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 516298731   1 MELVFEMLNTKQFVPTDLCQKTFKQAGGVIGRGDDCDWIIPDRKRHLSNHHALISYRDGSFFLTDTSSNGIQDSTNGTRL 80
Cdd:COG3456    1 MPLTLRIINSPDLESGSAASATFGRGGGTIGRSADCDWVLPDPDRSVSRRHAEIRFRDGAFCLTDLSTNGTFLNGSDHPL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731  81 RKGEVVRIEHGSEYILGDFEIRARLV-RDPAAFDVEVGRPQAAGS---------IIPDDAFLD---LDPLNALDQQERVy 147
Cdd:COG3456   81 GPGRPVRLRDGDRLRIGDYEIRVEISgEDEGADDPLAAAPEPAVSspsnlsdteAAPDAALAFsfsLDPLEALDEAATE- 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731 148 SEIEELISPSIALDDGRQRADYARIDMESllvPELVEVPKEPAPAPAPPPVERQTDGFWEKFGAALGVDLKGLDHDAKEA 227
Cdd:COG3456  160 APATADDPPSLLPEDWLPSAAPVADEAAA---QAIDQLPSAAAPAPEPEPAADADHALLAALLRGLGLDLELLDSQDAED 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731 228 LALNAARLLKQSVGGLQQSLRTRSELKNELRLAQTIVQGPQKNPLKFAVDAGEALDILLQANKPGQLPAEQAISRAFRDL 307
Cdd:COG3456  237 FLEELGRLLRAAVEGLLDLLRARAEFKNEFRLDQTMLRPIENNPLKFSPDYEEALALLLAPKSPGFLSAPAAVAESLRDL 316

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731 308 QAHQVALLTASRAAVRGTLEHFSPQQLMLRFERDNKPliATSGSRWRAYGRYHQALRQDTDWS-ERLLTRDFAQAYEEQI 386
Cdd:COG3456  317 RLHQLALLAAIQAALRALLDAFSPEALERRFERRLFG--SRKAKAWDMYEAYYQELSSERQQGfEKLFGEVFAQAYDRAL 394

                 ....*
gi 516298731 387 RLIST 391
Cdd:COG3456  395 RELKR 399

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 516298731  29 VIGRGDDCDWIIPDRkrHLSNHHALISYRDGSFFLTDTSsngiqdSTNGTRL---RKGEVVRIEHGSEYILGDFEIR 102
Cdd:cd00060   22 TIGRSPDCDIVLDDP--SVSRRHARIEVDGGGVYLEDLG------STNGTFVngkRITPPVPLQDGDVIRLGDTTFR 90

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 516298731   1 MELVFEMLNTKQFVPTDLCQKTFKQAGGVIGRGDDCDWIIPDRKRHLSNHHALISYRDGSFFLTDTSSNGIQDSTNGTRL 80
Cdd:COG3456    1 MPLTLRIINSPDLESGSAASATFGRGGGTIGRSADCDWVLPDPDRSVSRRHAEIRFRDGAFCLTDLSTNGTFLNGSDHPL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731  81 RKGEVVRIEHGSEYILGDFEIRARLV-RDPAAFDVEVGRPQAAGS---------IIPDDAFLD---LDPLNALDQQERVy 147
Cdd:COG3456   81 GPGRPVRLRDGDRLRIGDYEIRVEISgEDEGADDPLAAAPEPAVSspsnlsdteAAPDAALAFsfsLDPLEALDEAATE- 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731 148 SEIEELISPSIALDDGRQRADYARIDMESllvPELVEVPKEPAPAPAPPPVERQTDGFWEKFGAALGVDLKGLDHDAKEA 227
Cdd:COG3456  160 APATADDPPSLLPEDWLPSAAPVADEAAA---QAIDQLPSAAAPAPEPEPAADADHALLAALLRGLGLDLELLDSQDAED 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731 228 LALNAARLLKQSVGGLQQSLRTRSELKNELRLAQTIVQGPQKNPLKFAVDAGEALDILLQANKPGQLPAEQAISRAFRDL 307
Cdd:COG3456  237 FLEELGRLLRAAVEGLLDLLRARAEFKNEFRLDQTMLRPIENNPLKFSPDYEEALALLLAPKSPGFLSAPAAVAESLRDL 316

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731 308 QAHQVALLTASRAAVRGTLEHFSPQQLMLRFERDNKPliATSGSRWRAYGRYHQALRQDTDWS-ERLLTRDFAQAYEEQI 386
Cdd:COG3456  317 RLHQLALLAAIQAALRALLDAFSPEALERRFERRLFG--SRKAKAWDMYEAYYQELSSERQQGfEKLFGEVFAQAYDRAL 394

                 ....*
gi 516298731 387 RLIST 391
Cdd:COG3456  395 RELKR 399

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 516298731  29 VIGRGDDCDWIIPDRkrHLSNHHALISYRDGSFFLTDTSsngiqdSTNGTRL---RKGEVVRIEHGSEYILGDFEIR 102
Cdd:cd00060   22 TIGRSPDCDIVLDDP--SVSRRHARIEVDGGGVYLEDLG------STNGTFVngkRITPPVPLQDGDVIRLGDTTFR 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516298731  14 VPTDLCQKTFKqaggvIGRGDDCDWIIPDRKrHLSNHHALISY-RDGSFFLTDTSSNGiqdsT--NGTRLRKGEVVRIEH 90
Cdd:cd22672   14 PPILLRKDEFT-----IGRAKDCDLSFPGNK-LVSGDHCKIIRdEKGQVWLEDTSTNG----TlvNKVKVVKGQKVELKH 83

                 ...
gi 516298731  91 GSE 93
Cdd:cd22672   84 GDV 86

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 516298731  29 VIGRGDDCDWIIPDRkrHLSNHHALISYRDGSFFLTDtssngiQDSTNGTRLRKGEVV------RIEHGSEYILGDFE 100
Cdd:cd22665   24 VIGRDPSCSVVLPDK--SVSKQHACIEVDGGTHLIED------LGSTNGTRIGNKVRLkpnvryELIDGDLLLFGDVK 93

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 516298731  47 LSNHHALISYRDGSFFLTDT-SSNGiqdsT--NGTRLRKG 83
Cdd:cd22679   49 LSRNHALLWYDDGKFYLQDTkSSNG----TfvNNQRLSKG 84

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 516298731  30 IGRGDDCDWIIPDRKrhLSNHHALISYRDGSFFLTDTssngiqDSTNGTRLRKGEV--VRIEHGSEYILG 97
Cdd:cd22698   25 IGRSSNNDIRLNDHS--VSRHHARIVRQGDKCNLTDL------GSTNGTFLNGIRVgtHELKHGDRIQLG 86

first forkhead associated (FHA) domain found in Mycobacterium tuberculosis ABC transporter ATP-binding/permease protein Rv1747 and similar proteins; Rv1747 is a putative ATP-binding cassette (ABC) transporter involved in the translocation of an unknown substrate across the membrane. It is required for normal virulent infection by M. tuberculosis. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). Recruitment and phosphorylation of Rv1747 depend on the interaction between its two non-redundant FHA domains and the autophosphorylated form of serine/threonine protein kinase PknF. This model corresponds to the first FHA domain. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 516298731  29 VIGRGDDCDWIIPDRKrhLSNHHALISYRDGSFFLTDtssngiQDSTNGTRL--RKGEVVRIEHGSEYILGD 98
Cdd:cd22694   19 RIGRDPDADVRLDDPR--VSRRHALLEFDGDGWVYTD------LGSRNGTYLngRRVQQVKLSDGTRVRLGD 82

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 516298731  29 VIGRGDDCDwiIPDRKrhLSNHHALI--SYRDGSFFLTDTSSNGIQ---DSTNGTRLRKGEVVRIEHGS--EYILGDFEI 101
Cdd:cd22671   22 VLGRGPLLG--IRDKR--VSRKQAEItvDDDTGSVTVTQLGTNPSFvnrADGEGKVLKKGESVELKDGDviSLLPGKYPF 97

                 ....
gi 516298731 102 RARL 105
Cdd:cd22671   98 RVEI 101

forkhead associated (FHA) domain found in Mycobacterium tuberculosis FHA domain-containing protein FhaA and similar proteins; FhaA regulates cell growth and peptidoglycan synthesis by binding to MviN. It may inhibit the late stages of peptidoglycan synthesis. It contains an FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 516298731  29 VIGRGDDCDWIIPDRKrhLSNHHALISYRDGSFFLTDTssngiqDSTNGT-----------RLRKGEVVRIEHGS 92
Cdd:cd22668   21 IIGRGSDADFRLPDTG--VSRRHAEIRWDGQVAHLTDL------GSTNGTtvnnapvtpewRLADGDVITLGHSE 87