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 255725328  153 AYARLDFDNFTFFVQTLQVVLGRKSNDESLQ--QNVDVHLSSKKAISRRHAKIFYNFGSQRFEITILGRNGAFVDNVFVG 230
Cdd:cd22701     1 AYAKLDGDDFTYYVQKLEVVLGRNSKNSSSTaaDSVDIDLGPSKKISRRHARIFYDFTTQCFELSVLGRNGVKVDGILVK 80

                          90       100
                  ....*....|....*....|....*.
gi 255725328  231 KG-LTVPLKDGTKIQIGDIPFQFVLP 255
Cdd:cd22701    81 PGsPPVPLRSGSLIQIGGVLFYFLLP 106

Transcription factor of the Forkhead/HNF3 family [Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  613 SSSIYSRINGLDKIGKI--IPPRQPPPKLVAPVLLITSEPSAIRSRPPLRAITVSDASYLATFSYPKTIEEPSKYPKPKL 690
Cdd:COG5025   226 KSSALIRIPADSSSNLDvsLGHHISQPSTHTPVLDNHSSGEENISRINNSSQIDSPTPNYRMSSIDSSVNPSRLANNKDE 305

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  691 KKEPHKKS-------SKKVYTTDEIPTQYRSKPNINFQTMITNVLKTEAArNGLTISEITEAIREVYPYYKYCPDGWQFS 763
Cdd:COG5025   306 GRKGSKSSpvpkdaaPPSTLSDLSADVNRTSKPAFSYANSITQAILSSPS-GKMTLSEIYSWISSNLPYYRHKPTAWQNS 384

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 255725328  764 VNHCIKFTKIYKRLSKRGNE----WLYAMDELYINERENIRIKQRELAKARAKAEA 815
Cdd:COG5025   385 IRHNLSLNKSFEKVPRSASQpgkgCFWKIDYSYIYEKESKRNPRSPKKSPSAHSVH 440

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 255725328  153 AYARLDFDNFTFFVQTLQVVLGRKSNDESLQ--QNVDVHLSSKKAISRRHAKIFYNFGSQRFEITILGRNGAFVDNVFVG 230
Cdd:cd22701     1 AYAKLDGDDFTYYVQKLEVVLGRNSKNSSSTaaDSVDIDLGPSKKISRRHARIFYDFTTQCFELSVLGRNGVKVDGILVK 80

                          90       100
                  ....*....|....*....|....*.
gi 255725328  231 KG-LTVPLKDGTKIQIGDIPFQFVLP 255
Cdd:cd22701    81 PGsPPVPLRSGSLIQIGGVLFYFLLP 106

Forkhead (FH) domain found in Forkhead box (FOX) family of transcription factors and similar proteins; The FOX family comprises diverse tissue- and cell type-specific transcription factors with an evolutionary conserved "Forkhead (FH)" or "winged helix" DNA-binding domain. FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. The structure of the FH domain contains 2 flexible loops or "wings" in the C-terminal region, hence the term winged helix. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'. They participate in a variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism, and DNA damage response. Their expression can be regulated by multiple factors, and they can act as co-activators and/or transcriptional repressors. Fifty FOX-encoding genes in humans have been categorized into 19 subfamilies based on protein sequence homology (FOXA to FOXS).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 255725328  716 PNINFQTMITNVLKTeAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK------RGNEW 784
Cdd:cd00059     1 PPYSYAALIALAILS-SPDKRLTLSEIYKWIEDNFPYYRTATKGWKNSIRHNLSLNKCFVKVPRepsdpgKGSYW 74

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255725328   171 VVLGRKSNdeslqqnVDVHLSSKKaISRRHAKIFYNfGSQRFEITILG-RNGAFVDNVFVGKGlTVPLKDGTKIQI 245
Cdd:pfam00498    1 VTIGRSPD-------CDIVLDDPS-VSRRHAEIRYD-GGGRFYLEDLGsTNGTFVNGQRLGPE-PVRLKDGDVIRL 66

FORKHEAD; FORKHEAD, also known as a "winged helix"

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 255725328    715 KPNINFQTMITNVLKTEAARNgLTISEITEAIREVYPYYKYCPDGWQFSVNHCI----KFTKIYKRLSKRGNEWLYAMD 789
Cdd:smart00339    1 KPPYSYIALIAMAILSSPDKR-LTLSEIYKWIEDNFPYYRENRAGWQNSIRHNLslndCFVKVPREGDRPGKGSYWTLD 78

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328 1007 PSSRSATPASKSTTSISKVSTPAPAPASAPVVTPTSTTAPVPAKITQPAAPIVTPAVKSTTPAKIPTTTAtPPSISASPV 1086
Cdd:PHA03247 2710 PAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGP-PRRLTRPAV 2788

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328 1087 VVKTEPKSPAPQPPASSTTTKSSPTAAVVASPPAPPSTketiksppttattttttptvpapapapapapvqkPKPTPPTN 1166
Cdd:PHA03247 2789 ASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAG----------------------------------PLPPPTSA 2834

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 255725328 1167 LPRPSFGKPPGLKPGASLGrpsafgkPPSAAGGGFSRAAPT 1207
Cdd:PHA03247 2835 QPTAPPPPPGPPPPSLPLG-------GSVAPGGDVRRRPPS 2868

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 255725328  153 AYARLDFDNFTFFVQTLQVVLGRKSNDESLQ--QNVDVHLSSKKAISRRHAKIFYNFGSQRFEITILGRNGAFVDNVFVG 230
Cdd:cd22701     1 AYAKLDGDDFTYYVQKLEVVLGRNSKNSSSTaaDSVDIDLGPSKKISRRHARIFYDFTTQCFELSVLGRNGVKVDGILVK 80

                          90       100
                  ....*....|....*....|....*.
gi 255725328  231 KG-LTVPLKDGTKIQIGDIPFQFVLP 255
Cdd:cd22701    81 PGsPPVPLRSGSLIQIGGVLFYFLLP 106

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  153 AYARLDFDNFTFFVQTLQVVLGRKSNdeslQQNVDVHLSSKKAISRRHAKIFYNFGsqRFEITILGRNGAFVDNVFVGKG 232
Cdd:cd22688     3 AIARLEGREFEYLMRKSRVVIGRNSS----RGPVDVNMGHSSFISRKHLEIFYEGG--RFFLLCNGKNGIFVDGVFQRRG 76

                  ....*..
gi 255725328  233 ---LTVP 236
Cdd:cd22688    77 appLQLP 83

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 255725328  158 DFDNFTFFVQTLQVVLGRKSNDeslqqnvDVHLSSKKaISRRHAKIFYNFGsqRFEITILG-RNGAFVDNVFVGKglTVP 236
Cdd:cd00060     8 DGGGREFPLTKGVVTIGRSPDC-------DIVLDDPS-VSRRHARIEVDGG--GVYLEDLGsTNGTFVNGKRITP--PVP 75

                          90
                  ....*....|....*..
gi 255725328  237 LKDGTKIQIGDIPFQFV 253
Cdd:cd00060    76 LQDGDVIRLGDTTFRFE 92

Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  163 TFFVQTLQVVLGRKSNdeslqqnVDVHLSSKkAISRRHAKIFYNfgSQRFEITILG-RNGAFVDNVFVGKglTVPLKDGT 241
Cdd:COG1716    15 RFPLDGGPLTIGRAPD-------NDIVLDDP-TVSRRHARIRRD--GGGWVLEDLGsTNGTFVNGQRVTE--PAPLRDGD 82

                          90
                  ....*....|....
gi 255725328  242 KIQIGDIPFQFVLP 255
Cdd:COG1716    83 VIRLGKTELRFRLS 96

forkhead associated (FHA) domain found in forkhead box protein K2 (FOXK2) and similar proteins; 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 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 FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  153 AYARLDFDNFTFFVQTLQVVLGRKSNdeslQQNVDVHLSSKKAISRRHAKIF-------YNFGSQRFEITILGRNGAFVD 225
Cdd:cd22723     3 AVARLEGREFEYLMKKRSVTIGRNSS----QGSVDVSMGHSSFISRRHLEIFtagedggDGGGGGDFYLRCLGKNGVFVD 78

                  ....*..
gi 255725328  226 NVFVGKG 232
Cdd:cd22723    79 GVFQRRG 85

forkhead associated (FHA) domain found in forkhead box protein K1 (FOXK1) and similar proteins; FOXK1, also called myocyte nuclear factor (MNF), acts as a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of the myoglobin gene. It positively regulates Wnt/beta-catenin signaling by translocating DVL 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. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  153 AYARLDFDNFTFFVQTLQVVLGRKSNdeslQQNVDVHLSSKKAISRRHAKIfyNFGSQRFEITILGRNGAFVDNVFVGKG 232
Cdd:cd22722     3 ALARLEGRDFEFLMRQPTVTIGRNSS----QGSVDVNMGHSSFISRRHLQL--SFQEPHFYLRCLGKNGVFVDGAFQRRG 76

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 255725328  164 FFVQTLQVVLGRKSNDEslqqNVDVHLS-----SKkaISRRHAKI-FYNFGSqrFEITILGRNGAFVDNVFVGKGLTVPL 237
Cdd:cd22687    16 YLMRSREVTIGRSTKDN----QVDIDLSlegpaWK--ISRRQAVIkLKNDGD--FYIKNEGKRPIYVNGKPVPTGEKAIL 87

                          90
                  ....*....|....*
gi 255725328  238 KDGTKIQIGDIPFQF 252
Cdd:cd22687    88 NNNSLIEIGGLRFVF 102

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  171 VVLGR-KSNDESLQqnvdvhlSSKKAISRRHAKIfyNFGSQRFEITILGRNGAFVDN--VFVGKGLTVPLKDGTKIQIGD 247
Cdd:COG3456    28 GTIGRsADCDWVLP-------DPDRSVSRRHAEI--RFRDGAFCLTDLSTNGTFLNGsdHPLGPGRPVRLRDGDRLRIGD 98

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 255725328  248 IPFQFVLppssesNKEREFESSSKQFNPSDAINLKSNLYSATPTPKASPKKKSVDDSKSKL---ETEPPLAKAKPTSR 322
Cdd:COG3456    99 YEIRVEI------SGEDEGADDPLAAAPEPAVSSPSNLSDTEAAPDAALAFSFSLDPLEALdeaATEAPATADDPPSL 170

Forkhead (FH) domain found in the Forkhead box protein R (FOXR) subfamily; The FOXR subfamily includes two winged helix transcription factors, FOXR1-2. FOXR1, also called Forkhead box protein N5 (FOXN5), is required for proper cell division and survival possibly via the p21 and mTOR pathways. FOXR2, also called Forkhead box protein N6 (FOXN6), is an important player in a wide range of cellular processes such as proliferation, migration, differentiation, and apoptosis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 255725328  715 KPNINFQTMITNVLKTeAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNH--CIK--FTKIYKRLSKRGN 782
Cdd:cd20036     3 KPPLSYPNLIALALRN-SETGSLNVQEIYDFIRFHFPFFRTAPDGWKNSVRHnlSFSdsFEKVPTSVSGYGG 73

Forkhead (FH) domain found in Forkhead box protein J2 (FOXJ2) and similar proteins; FOXJ2, also called Fork head homologous X (FHX), plays an important role in tumorigenesis, progression, and metastasis of certain cancers. It acts as a transcriptional activator that can bind to two different type of DNA binding sites. It is specifically expressed in meiotic spermatocytes in adult mouse testes and appears to promote meiotic progression during spermatogenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 255725328  715 KPNINFQTMITNVLKTEAARNgLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK------RGNEWL 785
Cdd:cd20051     2 KPPYSYATLITYAINSSPAKK-MTLSEIYRWICDNFPYYRNAGVGWKNSIRHNLSLNKCFRKVPRprddpgKGSYWM 77

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  160 DNFTFfvqtlqvvlGR-KSNDESLQQNVDVHLSSKKAISRRHAKIFYNFGS----QRFeITILGRNGAFVDNVFVGKGLT 234
Cdd:cd22666    19 DEYTF---------GRdKSCDYCFDSPALKKTSYYRTYSKKHFRIFREKGSkntyPVF-LEDHSSNGTFVNGEKIGKGKK 88

                          90
                  ....*....|..
gi 255725328  235 VPLKDGTKIQIG 246
Cdd:cd22666    89 RPLNNNDEIALS 100

Forkhead (FH) domain found in Forkhead box proteins, FOXJ2, FOXJ3 and similar proteins; The FOXJ2-like subfamily includes two winged helix transcription factors, FOXJ2 and FOXJ3. FOXJ2, also called Forkhead homologous X (FHX), plays an important role in tumorigenesis, progression, and metastasis of certain cancers. It acts as a transcriptional activator that can bind to two different type of DNA binding sites. FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 255725328  715 KPNINFQTMITNVLKTEAARNgLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSKRGNE 783
Cdd:cd20024     1 KPPYSYATLITFAINSSPKKK-MTLSEIYTWICENFPYYREAGTGWKNSIRHNLSLNKCFKKVPRSKDD 68

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 255725328  172 VLGRKsndeslqqNVDVHLSSKKAISRRHAKI-------FYNFGSQRFEITI--LGRNGAFVDNVFVGKGLTVPLKDGTK 242
Cdd:cd22667    23 TVGRK--------DCDIIIVDDSSISRKHATLtvlhpeaNLSDPDTRPELTLkdLSKYGTFVNGEKLKGGSEVTLKDGDV 94

                  ....
gi 255725328  243 IQIG 246
Cdd:cd22667    95 ITFG 98

Forkhead (FH) domain found in Forkhead box protein J3 (FOXJ3) and similar proteins; FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. Polymorphisms in the FOXJ3 gene may be associated with the development of rheumatoid arthritis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 255725328  714 SKPNINFQTMITNVLKTeAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK------RGNEWL 785
Cdd:cd20052     1 GKPPYSYANLITFAINS-SPKKKMTLSEIYQWICDNFPYYREAGNGWKNSIRHNLSLNKCFLKVPRskddpgKGSYWA 77

Forkhead (FH) domain found in Forkhead box protein A1 (FOXA1) and similar proteins; FOXA1, also called hepatocyte nuclear factor 3-alpha (HNF-3-alpha or HNF-3A) or transcription factor 3A (TCF-3A), acts as a transcription factor that is essential for epithelial lineage differentiation. It has been found to be upregulated in numerous cancers. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 255725328  714 SKPNINFQTMITNVLKtEAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK------RGNEW 784
Cdd:cd20038    13 AKPPYSYISLITMAIQ-QAPSKMLTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVARspdkpgKGSYW 88

forkhead associated (FHA) domain found in Myxococcus xanthus EspA and similar proteins; EspA is a histidine protein kinase with a fork head-associated (FHA) domain at the N-terminus and a receiver domain at the C-terminus. It functions as an inhibitor of sporulation during early fruiting body development while cells are aggregating into raised mounds. EspA is part of a two-component signal transduction system that regulates the timing of sporulation initiation. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  184 QNVDVHLSSKKaISRRHAKIFYNFGsqRFEITILG-RNGAFVDNVFVGkglTVPLKDGTKIQIGDIPFQF 252
Cdd:cd22698    29 SNNDIRLNDHS-VSRHHARIVRQGD--KCNLTDLGsTNGTFLNGIRVG---THELKHGDRIQLGETIFRF 92

Forkhead (FH) 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 FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 255725328  715 KPNINFQTMITNVLKTEAARNgLTISEITEAIREVYPYYKYCPDGWQFSVNH 766
Cdd:cd20026     1 KPPYSYAQLIVQAISSAPDKQ-LTLSGIYAYITKNYPYYRTADKGWQNSIRH 51

Forkhead (FH) domain found in the Forkhead box protein A (FOXA) subfamily; The FOXA subfamily includes three winged helix transcription factors, FOXA1 (also called hepatocyte nuclear factor 3-alpha or transcription factor 3A), FOXA2 (also called hepatocyte nuclear factor 3-beta or transcription factor 3B), and FOXA3 (also called hepatocyte nuclear factor 3-gamma or transcription factor 3G). FOXA1 is essential for epithelial lineage differentiation and has been found to be upregulated in numerous cancers. FOXA2 controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis and may also have an important role in bone metabolism. FOXA3 acts as an essential transcriptional regulator engaged in adipogenesis and energy metabolism. This subfamily also includes Xenopus tropicalis FOXA4, Drosophila melanogaster protein fork head (dFKH), and similar proteins. FOXA4 is only present in amphibians, where it is required for the correct regionalization and maintenance of the central nervous system. dFKH promotes terminal as opposed to segmental development. In the absence of dFKH, this developmental switch does not occur. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 255725328  715 KPNINFQTMITNVLKTEAARNgLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK 779
Cdd:cd20015     1 KPPYSYISLITMAIQQSPSKM-LTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVPR 64

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 255725328  160 DNFTFFVQTLQVVLGRksndeSLQQNVDVHLSSkkaISRRHAKIFYNFGSqRFEITILGR-NGAFVDNVFVGKglTVPLK 238
Cdd:cd22673    12 DGSRFPLTKKSCTFGR-----DLSCDIRIQLPG---VSREHCRIEVDENG-KAYLENLSTtNPTLVNGKAIEK--SAELK 80

                          90
                  ....*....|....
gi 255725328  239 DGTKIQIGDIPFQF 252
Cdd:cd22673    81 DGDVITIGGRSFRF 94

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328   944 TATSLITKAVATTIAQVNSIGAKRGAGDNALGYLVEQAPQQVSKILGIALNNAIKEHEG--HSSGPSSRSATPASKSTTS 1021
Cdd:pfam17823  215 AATATGHPAAGTALAAVGNSSPAAGTVTAAVGTVTPAALATLAAAAGTVASAAGTINMGdpHARRLSPAKHMPSDTMARN 294

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  1022 ISKVSTPAPAPASAPVVT--PTSTTA--PVPAKITQPAAPIVTPAVKSTTPAKIPTTTATPPSISASPVVV-------KT 1090
Cdd:pfam17823  295 PAAPMGAQAQGPIIQVSTdqPVHNTAgePTPSPSNTTLEPNTPKSVASTNLAVVTTTKAQAKEPSASPVPVlhtsmipEV 374

                   ....*....
gi 255725328  1091 EPKSPAPQP 1099
Cdd:pfam17823  375 EATSPTTQP 383

Forkhead (FH) domain found in Forkhead box protein N3 (FOXN3); FOXN3, also called checkpoint suppressor 1 (CHES1), acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). It displays transcriptional inhibitory activity, and is involved in cell cycle regulation and tumorigenesis. Alterations in FOXN3 are found in of a variety of cancers including melanoma, osteosarcoma, and hepatocellular carcinoma. FOXN3 also regulates hepatic glucose utilization/metabolism by regulating gluconeogenic substrate selection. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 255725328  715 KPNINFQTMITNVLKtEAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK 779
Cdd:cd20059     1 KPPYSFSCLIFMAIE-DSPTKRLPVKDIYNWILEHFPYFANAPTGWKNSVRHNLSLNKCFKKVDK 64

Forkhead (FH) domain found in Forkhead box protein A2 (FOXA2) and similar proteins; FOXA2, also called hepatocyte nuclear factor 3-beta (HNF-3-beta or HNF-3B) or transcription factor 3B (TCF-3B), acts as a core transcription factor that controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis. It may also have an important role in bone metabolism. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255725328  714 SKPNINFQTMITNVLKtEAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNHCIKFTKIYKRLSK 779
Cdd:cd20039     4 AKPPYSYISLITMAIQ-QSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPR 68

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328   994 NNAIKEHEGHSSGPSSRSATPASKSTTSISKVSTPAPAPASAPV--VTPTST-TAPVPaKITQPAAPIVTPAVKSTTPA- 1069
Cdd:pfam05109  496 DNGTESKAPDMTSPTSAVTTPTPNATSPTPAVTTPTPNATSPTLgkTSPTSAvTTPTP-NATSPTPAVTTPTPNATIPTl 574

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 255725328  1070 --KIPTTTATPPSISA-SPVVVKTepkspAPQPPASSTTTKSSPTAAVVASPPAPPSTKET 1127
Cdd:pfam05109  575 gkTSPTSAVTTPTPNAtSPTVGET-----SPQANTTNHTLGGTSSTPVVTSPPKNATSAVT 630

Forkhead (FH) domain found in Forkhead box protein L2 (FOXL2) and similar proteins; FOXL2 is a transcriptional regulator that is essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Mutations in the FOXL2 gene cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I, a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II, the eyelid defect occurs as an isolated entity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328  715 KPNINFQTMITNVLKtEAARNGLTISEITEAIREVYPYYKYCPDGWQFSVNHCIK----FTKIYKR--LSKRGNEWlyAM 788
Cdd:cd20028     1 KPPYSYVALIAMAIR-ESPEKRLTLSGIYQYIIAKFPYYEKNKKGWQNSIRHNLSlnecFVKVPREggGERKGNYW--TL 77

                          90
                  ....*....|
gi 255725328  789 DELYINEREN 798
Cdd:cd20028    78 DPACEDMFEK 87

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255725328 1004 SSGPSSRSATPASkSTTSISKVSTPAPAPASAPVVTPTSTTAPVPAKITQPAAPIVTPAVKSTTPAKIPTTTATPPSisA 1083
Cdd:PRK07003  407 GAALAPKAAAAAA-ATRAEAPPAAPAPPATADRGDDAADGDAPVPAKANARASADSRCDERDAQPPADSGSASAPAS--D 483

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 255725328 1084 SPVVVKTEPKSPAPQPPASStttkssptaAVVASPPAPPSTKET 1127
Cdd:PRK07003  484 APPDAAFEPAPRAAAPSAAT---------PAAVPDARAPAAASR 518