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 386770909   1 MFVLTKDDEK---FVLFPGKkVYTIGRLATDLIVAQDLSISRNHAQLLIQT------EADGDDTLHIEDLgSRYGTFIfp 71
Cdd:cd22667    1 WWLLSEQDGAgtsYYLLPGG-EYTVGRKDCDIIIVDDSSISRKHATLTVLHpeanlsDPDTRPELTLKDL-SKYGTFV-- 76

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 386770909  72 kNSQkprKVPAKTSTPLPVGTRLRFGANMSIWQVTQ 107
Cdd:cd22667   77 -NGE---KLKGGSEVTLKDGDVITFGVLGSKFRVEY 108

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909  434 APAPAPVQRVTRQSKAIAEEKSVHPPVPAASKHITRKTKQVFCVDSSDEENENARKPKETPAPTIPSMAKKKTEAPVATR 513
Cdd:PHA03247 2774 APAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLG 2853

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909  514 ISPRLNGKSLATNITNQPADKHAVPAKRPVLSVAssdeedegdlfqfRKSPQKPAETVVQPRiagkgNAPARISVVDFLE 593
Cdd:PHA03247 2854 GSVAPGGDVRRRPPSRSPAAKPAAPARPPVRRLA-------------RPAVSRSTESFALPP-----DQPERPPQPQAPP 2915

                         170       180
                  ....*....|....*....|...
gi 386770909  594 KSQAQEPAPVPPQLESQSQTQPR 616
Cdd:PHA03247 2916 PPQPQPQPPPPPQPQPPPPPPPR 2938

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 386770909   1 MFVLTKDDEK---FVLFPGKkVYTIGRLATDLIVAQDLSISRNHAQLLIQT------EADGDDTLHIEDLgSRYGTFIfp 71
Cdd:cd22667    1 WWLLSEQDGAgtsYYLLPGG-EYTVGRKDCDIIIVDDSSISRKHATLTVLHpeanlsDPDTRPELTLKDL-SKYGTFV-- 76

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 386770909  72 kNSQkprKVPAKTSTPLPVGTRLRFGANMSIWQVTQ 107
Cdd:cd22667   77 -NGE---KLKGGSEVTLKDGDVITFGVLGSKFRVEY 108

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386770909   20 YTIGRLATDLIVAQDLSISRNHAQLLIqteaDGDDTLHIEDLGSRYGTFIfpkNSQKPRKVPaktsTPLPVGTRLRF 96
Cdd:pfam00498   1 VTIGRSPDCDIVLDDPSVSRRHAEIRY----DGGGRFYLEDLGSTNGTFV---NGQRLGPEP----VRLKDGDVIRL 66

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 386770909    20 YTIGRLATD-LIVAQDLSISRNHAQLliqtEADGDDTLHIEDLGSRYGTFI 69
Cdd:smart00240   1 VTIGRSSEDcDIQLDGPSISRRHAVI----VYDGGGRFYLIDLGSTNGTFV 47

BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilized head-to-tail BRCT-BRCT oligomerization mode. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386770909  111 VTTVSALTRSEVQELTKMLepmGGTVTSNWTEECSHLTMNEvsVTVKLLHAMLENKPIVTF 171
Cdd:pfam00533  13 ITGLDGLERDELKELIEKL---GGKVTDSLSKKTTHVIVEA--RTKKYLKAKELGIPIVTE 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 386770909   1 MFVLTKDDEK---FVLFPGKkVYTIGRLATDLIVAQDLSISRNHAQLLIQT------EADGDDTLHIEDLgSRYGTFIfp 71
Cdd:cd22667    1 WWLLSEQDGAgtsYYLLPGG-EYTVGRKDCDIIIVDDSSISRKHATLTVLHpeanlsDPDTRPELTLKDL-SKYGTFV-- 76

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 386770909  72 kNSQkprKVPAKTSTPLPVGTRLRFGANMSIWQVTQ 107
Cdd:cd22667   77 -NGE---KLKGGSEVTLKDGDVITFGVLGSKFRVEY 108

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 386770909   3 VLTKDDEKFVLFPGKKVYTIGRLATDLIVAQDLSISRNHAQLLIQteadgDDTLHIEDLGSRYGTFIfpkNSQkprkvPA 82
Cdd:cd00060    4 VLDGDGGGREFPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD-----GGGVYLEDLGSTNGTFV---NGK-----RI 70

                         90
                 ....*....|....*
gi 386770909  83 KTSTPLPVGTRLRFG 97
Cdd:cd00060   71 TPPVPLQDGDVIRLG 85

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909  17 KKVYTIGRLATDLIVAQDLSISRNHAQLLIQteadgDDTLHIEDLGSRYGTFIfpkNSQkprkvPAKTSTPLPVGTRLRF 96
Cdd:COG1716   20 GGPLTIGRAPDNDIVLDDPTVSRRHARIRRD-----GGGWVLEDLGSTNGTFV---NGQ-----RVTEPAPLRDGDVIRL 86

                 .
gi 386770909  97 G 97
Cdd:COG1716   87 G 87

C-terminal domain of the breast cancer suppressor protein (BRCA1) and related domains; The BRCT (BRCA1 C-terminus) domain is found within many DNA damage repair and cell cycle checkpoint proteins. BRCT domains interact with each other forming homo/hetero BRCT multimers, but are also involved in BRCT-non-BRCT interactions and interactions within DNA strand breaks. BRCT tandem repeats bind to phosphopeptides; it has been shown that the repeats in human BRCA1 bind specifically to pS-X-X-F motifs, mediating the interaction between BRCA1 and the DNA helicase BACH1, or BRCA1 and CtIP, a transcriptional corepressor. It is assumed that BRCT repeats play similar roles in many signaling pathways associated with the response to DNA damage.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386770909 110 LVTTVSALTRSEVQELTKMLEPMGGTVTSNWTEECSHLTMNEVSVTVKLLHAMLENKPIVTF 171
Cdd:cd00027    1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYYLAALAWGIPIVSP 62

forkhead associated (FHA) domain found in Sulfolobus Acidocaldarius FHA domain-containing protein ArnA and similar proteins; ArnA is an FHA domain-containing protein from Sulfolobus acidocaldarius that was shown to strongly interact with ArnB, a von Willebrand domain-containing protein. They act synergistically and negatively to modulate motility. ArnA is involved in regulating archaella expression in S. acidocaldarius. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909   9 EKFVLFPGKKVyTIGRLATDLIVAQDLSISRNHAQLLIQteadgDDTLHIEDLGSRYGTFIFPknsqkprKVPAKTSTPL 88
Cdd:cd22680   13 GKKFPFDFSSV-SIGRDPENVIVIPDPFVSRNHARITVD-----SNEIYIEDLGSTNGTFVND-------FKRIKGPAKL 79

                         90
                 ....*....|....
gi 386770909  89 PVGTRLRFGANMSI 102
Cdd:cd22680   80 HPNDIIKLGRTTVL 93

forkhead associated (FHA) domain found in protein phosphatase 1 regulatory inhibitor subunit 8 (PPP1R8) and similar proteins; PPP1R8, also called nuclear inhibitor of protein phosphatase 1 (NIPP-1), is an inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. It may also be involved in pre-mRNA splicing and binds DNA and might act as a transcriptional repressor. PPP1R8 seems to be required for cell proliferation. PPP1R8 contains an FHA domain that mediates interactions with threonine-phosphorylated maternal embryonic leucine zipper kinase (MELK). The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909   5 TKDDEKFVLFP--GKKVYTIGRLAT--DLIVAQDlSISRNHAQLLIQteaDGDDTLHIEDLGSRYGTFIfpknsqKPRKV 80
Cdd:cd22674   12 VKDGKLIEKLMidEKKYYLFGRNSDvcDFVLDHP-SCSRVHAALVYH---KHLNRVFLIDLGSTHGTFV------GGIRL 81

                         90
                 ....*....|....*...
gi 386770909  81 PAKTSTPLPVGTRLRFGA 98
Cdd:cd22674   82 EPHKPQQLPIDSTLRFGA 99

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 386770909  18 KVYTIGRLATDL-IVAQDLSISRNHAQLLIqteaDGDDTLHIEDLGSRYGTFI 69
Cdd:cd22696   21 KTYFIGKDPTVCdIVLQDPSISRQHARLSI----DQDNRVFIEDLSSKNGVLV 69

first BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins; MDC1, also termed 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 phase 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 family corresponds to the first BRCT domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 386770909 119 RSEVQELTKMLEPMGGTVTSNWtEECSHLTMNEVSVTVKLLHAMLENKPIVT 170
Cdd:cd17744    8 VSDKEEGEKIIKKLGGSVVDSV-EDCTHLVTDKVRRTVKFLCALARGIPIVS 58

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 386770909  20 YTIGRLATDLIVAQDLSISRNHAQLLIQteadgDDTLHIEDLGSRYGTFIfpkNSQKPRKVPAKTSTPLPVGTR-LRF 96
Cdd:cd22698   23 FTIGRSSNNDIRLNDHSVSRHHARIVRQ-----GDKCNLTDLGSTNGTFL---NGIRVGTHELKHGDRIQLGETiFRF 92

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386770909 110 LVTTVSALTRSEVQELTKMLEPMGGTVTSNWTEECSHLTMNEVSV-----TVKLLHAMLENKPIVTF 171
Cdd:cd17734    1 LVLLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERgvcprTMKYLMGILAGKWIVSF 67

Inner membrane component of T3SS, cytoplasmic domain; Yop-YscD-cpl is the cytoplasmic domain of Yop proteins like YscD from Proteobacteria. YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909   16 GKKVYTIGRLATDLIVAQDLSISRNHAQLliqtEADGDDTLhIEDLGSRYGTFIfpkNSQKprkvPAKTSTPLPVGTRLR 95
Cdd:pfam16697  15 EGGRYRIGSDPDCDIVLSDKEVSRVHLKL----EVDDEGWR-LDDLGSGNGTLV---NGQR----VTELGIALRPGDRIE 82

                  ..
gi 386770909   96 FG 97
Cdd:pfam16697  83 LG 84

forkhead associated (FHA) domain found in centrosomal protein of 170 kDa (Cep170) and similar proteins; Cep170, also called Cep170A, KARP-1-binding protein, or KARP1-binding protein, is a protein that localizes to centrosomes as well as spindle microtubules and plays a role in microtubule organization and microtubule assembly. It is required for centriole subdistal appendage assembly. Cep170 is phosphorylated during M phase and interacts with Polo-like kinase 1 (Plk1). The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909  22 IGRLATDLIVaQDLSISRNHAqlLIQTEADGDDTLhIEDLGSRYGTFIfpknsqKPRKVPAKTSTPLPVGTRLRFGANMS 101
Cdd:cd22724   25 VGRDDCELML-QSRSVDKQHA--VINYDASTDEHK-VKDLGSLNGTFV------NDVRIPEQTYITLKLDDKLRFGYDTN 94

                 ....*....
gi 386770909 102 IWQVTQLKL 110
Cdd:cd22724   95 LFTVVRGEM 103

forkhead associated (FHA) domain found in Saccharomyces cerevisiae meiosis-specific serine/threonine-protein kinase MEK1 and similar proteins; MEK1 (EC 2.7.11.1), also known as MRE4, is a meiosis-specific protein kinase required for chromosome synapsis and meiotic recombination. The recruitment and activation of MEK1 require the phosphorylation of the chromosome axis protein Hop1 at Thr318 (pT318), which is necessary for recognition by the MEK1 FHA domain. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386770909   6 KDDEKFVLF-PGKKVYTIGRLATDLIVAQDLSISRNHAQLL-IQTEADGDDTLHIEDLgSRYGTFI 69
Cdd:cd22670    9 PGSTDIVLPiYKNQVITIGRSPSCDIVINDPFVSRTHCRIYsVQFDESSAPLVYVEDL-SSNGTYL 73

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 386770909   8 DEKFVLFPGKKVYTIGRLATDLIVAQDLSISRNHAQLLIQteadgDDTLHIEDLGSRYGTFIfpknsqKPRKVPAKTStP 87
Cdd:cd22683   11 KEQKISITNRNVTTIGRSRSCDLVLSDPSISRFHAELRLE-----QNGINVIDNNSANGTFI------NGKRIKGKTY-I 78

                         90
                 ....*....|
gi 386770909  88 LPVGTRLRFG 97
Cdd:cd22683   79 LKNGDIIVFG 88

forkhead associated (FHA) domain found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. Specially, RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770909  13 LFPGKKVyTIGR---LATDLIVAQDLSISRNHAQLliqtEADGDDTLHIEDLGSRYGTFIfpkNSQkprKVPAKTSTPLP 89
Cdd:cd22663   17 LEDGKEV-TVGRglgVTYQLVSTCPLMISRNHCVL----KKNDEGQWTIKDNKSLNGVWV---NGE---RIEPLKPYPLN 85

                 ....*....
gi 386770909  90 VGTRLRFGA 98
Cdd:cd22663   86 EGDLIQLGV 94