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 332000015  38 CYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVvlralscplGMLTITDFINILHRYYKSALVQIYE 117
Cdd:cd04618    2 CYDLLPTSSKLVVLDTKLPVKKAFFALVQNGIRSAPLWDSEKQDFV---------GMLTITDFINILQYYYKSPSVQMEE 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332000015 118 LEEHKIETWREVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILK 183
Cdd:cd04618   73 LEEHTIETWREIERQIGVPPLVSVHPEDSLYDAALLLLQNKIHRLPVIDPLTGNVLSVLTHKRILK 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 332000015  38 CYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVvlralscplGMLTITDFINILHRYYKSALVQIYE 117
Cdd:cd04618    2 CYDLLPTSSKLVVLDTKLPVKKAFFALVQNGIRSAPLWDSEKQDFV---------GMLTITDFINILQYYYKSPSVQMEE 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332000015 118 LEEHKIETWREVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILK 183
Cdd:cd04618   73 LEEHTIETWREIERQIGVPPLVSVHPEDSLYDAALLLLQNKIHRLPVIDPLTGNVLSVLTHKRILK 138

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015 212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNL-----DVSVTKALQHRshyfegVL 286
Cdd:COG3448   11 DVVTVSPDTTLREALELMREHGIRGLPVVDEDGRLVGIVTERDLLRALLPDRLDELeerllDLPVEDVMTRP------VV 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 332000015 287 KCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALV 332
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 332000015   212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAA 260
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 332000015  285 VLKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALV 332
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 332000015  38 CYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVvlralscplGMLTITDFINILHRYYKSALVQIYE 117
Cdd:cd04618    2 CYDLLPTSSKLVVLDTKLPVKKAFFALVQNGIRSAPLWDSEKQDFV---------GMLTITDFINILQYYYKSPSVQMEE 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332000015 118 LEEHKIETWREVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILK 183
Cdd:cd04618   73 LEEHTIETWREIERQIGVPPLVSVHPEDSLYDAALLLLQNKIHRLPVIDPLTGNVLSVLTHKRILK 138

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015 212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNL-----DVSVTKALQHRshyfegVL 286
Cdd:COG3448   11 DVVTVSPDTTLREALELMREHGIRGLPVVDEDGRLVGIVTERDLLRALLPDRLDELeerllDLPVEDVMTRP------VV 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 332000015 287 KCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALV 332
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 332000015 212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKtYNNLDVSVTKALQhrshyfEGVLKCYLH 291
Cdd:cd02205    3 DVVTVDPDTTVREALELMAENGIGALPVVDDDGKLVGIVTERDILRALVEG-GLALDTPVAEVMT------PDVITVSPD 75

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 332000015 292 ETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQ 329
Cdd:cd02205   76 TDLEEALELMLEHGIRRLPVVDDDGKLVGIVTRRDILR 113

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015 212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVINLAAEKTYNnLDVSVtkalqhRSHYFEGVLKCYLH 291
Cdd:COG2524   95 DVITVSPDTTLEEALELMLEKGISGLPVVDD-GKLVGIITERDLLKALAEGRDL-LDAPV------SDIMTRDVVTVSED 166

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 332000015 292 ETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQAL 331
Cdd:COG2524  167 DSLEEALRLMLEHGIGRLPVVDDDGKLVGIITRTDILRAL 206

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 332000015  45 SSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQsfvvlralscPLGMLTITDFINILHRYYKSALVQIYELEEhkie 124
Cdd:cd02205    1 TRDVVTVDPDTTVREALELMAENGIGALPVVDDDGK----------LVGIVTERDILRALVEGGLALDTPVAEVMT---- 66

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 332000015 125 twrevylqdsfKPLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILK 183
Cdd:cd02205   67 -----------PDVITVSPDTDLEEALELMLEHGIRRLPVVD-DDGKLVGIVTRRDILR 113

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 332000015 136 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpesGNTLY-ILTHKRILK-----FLKLFITEFPKP-------EFMSKsl 202
Cdd:cd04584    8 KNVVTVTPDTSLAEARELMKEHKIRHLPVVD---DGKLVgIVTDRDLLRaspskATSLSIYELNYLlskipvkDIMTK-- 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 332000015 203 eelqigtyaNIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVINLA 259
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 332000015 212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRShyfegVLKCYLH 291
Cdd:cd04629    4 NPVTLTPDTSILEAVELLLEHKISGAPVVDEQGRLVGFLSEQDCLKALLEASYHCEPGGTVADYMSTE-----VLTVSPD 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 332000015 292 ETLETIINRLVEAEVHRLVVVDENDVVkGIVSLSDILQA 330
Cdd:cd04629   79 TSIVDLAQLFLKNKPRRYPVVEDGKLV-GQISRRDVLRA 116

CBS pair domain found in Hypoxic Response Protein 1 (HRP1) -like proteinds; Mycobacterium tuberculosis adapts to cellular stresses by upregulation of the dormancy survival regulon. Hypoxic response protein 1 (HRP1) is encoded by one of the most strongly upregulated genes in the dormancy survival regulon. HRP1 is a 'CBS-domain-only protein; however unlike other CBS containing proteins it does not appear to bind AMP. The biological function of the protein remains unclear, but is thought to contribute to the modulation of the host immune response. 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 332000015 212 NIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVV------DIyskfdVINLAAEktynNLDVSVTKALQHRSHyfeGV 285
Cdd:cd04622    4 DVVTVSPDTTLREAARLMRDLDIGALPVCEG-DRLVgmvtdrDI-----VVRAVAE----GKDPNTTTVREVMTG---DV 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 332000015 286 LKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDI 327
Cdd:cd04622   71 VTCSPDDDVEEAARLMAEHQVRRLPVVDDDGRLVGIVSLGDL 112

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 332000015   285 VLKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQAL 331
Cdd:smart00116   2 VVTVSPDTTLEEALELLRENGIRRLPVVDEEGRLVGIVTRRDIIKAL 48

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 332000015   137 PLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILKFLK 186
Cdd:smart00116   1 DVVTVSPDTTLEEALELLRENGIRRLPVVD-EEGRLVGIVTRRDIIKALA 49

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 332000015 225 ALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNN------------LDVSVtkalqhRSHYFEGVLKCYLHE 292
Cdd:cd04632   16 AINLLREHGISRLPVVDDNGKLVGIVTTYDIVDFVVRPGTKTrggdrggekermLDLPV------YDIMSSPVVTVTRDA 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 332000015 293 TLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQA 330
Cdd:cd04632   90 TVADAVERMLENDISGLVVTPDDNMVIGILTKTDVLRA 127

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 332000015 136 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpESGN------------TLYILTHKRILKFLKLFITEFPKPEFMSKSLE 203
Cdd:cd04586    3 TDVVTVTPDTSVREAARLLLEHRISGLPVVD-DDGKlvgivsegdllrREEPGTEPRRVWWLDALLESPERLAEEYVKAH 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 332000015 204 ELQIG---TyANIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVI 256
Cdd:cd04586   82 GRTVGdvmT-RPVVTVSPDTPLEEAARLMERHRIKRLPVVDD-GKLVGIVSRADLL 135

Predicted transcriptional regulator containing CBS domains [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015 209 TYANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAektynnlDVSVTKALQHRshyfegVLKC 288
Cdd:COG4109   23 TLEDVATLSEDDTVEDALELLEKTGHSRFPVVDENGRLVGIVTSKDILGKDD-------DTPIEDVMTKN------PITV 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 332000015 289 YLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQAL 331
Cdd:COG4109   90 TPDTSLASAAHKMIWEGIELLPVVDDDGRLLGIISRQDVLKAL 132

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015  45 SSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKqsfvvlralscPLGMLTITDFINILHRYYksalvqiyELEEHKIe 124
Cdd:COG2524   93 TKDVITVSPDTTLEEALELMLEKGISGLPVVDDGK-----------LVGIITERDLLKALAEGR--------DLLDAPV- 152

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 332000015 125 twREVYLqdsfKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPEsgNTLY-ILTHKRILKFL 185
Cdd:COG2524  153 --SDIMT----RDVVTVSEDDSLEEALRLMLEHGIGRLPVVDDD--GKLVgIITRTDILRAL 206

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 332000015 136 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDpesGNTLY-ILTHKRILKFL-----KLFITEFPKPEFMSKSLEELQigt 209
Cdd:cd17778    8 TPVVTIYPDDTLKEAMELMVTRGFRRLPVVS---GGKLVgIVTAMDIVKYFgsheaKKRLTTGDIDEAYSTPVEEIM--- 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 332000015 210 YANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVI 256
Cdd:cd17778   82 SKEVVTIEPDADIAEAARLMIKKNVGSLLVVDDEGELKGIITERDVL 128

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 332000015  285 VLKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALV 332
Cdd:pfam00571   9 VVTVSPDTTLEEALELMREHGISRLPVVDEDGKLVGIVTLKDLLRALL 56

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 332000015 136 KPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILKFLKLFITEFPKPEFMSKsleelqigtyaNIAM 215
Cdd:cd17772    2 SPVISVEPDTTIAEAAELMTRYNINALPVVDGGTGRLVGIITRQVAEKAIYHGLGDLPVSEYMTT-----------EFAT 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 332000015 216 VRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVINL 258
Cdd:cd17772   71 VTPDAPLSEIQEIIVEQRQRLVPVVED-GRLVGVITRTDLLNL 112

Predicted transcriptional regulator containing CBS domains [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015 139 VCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILKFLKLFITEfpkpEFMSKsleelqigtyaNIAMVRT 218
Cdd:COG4109   28 ATLSEDDTVEDALELLEKTGHSRFPVVD-ENGRLVGIVTSKDILGKDDDTPIE----DVMTK-----------NPITVTP 91

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 332000015 219 TTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVIN 257
Cdd:COG4109   92 DTSLASAAHKMIWEGIELLPVVDDDGRLLGIISRQDVLK 130

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 332000015 139 VCISPNASLFDAVSSLIRNKIHRLPVIdpESGNTLYILTHKRILKFL---KLF----------ITEFPKPEFMSKsleel 205
Cdd:cd04631   11 ITATPGTPIEDVAKIMVRNGFRRLPVV--SDGKLVGIVTSTDIMRYLgsgEAFeklktgniheVLNVPISSIMKR----- 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 332000015 206 qigtyaNIAMVRTTTPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVIN 257
Cdd:cd04631   84 ------DIITTTPDTDLGEAAELMLEKNIGALPVVDD-GKLVGIITERDILR 128

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332000015  81 SFVVLRALSCPLGMLTITDFIN-ILHRYYKSALVQIYEleehkIETwrevylqdsfKPLVCISPNASLFDAVSSLIRNKI 159
Cdd:COG2905   32 SLVVVDDDGRLVGIITDRDLRRrVLAEGLDPLDTPVSE-----VMT----------RPPITVSPDDSLAEALELMEEHRI 96

                         90       100
                 ....*....|....*....|....*..
gi 332000015 160 HRLPVIDpesGNTLY-ILTHKRILKFL 185
Cdd:COG2905   97 RHLPVVD---DGKLVgIVSITDLLRAL 120

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 332000015 138 LVCISPNASLFDAVSSLIRNKIHRLPVIDpESGNTLYILTHKRILKFLklfitefpkpefMSKSLEELQIGTYANIaM-- 215
Cdd:cd04629    5 PVTLTPDTSILEAVELLLEHKISGAPVVD-EQGRLVGFLSEQDCLKAL------------LEASYHCEPGGTVADY-Mst 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 332000015 216 -VRTTTP----VYVAlGIFVQHRVSALPVVDEkGRVVDIYSKFDVIN 257
Cdd:cd04629   71 eVLTVSPdtsiVDLA-QLFLKNKPRRYPVVED-GKLVGQISRRDVLR 115

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 332000015 141 ISPNASLFDAVSSLIRNKIHR-LPVIDpESGNTLYILTHKRILKFLKLFITEFPKPEFMSKSLEELQIGTYANIAM---- 215
Cdd:cd17785   15 VHENTSIRDVIDKMIEDPKTRsVYVVD-DDEKLLGIITLMELLKYIGYRFGVTIYKGVSFGLLLRISLKEKAKDIMlspi 93

                         90       100       110
                 ....*....|....*....|....*....|...
gi 332000015 216 -VRTTTPVYVALGIFVQHRVSALPVVDEKGRVV 247
Cdd:cd17785   94 yVKKEDTLEEALELMVKNRLQELPVVDENGKVI 126

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 332000015 136 KPLVCISPNASLFDAVSSLIRNKIHRLPVID 166
Cdd:cd04587   68 PPPVTIDADALVFEALLLMLERNIHHLPVVD 98

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in diguanylate cyclase/phosphodiesterase proteins with PAS sensors, repeat 1; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in diguanylate cyclase/phosphodiesterase proteins with PAS sensors. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in signal transduction. The GGDEF domain has been suggested to be homologous to the adenylyl cyclase catalytic domain and is thought to be involved in regulating cell surface adhesiveness 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 332000015 220 TPVYVALGIFVQHRVSALPVVDEkGRVVDIYSKFDVinLAaektynnLDVSVTKALQH--RSHYFEGVLKCYLHETLETI 297
Cdd:cd09833   14 TPLADAAARMAERRCSSILIVEN-GEIVGIWTERDA--LK-------LDFSDPDAFRRpiSEVMSSPVLTIPQDTTLGEA 83

                         90       100       110
                 ....*....|....*....|....*....|
gi 332000015 298 INRLVEAEVHRLVVVDENDVVKGIVSLSDI 327
Cdd:cd09833   84 AVRFRQEGVRHLLVVDDDGRPVGIVSQTDV 113

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 332000015 139 VCISPNASLFDAVSSLIRNKIHRLPVIDpeSGNTLY-ILTHKRILkflklFITEFPKP--EFMSK-----------SLEE 204
Cdd:cd04601    5 VTLSPDATVADVLELKAEYGISGVPVTE--DGGKLVgIVTSRDIR-----FETDLSTPvsEVMTPderlvtapegiTLEE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 332000015 205 lqigtyaniamvrtttpvyvALGIFVQHRVSALPVVDEKGRVVDI 249
Cdd:cd04601   78 --------------------AKEILHKHKIEKLPIVDDNGELVGL 102