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 1034577583 354 FDNQTLAVLRGRMVRYLMRSREITLGRATKDNQIDVDLSLEGPAWKISRKQGVIKLKNNGDFFIANEGRRPIYIDGRPVL 433
Cdd:cd22687     1 FDSGALAVLRGRLVRYLMRSREVTIGRSTKDNQVDIDLSLEGPAWKISRRQAVIKLKNDGDFYIKNEGKRPIYVNGKPVP 80

                          90       100
                  ....*....|....*....|....*
gi 1034577583 434 CGSKWRLSNNSVVEIASLRFVFLIN 458
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 1034577583 354 FDNQTLAVLRGRMVRYLMRSREITLGRATKDNQIDVDLSLEGPAWKISRKQGVIKLKNNGDFFIANEGRRPIYIDGRPVL 433
Cdd:cd22687     1 FDSGALAVLRGRLVRYLMRSREVTIGRSTKDNQVDIDLSLEGPAWKISRRQAVIKLKNDGDFYIKNEGKRPIYVNGKPVP 80

                          90       100
                  ....*....|....*....|....*
gi 1034577583 434 CGSKWRLSNNSVVEIASLRFVFLIN 458
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 1034577583 376 ITLGRATkdnqiDVDLSLEGPawKISRKQGVIKLKNNGDFFIANEG-RRPIYIDGRPVLcGSKWRLSNNSVVEI 448
Cdd:pfam00498   1 VTIGRSP-----DCDIVLDDP--SVSRRHAEIRYDGGGRFYLEDLGsTNGTFVNGQRLG-PEPVRLKDGDVIRL 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 1034577583 354 FDNQTLAVLRGRMVRYLMRSREITLGRATKDNQIDVDLSLEGPAWKISRKQGVIKLKNNGDFFIANEGRRPIYIDGRPVL 433
Cdd:cd22687     1 FDSGALAVLRGRLVRYLMRSREVTIGRSTKDNQVDIDLSLEGPAWKISRRQAVIKLKNDGDFYIKNEGKRPIYVNGKPVP 80

                          90       100
                  ....*....|....*....|....*
gi 1034577583 434 CGSKWRLSNNSVVEIASLRFVFLIN 458
Cdd:cd22687    81 TGEKAILNNNSLIEIGGLRFVFLIN 105

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 1034577583 368 RYLMRSREITLGRATkdnqiDVDLSLEGPawKISRKQGVIKLKNNGdFFIANEGRR-PIYIDGRPVlcGSKWRLSNNSVV 446
Cdd:cd00060    13 EFPLTKGVVTIGRSP-----DCDIVLDDP--SVSRRHARIEVDGGG-VYLEDLGSTnGTFVNGKRI--TPPVPLQDGDVI 82

                  ....*....
gi 1034577583 447 EIASLRFVF 455
Cdd:cd00060    83 RLGDTTFRF 91

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 1034577583 359 LAVLRGRMVRYLMRSREITLGRATKDNQIDVDLsleGPAWKISRKQGVIKLKnNGDFFIANEGRRPIYIDG 429
Cdd:cd22688     4 IARLEGREFEYLMRKSRVVIGRNSSRGPVDVNM---GHSSFISRKHLEIFYE-GGRFFLLCNGKNGIFVDG 70

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034577583 376 ITLGRATkdnqiDVDLSLEGPawKISRKQGVIKLKNNGDFFIANEG-RRPIYIDGRPVLcGSKWRLSNNSVVEI 448
Cdd:pfam00498   1 VTIGRSP-----DCDIVLDDP--SVSRRHAEIRYDGGGRFYLEDLGsTNGTFVNGQRLG-PEPVRLKDGDVIRL 66

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 1034577583 375 EITLGRAtkdnqIDVDLSLEGPAwkISRKQGVIKLKNNGDFFIANEGRRPIYIDGRPvLCGSKWRLSNNSVVEIASLRFV 454
Cdd:cd22683    22 VTTIGRS-----RSCDLVLSDPS--ISRFHAELRLEQNGINVIDNNSANGTFINGKR-IKGKTYILKNGDIIVFGKCSFL 93

                  .
gi 1034577583 455 F 455
Cdd:cd22683    94 I 94

forkhead associated (FHA) domain found in aprataxin, bifunctional polynucleotide phosphatase/kinase (PNKP), aprataxin and PNK-like factor (APLF), and similar proteins; The family includes aprataxin, PNKP, and APLF. Aprataxin (EC 3.6.1.71/EC 3.6.1.72), also called forkhead-associated domain histidine triad-like protein (FHA-HIT), is a DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair, and base excision repair. It catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. It can also hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity. Likewise, it catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA but has higher specific activity with 5'-linked adenosine (AppDNA). PNKP (EC 3.1.3.32/EC 2.7.1.78), also called DNA 5'-kinase/3'-phosphatase, or polynucleotide kinase-3'-phosphatase, plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNKP ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone. APLF, also called apurinic-apyrimidinic endonuclease APLF, PNK and APTX-like FHA domain-containing protein, or XRCC1-interacting protein 1 (XIP1), is a novel apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease with conserved zinc-finger-like motifs involved in single-strand and double-strand DNA break repair. It is recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. It can introduce nicks at hydroxyuracil and other types of pyrimidine base damage. Together with PARP3, APLF promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). Members of this family contain an FHA domain at their N-terminus. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034577583 369 YLMRSREITLGRATKDNQIDVdlslegpawKISRKQGVIKLKNNGD-FFIANEGRRPIYID-----GRPVLCGSKWRLSN 442
Cdd:cd22671    14 ELKEGGPTVLGRGPLLGIRDK---------RVSRKQAEITVDDDTGsVTVTQLGTNPSFVNradgeGKVLKKGESVELKD 84

                          90
                  ....*....|...
gi 1034577583 443 NSVVEIASLRFVF 455
Cdd:cd22671    85 GDVISLLPGKYPF 97