Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLLTGSYHCDTRTRVEDLMNRTPLSVSPDDS 87
Cdd:cd04629     1 MTRNPVTLTPDTSILEAVELLLEHKISGAPVVDEQGRLVGFLSEQDCLKALLEASYHCEPGGTVADYMSTEVLTVSPDTS 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1960140291  88 ILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQA 123
Cdd:cd04629    81 IVDLAQLFLKNKPRRYPVVEDGKLVGQISRRDVLRA 116

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLLTGSYHCDTRTRVEDLMNRTPLSVSPDDS 87
Cdd:cd04629     1 MTRNPVTLTPDTSILEAVELLLEHKISGAPVVDEQGRLVGFLSEQDCLKALLEASYHCEPGGTVADYMSTEVLTVSPDTS 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1960140291  88 ILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQA 123
Cdd:cd04629    81 IVDLAQLFLKNKPRRYPVVEDGKLVGQISRRDVLRA 116

CBS domain; CBS domains are small intracellular modules that pair together to form a stable globular domain. This family represents a single CBS domain. Pairs of these domains have been termed a Bateman domain. CBS domains have been shown to bind ligands with an adenosyl group such as AMP, ATP and S-AdoMet. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl carrying ligands. The region containing the CBS domains in Cystathionine-beta synthase is involved in regulation by S-AdoMet. CBS domain pairs from AMPK bind AMP or ATP. The CBS domains from IMPDH and the chloride channel CLC2 bind ATP.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1960140291  71 VEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGN-RVIGIISRRQVMQAL 124
Cdd:pfam00571   1 VKDIMTKDVVTVSPDTTLEEALELMREHGISRLPVVDEDgKLVGIVTLKDLLRAL 55

Domain in cystathionine beta-synthase and other proteins; Domain present in all 3 forms of cellular life. Present in two copies in inosine monophosphate dehydrogenase, of which one is disordered in the crystal structure. A number of disease states are associated with CBS-containing proteins including homocystinuria, Becker's and Thomsen disease.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1960140291   14 SLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQD 53
Cdd:smart00116   4 TVSPDTTLEEALELLRENGIRRLPVVDEEGRLVGIVTRRD 43

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLLTGSYHCDTRTRVEDLMNRTPLSVSPDDS 87
Cdd:cd04629     1 MTRNPVTLTPDTSILEAVELLLEHKISGAPVVDEQGRLVGFLSEQDCLKALLEASYHCEPGGTVADYMSTEVLTVSPDTS 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1960140291  88 ILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQA 123
Cdd:cd04629    81 IVDLAQLFLKNKPRRYPVVEDGKLVGQISRRDVLRA 116

Predicted transcriptional regulator, contains C-terminal CBS domains [Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   2 LNIRDHMSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDpQQRLIGFLSEQDCIPSLLTGSYHCDTRtrVEDLMNRTPLS 81
Cdd:COG2524    86 MKVKDIMTKDVITVSPDTTLEEALELMLEKGISGLPVVD-DGKLVGIITERDLLKALAEGRDLLDAP--VSDIMTRDVVT 162

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1960140291  82 VSPDDSILELARQMTEAKPKVYPVLEGN-RVIGIISRRQVMQAL 124
Cdd:COG2524   163 VSEDDSLEEALRLMLEHGIGRLPVVDDDgKLVGIITRTDILRAL 206

CBS domain [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   2 LNIRDHMSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLLTGSYHCDTRTrVEDLMNRTPLS 81
Cdd:COG0517     1 MKVKDIMTTDVVTVSPDATVREALELMSEKRIGGLPVVDEDGKLVGIVTDRDLRRALAAEGKDLLDTP-VSEVMTRPPVT 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1960140291  82 VSPDDSILELARQMTEAKPKVYPVLEGN-RVIGIISRRQVMQAL 124
Cdd:COG0517    80 VSPDTSLEEAAELMEEHKIRRLPVVDDDgRLVGIITIKDLLKAL 123

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the BON (bacterial OsmY and nodulation domain) domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the BON (bacterial OsmY and nodulation domain) domain. BON is a putative phospholipid-binding domain found in a family of osmotic shock protection proteins. It is also found in some secretins and a group of potential haemolysins. Its likely function is attachment to phospholipid membranes. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCI-----------PSLLTGSYHCDTR-------- 68
Cdd:cd04586     1 MTTDVVTVTPDTSVREAARLLLEHRISGLPVVDDDGKLVGIVSEGDLLrreepgteprrVWWLDALLESPERlaeeyvka 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1960140291  69 --TRVEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQA 123
Cdd:cd04586    81 hgRTVGDVMTRPVVTVSPDTPLEEAARLMERHRIKRLPVVDDGKLVGIVSRADLLRA 137

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the ACT domain; The putative Acetoin Utilization Protein (Acub) from Vibrio Cholerae contains a CBS pair domain. The acetoin utilization protein plays a role in growth and sporulation on acetoin or butanediol for use as a carbon source. Acetoin is an important physiological metabolite excreted by many microorganisms. It is used as an external energy store by a number of fermentive bacteria. Acetoin is produced by the decarboxylation of alpha-acetolactate. Once superior carbon sources are exhausted, and the culture enters stationary phase, acetoin can be utilised in order to maintain the culture density. The conversion of acetoin into acetyl-CoA or 2,3-butanediol is catalysed by the acetoin dehydrogenase complex and acetoin reductase/2,3-butanediol dehydrogenase, respectively. Acetoin utilization proteins, acetylpolyamine amidohydrolases, and histone deacetylases are members of an ancient protein superfamily.This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the acetoin utilization proteins in bacteria. Acetoin is a product of fermentative metabolism in many prokaryotic and eukaryotic microorganisms. They produce acetoin as an external carbon storage compound and then later reuse it as a carbon and energy source during their stationary phase and sporulation. In addition these CBS domains are associated with a downstream ACT (aspartate kinase/chorismate mutase/TyrA) domain, which is linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Pairs of ACT domains bind specifically to a particular amino acid leading to regulation of the linked enzyme. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   3 NIRDHMSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDpQQRLIGFLSEQD---CIPSLLTGS-----YHCDTRTRVEDL 74
Cdd:cd04584     1 LVKDIMTKNVVTVTPDTSLAEARELMKEHKIRHLPVVD-DGKLVGIVTDRDllrASPSKATSLsiyelNYLLSKIPVKDI 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1960140291  75 MNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQAL 124
Cdd:cd04584    80 MTKDVITVSPDDTVEEAALLMLENKIGCLPVVDGGKLVGIITETDILRAF 129

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLLTGSyhcDTRTRVEDLMNRTPLSVSPDDS 87
Cdd:cd09836     1 MSKPVVTVPPETTIREAAKLMAENNIGSVVVVDDDGKPVGIVTERDIVRAVAEGI---DLDTPVEEIMTKNLVTVSPDES 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1960140291  88 ILELARQMTEAKPKVYPVLE-GNRVIGIISRRQVMQALN 125
Cdd:cd09836    78 IYEAAELMREHNIRHLPVVDgGGKLVGVISIRDLARELS 116

Predicted transcriptional regulator, contains C-terminal CBS domains [Transcription];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1960140291  67 TRTRVEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQALN 125
Cdd:COG2524    84 LKMKVKDIMTKDVITVSPDTTLEEALELMLEKGISGLPVVDDGKLVGIITERDLLKALA 142

CBS pair domains found in archeal 5'-AMP-activated protein kinase gamma subunit-like proteins; Archeal gamma-subunit of 5'-AMP-activated protein kinase (AMPK) contains four CBS domains in tandem repeats, similar to eukaryotic homologs. AMPK is an important regulator of metabolism and of energy homeostasis. It is a heterotrimeric protein composed of a catalytic serine/threonine kinase subunit (alpha) and two regulatory subunits (beta and gamma). The gamma subunit senses the intracellular energy status by competitively binding AMP and ATP and is believed to be responsible for allosteric regulation of the whole complex. In humans mutations in gamma- subunit of AMPK are associated with hypertrophic cardiomiopathy, Wolff-Parkinson-White syndrome and glycogen storage in the skeletal muscle. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   4 IRDHMSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDpQQRLIG---------FLSEQDCIPSLLTGSYHCDTRTRVEDL 74
Cdd:cd04631     2 VEDYMTKNVITATPGTPIEDVAKIMVRNGFRRLPVVS-DGKLVGivtstdimrYLGSGEAFEKLKTGNIHEVLNVPISSI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1960140291  75 MNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQAL 124
Cdd:cd04631    81 MKRDIITTTPDTDLGEAAELMLEKNIGALPVVDDGKLVGIITERDILRAI 130

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in archaea, repeat 1; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVL-DPQQRLIGFLSEQDcipsLLTGSyhcdTRTRVEDLMNRTPLSVSPDD 86
Cdd:cd04638     1 MTKDVVTVTLPGTRDDVLEILKKKAISGVPVVkKETGKLVGIVTRKD----LLRNP----DEEQIALLMSRDPITISPDD 72

                          90       100       110
                  ....*....|....*....|....*....|
gi 1960140291  87 SILELARQMTEAKPKVYPVLEGNRVIGIIS 116
Cdd:cd04638    73 TLSEAAELMLEHNIRRVPVVDDDKLVGIVT 102

CBS domain; CBS domains are small intracellular modules that pair together to form a stable globular domain. This family represents a single CBS domain. Pairs of these domains have been termed a Bateman domain. CBS domains have been shown to bind ligands with an adenosyl group such as AMP, ATP and S-AdoMet. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl carrying ligands. The region containing the CBS domains in Cystathionine-beta synthase is involved in regulation by S-AdoMet. CBS domain pairs from AMPK bind AMP or ATP. The CBS domains from IMPDH and the chloride channel CLC2 bind ATP.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1960140291  71 VEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGN-RVIGIISRRQVMQAL 124
Cdd:pfam00571   1 VKDIMTKDVVTVSPDTTLEEALELMREHGISRLPVVDEDgKLVGIVTLKDLLRAL 55

CBS domain [Signal transduction mechanisms];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1960140291  70 RVEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVL-EGNRVIGIISRRQVMQALNTQ 127
Cdd:COG0517     2 KVKDIMTTDVVTVSPDATVREALELMSEKRIGGLPVVdEDGKLVGIVTDRDLRRALAAE 60

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the DHH and nucleotidyltransferase (NT) domains; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with an upstream DHH domain which performs a phosphoesterase function and a downstream nucleotidyltransferase (NT) domain of family X DNA polymerases. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  13 HSLTPQLGLADALDRLHDAGLSGLPVLDPQQrLIGFLSEQDCIPSLLTGSYHcdtrTRVEDLMNRTPLSVSPDDSILELA 92
Cdd:cd04595     5 KTVSPDTTIEEARKIMLRYGHTGLPVVEDGK-LVGIISRRDVDKAKHHGLGH----APVKGYMSTNVITIDPDTSLEEAQ 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1960140291  93 RQMTEAKPKVYPVLEGNRVIGIISRRQVMQA 123
Cdd:cd04595    80 ELMVEHDIGRLPVVEEGKLVGIVTRSDVLRY 110

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with family II inorganic pyrophosphatase; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with a subgroup of family II inorganic pyrophosphatases (PPases) that also contain a DRTGG domain. The homolog from Clostridium has been shown to be inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A), which has been shown to bind to the CBS domain. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  14 SLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCipslltgsyhcdTRTrVEDLMNRT-PLSVSPDDSILELA 92
Cdd:cd04597     9 PLSPETSIKDAWNLMDENNLKTLPVTDDNGKLIGLLSISDI------------ART-VDYIMTKDnLIVFKEDDYLDEVK 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1960140291  93 RQMTEAKPKVYPVL-EGNRVIGIISRRQVM 121
Cdd:cd04597    76 EIMLNTNFRNYPVVdENNKFLGTISRKHLI 105

Mg/Co/Ni transporter MgtE (contains CBS domain) [Inorganic ion transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAG-----LSGLPVLDPQQRLIGFLSEQDcipsLLTgsyhCDTRTRVEDLMNRTPLSV 82
Cdd:COG2239   135 MTTEFVAVREDWTVGEALRYLRRQAedpetIYYIYVVDDDGRLVGVVSLRD----LLL----ADPDTKVSDIMDTDVISV 206

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1960140291  83 SPDDSILELARQMTEakpkvY-----PVL-EGNRVIGIISRRQVMQAL 124
Cdd:COG2239   207 PADDDQEEVARLFER-----YdllalPVVdEEGRLVGIITVDDVVDVI 249

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found associated with the ABC transporter OpuCA; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in association with the ABC transporter OpuCA. OpuCA is the ATP binding component of a bacterial solute transporter that serves a protective role to cells growing in a hyperosmolar environment but the function of the CBS domains in OpuCA remains unknown. In the related ABC transporter, OpuA, the tandem CBS domains have been shown to function as sensors for ionic strength, whereby they control the transport activity through an electronic switching mechanism. ABC transporters are a large family of proteins involved in the transport of a wide variety of different compounds, like sugars, ions, peptides, and more complex organic molecules. They 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. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  14 SLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDcipslLTGSYHcdTRTRVEDLMNRTPLSVSPDDSILELAR 93
Cdd:cd04583     6 TITPERTLAQAIEIMREKRVDSLLVVDKDNVLLGIVDIED-----INRNYR--KAKKVGEIMERDVFTVKEDSLLRDTVD 78

                          90       100
                  ....*....|....*....|....*
gi 1960140291  94 QMTEAKPKVYPVL-EGNRVIGIISR 117
Cdd:cd04583    79 RILKRGLKYVPVVdEQGRLVGLVTR 103

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in archaea, repeat 2; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  14 SLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLL-------TGSYHCDTRTR----VEDLMNRTPLSV 82
Cdd:cd04632     6 TVNEDDTIGKAINLLREHGISRLPVVDDNGKLVGIVTTYDIVDFVVrpgtktrGGDRGGEKERMldlpVYDIMSSPVVTV 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1960140291  83 SPDDSILELARQMTEAKPKVYPVLEG-NRVIGIISRRQVMQA 123
Cdd:cd04632    86 TRDATVADAVERMLENDISGLVVTPDdNMVIGILTKTDVLRA 127

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the DHH and nucleotidyltransferase (NT) domains; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with an upstream DHH domain which performs a phosphoesterase function and a downstream nucleotidyltransferase (NT) domain of family X DNA polymerases. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1960140291  81 SVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQALNT-QMKA 130
Cdd:cd04595     6 TVSPDTTIEEARKIMLRYGHTGLPVVEDGKLVGIISRRDVDKAKHHgLGHA 56

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in bacteria; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC voltage-gated chloride channel. The CBS pairs here are found in the EriC CIC-type chloride channels in bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of chloride ions across biological membranes. CIC-type chloride channels come from all kingdoms of life, have several gene families, and can be gated by voltage. The members of the CIC-type chloride channel are double-barreled: two proteins forming homodimers at a broad interface formed by four helices from each protein. The two pores are not found at this interface, but are completely contained within each subunit, as deduced from the mutational analyses, unlike many other channels, in which four or five identical or structurally related subunits jointly form one pore. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  37 PVLDPQQRLIGFLSEQDcIPSLLTGSYHCDTRTrVEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEG---NRVIG 113
Cdd:cd04613    30 PVVDEQGRLTGILSIQD-VRGVLFEEELWDLVV-VKDLATTDVITVTPDDDLYTALLKFTSTNLDQLPVVDDddpGKVLG 107

                          90
                  ....*....|..
gi 1960140291 114 IISRRQVMQALN 125
Cdd:cd04613   108 MLSRRDVIAAYN 119

putative manganese-dependent inorganic diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  23 DALDRLHDAGLSGLPV---LDPQQRLIGFLSEQDCipSLLTGSYHCDTRTR-------VEDLMNRT-PLSVSPDDSILEL 91
Cdd:PRK14869  192 DIQLAAIEAGVRLLIItggAPVSEDVLELAKENGV--TVISTPYDTFTTARlinqsipVSYIMTTEdLVTFSKDDYLEDV 269

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1960140291  92 ARQMTEAKPKVYPVL-EGNRVIGIISRRQVMQ 122
Cdd:PRK14869  270 KEVMLKSRYRSYPVVdEDGKVVGVISRYHLLS 301

GuaB1 family IMP dehydrogenase-related protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  14 SLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCipsllTGsyhCDTRTRVEDLMNRTPLSVSPDDSILELAR 93
Cdd:PRK07807  101 TLSPDDTVGDALALLPKRAHGAVVVVDEEGRPVGVVTEADC-----AG---VDRFTQVRDVMSTDLVTLPAGTDPREAFD 172

                          90       100
                  ....*....|....*....|....*.
gi 1960140291  94 QMTEAKPKVYPVLEGN-RVIGIISRR 118
Cdd:PRK07807  173 LLEAARVKLAPVVDADgRLVGVLTRT 198

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains from plant CBSX proteins; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains of plant single cystathionine beta-synthase (CBS) pair proteins (CBSX). CBSX1 and CBSX2 have been identified as redox regulators of the thioredoxin (Trx) system. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  13 HSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIpSLLTGSYHCDTRT----------------------- 69
Cdd:cd17789     6 HVVKPNTTVDEALELLVENRITGLPVIDEDWRLVGVVSDYDLL-ALDSISGRSQTDNnfppadstwktfnevqkllsktn 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1960140291  70 --RVEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGN-RVIGIISRRQVMQA 123
Cdd:cd17789    85 gkVVGDVMTPSPLVVREKTNLEDAARILLETKFRRLPVVDSDgKLVGIITRGNVVRA 141

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the MET2 domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the MET2 domain. Met2 is a key enzyme in the biosynthesis of methionine. It encodes a homoserine transacetylase involved in converting homoserine to O-acetyl homoserine. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   3 NIRDHMSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCIPSLLTGSyhcdtrTRVEDLMNRTPLSV 82
Cdd:cd04605     1 LVEDIMSKDVATIREDISIEEAAKIMIDKNVTHLPVVSEDGKLIGIVTSWDISKAVALKK------DSLEEIMTRNVITA 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1960140291  83 SPDDSILELARQMTEAKPKVYPVLEG-NRVIGIIS 116
Cdd:cd04605    75 RPDEPIELAARKMEKHNISALPVVDDdRRVIGIIT 109

CBS domain; CBS domains are small intracellular modules that pair together to form a stable globular domain. This family represents a single CBS domain. Pairs of these domains have been termed a Bateman domain. CBS domains have been shown to bind ligands with an adenosyl group such as AMP, ATP and S-AdoMet. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl carrying ligands. The region containing the CBS domains in Cystathionine-beta synthase is involved in regulation by S-AdoMet. CBS domain pairs from AMPK bind AMP or ATP. The CBS domains from IMPDH and the chloride channel CLC2 bind ATP.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1960140291   4 IRDHMSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQDCI 55
Cdd:pfam00571   1 VKDIMTKDVVTVSPDTTLEEALELMREHGISRLPVVDEDGKLVGIVTLKDLL 52

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1960140291  68 RTRVEDLMNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIIS 116
Cdd:cd04630    65 LVNVYEIMTKPAISVSPDLDIKYAARLMARFNLKRAPVIENNELIGIVS 113

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with a ParBc (ParB-like nuclease) domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with a ParBc (ParB-like nuclease) domain downstream. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1960140291  75 MNRTPLSVSPDDSILELARQMTEAKPKVYPVLEGNRVIGIISRRQVMQA 123
Cdd:cd04610     1 MTRDVITVSPDDTVKDVIKLIKETGHDGFPVVDDGKVVGYVTAKDLLGK 49

IMP dehydrogenase / GMP reductase domain; This family is involved in biosynthesis of guanosine nucleotide. Members of this family contain a TIM barrel structure. In the inosine monophosphate dehydrogenases 2 CBS domains pfam00571 are inserted in the TIM barrel. This family is a member of the common phosphate binding site TIM barrel family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291  15 LTPQLGLADALDRLHDAGLSGLPVLDpQQRLIGFLSEQDCIPSLltgsyhcDTRTRVEDLMNRTPLSVSPDDSILELARQ 94
Cdd:pfam00478  93 LSPDATVADALALMERYGISGVPVVD-DGKLVGIVTNRDLRFET-------DLSQPVSEVMTKENLVTAPEGTTLEEAKE 164

                          90       100
                  ....*....|....*....|....*.
gi 1960140291  95 -MTEAKPKVYPVL-EGNRVIGIISRR 118
Cdd:pfam00478 165 iLHKHKIEKLPVVdDNGRLVGLITIK 190

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the bacterial CAP_ED (cAMP receptor protein effector domain) family of transcription factors, the NT (Nucleotidyltransferase) Pol-beta-like domain, and the DUF294 dom; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the bacterial CAP_ED (cAMP receptor protein effector domain) family of transcription factors, the NT_Pol-beta-like domain, and the DUF294 domain. Members of CAP_ED, include CAP which binds cAMP, FNR (fumarate and nitrate reductase) which uses an iron-sulfur cluster to sense oxygen, and CooA a heme containing CO sensor. In all cases binding of the effector leads to conformational changes and the ability to activate transcription. The NT_Pol-beta-like domain includes the Nucleotidyltransferase (NT) domains of DNA polymerase beta and other family X DNA polymerases, as well as the NT domains of class I and class II CCA-adding enzymes, RelA- and SpoT-like ppGpp synthetases and hydrolases, 2'5'-oligoadenylate (2-5A)synthetases, Escherichia coli adenylyltransferase (GlnE), Escherichia coli uridylyl transferase (GlnD), poly (A) polymerases, terminal uridylyl transferases, Staphylococcus aureus kanamycin nucleotidyltransferase, and similar proteins. DUF294 is a putative nucleotidyltransferase with a conserved DxD motif. CBS is a small domain originally identified in cystathionine beta-synthase and subsequently found in a wide range of different proteins. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1960140291   8 MSRLTHSLTPQLGLADALDRLHDAGLSGLPVLDPQqRLIGFLSEQD----CIPSLLtgsyhcDTRTRVEDLMNRTPLSVS 83
Cdd:cd04587     2 MSRPPVTVPPDATIQEAAQLMSEERVSSLLVVDDG-RLVGIVTDRDlrnrVVAEGL------DPDTPVSEIMTPPPVTID 74

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1960140291  84 PDDSILELARQMTEAKPKVYPVLEGNRVIGIIS 116
Cdd:cd04587    75 ADALVFEALLLMLERNIHHLPVVDDGRVVGVVT 107

Domain in cystathionine beta-synthase and other proteins; Domain present in all 3 forms of cellular life. Present in two copies in inosine monophosphate dehydrogenase, of which one is disordered in the crystal structure. A number of disease states are associated with CBS-containing proteins including homocystinuria, Becker's and Thomsen disease.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1960140291   14 SLTPQLGLADALDRLHDAGLSGLPVLDPQQRLIGFLSEQD 53
Cdd:smart00116   4 TVSPDTTLEEALELLRENGIRRLPVVDEEGRLVGIVTRRD 43