Double zinc ribbon; This family consists of a pair of zinc ribbon domains.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 499635904    4 CTACGYDkNPDDAEYCDACGSELQTVAAPTSTSSVAPT 41
Cdd:pfam12773   1 CPNCGHP-NPPGAKFCPACGTPLKPDRCPNCGAPVPPN 37

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 499635904  80 KLISKQPGSPIAEFSLDSNAVVgiF--DPDMgpvDIDLEefpgGNTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqt 157
Cdd:cd00060    1 RLIVLDGDGGGREFPLTKGVVT--IgrSPDC---DIVLD----DPSVSRRHARIEVDGGGVYLEDLGSTNGTFVN----- 66

                         90       100
                 ....*....|....*....|....*...
gi 499635904 158 rfGARITVPETINFGDEIAFGKVRFLFQ 185
Cdd:cd00060   67 --GKRITPPVPLQDGDVIRLGDTTFRFE 92

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 499635904   112 DIDLEefpgGNTVSRNHAEIYIEGG-VWKIKDLGSTNGVFI 151
Cdd:smart00240  11 DIQLD----GPSISRRHAVIVYDGGgRFYLIDLGSTNGTFV 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904  80 KLISKQPGSPIAEFSLDSNAVVgiF--DPDMgpvDIDLEefpgGNTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqt 157
Cdd:cd00060    1 RLIVLDGDGGGREFPLTKGVVT--IgrSPDC---DIVLD----DPSVSRRHARIEVDGGGVYLEDLGSTNGTFVN----- 66

                         90       100
                 ....*....|....*....|....*...
gi 499635904 158 rfGARITVPETINFGDEIAFGKVRFLFQ 185
Cdd:cd00060   67 --GKRITPPVPLQDGDVIRLGDTTFRFE 92

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904 101 VGIFDP-DMGPVDIDLEEFPGG-----------NTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARITVPET 168
Cdd:cd22698    5 IEQKGSeEGKDYELDQDEFTIGrssnndirlndHSVSRHHARIVRQGDKCNLTDLGSTNGTFLN-------GIRVGTHEL 77

                         90
                 ....*....|....*.
gi 499635904 169 INfGDEIAFGKVRFLF 184
Cdd:cd22698   78 KH-GDRIQLGETIFRF 92

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904  91 AEFSLDSNAVVGIFDPDmgpVDIDLEEFpggnTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARITVPETIN 170
Cdd:cd22684   14 ARFLLDQDVTTAGRHPE---SDIFLDDV----TVSRRHAEFRRAEGGFVVRDVGSLNGTYVN-------RERIDSAVLRN 79

                         90
                 ....*....|....*.
gi 499635904 171 fGDEIAFGKVRFLFQS 186
Cdd:cd22684   80 -GDEVQIGKFRLVFFA 94

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 499635904   112 DIDLEefpgGNTVSRNHAEIYIEGG-VWKIKDLGSTNGVFI 151
Cdd:smart00240  11 DIQLD----GPSISRRHAVIVYDGGgRFYLIDLGSTNGTFV 47

forkhead associated (FHA) domain found in Corynebacterium glutamicum oxoglutarate dehydrogenase inhibitor (OdhI) and similar proteins; OdhI is an essential component of the PknG signaling pathway. It regulates glutamate production under biotin non-limiting conditions. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904  79 AKLISKQPGSPIAEFSLDSNAVVGIFDPDmgpVDIDLEEFpggnTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKQSSQTR 158
Cdd:cd22721   10 ALLVVKRGPNAGARFLLDQPTTTAGRHPE---SDIFLDDV----TVSRRHAEFRINEGEFEVVDVGSLNGTYVNREPRNA 82

                         90       100
                 ....*....|....*....|....*...
gi 499635904 159 fgaritvpETINFGDEIAFGKVRFLFQS 186
Cdd:cd22721   83 --------QVMQTGDEIQIGKFRLVFLA 102

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 499635904 105 DPDmgpVDIDLEEfpggNTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARI-TVPetINFGDEIAFGKVR 181
Cdd:cd22694   23 DPD---ADVRLDD----PRVSRRHALLEFDGDGWVYTDLGSRNGTYLN-------GRRVqQVK--LSDGTRVRLGDPT 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 499635904  124 VSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARITVPE-TINFGDEIAFGKVRFLFQ 185
Cdd:pfam16697  36 VSRVHLKLEVDDEGWRLDDLGSGNGTLVN-------GQRVTELGiALRPGDRIELGQTEFCLV 91

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 499635904 125 SRNHAEIYIEGGVWKIKDLGSTNGVFI--KQSSQtrfGARITVPETINFGDEIAFG 178
Cdd:cd22679   50 SRNHALLWYDDGKFYLQDTKSSNGTFVnnQRLSK---GSEESEPRELHSGDIVQFG 102

forkhead associated (FHA) domain found in Saccharomyces cerevisiae DNA damage response protein kinase DUN1 and similar proteins; DUN1 is a protein kinase that controls the DNA damage response in yeast. It phosphorylates SML1 on serine residues and cooperates with the PAN deadenylation complex in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress. It contains an FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 499635904 111 VDIDLEEfpggNTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARI---TVPetINFGDEIAFGKVRFLFQS 186
Cdd:cd22683   31 CDLVLSD----PSISRFHAELRLEQNGINVIDNNSANGTFIN-------GKRIkgkTYI--LKNGDIIVFGKCSFLIKY 96

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904  91 AEFSLDSNA--VVGIfDPDMgpVDIDLEEFpggnTVSRNHAEIYI-EGGVWKIKDLGSTNGVFIKqssqtrfGARITVPE 167
Cdd:cd22696   13 AEFFLESGKtyFIGK-DPTV--CDIVLQDP----SISRQHARLSIdQDNRVFIEDLSSKNGVLVN-------GKPIEGKE 78

                         90
                 ....*....|....*.
gi 499635904 168 TINFGDEIAFGKVRFL 183
Cdd:cd22696   79 EISGSDVISLGTTSFL 94

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 499635904 123 TVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARITVPET--INFGDEIAFGKVRFLF 184
Cdd:cd22682   38 SVSRYHAKLAVNPSAVSIIDLGSTNGTIVN-------GKKIPKLAScdLQNGDQIKIGNTIFKF 94

forkhead associated (FHA) domain found in Mycobacterium tuberculosis transcriptional regulatory protein EmbR and similar proteins; EmbR is a transcriptional regulator of the embCAB operon encoding cell wall arabinosyltransferases (EmbC, -A, and -B), and is phosphorylated by the cognate mycobacterial serine/threonine protein kinase PknH. It interacts with RNA polymerase and possesses a phosphorylation-dependent ATPase activity. EmbR contains a regulatory C-terminal forkhead-associated (FHA) domain, which mediates binding to a threonine-phosphorylated site in PknH. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 499635904 124 VSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssqtrfGARITVPETINFGDEIAFGKVRFLFQ 185
Cdd:cd22669   35 VSRHHAVIVDTGTNYVINDLRSSNGVHVQ-------HERIRSAVTLNDGDHIRICDHEFTFQ 89

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904  78 TAKLISKQPGSPIAEFSLDSNAV-VGIFDPDmgpvDIDLEEfpggNTVSRNHAEIYIEGGVWKIKDLGSTNGVFIKqssq 156
Cdd:cd22737    1 TPMMKITRPDGDTLTFELPPQAVrIGRASDN----DIVIPE----GSVSRHHATLVPTPGGTQIRDLRSTNGTFVN---- 68

                         90       100
                 ....*....|....*....|....*....
gi 499635904 157 trfGARITVpETINFGDEIAFGKVRFLFQ 185
Cdd:cd22737   69 ---GLRVDA-ALLHDGDVVTIGDIDFVFE 93

forkhead associated (FHA) domain found in angiogenic factor with G patch and FHA domains 1 (AGGF1) and similar proteins; AGGF1, also called angiogenic factor VG5Q, or G patch domain-containing protein 7 (GPATC7), or vasculogenesis gene on 5q protein, is an angiogenic factor involved in vascular development, angiogenesis, specification of hemangioblasts, and differentiation of veins. It promotes angiogenesis and the proliferation of endothelial cells. It inhibits inflammatory effect and preserve vascular integrity in non-nervous system diseases. Mutated AGGF1 causes susceptibility to Klippel-Trenaunay syndrome, a vascular disorder. Increased AGGF1 expression is associated with tumor angiogenesis. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499635904 105 DPDMGPvDIDLEEFpggnTVSRNHAEIYI--EGGVWKIKDLGSTNGVFIKqssqtrfGARITVPETIN------FGDEIA 176
Cdd:cd22686   33 EKDHGH-TIRIPEL----GVSKFHAEIYYddDEQSYTIVDLGSQNGTYLN-------GVRISQPKEKSdpypltHGDELK 100

                 ....*...
gi 499635904 177 FGKVRFLF 184
Cdd:cd22686  101 IGETTLLF 108

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 499635904 111 VDIDLEEFPGGNTVSRNHAEIYIE---GGVWK--IKDLgSTNGVFIkqsSQTRFgaRITVPETINFGDEIAFGKV 180
Cdd:cd22685   39 CDVFLCSSQHPNLISREHAEIHAErdgNGNWKvlIEDR-STNGTYV---NDVRL--QDGQRRELSDGDTITFGHK 107

forkhead associated (FHA) domain found in Saccharomyces cerevisiae fork head protein homolog 1 (FKH1), 2 (FKH2) and similar proteins; This family includes FKH1 and FKH2, as well as pre-rRNA-processing protein FHL1. FKH1 and FKH2 are forkhead transcription factors that regulate the expression of the CLB2 cluster of genes during the G2/M phase of the mitotic cell cycle. The CLB2 cluster of genes includes mitotic regulators such as CLB1, CLB2, CDC5 and CDC20, as well as SWI5 and ACE2. FKH1 and FKH2 are involved in HMRa silencing. They associate with the coding regions of active genes and influence, in opposing ways, transcriptional elongation and termination, and coordinate early transcription elongation and pre-mRNA processing. Both FKH1 and FKH2 play a role as regulators of lifespan in collaboration with the anaphase-promoting complex (APC), likely through combined regulation of stress response, genomic stability, and cell cycle regulation. They also function in controlling yeast cell morphology by preventing pseudohyphal growth and act as rate-limiting replication origin activators via their interaction with the origin recognition complex (ORC). FHL1 is a forkhead protein that controls the pre-rRNA processing machinery in conjunction with IFH1. It might act as a transcriptional regulator of genes specifically involved in that process. IFH1 convert FHL1 from a repressor to an activator. This family also includes AtFHA1 and AtFHA2, which may play a role in the control of plant organ development. AtFHA2 is specifically involved in the regulation of stamen development. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 499635904 109 GPVDIDLEEFpggNTVSRNHAEIY--IEGGVWKIKDLGStNGVFI 151
Cdd:cd22701   34 DSVDIDLGPS---KKISRRHARIFydFTTQCFELSVLGR-NGVKV 74