PBZ domain; This domain is a zinc-finger motif that in humans is part of the APLF, aprataxin- and PNK-like forkhead association domain-containing protein. The ZnF is highly conserved both in primary sequence and in the spacing between the putative zinc coordinating residues and is configured CX5CX6HX5H. Many of the proteins containing the APLF-like ZnF are involved in DNA strand break repair and/or contain domains implicated in DNA metabolism.

                          10        20
                  ....*....|....*....|....*
gi 27734905   376 RTSCMYGANCYRKNPVHFQHFSHPG 400
Cdd:pfam10283   1 RPPCKYGAKCYRKNPQHFKEFSHPG 25

PBZ domain; This domain is a zinc-finger motif that in humans is part of the APLF, aprataxin- and PNK-like forkhead association domain-containing protein. The ZnF is highly conserved both in primary sequence and in the spacing between the putative zinc coordinating residues and is configured CX5CX6HX5H. Many of the proteins containing the APLF-like ZnF are involved in DNA strand break repair and/or contain domains implicated in DNA metabolism.

                          10        20
                  ....*....|....*....|....*
gi 27734905   376 RTSCMYGANCYRKNPVHFQHFSHPG 400
Cdd:pfam10283   1 RPPCKYGAKCYRKNPQHFKEFSHPG 25

FHA domain; This entry represents a divergent FHA domain which in PNK binds to phosphorylated segment of XRCC1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27734905    22 ETVIGRGPLLGITDKRVSRRHAILEV--AGGQLRIKPIHTNPCFYQSSeksqllPLKPNLWCYLNPGDSFSLLVDKYIFR 99
Cdd:pfam17913  20 PVVIGRGPETGITDKKCSRNQVELKAdcEKRYVKVKQLGANPSGLNGF------KLKKGESYELKHGDVLELLNGKHPHR 93

                  .
gi 27734905   100 I 100
Cdd:pfam17913  94 V 94

polynucleotide 5'-kinase 3'-phosphatase; This model represents the metazoan 5'-polynucleotide-kinase-3'-phosphatase, PNKP, which is believed to be involved in repair of oxidative DNA damage. Removal of 3' phosphates is essential for the further processing of the break by DNA polymerases. The central phosphatase domain is a member of the IIIA subfamily (TIGR01662) of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. As is common in this superfamily, the enzyme is magnesium dependent. A difference between this enzyme and other HAD-superfamily phosphatases is in the third conserved catalytic motif which usually contains two conserved aspartate residues believed to be involved in binding the magnesium ion. Here, the second aspartate is replaced by a conserved arginine residue which may indicate an interaction with the phosphate backbone of the substrate. Very close relatives of this domain are also found separate from the N- and C-terminal domains seen here, as in the 3'-phosphatase found in plants. The larger family of these domains is described by TIGR01664. Outside of the phosphatase domain is a P-loop ATP-binding motif associated with the kinase activity. The entry for the mouse homolog appears to be missing a large piece of sequence corresponding to the first conserved catalytic motif of the phosphatase domain as well as the conserved threonine of the second motif. Either this is a sequencing artifact or this may represent a pseudo- or non-functional gene. Note that the EC number for the kinase function is: 2.7.1.78

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27734905    21 GETVIGRGPLLGITDKRVSRRHAILEV--AGGQLRIKPIHTNPCFYQSSEksqllpLKPNLWCYLNPGDSFSLL 92
Cdd:TIGR01663  32 GALFLGRGPETGIRDRKCSKRQIELQAdlEKATVALKQLGVNPCGTGGLE------LKPGGEGELGHGDLLEIV 99

forkhead associated (FHA) domain found in aprataxin, bifunctional polynucleotide phosphatase/kinase (PNKP), aprataxin and PNK-like factor (APLF), and similar proteins; The family includes aprataxin, PNKP, and APLF. Aprataxin (EC 3.6.1.71/EC 3.6.1.72), also called forkhead-associated domain histidine triad-like protein (FHA-HIT), is a DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair, and base excision repair. It catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. It can also hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity. Likewise, it catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA but has higher specific activity with 5'-linked adenosine (AppDNA). PNKP (EC 3.1.3.32/EC 2.7.1.78), also called DNA 5'-kinase/3'-phosphatase, or polynucleotide kinase-3'-phosphatase, plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNKP ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone. APLF, also called apurinic-apyrimidinic endonuclease APLF, PNK and APTX-like FHA domain-containing protein, or XRCC1-interacting protein 1 (XIP1), is a novel apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease with conserved zinc-finger-like motifs involved in single-strand and double-strand DNA break repair. It is recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. It can introduce nicks at hydroxyuracil and other types of pyrimidine base damage. Together with PARP3, APLF promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). Members of this family contain an FHA domain at their N-terminus. The FHA domain is a small phosphopeptide recognition module.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27734905   6 ELQPRDGG--PRVALAP-GETVIGRGPLLGITDKRVSRRHAILEV--AGGQLRIKPIHTNPCFYQSSEKsQLLPLKPNLW 80
Cdd:cd22671   1 FLRPVDGGggPPIELKEgGPTVLGRGPLLGIRDKRVSRKQAEITVddDTGSVTVTQLGTNPSFVNRADG-EGKVLKKGES 79

                        90       100
                ....*....|....*....|
gi 27734905  81 CYLNPGDSFSLLVDKYIFRI 100
Cdd:cd22671  80 VELKDGDVISLLPGKYPFRV 99

PBZ domain; This domain is a zinc-finger motif that in humans is part of the APLF, aprataxin- and PNK-like forkhead association domain-containing protein. The ZnF is highly conserved both in primary sequence and in the spacing between the putative zinc coordinating residues and is configured CX5CX6HX5H. Many of the proteins containing the APLF-like ZnF are involved in DNA strand break repair and/or contain domains implicated in DNA metabolism.

                          10        20
                  ....*....|....*....|....*
gi 27734905   418 RPECPYGPSCYRKNPQHKIEYRHNT 442
Cdd:pfam10283   1 RPPCKYGAKCYRKNPQHFKEFSHPG 25

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 27734905   7 LQPRDGGPRVALAPGETVIGRGPL--LGITDKRVSRRHAILEVAGGQLRIKPIH-TNPCFYQSSeksqllPLKPnlWCYL 83
Cdd:cd00060   5 LDGDGGGREFPLTKGVVTIGRSPDcdIVLDDPSVSRRHARIEVDGGGVYLEDLGsTNGTFVNGK------RITP--PVPL 76

                        90
                ....*....|....*.
gi 27734905  84 NPGDSFSLLVDKYIFR 99
Cdd:cd00060  77 QDGDVIRLGDTTFRFE 92

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 27734905   7 LQPRDGGPRVALAPGETVIGRGP--LLGITDKRVSRRHAILEVAGGQLRIK 55
Cdd:COG1716   7 LEGPLAGRRFPLDGGPLTIGRAPdnDIVLDDPTVSRRHARIRRDGGGWVLE 57

forkhead associated (FHA) domain found in bifunctional polynucleotide phosphatase/kinase (PNKP) and similar proteins; PNKP (EC 3.1.3.32/EC 2.7.1.78), also called DNA 5'-kinase/3'-phosphatase, or polynucleotide kinase-3'-phosphatase, plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNKP ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone. PNKP 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27734905   7 LQPRDGG-PRVALAPGETVI-GRGPLLGITDKRVSRRHAIL--EVAGGQLRIKPIHTNPCfyqSSEKSQllplkpnlwcy 82
Cdd:cd22736   4 LVSVDGGhPPIFLPDGQALVlGRGPETRVTDRKCSRTQVELvaDYESRTVAVTQLGVNPS---SVGEQE----------- 69

                        90
                ....*....|....*.
gi 27734905  83 LNPGDSFSLLVDKYIF 98
Cdd:cd22736  70 LKPGLSGSLKEGQTLY 85

polynucleotide 5'-kinase 3'-phosphatase; This model represents the metazoan 5'-polynucleotide-kinase-3'-phosphatase, PNKP, which is believed to be involved in repair of oxidative DNA damage. Removal of 3' phosphates is essential for the further processing of the break by DNA polymerases. The central phosphatase domain is a member of the IIIA subfamily (TIGR01662) of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. As is common in this superfamily, the enzyme is magnesium dependent. A difference between this enzyme and other HAD-superfamily phosphatases is in the third conserved catalytic motif which usually contains two conserved aspartate residues believed to be involved in binding the magnesium ion. Here, the second aspartate is replaced by a conserved arginine residue which may indicate an interaction with the phosphate backbone of the substrate. Very close relatives of this domain are also found separate from the N- and C-terminal domains seen here, as in the 3'-phosphatase found in plants. The larger family of these domains is described by TIGR01664. Outside of the phosphatase domain is a P-loop ATP-binding motif associated with the kinase activity. The entry for the mouse homolog appears to be missing a large piece of sequence corresponding to the first conserved catalytic motif of the phosphatase domain as well as the conserved threonine of the second motif. Either this is a sequencing artifact or this may represent a pseudo- or non-functional gene. Note that the EC number for the kinase function is: 2.7.1.78

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27734905    21 GETVIGRGPLLGITDKRVSRRHAILEV--AGGQLRIKPIHTNPCFYQSSEksqllpLKPNLWCYLNPGDSFSLL 92
Cdd:TIGR01663  32 GALFLGRGPETGIRDRKCSKRQIELQAdlEKATVALKQLGVNPCGTGGLE------LKPGGEGELGHGDLLEIV 99