aprataxin related: Aprataxin, a HINT family hydrolase is mutated in ataxia oculomotor apraxia syndrome. All the members of this subgroup have the conserved HxHxHxx (where x is a hydrophobic residue) signature motif. Members of this subgroup are predominantly eukaryotic in origin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307746921 110 LGHWSQGLKISMQDPKMQVYKDEQVVVIKDKYPKARYHWLVLPWTSISSLKAVAREHLELLKHMHTVGEKVIVDFAGSSK 189
Cdd:cd01278    1 LCHFCDIAKRRDPDPEDQVYEDDRVVVFKDIYPKARHHYLVIPKEHIASLKALTKEDVPLLEHMETVGREKLLRSDNTDP 80

                         90       100
                 ....*....|....*....|....
gi 307746921 190 LRFRLGYHAIP--SMSHVHLHVIS 211
Cdd:cd01278   81 SEFRFGFHAPPftSVSHLHLHVIA 104

C2HE / C2H2 / C2HC zinc-binding finger; zf-C2HE is an unusual zinc-binding domain found in fungi, plants and metazoa. It is often found at the C-terminus of HIT-domain-containing proteins, pfam01230. In fungi the fourth ligand is a Glu, in plants it is Cys and in metazoans it is usually a His. The fourth ligand is often mutated in neurogenerative disease-states.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 307746921  229 NTEYFLESQAVIEMVQEAGRVTVRDGMPELLKLPLRCHECQQLLPSIPQLKEHLRKHWTQ 288
Cdd:pfam16278   1 NTPFFVPLDDVPEWLEEDGKIELLPSEVLLLKTPLKCHRCGNFGNNFPKLKAHLEEHFEK 60

aprataxin related: Aprataxin, a HINT family hydrolase is mutated in ataxia oculomotor apraxia syndrome. All the members of this subgroup have the conserved HxHxHxx (where x is a hydrophobic residue) signature motif. Members of this subgroup are predominantly eukaryotic in origin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307746921 110 LGHWSQGLKISMQDPKMQVYKDEQVVVIKDKYPKARYHWLVLPWTSISSLKAVAREHLELLKHMHTVGEKVIVDFAGSSK 189
Cdd:cd01278    1 LCHFCDIAKRRDPDPEDQVYEDDRVVVFKDIYPKARHHYLVIPKEHIASLKALTKEDVPLLEHMETVGREKLLRSDNTDP 80

                         90       100
                 ....*....|....*....|....
gi 307746921 190 LRFRLGYHAIP--SMSHVHLHVIS 211
Cdd:cd01278   81 SEFRFGFHAPPftSVSHLHLHVIA 104

forkhead associated (FHA) domain found in aprataxin and similar proteins; 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). Mutations in the gene APTX have been associated with ataxia-ocular apraxia. Aprataxin contains an FHA domain at its N-terminus. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 307746921   3 RVCWLVRQDSRHQRIRLPHLEAVVIGRGPETKITDKKCSRQQ 44
Cdd:cd22735    1 RVCWLVSKDGRHLRIRLPHLEAVVIGRGPETKITDKKCSRHQ 42

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 307746921    5 CWLVRQDSRHQRIRLPHLEAVVIGRGPETKITDKKCSRQQ 44
Cdd:pfam17913   1 CYLVSLEGTHPPIPLPHGQPVVIGRGPETGITDKKCSRNQ 40

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
                  ....*....|....*....|....*....|....*....|..
gi 307746921    3 RVCWLVRQDSRHQRIRLPHlEAVVIGRGPETKITDKKCSRQQ 44
Cdd:TIGR01663  13 RICTLKPGEAEHHFIHLDA-GALFLGRGPETGIRDRKCSKRQ 53

aprataxin related: Aprataxin, a HINT family hydrolase is mutated in ataxia oculomotor apraxia syndrome. All the members of this subgroup have the conserved HxHxHxx (where x is a hydrophobic residue) signature motif. Members of this subgroup are predominantly eukaryotic in origin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307746921 110 LGHWSQGLKISMQDPKMQVYKDEQVVVIKDKYPKARYHWLVLPWTSISSLKAVAREHLELLKHMHTVGEKVIVDFAGSSK 189
Cdd:cd01278    1 LCHFCDIAKRRDPDPEDQVYEDDRVVVFKDIYPKARHHYLVIPKEHIASLKALTKEDVPLLEHMETVGREKLLRSDNTDP 80

                         90       100
                 ....*....|....*....|....
gi 307746921 190 LRFRLGYHAIP--SMSHVHLHVIS 211
Cdd:cd01278   81 SEFRFGFHAPPftSVSHLHLHVIA 104

forkhead associated (FHA) domain found in aprataxin and similar proteins; 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). Mutations in the gene APTX have been associated with ataxia-ocular apraxia. Aprataxin contains an FHA domain at its N-terminus. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 307746921   3 RVCWLVRQDSRHQRIRLPHLEAVVIGRGPETKITDKKCSRQQ 44
Cdd:cd22735    1 RVCWLVSKDGRHLRIRLPHLEAVVIGRGPETKITDKKCSRHQ 42

forkhead associated (FHA) domain found in aprataxin, bifunctional polynucleotide phosphatase/kinase (PNKP), and similar proteins; The subfamily includes aprataxin and PNKP. 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. Both aprataxin and PNKP contain an FHA domain at their N-terminus. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 307746921   6 WLVRQDSRHQRIRLPHLEAVVIGRGPETKITDKKCSRQQ 44
Cdd:cd22716    1 ILVCCSSSHPPIPLPDGVPVILGRGPQTQITDKRCSRQQ 39

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
                 ....*....|....*....|....*....|....*....|
gi 307746921   5 CWLVRQDSRHQRIRLPHLEAVVIGRGPETKITDKKCSRQQ 44
Cdd:cd22736    2 CWLVSVDGGHPPIFLPDGQALVLGRGPETRVTDRKCSRTQ 41

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
                 ....*....|....*....|....*....|....*....|
gi 307746921   6 WLVRQDSR-HQRIRLPHLEAVVIGRGPETKITDKKCSRQQ 44
Cdd:cd22671    1 FLRPVDGGgGPPIELKEGGPTVLGRGPLLGIRDKRVSRKQ 40

HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified in the literacture into three major branches: the Hint branch, which consists of adenosine 5' -monophosphoramide hydrolases, the Fhit branch, that consists of diadenosine polyphosphate hydrolases, and the GalT branch consisting of specific nucloside monophosphate transferases. Further sequence analysis reveals several new closely related, yet uncharacterized subgroups.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307746921 128 VYKDEQVVVIKDKYPKARYHWLVLPWTSISSL----KAVAREHLELLKHMHTVGEKvivDFAGSSkLRFRLGYHAIP--S 201
Cdd:cd00468    1 VPDDEHSFAFVNLKPAAPGHVLVCPKRHVETLpdldEALLADLVITAQRVAAELEK---HGNVPS-LTVFVNDGAAAgqS 76

                 ....*....
gi 307746921 202 MSHVHLHVI 210
Cdd:cd00468   77 VPHVHLHVL 85