forkhead associated (FHA) domain found in kanadaptin and similar proteins; Kanadaptin, also called human lung cancer oncogene 3 protein (HLC-3), kidney anion exchanger adapter protein, or solute carrier family 4 anion exchanger member 1 adapter protein (SLC4A1AP), is a nuclear protein widely expressed in mammalian tissues. It was originally isolated as a kidney Cl-/HCO3- anion exchanger 1 (kAE1)-binding protein. It is a highly mobile nucleocytoplasmic shuttling and multilocalizing protein. Its role in mammalian cells remains unclear. It contains an FHA domain, which is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 112 PYSLETLKGGTILGTRTLKDTSCCFFGRLASCDICLEHPSVSRYHAVLQHRGadpsgDSEGHEQGFYLYDLGSTHGTFLN 191
Cdd:cd22677     1 PYSLEVLKNGVIVETLDLNGKSFYVFGRLPGCDVVLEHPSISRYHAVLQYRG-----DADDHDGGFYLYDLGSTHGTFLN 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1316032090 192 KTRIPPRTYCRVHVGHVMRFGGSTRLFILQG 222
Cdd:cd22677    76 KQRIPPKQYYRLRVGHVLKFGGSTRLYILQG 106

forkhead associated (FHA) domain found in kanadaptin and similar proteins; Kanadaptin, also called human lung cancer oncogene 3 protein (HLC-3), kidney anion exchanger adapter protein, or solute carrier family 4 anion exchanger member 1 adapter protein (SLC4A1AP), is a nuclear protein widely expressed in mammalian tissues. It was originally isolated as a kidney Cl-/HCO3- anion exchanger 1 (kAE1)-binding protein. It is a highly mobile nucleocytoplasmic shuttling and multilocalizing protein. Its role in mammalian cells remains unclear. It contains an FHA domain, which is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 112 PYSLETLKGGTILGTRTLKDTSCCFFGRLASCDICLEHPSVSRYHAVLQHRGadpsgDSEGHEQGFYLYDLGSTHGTFLN 191
Cdd:cd22677     1 PYSLEVLKNGVIVETLDLNGKSFYVFGRLPGCDVVLEHPSISRYHAVLQYRG-----DADDHDGGFYLYDLGSTHGTFLN 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1316032090 192 KTRIPPRTYCRVHVGHVMRFGGSTRLFILQG 222
Cdd:cd22677    76 KQRIPPKQYYRLRVGHVLKFGGSTRLYILQG 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 138 GRLASCDICLEHPSVSRYHAVLQHRGadpsgdsegheQGFYLYDLGSTHGTFLNKTRIppRTYCRVHVGHVMRFGGSTRL 217
Cdd:COG1716    26 GRAPDNDIVLDDPTVSRRHARIRRDG-----------GGWVLEDLGSTNGTFVNGQRV--TEPAPLRDGDVIRLGKTELR 92

                  ....
gi 1316032090 218 FILQ 221
Cdd:COG1716    93 FRLS 96

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1316032090  136 FFGRL-ASCDICLEHPSVSRYHAVLQHRgadpsGDSEgheqgFYLYDLGSTHGTFLNKTRI 195
Cdd:smart00240   2 TIGRSsEDCDIQLDGPSISRRHAVIVYD-----GGGR-----FYLIDLGSTNGTFVNGKRI 52

forkhead associated (FHA) domain found in kanadaptin and similar proteins; Kanadaptin, also called human lung cancer oncogene 3 protein (HLC-3), kidney anion exchanger adapter protein, or solute carrier family 4 anion exchanger member 1 adapter protein (SLC4A1AP), is a nuclear protein widely expressed in mammalian tissues. It was originally isolated as a kidney Cl-/HCO3- anion exchanger 1 (kAE1)-binding protein. It is a highly mobile nucleocytoplasmic shuttling and multilocalizing protein. Its role in mammalian cells remains unclear. It contains an FHA domain, which is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 112 PYSLETLKGGTILGTRTLKDTSCCFFGRLASCDICLEHPSVSRYHAVLQHRGadpsgDSEGHEQGFYLYDLGSTHGTFLN 191
Cdd:cd22677     1 PYSLEVLKNGVIVETLDLNGKSFYVFGRLPGCDVVLEHPSISRYHAVLQYRG-----DADDHDGGFYLYDLGSTHGTFLN 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1316032090 192 KTRIPPRTYCRVHVGHVMRFGGSTRLFILQG 222
Cdd:cd22677    76 KQRIPPKQYYRLRVGHVLKFGGSTRLYILQG 106

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 1316032090 107 SPATAPYSLETLKGGTILGTRTLKDTSCCFFGRLAS-CDICLEHPSVSRYHAVLQHrgadpsgdsEGHEQGFYLYDLGST 185
Cdd:cd22674     1 GKPPPGLHLDVVKDGKLIEKLMIDEKKYYLFGRNSDvCDFVLDHPSCSRVHAALVY---------HKHLNRVFLIDLGST 71

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1316032090 186 HGTFLNKTRIPPRTYCRVHVGHVMRFGGSTRLFILQG 222
Cdd:cd22674    72 HGTFVGGIRLEPHKPQQLPIDSTLRFGASTRRYILRE 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 1316032090 115 LETLKGGTILGTRTLKDtSCCFFGRLASCDICLEHPSVSRYHAVLQHRGadpsgdsegheQGFYLYDLGSTHGTFLNKTR 194
Cdd:cd00060     2 LIVLDGDGGGREFPLTK-GVVTIGRSPDCDIVLDDPSVSRRHARIEVDG-----------GGVYLEDLGSTNGTFVNGKR 69

                          90       100
                  ....*....|....*....|.
gi 1316032090 195 IPPRTycRVHVGHVMRFGGST 215
Cdd:cd00060    70 ITPPV--PLQDGDVIRLGDTT 88

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1316032090 137 FGRLASCDICLEHPSVSRYHAVLQHRGadpsgdseghEQGFYLYDLGSTHGTFLNKTRIPPRTYcRVHVGHVMRF 211
Cdd:pfam00498   3 IGRSPDCDIVLDDPSVSRRHAEIRYDG----------GGRFYLEDLGSTNGTFVNGQRLGPEPV-RLKDGDVIRL 66

forkhead associated (FHA) domain found in Smad nuclear-interacting protein 1 (SNIP1) and similar proteins; SNIP1 is an FHA domain-containing protein required for pre-mRNA splicing as a component of the spliceosome. It inhibits NF-kappaB signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional co-activators. It is involved in microRNA (miRNA) biogenesis. SNIP1 is a regulator of the cell cycle and cyclin D1 expression and may be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex, which associates with both the 3'end of the CCND1 gene and its mRNA. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 100 YREPSWGSPATAPYSLETLKGGTILGTRTLKDTSCCFFGRLAS-CDICLEHPSVSRYHAVLQHRGAD---PSGdSEGHEQ 175
Cdd:cd22718    23 YSEPPEARKPKKRWRLYPFKGDEALPVLYIHRQSAYLLGRDRKiADIPIDHPSCSKQHAVLQYRLVEytrPDG-TKGRRV 101

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1316032090 176 GFYLYDLGSTHGTFLNKTRIPPRTYCRVHVGHVMRFGGSTRLFIL 220
Cdd:cd22718   102 RPYIIDLESANGTFLNNKKIEPQRYYELKEKDVLKFGFSSREYVL 146

forkhead associated (FHA) domain found in Trypanosoma brucei Parvulin 42 (TbPar42) and similar proteins; TbPar42 is a nuclear protein that plays a key role in parasite cell proliferation. It exhibits an N-terminal forkhead associated (FHA)-domain and a peptidyl-prolyl-cis/trans-isomerase (PPIase) domain, both connected by a linker. Its PPIase domain adopts a parvulin fold and reflects structural elements of Pin1-type proteins but is catalytically inactive. Its FHA domain may be involved in the binding of phosphorylated target proteins. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 106 GSPATAPYsLETLKGGTILGTRTLKDTSCCFFGRLASCDICLEHPSVSRYHAVLQHRGAdpsgdseghEQGFYLYDLGST 185
Cdd:cd22675     3 ALPAVACH-LQCLRDGVPLPPLGLDRFPFYLFGRSPVCDYVLEHPSISSVHAVLVFHGE---------QKCFVLMDLGST 72

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1316032090 186 HGTFLNKTRIPPRTYCRVHVGHVMRFGGSTRLFILQ-GP 223
Cdd:cd22675    73 NGVKLNGKRIEKGRPLPLPVGSVIQFGFSARKYKVRkGP 111

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 1316032090 138 GRLASCDICLEHPSVSRYHAVLQHRGADpsgdsegheqgFYLYDLGSTHGTFLN-KTRIPPRTYCRVHVGHVMRFG 212
Cdd:cd22665    26 GRDPSCSVVLPDKSVSKQHACIEVDGGT-----------HLIEDLGSTNGTRIGnKVRLKPNVRYELIDGDLLLFG 90

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 1316032090 125 GTRTLKDTSCCFFGRlASCDICLEHPSVSRYHAVLQHRGAdpsgdSEGHEqgfyLYDLGSTHGTFLNKTRIPPRTYCRVH 204
Cdd:cd22724    13 GTRHRLPREMIFVGR-DDCELMLQSRSVDKQHAVINYDAS-----TDEHK----VKDLGSLNGTFVNDVRIPEQTYITLK 82

                          90
                  ....*....|....*....
gi 1316032090 205 VGHVMRFGGSTRLF-ILQG 222
Cdd:cd22724    83 LDDKLRFGYDTNLFtVVRG 101

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1316032090 138 GRLASCDICLEHPSVSRYHAVLQHRGadpsgdsegheQGFYLYDLGSTHGTFLNKTRIP 196
Cdd:cd22694    21 GRDPDADVRLDDPRVSRRHALLEFDG-----------DGWVYTDLGSRNGTYLNGRRVQ 68

forkhead associated (FHA) domain found in centrosomal protein of 170 kDa protein B (Cep170B) and similar proteins; Cep170B, also called centrosomal protein 170B, plays a role in microtubule organization. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 125 GTRTLKDTSCCFFGRlASCDICLEHPSVSRYHAVLQHrgaDPSGDSEgheqgfYLYDLGSTHGTFLNKTRIPPRTYCRVH 204
Cdd:cd22725    13 GTRHRLPREMIFVGR-EDCELMLQSRSVDKQHAVINY---DQDTDEH------WVKDLGSLNGTFVNDVRIPDQKYITLK 82

                          90
                  ....*....|....*..
gi 1316032090 205 VGHVMRFGGSTRLFILQ 221
Cdd:cd22725    83 LNDVIRFGYDSNMYVLE 99

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1316032090 137 FGRlASCDICLEH-PSVSRYHAVLQHRGADPSGDSEGHEQGFYLYDLgSTHGTFLNKTRIPPRTYCRVHVGHVMRFG 212
Cdd:cd22667    24 VGR-KDCDIIIVDdSSISRKHATLTVLHPEANLSDPDTRPELTLKDL-SKYGTFVNGEKLKGGSEVTLKDGDVITFG 98

second forkhead associated (FHA) domain found in Saccharomyces cerevisiae Serine/threonine-protein kinase RAD53 and similar proteins; RAD53, also called CHEK2 homolog, or serine-protein kinase 1 (Spk1), is a nuclear protein kinase that phosphorylates proteins on serine, threonine, and tyrosine. It controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints and prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. It may be involved in the phosphorylation of RPH1. RAD53 contains two FHA domains. This model corresponds to the second one. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1316032090 136 FFGRLASCDICLEHPSVSRYHAVLqHRgaDPSGDSEGHeqgFYLYDLgSTHGTFLNKTRIPPRTYCRVHVG 206
Cdd:cd22690    22 FIGRSKDCDEEITDPRISKHHCII-TR--KRSGKGLDD---VYVTDT-STNGTFINNNRLGKGSQSLLQDG 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 131 DTSCCFFGRLASCDICLEHPSVSRYHAVLqhrgadpsgdsEGHEQG-FYLYDLGSTHGTFLNKTRIPPRT 199
Cdd:cd22673    19 TKKSCTFGRDLSCDIRIQLPGVSREHCRI-----------EVDENGkAYLENLSTTNPTLVNGKAIEKSA 77

forkhead associated (FHA) domain found in Mycobacterium tuberculosis GarA, Corynebacterium glutamicum OdhI and similar proteins; This family includes Mycobacterium tuberculosis glycogen accumulation regulator GarA and Corynebacterium glutamicum oxoglutarate dehydrogenase inhibitor (OdhI). GarA is involved in the regulation of glutamate metabolism. It acts as a phosphorylation-dependent molecular switch that modulates the activities of Kgd, Gdh and GltB. GarA binds to Kgd, Gdh, GltB, PknB, and the N-terminal region of PknG via its FHA domain. OdhI is an essential component of the PknG signaling pathway. It can inhibit the activity of 2-oxoglutarate dehydrogenase only when it is unphosphorylated. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1316032090 119 KGGTILGTRTLKDTSCCFFGRLASCDICLEHPSVSRYHAVLQHRGAdpsgdsegheqGFYLYDLGSTHGTFLNKTRI 195
Cdd:cd22684     7 RRGPNAGARFLLDQDVTTAGRHPESDIFLDDVTVSRRHAEFRRAEG-----------GFVVRDVGSLNGTYVNRERI 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1316032090 136 FFGRLASCDICLEHPSVSRYHAVLQHRGadpsgdseGHeqgFYLYDLGSTHGTFLNKTRI 195
Cdd:cd22698    24 TIGRSSNNDIRLNDHSVSRHHARIVRQG--------DK---CNLTDLGSTNGTFLNGIRV 72

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 1316032090 135 CFFGRLASCDICLEHPSVSRYHAVLQHRGADPSGDSEgheqgFYLYDLgSTHGTFLNKTRI 195
Cdd:cd22670    24 ITIGRSPSCDIVINDPFVSRTHCRIYSVQFDESSAPL-----VYVEDL-SSNGTYLNGKLI 78

second 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 second FHA domain, which has a circularly permuted FHA domain fold with a conserved pThr-binding interface.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1316032090 137 FGRLASCDICLEHPSVSRYHAVLQHRGAdpsgdsegheqGFYLYDLGSTHGTFLNKTRIpprTYCRVHVGHVMRFG 212
Cdd:cd22737    25 IGRASDNDIVIPEGSVSRHHATLVPTPG-----------GTQIRDLRSTNGTFVNGLRV---DAALLHDGDVVTIG 86

first forkhead associated (FHA) domain found in Saccharomyces cerevisiae Serine/threonine-protein kinase RAD53 and similar proteins; RAD53, also called CHEK2 homolog, or serine-protein kinase 1 (Spk1), is a nuclear protein kinase that phosphorylates proteins on serine, threonine, and tyrosine. It controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints and prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. It may be involved in the phosphorylation of RPH1. RAD53 contains two FHA domains. This model corresponds to the first one. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1316032090 137 FGRLASCDICLEHPSVSRYH-AVLQhrgadpsGDSEGHEQGFYLYDLgSTHGTFLNKTRIPPRTY 200
Cdd:cd22689    49 FGRHPACDYHLGNSRLSNKHfQILL-------GESDPSDGNVLLNDI-SSNGTWLNGQRLEKNSN 105

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 1316032090 118 LKGGTILGTRTLKDTSCCFFGRLASCDICleHPS---VSRYHAVLQHrgaDPSGdsegheqGFYLYDLgSTHGTFLNKTR 194
Cdd:cd22672     6 VRLTEESSPPILLRKDEFTIGRAKDCDLS--FPGnklVSGDHCKIIR---DEKG-------QVWLEDT-STNGTLVNKVK 72

                  .
gi 1316032090 195 I 195
Cdd:cd22672    73 V 73

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.

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gi 1316032090 143 CDI-CLEHPSVSRYHAVLQHrgadpsgDSEGHeqgFYLYDLGSTHGTFLNKTRIPPRTYCRVHVGHVMRFG 212
Cdd:cd22663    33 YQLvSTCPLMISRNHCVLKK-------NDEGQ---WTIKDNKSLNGVWVNGERIEPLKPYPLNEGDLIQLG 93

Double-stranded RNA binding motif; Sequences gathered for seed by HMM_iterative_training Putative motif shared by proteins that bind to dsRNA. At least some DSRM proteins seem to bind to specific RNA targets. Exemplified by Staufen, which is involved in localization of at least five different mRNAs in the early Drosophila embryo. Also by interferon-induced protein kinase in humans, which is part of the cellular response to dsRNA.

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gi 1316032090 316 PKKALQGFFDREGEELEYEF-DEQGHS---TWLCRVRLpvddstGKQLVAEAIhSGKKKEAMVQCSLEACRVL 384
Cdd:pfam00035   1 PKSLLQEYAQKNGKPPPYEYvSEEGPPhspKFTVTVKV------DGKLYGSGT-GSSKKEAEQLAAEKALEKL 66