FKH1 and FKH2 are involved in HMRa silencing. They associate with the coding regions of active genes and influence, in opposing ways, transcriptional elongation and termination, and coordinate early transcription elongation and pre-mRNA processing. Both FKH1 and FKH2 play a role as regulators of lifespan in collaboration with the anaphase-promoting complex (APC), likely through combined regulation of stress response, genomic stability, and cell cycle regulation. They also function in controlling yeast cell morphology by preventing pseudohyphal growth and act as rate-limiting replication origin activators via their interaction with the origin recognition complex (ORC). FHL1 is a forkhead protein that controls the pre-rRNA processing machinery in conjunction with IFH1. It might act as a transcriptional regulator of genes specifically involved in that process. IFH1 convert FHL1 from a repressor to an activator. This family also includes AtFHA1 and AtFHA2, which may play a role in the control of plant organ development. AtFHA2 is specifically involved in the regulation of stamen development. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410049 587 AFAVLYGRYSKHYIKKPEVLVGRSTEDLA------VDIDLGREKrgsKISRRQAIIRLGDD-GSFHIKNLGKYSISVNEK 659
Cdd:cd22701   1 AYAKLDGDDFTYYVQKLEVVLGRNSKNSSstaadsVDIDLGPSK---KISRRHARIFYDFTtQCFELSVLGRNGVKVDGI 77

                        90       100
                ....*....|....*....|....*.
gi 18410049 660 EVDPG-QSLILKSDCLVEIRGMPFIF 684
Cdd:cd22701  78 LVKPGsPPVPLRSGSLIQIGGVLFYF 103

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 18410049 596 SKHYIKKPEVLVGRSTEDlavDIDLgrekRGSKISRRQAIIRLgDDGSFHIKNLG-KYSISVNEKEVDPGQslILKSDCL 674
Cdd:cd00060  12 REFPLTKGVVTIGRSPDC---DIVL----DDPSVSRRHARIEV-DGGGVYLEDLGsTNGTFVNGKRITPPV--PLQDGDV 81

                        90
                ....*....|.
gi 18410049 675 VEIRGMPFIFE 685
Cdd:cd00060  82 IRLGDTTFRFE 92

forkhead associated (FHA) domain found in the Forkhead box protein K (FOXK) subfamily; The FOXK subfamily includes two-winged helix transcription factors, FOXK1 and FOXK2. FOXK1, also called myocyte nuclear factor (MNF), acts as a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of myoglobin genes. It positively regulates Wnt/beta-catenin signaling by translocating dishevelled (DVL) proteins into the nucleus. It also reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression. In addition, FOXK1 plays important roles in multiple human cancers. FOXK2, also called cellular transcription factor ILF-1 or interleukin enhancer-binding factor 1, is a transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. It binds to NFAT-like motifs (purine-rich) in the IL2 promoter. It also binds to the HIV-1 long terminal repeat. FOXK2 may be involved in both positive and negative regulation of important viral and cellular promoter elements. In addition, FOXK2 plays a critical role in suppressing tumorigenesis. The Forkhead (FH) domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18410049 587 AFAVLYGRYSKHYIKKPEVLVGRSTEDLAVDIDLGrekRGSKISRRQAIIRLgDDGSFHIKNLGKYSISVN 657
Cdd:cd22688   3 AIARLEGREFEYLMRKSRVVIGRNSSRGPVDVNMG---HSSFISRKHLEIFY-EGGRFFLLCNGKNGIFVD 69

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 18410049 596 SKHYIKKPEVLVGRSTEDLAVDIDlgrekrgSKISRRQAIIRLGDDGS----------FHIKNLGKYSISVNEKEVDPGQ 665
Cdd:cd22667  13 SYYLLPGGEYTVGRKDCDIIIVDD-------SSISRKHATLTVLHPEAnlsdpdtrpeLTLKDLSKYGTFVNGEKLKGGS 85

                        90
                ....*....|
gi 18410049 666 SLILKSDCLV 675
Cdd:cd22667  86 EVTLKDGDVI 95