Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the DRTGG domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with a DRTGG domain upstream. The function of the DRTGG domain, named after its conserved residues, is unknown. 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 327439232 198 MEDTAVLKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMI 277
Cdd:cd04596    1 LEETGYLRETDTVRDYKQLSEETGHSRFPVVDEENRVVGIVTAKDVIGKEDDTPIEKVMTKNPITVKPKTSVASAAHMMI 80

                         90       100
                 ....*....|....*....|....*...
gi 327439232 278 WEGIDLLPVIDEEGLLKGVISRQDVLKA 305
Cdd:cd04596   81 WEGIELLPVVDENRKLLGVISRQDVLKA 108

The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl carrier protein (ACP)-dehydratase) structure and subsequently in 4HBT (4-hydroxybenzoyl-CoA thioesterase) from Pseudomonas. A number of other seemingly unrelated proteins also share the hotdog fold. These proteins have related, but distinct, catalytic activities that include metabolic roles such as thioester hydrolysis in fatty acid metabolism, and degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. This superfamily also includes the PaaI-like protein FapR, a non-catalytic bacterial homolog involved in transcriptional regulation of fatty acid biosynthesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 335 IEVEFTVTPQMTNQFGAISYGAFTILLSEVGAFALKR--RKRGEAVVENMNIYFIKPVQMESVLTVRPRILDMSRKFVKM 412
Cdd:cd03440    1 FVLRLTVTPEDIDGGGIVHGGLLLALADEAAGAAAARlgGRGLGAVTLSLDVRFLRPVRPGDTLTVEAEVVRVGRSSVTV 80

                         90
                 ....*....|....*....
gi 327439232 413 DFEVYSATN-LVGKAMMTF 430
Cdd:cd03440   81 EVEVRNEDGkLVATATATF 99

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the DRTGG domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with a DRTGG domain upstream. The function of the DRTGG domain, named after its conserved residues, is unknown. 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 327439232 198 MEDTAVLKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMI 277
Cdd:cd04596    1 LEETGYLRETDTVRDYKQLSEETGHSRFPVVDEENRVVGIVTAKDVIGKEDDTPIEKVMTKNPITVKPKTSVASAAHMMI 80

                         90       100
                 ....*....|....*....|....*...
gi 327439232 278 WEGIDLLPVIDEEGLLKGVISRQDVLKA 305
Cdd:cd04596   81 WEGIELLPVVDENRKLLGVISRQDVLKA 108

DRTGG domain; This presumed domain is about 120 amino acids in length. It is found associated with CBS domains pfam00571, as well as the CbiA domain pfam01656. The function of this domain is unknown. It is named the DRTGG domain after some of the most conserved residues. This domain may be very distantly related to a pair of CBS domains. There are no significant sequence similarities, but its length and association with CBS domains supports this idea (Bateman A, pers. obs.).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232   76 EIVNIIDGQVLGGKSGLHKTLTKFVIGAMKLDDMMRYTDAGSLLIV-GNRTQAHEYALKTG-AAVLITGGFDTTESTKDL 153
Cdd:pfam07085   1 DIARILGAEVLNGGDGLLRRVGKVVVGAMSVENMLKYLRPGDLVITpGDREDIQLAALEAGiAGLILTGGFEPSPEVLKL 80

                          90       100
                  ....*....|....*....|....*
gi 327439232  154 ADELDLPIISTTYDTFTVATMINRA 178
Cdd:pfam07085  81 AEELGLPVLSTPYDTFTTASRINRA 105

BioD-like N-terminal domain of phosphotransacetylase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232  75 AEIVNIIDGQVLGGKSGLHKTLTKFVIGAMKLDDMMRYTDAGSLLIV-GNRT-------QAHEYALKTGAAVLITGGFDT 146
Cdd:COG0857  217 RDLAEALGAEVLNGGELLDRRVESVVVGAMSVPNALERLREGALVITpGDRSdillaalLAALSGTPSIAGLILTGGLPP 296

                         90       100       110
                 ....*....|....*....|....*....|....
gi 327439232 147 TESTKDLADELD--LPIISTTYDTFTVATMINRA 178
Cdd:COG0857  297 DPAVLRLAEGLGqtLPILSVELDTYTTAERLERV 330

GuaB1 family IMP dehydrogenase-related protein;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 200 DTAV-LKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMIW 278
Cdd:PRK07807  97 DTPVtLSPDDTVGDALALLPKRAHGAVVVVDEEGRPVGVVTEADCAGVDRFTQVRDVMSTDLVTLPAGTDPREAFDLLEA 176

                         90       100
                 ....*....|....*....|....*..
gi 327439232 279 EGIDLLPVIDEEGLLKGVISRQDVLKA 305
Cdd:PRK07807 177 ARVKLAPVVDADGRLVGVLTRTGALRA 203

Acyl-CoA thioesterase PaaI, contains HGG motif [Secondary metabolites biosynthesis, transport and catabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 326 EMRVMGEEDIEVEFTVTPQMTNQFGAISYGAFTILLSEVGAFALKRRKRGE--AVVENMNIYFIKPVQMESVLTVRPRIL 403
Cdd:COG2050   24 ELVEVEPGRAVLRLPVRPEHLNPPGTVHGGALAALADSAAGLAANSALPPGrrAVTIELNINFLRPARLGDRLTAEARVV 103

                         90       100       110
                 ....*....|....*....|....*....|...
gi 327439232 404 DMSRKFVKMDFEVYSAT-NLVGKAMMTFQLLER 435
Cdd:COG2050  104 RRGRRLAVVEVEVTDEDgKLVATATGTFAVLPK 136

Winged helix-turn-helix (WHTH) DNA-binding domain of the GntR family of transcriptional regulators; This CD represents the winged HTH DNA-binding domain of the GntR (named after the gluconate operon repressor in Bacillus subtilis) family of bacterial transcriptional regulators and their putative homologs found in eukaryota and archaea. The GntR family has over 6000 members distributed among almost all bacterial species, which is comprised of FadR, HutC, MocR, YtrA, AraR, PlmA, and other subfamilies for the regulation of the most varied biological process. The monomeric proteins of the GntR family are characterized by two function domains: a small highly conserved winged helix-turn-helix prokaryotic DNA binding domain in the N-terminus, and a very diverse regulatory ligand-binding domain in the C-terminus for effector-binding/oligomerization, which provides the basis for the subfamily classifications. Binding of the effector to GntR-like transcriptional regulators is presumed to result in a conformational change that regulates the DNA-binding affinity of the repressor. The GntR-like proteins bind as dimers, where each monomer recognizes a half-site of 2-fold symmetric DNA sequences.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 327439232   6 EKILQYIES--LPVGDKI-SVRQIAKEMQVSEGTAYRAIKEAENRRLVSSIERVGTI 59
Cdd:cd07377    8 DQLREAILSgeLKPGDRLpSERELAEELGVSRTTVREALRELEAEGLVERRPGRGTF 64

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 327439232   200 DTAVLKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEE 248
Cdd:smart00116   1 DVVTVSPDTTLEEALELLRENGIRRLPVVDEEGRLVGIVTRRDIIKALA 49

CRISPR locus-related DNA-binding protein; Most but not all examples of this family are associated with CRISPR loci, a combination of DNA repeats and characteristic proteins encoded near the repeat cluster. The C-terminal region of this protein is homologous to DNA-binding helix-turn-helix domains with predicted transcriptional regulatory activity. [Regulatory functions, DNA interactions, , ]

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 327439232    7 KILQYIESLPvgdKISVRQIAKEMQVSEGTAYRAIKEAENRRLVSSIERVGTIRIEKK 64
Cdd:TIGR01884 147 KILEVLKATG---EKSVKNIAKKLGKSLSTISRHLAELEKKGLVEQKGRKGKRYSLTK 201

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the DRTGG domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with a DRTGG domain upstream. The function of the DRTGG domain, named after its conserved residues, is unknown. 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 327439232 198 MEDTAVLKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMI 277
Cdd:cd04596    1 LEETGYLRETDTVRDYKQLSEETGHSRFPVVDEENRVVGIVTAKDVIGKEDDTPIEKVMTKNPITVKPKTSVASAAHMMI 80

                         90       100
                 ....*....|....*....|....*...
gi 327439232 278 WEGIDLLPVIDEEGLLKGVISRQDVLKA 305
Cdd:cd04596   81 WEGIELLPVVDENRKLLGVISRQDVLKA 108

DRTGG domain; This presumed domain is about 120 amino acids in length. It is found associated with CBS domains pfam00571, as well as the CbiA domain pfam01656. The function of this domain is unknown. It is named the DRTGG domain after some of the most conserved residues. This domain may be very distantly related to a pair of CBS domains. There are no significant sequence similarities, but its length and association with CBS domains supports this idea (Bateman A, pers. obs.).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232   76 EIVNIIDGQVLGGKSGLHKTLTKFVIGAMKLDDMMRYTDAGSLLIV-GNRTQAHEYALKTG-AAVLITGGFDTTESTKDL 153
Cdd:pfam07085   1 DIARILGAEVLNGGDGLLRRVGKVVVGAMSVENMLKYLRPGDLVITpGDREDIQLAALEAGiAGLILTGGFEPSPEVLKL 80

                          90       100
                  ....*....|....*....|....*
gi 327439232  154 ADELDLPIISTTYDTFTVATMINRA 178
Cdd:pfam07085  81 AEELGLPVLSTPYDTFTTASRINRA 105

CBS domain [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 207 NDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEESE-------PIDKVMTKNPIAASMKTSVASAGHRMIWE 279
Cdd:COG0517   17 DATVREALELMSEKRIGGLPVVDEDGKLVGIVTDRDLRRALAAEgkdlldtPVSEVMTRPPVTVSPDTSLEEAAELMEEH 96

                         90       100
                 ....*....|....*....|....*...
gi 327439232 280 GIDLLPVIDEEGLLKGVISRQDVLKAIQ 307
Cdd:COG0517   97 KIRRLPVVDDDGRLVGIITIKDLLKALL 124

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 208 DTIADFHRQNRRTTHGAFPVVTGqNRLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVI 287
Cdd:cd04610   12 DTVKDVIKLIKETGHDGFPVVDD-GKVVGYVTAKDLLGKDDDEKVSEIMSRDTVVADPDMDITDAARVIFRSGISKLPVV 90

                         90
                 ....*....|....*..
gi 327439232 288 DEEGLLKGVISRQDVLK 304
Cdd:cd04610   91 DDEGNLVGIITNMDVIR 107

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 207 NDTIADFHRQNRRTTHGAFPVVTGqNRLVGMITSKDVI------GKEESEPIDKVMTKNPIAASMKTSVASAGHRMIWEG 280
Cdd:COG2524  102 DTTLEEALELMLEKGISGLPVVDD-GKLVGIITERDLLkalaegRDLLDAPVSDIMTRDVVTVSEDDSLEEALRLMLEHG 180

                         90       100
                 ....*....|....*....|....*.
gi 327439232 281 IDLLPVIDEEGLLKGVISRQDVLKAI 306
Cdd:COG2524  181 IGRLPVVDDDGKLVGIITRTDILRAL 206

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 327439232 199 EDTAVLKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDV-IGKEESEPIDKVMTKN--PIAASMKTSVASAgHR 275
Cdd:cd04601    2 TDPVTLSPDATVADVLELKAEYGISGVPVTEDGGKLVGIVTSRDIrFETDLSTPVSEVMTPDerLVTAPEGITLEEA-KE 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 327439232 276 MIWEG-IDLLPVIDEEGLLKGVISRQDVLK 304
Cdd:cd04601   81 ILHKHkIEKLPIVDDNGELVGLITRKDIEK 110

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 327439232 207 NDTIADFHRQNRRTTHGAFPVVTGqNRLVGMITSKDV----IGKEESEPIDKVMTKNPIAASMKTSVASAGHRMIWEGID 282
Cdd:cd04595   10 DTTIEEARKIMLRYGHTGLPVVED-GKLVGIISRRDVdkakHHGLGHAPVKGYMSTNVITIDPDTSLEEAQELMVEHDIG 88

                         90       100
                 ....*....|....*....|...
gi 327439232 283 LLPVIdEEGLLKGVISRQDVLKA 305
Cdd:cd04595   89 RLPVV-EEGKLVGIVTRSDVLRY 110

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 223 GAFPVVTGQNRLVGMITSKDVI-----GKEESEPIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVIDEEGLLKGVI 297
Cdd:cd09836   27 GSVVVVDDDGKPVGIVTERDIVravaeGIDLDTPVEEIMTKNLVTVSPDESIYEAAELMREHNIRHLPVVDGGGKLVGVI 106

                 ....*....
gi 327439232 298 SRQDVLKAI 306
Cdd:cd09836  107 SIRDLAREL 115

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in the metalloprotease peptidase M50; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in peptidase M50. Members of the M50 metallopeptidase family include mammalian sterol-regulatory element binding protein (SREBP) site 2 proteases and various hypothetical bacterial homologues. 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 327439232 219 RTTHGAFPVVTGqNRLVGMITSKDVIGKEESE----PIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVIDeEGLLK 294
Cdd:cd04801   25 EEKHLGYPVVEN-GRLVGIVTLEDIRKVPEVEreatRVRDVMTKDVITVSPDADAMEALKLMSQNNIGRLPVVE-DGELV 102

                         90
                 ....*....|.
gi 327439232 295 GVISRQDVLKA 305
Cdd:cd04801  103 GIISRTDLMRA 113

phosphate acetyltransferase; Reviewed

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232  73 TFAEIVNIIDGQVLGGKSGLHKTLTKFVIGAMKLDDMMRYTDAGSLLIV-GNRT-------QAHEYALKTgAAVLITGGF 144
Cdd:PRK05632 203 RVIDIAKHLGATVLNEGDILTRRVKSVTVCARSIPNMLEHLKPGSLVVTpGDRSdvilaalLAAMNGPPI-AGLLLTGGY 281

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 327439232 145 DTTESTKDL---ADELDLPIISTTYDTFTVATMINR 177
Cdd:PRK05632 282 EPDPRIAKLcegAFETGLPVLSVDTNTYQTALRLQS 317

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 327439232 226 PVVTGqNRLVGMITSKDVI---GKEE--------------SEPIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVID 288
Cdd:cd17778   35 PVVSG-GKLVGIVTAMDIVkyfGSHEakkrlttgdideaySTPVEEIMSKEVVTIEPDADIAEAARLMIKKNVGSLLVVD 113

                         90
                 ....*....|....*...
gi 327439232 289 EEGLLKGVISRQDVLKAI 306
Cdd:cd17778  114 DEGELKGIITERDVLIAL 131

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains present in archaea, repeat 2; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains found in Inosine monophosphate (IMP) dehydrogenases and related proteins including IMP dehydrogenase IX from Methanothermobacter. IMP dehydrogenase is an essential enzyme in the de novo biosynthesis of Guanosine monophosphate (GMP), catalyzing the NAD-dependent oxidation of IMP to xanthosine monophosphate (XMP). 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 327439232 224 AFPVVTGQNRLVGMITSKDVIGK---EESE-------------------------------------PIDKVMTKNPIAA 263
Cdd:cd04614   29 AAPVLDSEGKLVGIVTERDLIDVsriVESEeesgmsiaddedewswegirdvmslyyptsnvelpdkPVKDVMTKDVVTA 108

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 327439232 264 SMKTSVASAGHRMIWEGIDLLPVIDEEGLLKGVISRQDVLKA 305
Cdd:cd04614  109 FPSSTVSEAAKKMIRNDIEQLPVVSGEGDLAGMLRDVDLLKA 150

GuaB1 family IMP dehydrogenase-related protein;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 200 DTAV-LKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMIW 278
Cdd:PRK07807  97 DTPVtLSPDDTVGDALALLPKRAHGAVVVVDEEGRPVGVVTEADCAGVDRFTQVRDVMSTDLVTLPAGTDPREAFDLLEA 176

                         90       100
                 ....*....|....*....|....*..
gi 327439232 279 EGIDLLPVIDEEGLLKGVISRQDVLKA 305
Cdd:PRK07807 177 ARVKLAPVVDADGRLVGVLTRTGALRA 203

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 218 RRTTHGAFPVVTGQN-RLVGMITSKDVIGKEESEPIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVIDEEGLLkGV 296
Cdd:cd04638   22 KKKAISGVPVVKKETgKLVGIVTRKDLLRNPDEEQIALLMSRDPITISPDDTLSEAAELMLEHNIRRVPVVDDDKLV-GI 100

                 ....*....
gi 327439232 297 ISRQDVLKA 305
Cdd:cd04638  101 VTVADLVRA 109

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 197 PMEDTAVLKNNDTIADFHRQNRRTTHGAFPVVTGQNRLVGMITSKDVIG--KEES----EPIDKVMTKNPIAASMKTSVA 270
Cdd:cd04613    1 MPRKVTVLPEGMTFRQFTEFIAGTRQHYFPVVDEQGRLTGILSIQDVRGvlFEEElwdlVVVKDLATTDVITVTPDDDLY 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 327439232 271 SAGHRMIWEGIDLLPVIDEE--GLLKGVISRQDVLKA 305
Cdd:cd04613   81 TALLKFTSTNLDQLPVVDDDdpGKVLGMLSRRDVIAA 117

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 327439232 223 GAFPVVTGQNRLVGMITSKDVI------GKE-ESEPIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVIDEEGLLkG 295
Cdd:cd04623   26 GALVVVDDGGRLVGILSERDYVrklalrGASsLDTPVSEIMTRDVVTCTPDDTVEECMALMTERRIRHLPVVEDGKLV-G 104

                 ....*....
gi 327439232 296 VISRQDVLK 304
Cdd:cd04623  105 IVSIGDVVK 113

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains similar to MUG70 repeat1; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domain, present in MUG70. The MUG70 protein, encoded by the Meiotically Up-regulated Gene 70, plays a role in meiosis and contains, beside the two CBS pairs, a PB1 domain. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 327439232 227 VVTGQNRLVGMITSKD----VIGKE---ESEPIDKVMTKNPIAASMKTSVASAGHRMIWEGIDLLPVIDEEGLLKGVIS 298
Cdd:cd17781   30 VVDDDGGLSGIFTDKDlarrVVASGldpRSTLVSSVMTPNPLCVTMDTSATDALDLMVEGKFRHLPVVDDDGDVVGVLD 108

The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl carrier protein (ACP)-dehydratase) structure and subsequently in 4HBT (4-hydroxybenzoyl-CoA thioesterase) from Pseudomonas. A number of other seemingly unrelated proteins also share the hotdog fold. These proteins have related, but distinct, catalytic activities that include metabolic roles such as thioester hydrolysis in fatty acid metabolism, and degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. This superfamily also includes the PaaI-like protein FapR, a non-catalytic bacterial homolog involved in transcriptional regulation of fatty acid biosynthesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 335 IEVEFTVTPQMTNQFGAISYGAFTILLSEVGAFALKR--RKRGEAVVENMNIYFIKPVQMESVLTVRPRILDMSRKFVKM 412
Cdd:cd03440    1 FVLRLTVTPEDIDGGGIVHGGLLLALADEAAGAAAARlgGRGLGAVTLSLDVRFLRPVRPGDTLTVEAEVVRVGRSSVTV 80

                         90
                 ....*....|....*....
gi 327439232 413 DFEVYSATN-LVGKAMMTF 430
Cdd:cd03440   81 EVEVRNEDGkLVATATATF 99

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains similar to MUG70 repeat2; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domain, present in MUG70. The MUG70 protein, encoded by the Meiotically Up-regulated Gene 70, plays a role in meiosis and contains, beside the two CBS pairs, a PB1 domain. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. 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 327439232 218 RRTThgAFPVVTGQNRLVGMITSKD----VIGKE---ESEPIDKVMTKNPIAASMKTSVASAGHRMIwEGIDL-LPVIDE 289
Cdd:cd17782   23 NRTT--AVLVMDNSGKVIGIFTSKDvvlrVLAAGldpATTSVVRVMTPNPETAPPSTTILDALHKMH-EGKFLnLPVVDD 99

                         90
                 ....*....|....*
gi 327439232 290 EGLLKGVIsrqDVLK 304
Cdd:cd17782  100 EGEIVGLV---DVLQ 111

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 327439232 207 NDTIADFHRQNRRTTHGAFPVVtGQNRLVGMITSKD-VI-----GKE-ESEPIDKVMTKNPIAASMKTSVASAGHRMIWE 279
Cdd:cd04622   11 DTTLREAARLMRDLDIGALPVC-EGDRLVGMVTDRDiVVravaeGKDpNTTTVREVMTGDVVTCSPDDDVEEAARLMAEH 89

                         90
                 ....*....|....*....
gi 327439232 280 GIDLLPVIDEEGLLKGVIS 298
Cdd:cd04622   90 QVRRLPVVDDDGRLVGIVS 108

inosine-5'-monophosphate dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327439232 199 EDTAVLKNNDTIADFHRQNRRTTHGAFPV-VTGQ--NRLVGMITSKDVI-GKEESEPIDKVMT--KNPIAASMKTSVASA 272
Cdd:PTZ00314 104 MDPYVLSPNHTVADVLEIKEKKGFSSILItVDGKvgGKLLGIVTSRDIDfVKDKSTPVSEVMTprEKLVVGNTPISLEEA 183