match no.	target id	target length	alignment length	probability	E-value	coverage	match description
1	pfam09623	225	153	98.7	1.6E-07	[----------------                                 ]	Cas_NE0113	CRISPR-associated protein NE0113 (Cas_NE0113). Members of this minor CRISPR-associated (Cas) protein family are encoded in cas gene clusters in Vibrio vulnificus YJ016, Nitrosomonas europaea ATCC 19718, Mannheimia succiniciproducens MBEL55E, and Verrucomicrobium spinosum.
2	cd09741	219	131	98.5	1.9E-06	[--------------                                   ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as NE0113 family
3	cd09723	132	122	98.5	1.3E-06	[-------------                                    ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as csx13 family
4	TIGR03642	124	115	97.9	0.00014	[-------------                                    ]	cas_csx14	CRISPR-associated protein, Csx14 family. This model describes a protein N-terminal protein sequence domain strictly associated with CRISPR and CRISPR-associated protein systems. This model and TIGR02584 identify two separate clades from a larger homology domain family, both CRISPR-associated, while other homologs are found that may not be. Members are found in bacteria that include Pelotomaculum thermopropionicum SI, Thermoanaerobacter tengcongensis MB4, and Roseiflexus sp. RS-1, and in archaea that include Thermoplasma volcanium, Picrophilus torridus, and Methanospirillum hungatei. The molecular function is unknown.
5	cd09880	139	113	97.7	0.00015	[                           --------------        ]	PIN_Smg5-Smg6-like	PIN domain. 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. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. 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. Eukaryotic Smg5 and Smg6-like PIN domains are present at the C-terminal end of telomerase activating proteins, Est1. Many of the bacterial homologs in this group have an N-terminal PIN domain and a C-terminal PhoH-like ATPase domain.
6	pfam09651	136	111	97.5	0.0014	[ ------------                                    ]	Cas_APE2256	CRISPR-associated protein (Cas_APE2256). This entry represents a conserved region of about 150 amino acids found in at least five archaeal and three bacterial species. These species all contain CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats). In six of eight species, the protein is encoded the vicinity of a CRISPR/Cas locus.
7	pfam13638	130	37	97.4	0.00097	[                                     ----        ]	PIN_4	PIN domain. Members of this family of bacterial domains are predicted to be RNases (from similarities to 5'-exonucleases).
8	cd09879	117	110	97.2	0.0016	[                            --------------       ]	PIN_AF0591	PIN domain of Archaeoglobus fulgidus AF0591 protein and other similar archaeal homologs. PIN (PilT N terminus) domain of Archaeoglobus fulgidus AF0591 protein and other similar uncharacterized archaeal homologs are included in this family. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains within this subgroup contain four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule.
9	COG1412	136	115	97.0	0.0032	[                           ---------------       ]	Fcf1	rRNA-processing protein FCF1
10	cd09742	183	114	96.9	0.0064	[ ------------                                    ]	Csm6_III-A	CRISPR/Cas system-associated protein Csm6. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; loosely associated with CRISPR/Cas systems; also known as APE2256 family
11	cd09883	147	42	96.6	0.0036	[                                     ----        ]	PIN_PhoHL-ATPase	PIN domain of bacterial Smg6-like homologs with PhoH-like ATPase domains. PIN (PilT N terminus) domain of Smg6-like bacterial proteins with C-terminal PhoH-like ATPase domains and other similar homologs are included in this family. Eukaryotic Smg5 and Smg6 nucleases are essential factors in nonsense-mediated mRNA decay (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. These PIN domains are homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains within this subgroup contain four highly conserved acidic residues (putative metal-binding, active site residues). Many of the bacterial homologs in this group have an N-terminal PIN domain and a C-terminal PhoH-like ATPase domain and are predicted to be ATPases which are induced by phosphate starvation.
12	pfam09455	372	89	96.0	0.12	[  ----------                                     ]	Cas_DxTHG	CRISPR-associated (Cas) DxTHG family. CRISPR is a term for Clustered Regularly Interspaced Short Palidromic Repeats. A number of protein families appear only in association with these repeats and are designated Cas (CRISPR associated) proteins. The family describes Cas proteins of about 400 residues that include the motif
13	cd09747	378	90	95.5	0.084	[  ----------                                     ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as Cas02710 family
14	TIGR01884	203	108	94.4	0.79	[-------------                                    ]	cas_HTH	CRISPR locus-related DNA-binding protein. Most but not all examples of this family are associated with CRISPR loci, a combination of DNA repeats and characteristic proteins encoded near the repeat cluster. The C-terminal region of this protein is homologous to DNA-binding helix-turn-helix domains with predicted transcriptional regulatory activity.
15	cd09732	221	114	93.9	0.5	[  -------------                                  ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as TM1812 family
16	pfam09670	379	90	93.7	0.45	[  ----------                                     ]	Cas_Cas02710	CRISPR-associated protein (Cas_Cas02710). Members of this family are found, exclusively in the vicinity of CRISPR repeats and other CRISPR-associated (cas) genes, in Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum), Thermus thermophilus (Deinococcus-Thermus), Chloroflexus aurantiacus (Chloroflexi), and Thermomicrobium roseum (Thermomicrobia).
17	cd09878	124	99	93.6	0.096	[                            ------------         ]	PIN_VirB11L-ATPase	PIN domain of the Methanocaldococcus Jannaschii Dsm 2661 protein, Thermococcus sibiricus MM 739 predicted ATPase, and other similar archaeal homologs. PIN (PilT N terminus) domain present N-terminal of AAA+, VirB11-like ATPases, as well as, the PIN domains of proteins from Methanopyrus kandleri AV19 and Thermococcus sibiricus MM 739, and other similar archaeal homologs are included in this family. Several members of this subfamily possess an AAA+, VirB11-like ATPase domain, flanked by PIN and KH nucleic acid-binding domains. VirB11-ATPase is a type IV secretory pathway component required for T-pilus biogenesis and virulence. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains within this subgroup contain four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule.
18	COG4006	278	151	92.6	0.47	[ ----------------                                ]	COG4006	CRISPR/Cas system-associated protein Csm6, COG1517 family
19	cd09885	182	46	90.9	0.13	[                                     -----       ]	PIN_Smg6	PIN domain of human telomerase-binding protein EST1, Smg6, and other similar eukaryotic homologs. Nonsense-mediated decay (NMD) factors, Smg5 and Smg6 are essential to the post-transcriptional regulatory pathway, NMD, which recognizes and rapidly degrades mRNAs containing premature translation termination codons. In vivo, the Smg6 PIN (PilT N terminus) domain elicits degradation of bound mRNAs, as well as, metal ion dependent, degradation of single-stranded RNA, in vitro. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains within this subgroup contain four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. 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. Eukaryotic Smg6 PIN domains are present at the C-terminal end of the telomerase activating proteins, Est1.
20	cd09728	400	119	89.9	3.4	[------------                                     ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as DxTHG family
21	cd09686	209	140	88.7	4.9	[---------------                                  ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as NE0113 family
22	cd09655	198	107	88.1	5.7	[------------                                     ]	CasRa_I-A	CRISPR/Cas system-associated transcriptional regulator CasRa. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Predicted transcriptional regulator of CRISPR/Cas system
23	pfam09002	379	98	87.5	3.1	[  -------------                                  ]	DUF1887	Domain of unknown function (DUF1887). This domain is found in a set of hypothetical bacterial proteins.
24	TIGR02584	209	140	87.4	6.3	[---------------                                  ]	cas_NE0113	CRISPR-associated protein, NE0113 family. Members of this minor CRISPR-associated (Cas) protein family are found in cas gene clusters in Vibrio vulnificus YJ016, Nitrosomonas europaea ATCC 19718, Mannheimia succiniciproducens MBEL55E, and Verrucomicrobium spinosum.
25	COG1875	436	47	87.1	0.55	[                                    -----        ]	YlaK	Predicted ribonuclease YlaK, contains NYN-type RNase and PhoH-family ATPase domains
26	cd09863	125	101	87.0	2.4	[                            -------------        ]	PIN_Smg6-like	PIN domain of human telomerase-binding protein EST1, Smg6, and ribosome assembly factor, Nob1, Archaeoglobus fulgidus AF0591 protein and other eukaryotic, bacterial, and archaeal homologs. PIN (PilT N terminus) domains of eukaryotic ribonucleases such as Smg5 and Smg6, essential factors in nonsense-mediated mRNA decay (NMD), and Nob1, a ribosome assembly factor critical in pre-rRNA processing, as well as, the uncharacterized archaeal Archaeoglobus fulgidus AF0591 protein and other eukaryotic, bacterial, and archaeal 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 Nob1 PIN domain binds the single-stranded cleavage site D at the 3'end of 18S rRNA. Recombinant Nob1 binds as a tetramer to pre-18S rRNA fragments containing cleavage site D and believed to cleave at this site. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, that is seen in FEN1-like PIN domains. PIN domains within this group typically contain three or four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule
27	cd09864	143	116	86.3	6.7	[                           ---------------       ]	PIN_Fcf1	PIN domain of rRNA-processing protein, Fcf1 (Utp24, YDR339C), and other eukaryotic homologs. Fcf1/Utp24 (FAF1-copurifying factor 1/U three-associated protein 24) is an essential protein involved in pre-rRNA processing and 40S ribosomal subunit assembly. Component of the small subunit (SSU) processome, Fcf1 is an essential nucleolar protein that is required for processing of the 18S pre-rRNA at sites A0-A2. The Fcf1 protein was reported to interact with Pmc1p (vacuolar Ca2+ ATPase) and Cor1p (core subunit of the ubiquinol-cytochrome c reductase complex). The PIN (PilT N terminus) domain of this protein is a homolog of flap endonuclease-1 (FEN1)-like PIN domains, but apparently lack the H3TH domain or extensive arch/clamp region seen in the latter. PIN domains typically contain three or four conserved acidic residues (putative metal-binding, active site residues). The Fcf1 PIN domain subfamily has four of these putative active site residues and the Fcf1-Utp23 homolog PIN domain subfamily has three of them. Point mutation studies of the conserved acidic residues in the putative active site of Saccharomyces cerevisiae Fcf1 determined they were essential for pre-rRNA processing at sites A1 and A2, whereas the presence of the Fcf1 protein itself is also required for cleavage at site A0.
28	cd09862	182	44	83.8	0.62	[                           -----                 ]	PIN_Rrp44	PIN domain of yeast exosome subunit Rrp44 endoribonuclease and other eukaryotic homologs. PIN (PilT N terminus) domain of the Saccharomyces cerevisiae exosome subunit Rrp44 (Ribosomal RNA-processing protein 44 or Protein Dis3 homolog) and other similar eukaryotic homologs are included in this family. The eukaryotic exosome is a conserved macromolecular complex responsible for many RNA-processing and RNA-degradation reactions. It is composed of nine core subunits that directly binds Rrp44. The Rrp44 nuclease is the catalytic subunit of the exosome and has endonuclease activity in the PIN domain and an exoribonuclease activity in its RNase II-like region. Rrp44 binding to the exosome is mediated mainly by the PIN domain and by subunits Rrp41-Rrp45, and binding predictions indicate that the PIN domain active site is positioned on the outer surface of the exosome. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains within this subgroup contain four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. Recombinant Rrp44 was shown to possess manganese-dependent endonuclease activity in vitro that was abolished by point mutations in the putative metal binding residues of its PIN domain.
29	PRK13764	602	116	81.8	1.5	[                           ---------------       ]	PRK13764	ATPase; Provisional
30	pfam13470	80	40	75.8	3.3	[                            ----                 ]	PIN_3	PIN domain. Members of this family of bacterial domains are predicted to be RNases (from similarities to 5'-exonucleases).
31	pfam01850	120	41	75.7	4.3	[                            ----                 ]	PIN	PIN domain.
32	cd09660	394	94	75.1	27	[  ----------                                     ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as MJ1666 family
33	COG1569	142	41	73.7	8.6	[                            ----                 ]	COG1569	Predicted nucleic acid-binding protein, contains PIN domain
34	pfam05913	357	64	73.3	8.1	[   -------                                       ]	DUF871	Bacterial protein of unknown function (DUF871). This family consists of several conserved hypothetical proteins from bacteria and archaea. The function of this family is unknown.
35	TIGR02710	380	91	70.9	9.4	[ -----------                                     ]	TIGR02710	CRISPR-associated protein, TIGR02710 family. Members of this family are found, exclusively in the vicinity of CRISPR repeats and other CRISPR-associated (cas) genes, in Methanothermobacter thermautotrophicus (Archaea), Thermus thermophilus (Deinococcus-Thermus), Chloroflexus aurantiacus (Chloroflexi), and Thermomicrobium roseum (Thermomicrobia).
36	TIGR02619	149	112	64.1	60	[ ------------                                    ]	TIGR02619	putative CRISPR-associated protein, APE2256 family. This model represents a conserved domain of about 150 amino acids found in at least five archaeal species and three bacterial species, exclusively in species with CRISPR (Clustered Regularly Interspaced Short Palidromic Repeats). In six of eight species, the member of this family is in the vicinity of a CRISPR/Cas locus.
37	TIGR01897	410	95	63.5	45	[  ----------                                     ]	cas_MJ1666	CRISPR-associated protein, MJ1666 family. CRISPR is a term for Clustered, Regularly Interspaced Short Palidromic Repeats. A number of protein families appear only in association with these repeats and are designated Cas (CRISPR-Associated) proteins. This model describes a Cas protein about 400 residues in length, found mostly in the Archaea but also in Aquifex.
38	pfam02739	169	90	63.3	27	[                                  ----------     ]	5_3_exonuc_N	5'-3' exonuclease, N-terminal resolvase-like domain.
39	pfam01936	141	74	63.2	15	[                                 --------        ]	NYN	NYN domain. These domains are found in the eukaryotic proteins typified by the Nedd4-binding protein 1 and the bacterial YacP-like proteins (Nedd4-BP1, YacP nucleases; NYN domains). The NYN domain shares a common protein fold with two other previously characterized groups of nucleases, namely the PIN (PilT N-terminal) and FLAP/5' --> 3' exonuclease superfamilies. These proteins share a common set of 4 acidic conserved residues that are predicted to constitute their active site. Based on the conservation of the acidic residues and structural elements Aravind and colleagues suggest that PIN and NYN domains are likely to bind only a single metal ion, unlike the FLAP/5' --> 3' exonuclease superfamily, which binds two metal ions. Based on conserved gene neighborhoods Aravind and colleagues infer that the bacterial members are likely to be components of the processome/degradsome that process tRNAs or ribosomal RNAs.
40	pfam04900	101	85	60.9	29	[                               -----------       ]	Fcf1	Fcf1. Fcf1 is a nucleolar protein involved in pre-rRNA processing. Depletion of yeast Fcf1 and Fcf2 leads to a decrease in synthesis of the 18S rRNA and results in a deficit in 40S ribosomal subunits.
41	cd13522	368	108	60.7	18	[   ------------                                  ]	PBP2_ABC_oligosaccharides	The periplasmic-binding component of ABC transport systems specific for maltose and related oligosaccharides; possess type 2 periplasmic binding fold. This family represents the periplasmic binding component of ABC transport systems involved in uptake of oligosaccharides including maltose, trehalose, maltodextrin, and cyclodextrin. Members of this family belong to the type 2 periplasmic-binding fold superfamily. PBP2 is comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. The majority of PBP2 proteins function in the uptake of small soluble substrates in eubacteria and archaea. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.
42	cd09694	181	110	59.7	66	[ ------------                                    ]	Csm6_III-A	CRISPR/Cas system-associated protein Csm6. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; loosely associated with CRISPR/Cas systems
43	pfam14826	162	70	59.1	44	[  --------                                       ]	FACT-Spt16_Nlob	FACT complex subunit SPT16 N-terminal lobe domain. The FACT or facilitator of chromatin transcription complex binds to and alters the properties of nucleosomes. This family represents the N-terminal lobe of the NTD, or N-terminal domain, and acts as a protein-protein interaction domain presumably with partners outside of the FACT complex. Knockout of the whole NTD domain, 1-450 residues in UniProt:P32558, in yeast serves to tender the cells sensitive to DNA replication stress but is not lethal. The C-terminal half of NTD is structurally similar to aminopeptidases, and the most highly conserved surface residues line a cleft equivalent to the aminopeptidase substrate-binding site, family peptidase_M24, pfam00557.
44	cd09702	378	101	59.1	20	[ ------------                                    ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as TIGR02710 family
45	TIGR02221	218	119	57.9	56	[ --------------                                  ]	cas_TM1812	CRISPR-associated protein, TM1812 family. CRISPR is a term for Clustered Regularly Interspaced Short Palidromic Repeats. A number of protein families appear only in association with these repeats and are designated Cas (CRISPR associated) proteins. This family, represented by TM1812 of Thermotoga maritima, is found also in Vibrio vulnificus YJ016, Nitrosomonas europaea ATCC 19718, a large plasmid of Synechocystis sp. PCC 6803, and Fibrobacter succinogenes S85.
46	cd11297	133	53	54.9	7.2	[                                     ------      ]	LabA_like_N_1	Uncharacterized subfamily of N-terminal LabA-like domains. This N-terminal domain is found in a well conserved group of mainly bacterial proteins with no defined function, which contain a C-terminal LabA_like_C domain. LabA from Synechococcus elongatus PCC 7942, (which does not contain this C-terminal domain), has been shown to play a role in cyanobacterial circadian timing. The LabA-like C-terminal domains characteristic of this subfamily may be related to the LOTUS domain family (which also co-occurs with LabA-like N-terminal domains). The function of the N-terminal domain is unknown. LabA_like domains exhibit some similarity to the NYN domain, a distant relative of the PIN-domain nucleases.
47	cd09852	120	17	49.9	51	[                                       --        ]	PIN_SF	PIN (PilT N terminus) domain: Superfamily. PIN_SF The PIN (PilT N terminus) domain belongs to a large nuclease superfamily with representatives from eukaryota, eubacteria, and archaea. PIN domains were originally named for their sequence similarity to the N-terminal domain of an annotated pili biogenesis protein, PilT, a domain fusion between a PIN-domain and a PilT ATPase domain. 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. Seen here, are two major divisions in the PIN domain superfamily. The first major division, the structure-specific 5' nuclease family, is represented by FEN1, the 5'-3' exonuclease of DNA polymerase I, and T4 RNase H nuclease PIN domains. These 5' nucleases are involved in DNA replication, repair, and recombination. They are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated DNA, in an endonucleolytic, structure-specific manner. Unique to FEN1-like nucleases, the PIN domain has a helical arch/clamp region (I domain) of variable length (approximately 16 to 800 residues) and, inserted within the C-terminal region of the PIN domain, a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included here) and the helical arch/clamp region are involved in DNA binding. With the exception of Mkt1, these nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+, Mn2+, Zn2+, or Co2+). The second major division of the PIN domain superfamily, the VapC-Smg6 family, includes such eukaryotic ribonucleases as, Smg6, an essential factor in nonsense-mediated mRNA decay; Rrp44, the catalytic subunit of the exosome; and Nob1, a ribosome assembly factor critical in pre-rRNA processing. A large percentage of members in this family are bacterial ribonuclease toxins of TA operons such as Mycobacterium tuberculosis VapC and Neisseria gonorrhoeae FitB, as well as, archaeal homologs, Pyrobaculum aerophilum Pea0151 and P. aerophilum Pae2754. Also included are the eukaryotic Fcf1/ Utp24 (FAF1-copurifying factor 1/U three-associated protein 24) and Utp23-like proteins. Components of the small subunit processome, Fcf1/Utp24 and Utp23 are essential proteins involved in pre-rRNA processing and 40S ribosomal subunit assembly.
48	cd09668	214	75	49.7	34	[      ---------                                  ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as TM1812 family
49	cd10910	145	45	49.3	18	[                                     ----        ]	limkain_b1_N_like	N-terminal LabA-like domain of limkain b1 and similar proteins. This eukaryotic subfamily of LabA-like domains contains the N-terminal domain of human limkain b1, a human autoantigen, localized to a subset of ABCD3 and PXF marked peroxisomes. Limkain b1 may be a relatively common target of human autoantibodies reactive to cytoplasmic vesicle-like structures. Limkain b1 contains multiple copies of LOTUS domains and a conserved RNA recognition motif, its - and similar - domain architectures are shared by several members of this family, and a function of these architectures in RNA binding or RNA metabolism has been suggested. The function of the N-terminal domain is unknown. LabA_like domains exhibit some similarity to the NYN domain, a distant relative of the PIN-domain nucleases.
50	pfam01261	202	24	46.7	35	[           ---                                   ]	AP_endonuc_2	Xylose isomerase-like TIM barrel. This TIM alpha/beta barrel structure is found in xylose isomerase and in endonuclease IV (EC:3.1.21.2). This domain is also found in the N termini of bacterial myo-inositol catabolism proteins. These are involved in the myo-inositol catabolism pathway, and is required for growth on myo-inositol in Rhizobium leguminosarum bv. viciae.
51	cd06167	151	45	40.8	51	[                                     ----        ]	LabA_like	LabA_like proteins. A well conserved group of domains found in all three kingdoms of life, with no defined function. LabA, a member from Synechococcus elongatus PCC 7942, has been shown to play a role in cyanobacterial circadian timing. It is required for negative feedback regulation of the autokinase/autophosphatase KaiC, a central component of the circadian clock system. In particular, LabA seems necessary for KaiC-dependent repression of gene expression. Another member is the N-terminal domain of limkain b1, a human autoantigen associated with cytoplasmic vesicles. Curiously, a gene labeled NicB from Pseudomonas putida S16, which is described as a putative NADH-dependent hydroxylase involved in the microbial degradation of nicotine also falls in the LabA_like family. LabA_like domains exhibit some similarity to the NYN domain, a distant relative of the PIN-domain nucleases.
52	cd06424	315	113	38.2	1.2E+02	[               --------------                    ]	UGGPase	UGGPase catalyzes the synthesis of UDP-Glucose/UDP-Galactose. UGGPase: UDP-Galactose/Glucose Pyrophosphorylase catalyzes the reversible production of UDP-Glucose/UDP-Galactose and pyrophosphate (PPi) from Glucose-1-phosphate/Galactose-1-phosphate and UTP. Its dual substrate specificity distinguishes it from the single substrate enzyme UDP-glucose pyrophosphorylase. It may play a key role in the galactose metabolism in raffinose oligosaccharide (RFO) metabolizing plants. RFO raffinose is a major photoassimilate and is a galactosylderivative of sucrose (Suc) containing a galactose (Gal) moiety. Upon arriving at the sink tissue, the Gal moieties of the RFOs are initially removed by alpha-galactosidase and then are phosphorylated to Gal-1-P. Gal-1-P is converted to UDP-Gal. The UDP-Gal is further metabolized to UDP-Glc via an epimerase reaction. The UDP-Glc can be directly utilized in cell wall metabolism or in Suc synthesis. However, for the Suc synthesis UDP-Glc must be further metabolized to Glc-1-P. This can be carried out either by the UGPase in the reverse direction or by the dual substrate PPase itself operating in the reverse direction. According to the latter possibility, the three-step pathway of Gal-1-P to Glc-1-P could be carried out by a single PPase, functioning sequentially in reverse directions separated by the epimerase reaction.
53	cd09671	346	98	37.5	1.2E+02	[ -----------                                     ]	Csx1_III-U	CRISPR/Cas system-associated protein Csx1. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA; Protein of this family often fused to HTH domain; Some proteins could have an additional fusion with RecB-family nuclease domain; Core domain appears to have a Rossmann-like fold; loosely associated with CRISPR/Cas systems; also known as DxTHG family
54	PRK08311	237	107	37.1	1E+02	[                       ------------              ]	PRK08311	putative RNA polymerase sigma factor SigI; Reviewed
55	cd06828	373	63	36.8	94	[  --------                                       ]	PLPDE_III_DapDC	Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Diaminopimelate Decarboxylase. Diaminopimelate decarboxylase (DapDC, EC 4.1.1.20) participates in the last step of lysine biosynthesis. It converts meso-2,6-diaminoheptanedioate to L-lysine. It is a fold type III PLP-dependent enzyme that contains an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain, similar to bacterial alanine racemases. DapDC exists as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. Homodimer formation and the presence of the PLP cofactor are required for catalytic activity.
56	pfam12427	23	13	33.4	23	[                                  -              ]	DUF3665	Branched-chain amino acid aminotransferase. This domain family is found in bacteria, and is typically between 23 and 35 amino acids in length. The family is found in association with pfam01063. There is a conserved TRT sequence motif.
57	cd02982	103	68	32.9	2.6E+02	[                                     -------     ]	PDI_b'_family	Protein Disulfide Isomerase (PDIb') family, redox inactive TRX-like domain b'; composed of eukaryotic proteins involved in oxidative protein folding in the endoplasmic reticulum (ER) by acting as catalysts and folding assistants. Members of this family include PDI, calsequestrin and other PDI-related proteins like ERp72, ERp57 (or ERp60), ERp44, P5 and PDIR. PDI, ERp57, ERp72, P5 and PDIR are all oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. These proteins contain multiple copies of a redox active TRX (a) domain containing a CXXC motif, and one or more redox inactive TRX-like (b) domains. The molecular structure of PDI is abb'a'. Also included in this family is the PDI-related protein ERp27, which contains only redox-inactive TRX-like (b and b') domains. The redox inactive domains are implicated in substrate recognition with the b' domain serving as the primary substrate binding site. Only the b' domain is necessary for the binding of small peptide substrates. In addition to the b' domain, other domains are required for the binding of larger polypeptide substrates. The b' domain is also implicated in chaperone activity.
58	cd10967	202	56	32.3	1.5E+02	[   -------                                       ]	CE4_GLA_like_6s	Putative catalytic NodB homology domain of gellan lyase and similar proteins. This family is represented by the extracellular polysaccharide-degrading enzyme, gellan lyase (gellanase, EC 4.2.2.-), from Bacillus sp. The enzyme acts on gellan exolytically and releases a tetrasaccharide of glucuronyl-glucosyl-rhamnosyl-glucose with unsaturated glucuronic acid at the nonreducing terminus. The family also includes many uncharacterized prokaryotic polysaccharide deacetylases, which show high sequence similarity to Bacillus sp. gellan lyase. Although their biological functions remain unknown, all members of the family contain a conserved domain with a 6-stranded beta/alpha barrel, which is similar to the catalytic NodB homology domain of rhizobial NodB-like proteins, belonging to the larger carbohydrate esterase 4 (CE4) superfamily.
59	pfam03693	81	50	32.0	50	[                        -----                    ]	RHH_2	Uncharacterized protein family (UPF0156). This family of proteins are about 80 amino acids in length and their function is unknown. The proteins contain a conserved GRY motif. This family appears to be related to ribbon-helix-helix DNA-binding proteins.
60	cd03769	134	54	31.9	78	[   ------                                        ]	SR_IS607_transposase_like	Serine Recombinase (SR) family, IS607-like transposase subfamily, catalytic domain; members contain a DNA binding domain with homology to MerR/SoxR located N-terminal to the catalytic domain. Serine recombinases catalyze site-specific recombination of DNA molecules by a concerted, four-strand cleavage and rejoining mechanism which involves a transient phosphoserine linkage between DNA and the enzyme. They are functionally versatile and include resolvases, invertases, integrases, and transposases. This subfamily is composed of proteins that catalyze the transposition of insertion sequence (IS) elements such as IS607 from Helicobacter and IS1535 from Mycobacterium, and similar proteins from other bacteria and several archaeal species. IS elements are DNA segments that move to new sites in prokaryotic and eukaryotic genomes causing insertion mutations and gene rearrangements.
61	cd00739	257	106	30.3	91	[    ----------------                             ]	DHPS	DHPS subgroup of Pterin binding enzymes. DHPS (dihydropteroate synthase), a functional homodimer, catalyzes the condensation of p-aminobenzoic acid (pABA) in the de novo biosynthesis of folate, which is an essential cofactor in both nucleic acid and protein biosynthesis. Prokaryotes (and some lower eukaryotes) must synthesize folate de novo, while higher eukaryotes are able to utilize dietary folate and therefore lack DHPS. Sulfonamide drugs, which are substrate analogs of pABA, target DHPS.
62	TIGR02095	473	53	30.2	81	[                                     ------      ]	glgA	glycogen/starch synthase, ADP-glucose type. This family consists of glycogen (or starch) synthases that use ADP-glucose (EC 2.4.1.21), rather than UDP-glucose (EC 2.4.1.11) as in animals, as the glucose donor. This enzyme is found in bacteria and plants. Whether the name given is glycogen synthase or starch synthase depends on context, and therefore on substrate.
63	COG4956	356	105	29.8	1E+02	[                           -------------         ]	COG4956	Uncharacterized conserved protein YacL, contains PIN and TRAM domains
64	COG1855	604	114	29.4	1.2E+02	[                           ---------------       ]	COG1855	Predicted ATPase, PilT family
65	cd13586	367	106	29.4	1.1E+02	[   ------------                                  ]	PBP2_Maltose_binding_like	The periplasmic-binding component of ABC transport systems specific for maltose and related polysaccharides; possess type 2 periplasmic binding fold. This subfamily represents the periplasmic binding component of ABC transport systems involved in uptake of polysaccharides including maltose, maltodextrin, and cyclodextrin. Members of this family belong to the type 2 periplasmic-binding fold superfamily. PBP2 is comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. The majority of PBP2 proteins function in the uptake of small soluble substrates in eubacteria and archaea. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.
66	cd03083	80	41	27.9	58	[   ----                                          ]	TRX_Fd_NuoE_hoxF	TRX-like
67	TIGR00305	114	97	27.8	2.2E+02	[                            ------------         ]	TIGR00305	putative toxin-antitoxin system toxin component, PIN family. This uncharacterized protein family, part of the PIN domain superfamily, is restricted to bacteria and archaea. A comprehensive in silico study of toxin-antitoxin systems by Makarova, et al. (2009) finds evidence this family represents the toxin-like component of one class of type 2 toxin-antitoxin systems.
68	PRK08345	289	57	27.7	1.4E+02	[------                                           ]	PRK08345	cytochrome-c3 hydrogenase subunit gamma; Provisional
69	cd09877	127	101	27.3	1.3E+02	[                            ------------         ]	PIN_YacL	PIN domain of Thermus Thermophilus Hb8, uncharacterized Bacillus subtilis YacL, and other bacterial homologs. PIN (PilT N terminus) domain of the conserved membrane protein of unknown function of Thermus Thermophilus Hb8, Bacillus subtilis YacL and other similar homologs are included in this family. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domain homologs within this group contain four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. Proteins in this group have a C-terminal TRAM domain whose function is unknown but predicted to be a RNA-binding domain common to tRNA uracil methylation and adenine thiolation enzymes.
70	TIGR00593	887	98	27.2	1.9E+02	[                                  -----------    ]	pola	DNA polymerase I. All proteins in this family for which functions are known are DNA polymerases Many also have an exonuclease motif. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).
71	cd03230	173	73	25.7	41	[  --------                                       ]	ABC_DR_subfamily_A	ATP-binding cassette domain of the drug resistance transporter and related proteins, subfamily A. This family of ATP-binding proteins belongs to a multi-subunit transporter involved in drug resistance (BcrA and DrrA), nodulation, lipid transport, and lantibiotic immunity. In bacteria and archaea, these transporters usually include an ATP-binding protein and one or two integral membrane proteins. Eukaryotic systems of the ABCA subfamily display ABC domains that are quite similar to this family. The ATP-binding domain shows the highest similarity between all members of the ABC transporter family. ABC transporters are a subset of nucleotide hydrolases that contain a signature motif, Q-loop, and H-loop/switch region, in addition to, the Walker A motif/P-loop and Walker B motif commonly found in a number of ATP- and GTP-binding and hydrolyzing proteins.
72	TIGR02824	325	137	25.3	2.6E+02	[ -----------------                               ]	quinone_pig3	putative NAD(P)H quinone oxidoreductase, PIG3 family. Members of this family are putative quinone oxidoreductases that belong to the broader superfamily (modeled by Pfam pfam00107) of zinc-dependent alcohol (of medium chain length) dehydrogenases and quinone oxiooreductases. The alignment shows no motif of conserved Cys residues as are found in zinc-binding members of the superfamily, and members are likely to be quinone oxidoreductases instead. A member of this family in Homo sapiens, PIG3, is induced by p53 but is otherwise uncharacterized.
73	TIGR02549	21	16	25.3	30	[          -                                      ]	CRISPR_DxTHG	CRISPR-associated DxTHG motif protein. This model describes a short region highly conserved between two otherwise substantially different CRISPR-associated (cas) proteins, TIGR02221 and TIGR01987. This region includes the motif
74	cd10911	155	49	25.2	76	[                                     -----       ]	LabA	LabA_like proteins. A well conserved group of bacterial and archaeal proteins with no defined function. LabA, a member from Synechococcus elongatus PCC 7942, has been shown to play a role in cyanobacterial circadian timing. It is required for negative feedback regulation of the autokinase/autophosphatase KaiC, a central component of the circadian clock system. In particular, LabA seems necessary for KaiC-dependent repression of gene expression. LabA_like domains exhibit some similarity to the NYN domain, a distant relative of the PIN-domain nucleases.
75	cd09854	125	111	24.7	59	[                            -------------        ]	PIN_VapC-Smg6_family	PIN domains of VapC and Smg6 ribonucleases, ribosome assembly factor NOB1, rRNA-processing protein Fcf1, Archaeoglobus fulgidus AF0591 protein, and homologs. PIN (PilT N terminus) domains of such ribonucleases as the toxins of prokaryotic toxin/antitoxin operons FitAB and VapBC, as well as, eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and, rRNA-processing protein Fcf1, are included in this family. Also included are the PIN domains of the Pyrobaculum aerophilum Pea0151 and Archaeoglobus fulgidus AF0591 proteins and other similar archaeal homologs. These PIN domains are structural homologs of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains typically contain three or four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule.
76	TIGR01496	257	52	23.4	1.5E+02	[    -------                                      ]	DHPS	dihydropteroate synthase. This model represents dihydropteroate synthase, the enzyme that catalyzes the second to last step in folic acid biosynthesis. The gene is usually designated folP (folic acid biosynthsis) or sul (sulfanilamide resistance). This model represents one branch of the family of pterin-binding enzymes (pfam00809) and of a cluster of dihydropteroate synthase and related enzymes (COG0294). Other members of pfam00809 and COG0294 are represented by model TIGR00284.
77	COG3589	360	64	21.9	1.9E+02	[   -------                                       ]	COG3589	Uncharacterized protein
78	COG0297	487	49	21.8	1.5E+02	[                                     -----       ]	GlgA	Glycogen synthase
79	pfam04028	74	45	21.6	1.5E+02	[                        ----                     ]	DUF374	Domain of unknown function (DUF374). Bacterial domain of unknown function.
80	cd03729	42	11	21.5	49	[                             -                   ]	SOCS_ASB13	SOCS (suppressors of cytokine signaling) box of ASB13-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.
81	COG0028	550	74	21.5	4E+02	[---------                                        ]	IlvB	Acetolactate synthase large subunit or other thiamine pyrophosphate-requiring enzyme
82	pfam04665	241	61	21.1	2.6E+02	[------                                           ]	Pox_A32	Poxvirus A32 protein. The A32 protein is thought to be involved in viral DNA packaging.
83	COG0148	423	68	21.0	2E+02	[ --------                                        ]	Eno	Enolase
84	pfam11017	314	48	20.8	36	[              ------                             ]	DUF2855	Protein of unknown function (DUF2855). This family of proteins has no known function.
85	PRK06836	394	94	20.6	1E+02	[    ------------                                 ]	PRK06836	aspartate aminotransferase; Provisional
86	cd09859	174	46	20.6	1.5E+02	[                                    -----        ]	PIN_53EXO	PIN domain of the 5'-3' exonuclease of Taq DNA polymerase I and homologs. The 5'-3' exonuclease (53EXO) PIN (PilT N terminus) domain of multi-domain DNA polymerase I and single domain protein homologs are included in this family. Taq contains a polymerase domain for synthesizing a new DNA strand and a 53EXO PIN domain for cleaving RNA primers or damaged DNA strands. Taq's 53EXO PIN domain recognizes and endonucleolytically cleaves a structure-specific DNA substrate that has a bifurcated downstream duplex and an upstream template-primer duplex that overlaps the downstream duplex by 1 bp. The 53EXO PIN domain cleaves the unpaired 5'-arm of the overlap flap DNA substrate. 5'-3' exonucleases are members of the structure-specific, 5' nuclease family that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. These nucleases contain a PIN domain with a helical arch/clamp region (I domain) of variable length (approximately 16 residues in 53EXO PIN domains) and a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included here) and the helical arch/clamp region are involved in DNA/RNA binding. The active site includes a set of conserved acidic residues that are essential for binding divalent metal ions required for nuclease activity.
87	pfam06745	231	67	20.5	4.5E+02	[   --------                                      ]	KaiC	KaiC. This family represents a conserved region within bacterial and archaeal proteins, most of which are hypothetical. More than one copy is sometimes found in each protein. This family includes KaiC, which is one of the Kai proteins among which direct protein-protein association may be a critical process in the generation of circadian rhythms in cyanobacteria.
88	cd08266	342	101	20.4	5.7E+02	[ ------------                                    ]	Zn_ADH_like1	Alcohol dehydrogenases of the MDR family. This group contains proteins related to the zinc-dependent alcohol dehydrogenases. However, while the group has structural zinc site characteristic of these enzymes, it lacks the consensus site for a catalytic zinc. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H)-binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine, the ribose of NAD, a serine, then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction.
89	pfam08763	32	15	20.3	56	[          --                                     ]	Ca_chan_IQ	Voltage gated calcium channel IQ domain. Voltage gated calcium channels control cellular calcium entry in response to changes in membrane potential. The isoleucine-glutamine (IQ) motif in the voltage gated calcium channel IQ domain interacts with hydrophobic pockets of Ca2+/calmodulin. The interaction regulates two self-regulatory calcium dependent feedback mechanism, calcium dependent inactivation (CDI), and calcium-dependent facilitation (CDF).
90	TIGR01048	414	67	20.2	1.9E+02	[  --------                                       ]	lysA	diaminopimelate decarboxylase. This family consists of diaminopimelate decarboxylase, an enzyme which catalyzes the conversion of diaminopimelic acid into lysine during the last step of lysine biosynthesis.