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 1002304355   16 FAVSKGGVVLKNIFLNAPPSPlpveeaargrggEEEDPPVMFGRHPECHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSS 95
Cdd:cd22691      4 LTVLKNGSVLKNIFLHGKFSK------------SEEEDILVVGRHPDCDIVLDHPSISRFHLEIRIIPSRRKITLTDLSS 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1002304355   96 VHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRLHWLSLP 137
Cdd:cd22691     72 VHGTWVNGQRIEPGVPVELEEGDTVRLGASTRVYRLHWIPVS 113

forkhead associated (FHA) domain found in Arabidopsis thaliana Protein PARALLEL SPINDLE 1 (PS1) and similar proteins; PS1 is an FHA domain-containing protein required for normal spindle orientation at male meiosis II and normal formation of tetrad of microspores. It is not involved in female meiosis. Mutations in PS1 lead to the production of diploid pollen grains. The FHA domain is a small phosphopeptide recognition module.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   16 FAVSKGGVVLKNIFLNAPPSPlpveeaargrggEEEDPPVMFGRHPECHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSS 95
Cdd:cd22691      4 LTVLKNGSVLKNIFLHGKFSK------------SEEEDILVVGRHPDCDIVLDHPSISRFHLEIRIIPSRRKITLTDLSS 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1002304355   96 VHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRLHWLSLP 137
Cdd:cd22691     72 VHGTWVNGQRIEPGVPVELEEGDTVRLGASTRVYRLHWIPVS 113

VapC-like PIN domain of nonsense-mediated decay (NMD) factors, Smg5 and Smg6, and related proteins; PIN (PilT N terminus) domain of nonsense-mediated decay (NMD) factors, Smg5 and Smg6, and homologs are included in this family. Smg5 and Smg6 are essential factors in NMD, a post-transcriptional regulatory pathway that recognizes and rapidly degrades mRNAs containing premature translation termination codons. In vivo, the Smg6 PIN domain elicits degradation of bound mRNAs, as well as, metal-ion dependent, degradation of single-stranded RNA, in vitro. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases (also known as Flap endonuclease-1-like), PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. Point mutation studies of the conserved aspartate residues in the catalytic center of the Smg6 PIN domain revealed that Smg6 is the endonuclease involved in human NMD. However, Smg5 lacks several of these key catalytic residues and does not degrade single-stranded RNA, in vivo. Many of the bacterial homologs in this group have an N-terminal PIN domain and a C-terminal PhoH-like ATPase domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  857 VTDMECLLDDEsrKSIMLLRGLKGTQLVIPMIVIRELECLKKRERlfRMLSKATSMLQWINECMEKESWWIHVQSSTEML 936
Cdd:cd09880      1 VFDTNILLSHL--DVLKLLVESGKWTVVIPLIVITELDGLKKNPD--PLGPKARSALRYIEACLKKHSRWLRVQTSKGNY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  937 pvaptppatptaLCNNGEReisagtfnpialFSPRSF-SDIVSPKTEDRVLDCALLFNK-----LKGNQNIVILSNSVTL 1010
Cdd:cd09880     77 ------------LADLTIR------------SEQLSDaSELRRRNNDDRILECALWQQKhfvdrEDGDGKVVLVTNDRNL 132

                          170
                   ....*....|....*....
gi 1002304355 1011 KIKAMAEGFPCEGAKEFRE 1029
Cdd:cd09880    133 RLKARARGVEAVTVKELLK 151

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1002304355   55 VMFGRHPECHVLVDHPSVSRFHLEVrSRRRQRRITVTDLSSVHGTWISGRRIPPNtPVELTAGDVLRL 122
Cdd:pfam00498    1 VTIGRSPDCDIVLDDPSVSRRHAEI-RYDGGGRFYLEDLGSTNGTFVNGQRLGPE-PVRLKDGDVIRL 66

type VI secretion system FHA domain protein; Members of this protein family are FHA (forkhead-associated) domain-containing proteins that are part of type VI secretion loci in a considerable number of bacteria, most of which are known pathogens. Species include Pseudomonas aeruginosa PAO1, Aeromonas hydrophila, Yersinia pestis, Burkholderia mallei, etc. [Protein fate, Protein and peptide secretion and trafficking, Cellular processes, Pathogenesis]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   39 VEEAARGRGGEeedppvmFGRHPECHVLVDHP--SVSRFHLEVRSRRRQRRITvtDLSSvHGTWI--SGRRIPPNTPVEL 114
Cdd:TIGR03354   17 AQKTFGTNGGT-------IGRSEDCDWVLPDPerHVSGRHARIRYRDGAYLLT--DLST-NGVFLngSGSPLGRGNPVRL 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  115 TAGDVLRLGSSRREYRLH---WLSLPEAFDMEDLLPplleEDKEELSTCQEASKQLEP---DQKESADTETHQETSQQV- 187
Cdd:TIGR03354   87 EQGDRLRLGDYEIRVSLGdplVSRQASESRADTSLP----TAGGPPTPDPAPLAQLDPlkaLDQEPLSAADLDDLSAPLf 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1002304355  188 --VSEQIDFHANVIPSAPPI-PEFADLFALEESSVPEFDDSREGR 229
Cdd:TIGR03354  163 ppLDARLPAFAAPIDAEPTMvPPFVPLPAPEPAPAPASQAPSSDA 207

forkhead associated (FHA) domain found in Arabidopsis thaliana Protein PARALLEL SPINDLE 1 (PS1) and similar proteins; PS1 is an FHA domain-containing protein required for normal spindle orientation at male meiosis II and normal formation of tetrad of microspores. It is not involved in female meiosis. Mutations in PS1 lead to the production of diploid pollen grains. The FHA domain is a small phosphopeptide recognition module.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   16 FAVSKGGVVLKNIFLNAPPSPlpveeaargrggEEEDPPVMFGRHPECHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSS 95
Cdd:cd22691      4 LTVLKNGSVLKNIFLHGKFSK------------SEEEDILVVGRHPDCDIVLDHPSISRFHLEIRIIPSRRKITLTDLSS 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1002304355   96 VHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRLHWLSLP 137
Cdd:cd22691     72 VHGTWVNGQRIEPGVPVELEEGDTVRLGASTRVYRLHWIPVS 113

VapC-like PIN domain of nonsense-mediated decay (NMD) factors, Smg5 and Smg6, and related proteins; PIN (PilT N terminus) domain of nonsense-mediated decay (NMD) factors, Smg5 and Smg6, and homologs are included in this family. Smg5 and Smg6 are essential factors in NMD, a post-transcriptional regulatory pathway that recognizes and rapidly degrades mRNAs containing premature translation termination codons. In vivo, the Smg6 PIN domain elicits degradation of bound mRNAs, as well as, metal-ion dependent, degradation of single-stranded RNA, in vitro. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases (also known as Flap endonuclease-1-like), PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. Point mutation studies of the conserved aspartate residues in the catalytic center of the Smg6 PIN domain revealed that Smg6 is the endonuclease involved in human NMD. However, Smg5 lacks several of these key catalytic residues and does not degrade single-stranded RNA, in vivo. Many of the bacterial homologs in this group have an N-terminal PIN domain and a C-terminal PhoH-like ATPase domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  857 VTDMECLLDDEsrKSIMLLRGLKGTQLVIPMIVIRELECLKKRERlfRMLSKATSMLQWINECMEKESWWIHVQSSTEML 936
Cdd:cd09880      1 VFDTNILLSHL--DVLKLLVESGKWTVVIPLIVITELDGLKKNPD--PLGPKARSALRYIEACLKKHSRWLRVQTSKGNY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  937 pvaptppatptaLCNNGEReisagtfnpialFSPRSF-SDIVSPKTEDRVLDCALLFNK-----LKGNQNIVILSNSVTL 1010
Cdd:cd09880     77 ------------LADLTIR------------SEQLSDaSELRRRNNDDRILECALWQQKhfvdrEDGDGKVVLVTNDRNL 132

                          170
                   ....*....|....*....
gi 1002304355 1011 KIKAMAEGFPCEGAKEFRE 1029
Cdd:cd09880    133 RLKARARGVEAVTVKELLK 151

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002304355   56 MFGRHPE-CHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSSVHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRL 131
Cdd:cd22674     30 LFGRNSDvCDFVLDHPSCSRVHAALVYHKHLNRVFLIDLGSTHGTFVGGIRLEPHKPQQLPIDSTLRFGASTRRYIL 106

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   51 EDPPVMFGRHPECHVLVDHPSVSRFHLEVrsRRRQRRITVTDLSSVHGTWISGRRIppNTPVELTAGDVLRLGSSRREYR 130
Cdd:COG1716     19 DGGPLTIGRAPDNDIVLDDPTVSRRHARI--RRDGGGWVLEDLGSTNGTFVNGQRV--TEPAPLRDGDVIRLGKTELRFR 94

                   .
gi 1002304355  131 L 131
Cdd:COG1716     95 L 95

VapC-like PIN domain of Saccharomyces cerevisiae Swt1p, human SWT1 and related proteins; Saccharomyces cerevisiae mRNA-processing endoribonuclease Swt1p plays an important role in quality control of nuclear mRNPs in eukaryotes. Human transcriptional protein SWT1 (RNA endoribonuclease homolog, also known as HsSwt1, C1orf26, and chromosome 1 open reading frame 26) is an RNA endonuclease that participates in quality control of nuclear mRNPs and can associate with the nuclear pore complex (NPC). This subfamily belongs to the Smg5 and Smg6-like PIN domain family. Smg5 and Smg6 are essential factors in NMD, a post-transcriptional regulatory pathway that recognizes and rapidly degrades mRNAs containing premature translation termination codons. In vivo, the Smg6 PIN domain elicits degradation of bound mRNAs, as well as, metal-ion dependent, degradation of single-stranded RNA, in vitro. The PIN (PilT N terminus) domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases (also known as Flap endonuclease-1-like), PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. Point mutation studies of the conserved aspartate residues in the catalytic center of the Smg6 PIN domain revealed that Smg6 is the endonuclease involved in human NMD. However, Smg5 lacks several of these key catalytic residues and does not degrade single-stranded RNA, in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  882 QLVIPMIVIRELECLKKRERLFRMLSKATSMLQWINECMEKESWWIHVQSSTEMLpvaptPPATPTALCNngereisagt 961
Cdd:cd18727     29 VIVIPWVVLQELDGLKKSKRKSSLGWLARRASTWLLEKLRSKHPRVRGQALSETL-----RASGDPGESN---------- 93

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1002304355  962 fnpialfsprsfsDivspkteDRVLDCALLFNKLKGNqNIVILSNSVTLKIKAMAEG 1018
Cdd:cd18727     94 -------------D-------DAILDCCLYFQEKYGA-PVVLLSNDKNLCNKALING 129

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   45 GRGGEEEDPPVMFGRHPECHVLVDHPSVSRFHLEVRSRRRQRriTVTDLSSVHGTWISGRRIPpntPVELTAGDVLRLGS 124
Cdd:cd22694      8 GELRFDPGSSVRIGRDPDADVRLDDPRVSRRHALLEFDGDGW--VYTDLGSRNGTYLNGRRVQ---QVKLSDGTRVRLGD 82

                   ....*...
gi 1002304355  125 SRREYRLH 132
Cdd:cd22694     83 PTDGPALT 90

forkhead associated (FHA) domain found in chloroplastic zeaxanthin epoxidase (ZEP) and similar proteins; ZEP, also called protein ABA DEFICIENT 1, ABA1, protein IMPAIRED IN BABA-INDUCED STERILITY 3, protein LOW EXPRESSION OF OSMOTIC STRESS-RESPONSIVE GENES 6, or protein NON-PHOTOCHEMICAL QUENCHING 2, plays an important role in the xanthophyll cycle and abscisic acid (ABA) biosynthesis. It converts zeaxanthin into antheraxanthin and subsequently violaxanthin. ZEP is required for resistance to osmotic and drought stresses, ABA-dependent stomatal closure, seed development and dormancy, modulation of defense gene expression, and disease resistance and non-photochemical quencing (NPQ). The FHA domain is a small phosphopeptide recognition module.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   50 EEDPPVMFGRHPEC-----HVLVDHPSVSRFHLEVRSRRRQrrITVTDLSSVHGTWIS---GRR--IPPNTPVELTAGDV 119
Cdd:cd22702     29 DEKQPCIIGSDPHQaisgiSVVIPSPQVSELHARITCKNGA--FFLTDLGSEHGTWINdneGRRyrAPPNFPVRLHPSDV 106

                   ....*
gi 1002304355  120 LRLGS 124
Cdd:cd22702    107 IEFGS 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1002304355   58 GRHPECHVLVDHPSVSRFH--LEVrsrrRQRRITVTDLSSVHGTWI-SGRRIPPNTPVELTAGDVLRLG 123
Cdd:cd22665     26 GRDPSCSVVLPDKSVSKQHacIEV----DGGTHLIEDLGSTNGTRIgNKVRLKPNVRYELIDGDLLLFG 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 1002304355   51 EDPPVMFGRHPECHVLVDHPS--VSRFHLEVRSRRRQrrITVTDLSSvHGTWI--SGRRIPPNTPVELTAGDVLRLGssr 126
Cdd:COG3456     24 GRGGGTIGRSADCDWVLPDPDrsVSRRHAEIRFRDGA--FCLTDLST-NGTFLngSDHPLGPGRPVRLRDGDRLRIG--- 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355  127 rEYRL--HWLSLPEAFDMEDLLPPLLEEDKEELSTCQEASKQLEPDQKESADT-------ETHQETSQQVVSEQIDfhAN 197
Cdd:COG3456     98 -DYEIrvEISGEDEGADDPLAAAPEPAVSSPSNLSDTEAAPDAALAFSFSLDPlealdeaATEAPATADDPPSLLP--ED 174

                          170       180
                   ....*....|....*....|...
gi 1002304355  198 VIPSAPPIPEFADLFALEESSVP 220
Cdd:COG3456    175 WLPSAAPVADEAAAQAIDQLPSA 197

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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1002304355   57 FGRHPECHVLVDHPSVSRFHLE---VRSRRRQRRIT-VTDLSSvHGTWISGRRIPPNTPVELTAGDVLRLGSS 125
Cdd:cd22670     26 IGRSPSCDIVINDPFVSRTHCRiysVQFDESSAPLVyVEDLSS-NGTYLNGKLIGRNNTVLLSDGDVIEIAHS 97

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1002304355   55 VMFGRHPECHVLVDHPSVSRFHLEVRSRRRQrrITVTDLSSVHGTWISGRRIPPNTpVELTAGDVLRLG 123
Cdd:cd22683     23 TTIGRSRSCDLVLSDPSISRFHAELRLEQNG--INVIDNNSANGTFINGKRIKGKT-YILKNGDIIVFG 88

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   55 VMFGRHPECHVLVDHPSVSRFHLEVrsRRRQRRITVTDLSSVHGTWI-SGRRIPPNTPVEltAGDVLRLG 123
Cdd:cd22680     23 VSIGRDPENVIVIPDPFVSRNHARI--TVDSNEIYIEDLGSTNGTFVnDFKRIKGPAKLH--PNDIIKLG 88

forkhead associated (FHA) domain found in forkhead-associated domain-containing protein 1 (FHAD1) and similar proteins; FHAD1, also called FHA domain-containing protein 1, is an uncharacterized FHA domain-containing protein. The FHA domain is a small phosphopeptide recognition module.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1002304355   58 GRHpECHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSSVHGTWISGRRIPpNTPVELTAGDVLRLGSSRREYRL 131
Cdd:cd22700     21 GRE-GCDLVLQSPGVEEQHAVIEYSEQENCFVLQDLNTAQGTYVNDCRIQ-NAAVRLAPGDVLRFGFGGLPYEL 92

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002304355   57 FGRHPECHVLVDHPSVSRFHLEVrSRRRQRRITVTDLSSVHGTWISGRRIppNTPVELTAGDVLRLG 123
Cdd:cd22673     25 FGRDLSCDIRIQLPGVSREHCRI-EVDENGKAYLENLSTTNPTLVNGKAI--EKSAELKDGDVITIG 88

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 1002304355   21 GGVVLKnifLNAPPsplpveEA----ARGR----GGEEEDPPV--------MFGRHPE-CHVLVDHPSVSRFH------- 76
Cdd:cd22718     17 RGVVIK---YSEPP------EArkpkKRWRlypfKGDEALPVLyihrqsayLLGRDRKiADIPIDHPSCSKQHavlqyrl 87

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1002304355   77 LEVRSRRRQRRITV----TDLSSVHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRL 131
Cdd:cd22718     88 VEYTRPDGTKGRRVrpyiIDLESANGTFLNNKKIEPQRYYELKEKDVLKFGFSSREYVL 146

forkhead associated (FHA) domain found in the centrosomal protein of 170 kDa protein (Cep170) family; The Cep170 family includes Cep170 and Cep170B. 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). 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 1002304355   53 PPVMF-GRHpECHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSSVHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRL 131
Cdd:cd22704     16 RSMLFvGRE-DCDLILQSRSVDKQHAVITYDQIDNEFKIKDLGSLNGTFVNDSRIPEQTYITLKLGDSIRFGYDTNVYRF 94

                   ....*
gi 1002304355  132 HWLSL 136
Cdd:cd22704     95 EQLSL 99

forkhead associated (FHA) domain found in transcription factor 19 (TCF-19) and similar proteins; TCF-19, also called transcription factor SC1, was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It also functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. TCF-19 contains an N-terminal fork head association domain (FHA), a proline rich region, and a C-terminal plant homeodomain (PHD) finger. The FHA domain may serve as a nuclear signaling domain or as a phosphoprotein binding domain. The proline rich region is a common characteristic of trans-activating factors. The PHD finger may allow TCF-19 to interact with chromatin via methylated histone H3.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1002304355   57 FGRHPE-CHVLVD---HPS-VSRFHLEVRSRRRQRR---ITVTDlSSVHGTWISGRRIPPNTPVELTAGDVLRLG 123
Cdd:cd22685     32 IGRNPEvCDVFLCssqHPNlISREHAEIHAERDGNGnwkVLIED-RSTNGTYVNDVRLQDGQRRELSDGDTITFG 105

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 1002304355   58 GRHPECHVLVDHPSVSRFHLEVrsRRRQRRITVTDLSSVHGTWISGRRIppnTPVELTAGDVLRLGSS 125
Cdd:cd22698     26 GRSSNNDIRLNDHSVSRHHARI--VRQGDKCNLTDLGSTNGTFLNGIRV---GTHELKHGDRIQLGET 88

forkhead associated (FHA) domain found in Arabidopsis thaliana FHA domain-containing protein DDL and similar proteins; DDL, also called protein DAWDLE, is involved in microRNA (miRNA) and short interfering RNA (siRNA) biogenesis. It may facilitate DCL1 to access or recognize primary miRNAs. DDL binds RNA non-specifically. The FHA domain is a small phosphopeptide recognition module.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002304355   46 RGGEEEDPPV--------MFGRHPE-CHVLVDHPSVSRFHL---------EVRSRRRQRRIT--VTDLSSVHGTWISGRR 105
Cdd:cd22719     22 KDGEPLNEPLhihrqscyLFGRERKvADIPTDHPSCSKQHAviqyrltekEGGDGMMGKAVRpyIMDLGSTNGTFLNGER 101

                           90       100
                   ....*....|....*....|....*.
gi 1002304355  106 IPPNTPVELTAGDVLRLGSSRREYRL 131
Cdd:cd22719    102 IEPQRYYELLEKDTIKFGNSSREYVL 127

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 1002304355   55 VMFGRHPECHVLVDHPSVSRFHLEVRSRRRQRRItvTDLSSVHGTWISGRRIppnTPVELTAGDVLRLGSSR 126
Cdd:cd22737     23 VRIGRASDNDIVIPEGSVSRHHATLVPTPGGTQI--RDLRSTNGTFVNGLRV---DAALLHDGDVVTIGDID 89

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002304355   55 VMFGRHpECHVLVDHPSVSRFHLEVRSRRRQRRITVTDLSSVHGTWISGRRIPPNTPVELTAGDVLRLGSSRREYRL 131
Cdd:cd22725     23 IFVGRE-DCELMLQSRSVDKQHAVINYDQDTDEHWVKDLGSLNGTFVNDVRIPDQKYITLKLNDVIRFGYDSNMYVL 98

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 1002304355   54 PVMFGRHPECHVLVDHPSVSRFHLEVRSRRRQRRITvtDLSSVHGTWISGRRIPPntPVELTAGDVLRLGSSRREYR 130
Cdd:cd22668     19 SNIIGRGSDADFRLPDTGVSRRHAEIRWDGQVAHLT--DLGSTNGTTVNNAPVTP--EWRLADGDVITLGHSEIIVR 91