Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in AMP-activated protein kinase gamma-like proteins, repeat 1; AMP-activated protein kinase (AMPK) plays multiple roles in the body's overall metabolic balance and response to exercise, nutritional stress, hormonal stimulation, and the glucose-lowering drugs metformin and rosiglitazone. AMPK consists of a catalytic alpha subunit and two non-catalytic subunits, beta and gamma, each with multiple isoforms that form active 1:1:1 heterotrimers. This cd contains 2 tandem repeats of the CBS domains found in the gamma subunits of AMPK. 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 6981392   37 CYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVGMLTITDFINILHRYYKSALVQIYELEEHKIETW 116
Cdd:cd04618   2 CYDLLPTSSKLVVLDTKLPVKKAFFALVQNGIRSAPLWDSEKQDFVGMLTITDFINILQYYYKSPSVQMEELEEHTIETW 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6981392  117 REVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILK 173
Cdd:cd04618  82 REIERQIGVPPLVSVHPEDSLYDAALLLLQNKIHRLPVIDPLTGNVLSVLTHKRILK 138

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in AMP-activated protein kinase gamma-like proteins, repeat 1; AMP-activated protein kinase (AMPK) plays multiple roles in the body's overall metabolic balance and response to exercise, nutritional stress, hormonal stimulation, and the glucose-lowering drugs metformin and rosiglitazone. AMPK consists of a catalytic alpha subunit and two non-catalytic subunits, beta and gamma, each with multiple isoforms that form active 1:1:1 heterotrimers. This cd contains 2 tandem repeats of the CBS domains found in the gamma subunits of AMPK. 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 6981392   37 CYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVGMLTITDFINILHRYYKSALVQIYELEEHKIETW 116
Cdd:cd04618   2 CYDLLPTSSKLVVLDTKLPVKKAFFALVQNGIRSAPLWDSEKQDFVGMLTITDFINILQYYYKSPSVQMEELEEHTIETW 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6981392  117 REVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILK 173
Cdd:cd04618  82 REIERQIGVPPLVSVHPEDSLYDAALLLLQNKIHRLPVIDPLTGNVLSVLTHKRILK 138

CBS-domain-containing membrane protein [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392  202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNL-----DVSVTKALQHRshyfegVL 276
Cdd:COG3448  11 DVVTVSPDTTLREALELMREHGIRGLPVVDEDGRLVGIVTERDLLRALLPDRLDELeerllDLPVEDVMTRP------VV 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6981392  277 KCYLHETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQALV 322
Cdd:COG3448  85 TVTPDTPLEEAAELMLEHGIHRLPVVDDDGRLVGIVTRTDLLRALA 130

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 6981392     202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAA 250
Cdd:smart00116   1 DVVTVSPDTTLEEALELLRENGIRRLPVVDEEGRLVGIVTRRDIIKALA 49

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
                  ....*....|....*....|....*....|....*....|....*...
gi 6981392    275 VLKCYLHETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQALV 322
Cdd:pfam00571   9 VVTVSPDTTLEEALELMREHGISRLPVVDEDGKLVGIVTLKDLLRALL 56

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in AMP-activated protein kinase gamma-like proteins, repeat 1; AMP-activated protein kinase (AMPK) plays multiple roles in the body's overall metabolic balance and response to exercise, nutritional stress, hormonal stimulation, and the glucose-lowering drugs metformin and rosiglitazone. AMPK consists of a catalytic alpha subunit and two non-catalytic subunits, beta and gamma, each with multiple isoforms that form active 1:1:1 heterotrimers. This cd contains 2 tandem repeats of the CBS domains found in the gamma subunits of AMPK. 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 6981392   37 CYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVGMLTITDFINILHRYYKSALVQIYELEEHKIETW 116
Cdd:cd04618   2 CYDLLPTSSKLVVLDTKLPVKKAFFALVQNGIRSAPLWDSEKQDFVGMLTITDFINILQYYYKSPSVQMEELEEHTIETW 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6981392  117 REVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILK 173
Cdd:cd04618  82 REIERQIGVPPLVSVHPEDSLYDAALLLLQNKIHRLPVIDPLTGNVLSVLTHKRILK 138

CBS-domain-containing membrane protein [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392  202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNL-----DVSVTKALQHRshyfegVL 276
Cdd:COG3448  11 DVVTVSPDTTLREALELMREHGIRGLPVVDEDGRLVGIVTERDLLRALLPDRLDELeerllDLPVEDVMTRP------VV 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6981392  277 KCYLHETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQALV 322
Cdd:COG3448  85 TVTPDTPLEEAAELMLEHGIHRLPVVDDDGRLVGIVTRTDLLRALA 130

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily; 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 6981392  202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKtYNNLDVSVTKALQhrshyfEGVLKCYLH 281
Cdd:cd02205   3 DVVTVDPDTTVREALELMAENGIGALPVVDDDGKLVGIVTERDILRALVEG-GLALDTPVAEVMT------PDVITVSPD 75

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6981392  282 ETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQ 319
Cdd:cd02205  76 TDLEEALELMLEHGIRRLPVVDDDGKLVGIVTRRDILR 113

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily; 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 6981392   44 SSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQsFVGMLTITDFINILHRYYKSALVQIYELEEhkietwrevylqd 123
Cdd:cd02205   1 TRDVVTVDPDTTVREALELMAENGIGALPVVDDDGK-LVGIVTERDILRALVEGGLALDTPVAEVMT------------- 66

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 6981392  124 sfKPLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILK 173
Cdd:cd02205  67 --PDVITVSPDTDLEEALELMLEHGIRRLPVVD-DDGKLVGIVTRRDILR 113

Signal-transduction protein containing cAMP-binding, CBS, and nucleotidyltransferase domains [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392  202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRshyfegVLKCYLH 281
Cdd:COG2905   8 DVVTVSPDATVREAARLMTEKGVGSLVVVDDDGRLVGIITDRDLRRRVLAEGLDPLDTPVSEVMTRP------PITVSPD 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6981392  282 ETLEAIINRLVEAEVHRLVVVDEHDVVkGIVSLSDILQAL 321
Cdd:COG2905  82 DSLAEALELMEEHRIRHLPVVDDGKLV-GIVSITDLLRAL 120

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 6981392  126 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpesGNTLY-ILTHKRILK-----FLKLFITEFPKP-------EFMSKsl 192
Cdd:cd04584   8 KNVVTVTPDTSLAEARELMKEHKIRHLPVVD---DGKLVgIVTDRDLLRaspskATSLSIYELNYLlskipvkDIMTK-- 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6981392  193 eelqigtyaNIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVINLA 249
Cdd:cd04584  83 ---------DVITVSPDDTVEEAALLMLENKIGCLPVVDG-GKLVGIITETDILRAF 129

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 6981392  202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRShyfegVLKCYLH 281
Cdd:cd04629   4 NPVTLTPDTSILEAVELLLEHKISGAPVVDEQGRLVGFLSEQDCLKALLEASYHCEPGGTVADYMSTE-----VLTVSPD 78

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 6981392  282 ETLEAIINRLVEAEVHRLVVVDEHDVVkGIVSLSDILQA 320
Cdd:cd04629  79 TSIVDLAQLFLKNKPRRYPVVEDGKLV-GQISRRDVLRA 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392   44 SSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKqsFVGMLTITDFINILHRYYksalvqiyELEEHKIetwREVYLqd 123
Cdd:COG2524  93 TKDVITVSPDTTLEEALELMLEKGISGLPVVDDGK--LVGIITERDLLKALAEGR--------DLLDAPV---SDIMT-- 157

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 6981392  124 sfKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPEsgNTLY-ILTHKRILKFL 175
Cdd:COG2524 158 --RDVVTVSEDDSLEEALRLMLEHGIGRLPVVDDD--GKLVgIITRTDILRAL 206

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the HPP motif domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the HPP motif domain. These proteins are integral membrane proteins with four transmembrane spanning helices. The function of these proteins is uncertain, but they are thought to be transporters. 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 6981392  206 VRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRSHYFEGV-------LKC 278
Cdd:cd04600   8 VTPDTSLEEAWRLLRRHRIKALPVVDRARRLVGIVTLADLLKHADLDPPRGLRGRLRRTLGLRRDRPETVgdimtrpVVT 87

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 6981392  279 YLHET-LEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQAL 321
Cdd:cd04600  88 VRPDTpIAELVPLFSDGGLHHIPVVDADGRLVGIVTQSDLIAAL 131

Signal-transduction protein containing cAMP-binding, CBS, and nucleotidyltransferase domains [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392  126 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILKFLKLfitefpkpefMSKSLEELQIGTY--ANI 203
Cdd:COG2905   7 RDVVTVSPDATVREAARLMTEKGVGSLVVVD-DDGRLVGIITDRDLRRRVLA----------EGLDPLDTPVSEVmtRPP 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 6981392  204 AMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVINLAAE 251
Cdd:COG2905  76 ITVSPDDSLAEALELMEEHRIRHLPVVDD-GKLVGIVSITDLLRALSE 122

CBS-domain-containing membrane protein [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392   56 VKKAFFALVTNGVRAAPLWDSKKQsFVGMLTITDFINILHRYYKSALVqiYELEEHKIEtwrEVYLqdsfKPLVCISPNA 135
Cdd:COG3448  21 LREALELMREHGIRGLPVVDEDGR-LVGIVTERDLLRALLPDRLDELE--ERLLDLPVE---DVMT----RPVVTVTPDT 90

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6981392  136 SLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILKFL 175
Cdd:COG3448  91 PLEEAAELMLEHGIHRLPVVD-DDGRLVGIVTRTDLLRAL 129

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 6981392  126 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGN------------TLYILTHKRILKFLKLFITEFPKPEFMSKSLE 193
Cdd:cd04586   3 TDVVTVTPDTSVREAARLLLEHRISGLPVVD-DDGKlvgivsegdllrREEPGTEPRRVWWLDALLESPERLAEEYVKAH 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 6981392  194 ELQIG---TyANIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVI 246
Cdd:cd04586  82 GRTVGdvmT-RPVVTVSPDTPLEEAARLMERHRIKRLPVVDD-GKLVGIVSRADLL 135

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 6981392     275 VLKCYLHETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQAL 321
Cdd:smart00116   2 VVTVSPDTTLEEALELLRENGIRRLPVVDEEGRLVGIVTRRDIIKAL 48

CBS pair domains found in archeal proteins, repeat 2; CBS pair domains found in archeal proteins that contain 2 repeats. 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 6981392  126 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpesGNTLY-ILTHKRILKFL-----KLFITEFPKPEFMSKSLEELQigt 199
Cdd:cd17778   8 TPVVTIYPDDTLKEAMELMVTRGFRRLPVVS---GGKLVgIVTAMDIVKYFgsheaKKRLTTGDIDEAYSTPVEEIM--- 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 6981392  200 YANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVI 246
Cdd:cd17778  82 SKEVVTIEPDADIAEAARLMIKKNVGSLLVVDDEGELKGIITERDVL 128

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 6981392  199 TYANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAA----EKTYNNL--DVSVTKAlqhrshyF 272
Cdd:cd17789   1 PKGKLHVVKPNTTVDEALELLVENRITGLPVIDEDWRLVGVVSDYDLLALDSisgrSQTDNNFppADSTWKT-------F 73

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6981392  273 EGVLKCYL--------------------HETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQA 320
Cdd:cd17789  74 NEVQKLLSktngkvvgdvmtpsplvvreKTNLEDAARILLETKFRRLPVVDSDGKLVGIITRGNVVRA 141

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria and eukaryotes; 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 6981392  202 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRshyfegVLKCYLH 281
Cdd:cd04623   3 DVVTVSPDATVAEALRLLAEKNIGALVVVDDGGRLVGILSERDYVRKLALRGASSLDTPVSEIMTRD------VVTCTPD 76

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 6981392  282 ETLEAIINRLVEaevHR---LVVVDEHDVVkGIVSLSDI 317
Cdd:cd04623  77 DTVEECMALMTE---RRirhLPVVEDGKLV-GIVSIGDV 111

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
                  ....*....|....*....|....*....|....*....|....*...
gi 6981392    275 VLKCYLHETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQALV 322
Cdd:pfam00571   9 VVTVSPDTTLEEALELMREHGISRLPVVDEDGKLVGIVTLKDLLRALL 56

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 6981392  129 VCISPNASLFDAVSSLIRNKIHRLPVIdpESGNTLYILTHKRILKFL---KLF----------ITEFPKPEFMSKsleel 195
Cdd:cd04631  11 ITATPGTPIEDVAKIMVRNGFRRLPVV--SDGKLVGIVTSTDIMRYLgsgEAFeklktgniheVLNVPISSIMKR----- 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 6981392  196 qigtyaNIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVIN 247
Cdd:cd04631  84 ------DIITTTPDTDLGEAAELMLEKNIGALPVVDD-GKLVGIITERDILR 128

CBS pair domains found in archeal proteins, repeat 1; CBS pair domains found in archeal proteins that contain 2 repeats. 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 6981392  126 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpesGNTLY-ILTHKRILKFL---KLFITEFPKPEF-MSKSLEELQIGTY 200
Cdd:cd17777  10 PPVLSISPSAPILSAFEKMNRRGIRRLVVVD---ENKLEgILSARDLVSYLgggCLFKIVESRHQGdLYSALNREVVETI 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 6981392  201 --ANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVI 246
Cdd:cd17777  87 mtPNPVYVYEDSDLIEALTIMVTRGIGSLPVVDRDGRPVGIVTERDLV 134

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria and archaea; 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 6981392  203 IAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFD-VINLAAEktynNLDVSVTKALQHRShyfEGVLKCYLH 281
Cdd:cd17775   5 VVTASPDTSVLEAARLMRDHHVGSVVVVEEDGKPVGIVTDRDiVVEVVAK----GLDPKDVTVGDIMS---ADLITARED 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6981392  282 ETLEAIINRLVEAEVHRLVVVDEHDVVKGIVSLSDILQAL 321
Cdd:cd17775  78 DGLFEALERMREKGVRRLPVVDDDGELVGIVTLDDILELL 117

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 6981392    129 VCISPNASLFDAVSSLIRNKIHRLPVIDpeSGNTLYILThKRILKFLKLFITefPKPEFMsksleelqigTYANIAMVRT 208
Cdd:pfam00478  91 VTLSPDATVADALALMERYGISGVPVVD--DGKLVGIVT-NRDLRFETDLSQ--PVSEVM----------TKENLVTAPE 155

                          90       100
                  ....*....|....*....|....*....
gi 6981392    209 TTPVYVALGIFVQHRVSALPVVDEKGRVV 237
Cdd:pfam00478 156 GTTLEEAKEILHKHKIEKLPVVDDNGRLV 184

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in bacteria and archaea; 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 6981392  131 ISPNASLFDAVSSLIRNKIHR-LPVIDpESGNTLYILTHKRILKFLKLFITEFPKPEFMSKSLEELQIGTYANIAM---- 205
Cdd:cd17785  15 VHENTSIRDVIDKMIEDPKTRsVYVVD-DDEKLLGIITLMELLKYIGYRFGVTIYKGVSFGLLLRISLKEKAKDIMlspi 93

                        90       100       110
                ....*....|....*....|....*....|...
gi 6981392  206 -VRTTTPVYVALGIFVQHRVSALPVVDEKGRVV 237
Cdd:cd17785  94 yVKKEDTLEEALELMVKNRLQELPVVDENGKVI 126

Predicted transcriptional regulator containing CBS domains [Transcription];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6981392   25 SSVYTTFMKSHRCYDLIpTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQsFVGMLTITDFINilhryyKSALVQ 104
Cdd:COG4109   6 STSYDTFKEILLVEDIM-TLEDVATLSEDDTVEDALELLEKTGHSRFPVVDENGR-LVGIVTSKDILG------KDDDTP 77

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6981392  105 IYELEEhkietwrevylqdsfKPLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILKFLK 176
Cdd:COG4109  78 IEDVMT---------------KNPITVTPDTSLASAAHKMIWEGIELLPVVD-DDGRLLGIISRQDVLKALQ 133

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
                ....*....|....*....|....*....|.
gi 6981392  126 KPLVCISPNASLFDAVSSLIRNKIHRLPVID 156
Cdd:cd04587  68 PPPVTIDADALVFEALLLMLERNIHHLPVVD 98

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the inosine 5' monophosphate dehydrogenase (IMPDH) protein; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the inosine 5' monophosphate dehydrogenase (IMPDH) protein. IMPDH is an essential enzyme that catalyzes the first step unique to GTP synthesis, playing a key role in the regulation of cell proliferation and differentiation. 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 6981392  129 VCISPNASLFDAVSSLIRNKIHRLPVIDpeSGNTLY-ILTHKRILkflklFITEFPKP--EFMSK-----------SLEE 194
Cdd:cd04601   5 VTLSPDATVADVLELKAEYGISGVPVTE--DGGKLVgIVTSRDIR-----FETDLSTPvsEVMTPderlvtapegiTLEE 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 6981392  195 lqigtyaniamvrtttpvyvALGIFVQHRVSALPVVDEKGRVVDI 239
Cdd:cd04601  78 --------------------AKEILHKHKIEKLPIVDDNGELVGL 102