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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B       25 GQLRLFSGTHGPERdFPLYLGKNVVGRSPDCSVALPFPSISKQHAVIEISawNKAPILQDCGSLNGTQI----VKPPRVL 100
Cdd:COG1716   2 ARLVVLEGPLAGRR-FPLDGGPLTIGRAPDNDIVLDDPTVSRRHARIRRD--GGGWVLEDLGSTNGTFVngqrVTEPAPL 78

                ...
3VA4_B      101 PPG 103
Cdd:COG1716  79 RDG 81

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
3VA4_B          48 VVGRSP-DCSVALPFPSISKQHAVIEISAWNKApILQDCGSLNGTQI 93
Cdd:smart00240   2 TIGRSSeDCDIQLDGPSISRRHAVIVYDGGGRF-YLIDLGSTNGTFV 47

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B       27 LRLFSGTHGPERdFPLYLGKNVVGRSPDCSVALPFPSISKQHAVIEISawNKAPILQDCGSLNGTQI----VKPPRVLPP 102
Cdd:cd00060   2 LIVLDGDGGGRE-FPLTKGVVTIGRSPDCDIVLDDPSVSRRHARIEVD--GGGVYLEDLGSTNGTFVngkrITPPVPLQD 78

                .
3VA4_B      103 G 103
Cdd:cd00060  79 G 79

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
3VA4_B         48 VVGRSPDCSVALPFPSISKQHAVIEISAwNKAPILQDCGSLNGT-----QIVKPPRVLPPG 103
Cdd:pfam00498   2 TIGRSPDCDIVLDDPSVSRRHAEIRYDG-GGRFYLEDLGSTNGTfvngqRLGPEPVRLKDG 61

forkhead associated (FHA) domain found in Arabidopsis thaliana protein phosphatase 2C 70 (AtPP2C70) and similar proteins; AtPP2C70, also called kinase-associated protein phosphatase, or protein ROOT ATTENUATED GROWTH 1, dephosphorylates the serine/threonine receptor-like kinase RLK5. It may function as a signaling component in a pathway involving RLK5. It acts as a negative regulator of the CLAVATA1 signaling in plant development by binding and dephosphorylating CLAVATA1. It is also a component of a signaling pathway which mediates adaptation to NaCl stress. It contains an FHA domain, which is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
3VA4_B       49 VGRSPDCSVALPFPSISKQHAVIEISAWNKAPILQDCGSLNGTQIVKPPRVlPPGVSHRLRDQELILFADF 119
Cdd:cd22678  27 IGRIQRGDIALKDDEVSGKHARIEWNSTGSKWELVDLGSLNGTLVNGESIS-PNGRPVVLSSGDVITLGSE 96

forkhead associated (FHA) domain found in Bdellovibrio bacteriovorus GGDEF domain protein DgcB and similar proteins; DgcB is a GGDEF enzyme that produces cyclic-di-GMP in response to an unknown stimulus. It appends the C-terminal GGDEF enzymatic domain with an N-terminal forkhead-associated (FHA) domain that acts as a consensus phosphopeptide sensor. The GGDEF and sensory FHA domains form an asymmetrical dimer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B       31 SGTHGPERDFPLYLGKNVVGRSPDCSVALPFPSISKQHAVIEISAwnKAPILQDCGSLNGTQIvkPPRVLPPGVSHRLRD 110
Cdd:cd22682   6 IGPPGVGKQFPITESTIVIGRSVESQVQIDDDSVSRYHAKLAVNP--SAVSIIDLGSTNGTIV--NGKKIPKLASCDLQN 81

                ....
3VA4_B      111 QELI 114
Cdd:cd22682  82 GDQI 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B       25 GQLRLF--SGTHGPErdFPLYLGKNVVGRSPDCSVALPFPSISKQHAVIEISAWNKApILQDCGSLNGTQI----VKPPR 98
Cdd:cd22673   1 GKLVVIkkDGTDGSR--FPLTKKSCTFGRDLSCDIRIQLPGVSREHCRIEVDENGKA-YLENLSTTNPTLVngkaIEKSA 77

                ..
3VA4_B       99 VL 100
Cdd:cd22673  78 EL 79

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
                ....*....|....*....|....*....|....*....|...
3VA4_B       49 VGRSpDCSVALPFPSISKQHAVIEISAWNKAPILQDCGSLNGT 91
Cdd:cd22704  21 VGRE-DCDLILQSRSVDKQHAVITYDQIDNEFKIKDLGSLNGT 62

forkhead associated (FHA) domain found in Smad nuclear-interacting protein 1 (SNIP1), FHA domain-containing protein DDL, 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. This family also includes Arabidopsis thaliana FHA domain-containing protein DDL and similar proteins. DDL, also called protein DAWDLE, is involved in the 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B       41 PLYLGKN---VVGRSPD-CSVALPFPSISKQHAVIEISAWNK----------APILQDCGSLNGTQIVKPPrvLPPGVSH 106
Cdd:cd22676  14 TIDIHRQsayLIGRDRRvADIPLDHPSCSKQHAVIQFREVEKrnegdvieniRPYIIDLGSTNGTFLNGEK--IEPRRYY 91

                        90
                ....*....|....*..
3VA4_B      107 RLRDQELILFADFPCQY 123
Cdd:cd22676  92 ELREKDVLKFGLSTREY 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B       14 LVPRGSHMEPIGQLRLFSGTHGPerdfplylgkNVVGRSPDC-----SVALPFPSISKQHAviEISAWNKAPILQDCGSL 88
Cdd:cd22702  11 LLPLGNDMDGGSPIRLTRDEKQP----------CIIGSDPHQaisgiSVVIPSPQVSELHA--RITCKNGAFFLTDLGSE 78

                        90       100       110
                ....*....|....*....|....*....|.
3VA4_B       89 NGTQIV-KPPRV--LPPGVSHRLRDQELILF 116
Cdd:cd22702  79 HGTWINdNEGRRyrAPPNFPVRLHPSDVIEF 109

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
                ....*....|....*....|....*....|....*....|....*.
3VA4_B       48 VVGRSPDCSVALPFPSISKQHAVIEI--SAWnkapILQDCGSLNGT 91
Cdd:cd22694  19 RIGRDPDADVRLDDPRVSRRHALLEFdgDGW----VYTDLGSRNGT 60

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
                ....*....|....*....|....*....|....*....|....*....|....*..
3VA4_B       35 GPERDFPLYLGKNVVGRSpDCSVALPFPSISKQHAVIEISAWNKAPILQDCGSLNGT 91
Cdd:cd22700   6 SSDGIFQLDPKVTTIGRE-GCDLVLQSPGVEEQHAVIEYSEQENCFVLQDLNTAQGT 61

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
                ....*....|....*....|....*....|....*....|....*....|....*
3VA4_B       39 DFPLYLGKN-VVGRSPD-CSVALPFPSISKQHAVIEISAWNKAPIlQDCGSLNGT 91
Cdd:cd22696  14 EFFLESGKTyFIGKDPTvCDIVLQDPSISRQHARLSIDQDNRVFI-EDLSSKNGV 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3VA4_B         28 RLFSGTH-GPErdFPLYLGKNVVGRSPDCSVALPFPSISKQHAVIEISA--WnkapILQDCGS-----LNGTQIVKPPRV 99
Cdd:pfam16697   1 RVLSGPHaGAE--FPLEGGRYRIGSDPDCDIVLSDKEVSRVHLKLEVDDegW----RLDDLGSgngtlVNGQRVTELGIA 74

                  ....
3VA4_B        100 LPPG 103
Cdd:pfam16697  75 LRPG 78

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
                ....*....|....*....|....*....|....*....|...
3VA4_B       49 VGRSpDCSVALPFPSISKQHAVIEISAWNKAPILQDCGSLNGT 91
Cdd:cd22725  25 VGRE-DCELMLQSRSVDKQHAVINYDQDTDEHWVKDLGSLNGT 66

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
                ....*....|....*....|....*....|....*....|...
3VA4_B       49 VGRSPDCSVALPFPSISKQHAVIEISawNKAPILQDCGSLNGT 91
Cdd:cd22737  25 IGRASDNDIVIPEGSVSRHHATLVPT--PGGTQIRDLRSTNGT 65

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
3VA4_B       33 THGPERDFPLYLGKNVV--GRSPDCSVALPFPSISKQHAviEISAWNKAPILQDCGSLNGT 91
Cdd:cd22684   7 RRGPNAGARFLLDQDVTtaGRHPESDIFLDDVTVSRRHA--EFRRAEGGFVVRDVGSLNGT 65

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
                ....*....|....*....|....*....|....*....|....*
3VA4_B       49 VGRSPDCSVALPFPSISKQHAVIEISawNKAPILQDCGSLNGTQI 93
Cdd:cd22683  25 IGRSRSCDLVLSDPSISRFHAELRLE--QNGINVIDNNSANGTFI 67