Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains the majority of which are associated with the CorC_HlyC domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains the majority of which are associated with the CorC_HlyC domain. CorC_HlyC is a transporter associated domain. This small domain is found in Na+/H+ antiporters, in proteins involved in magnesium and cobalt efflux, and in association with some proteins of unknown function. The function of the CorC_HlyC domain is uncertain but it might be involved in modulating transport of ion substrates. These CBS domains are found in highly conserved proteins that either have unknown function or are puported to be hemolysins, exotoxins involved in lysis of red blood cells in vitro. 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 1064788230 428 VVEEVLTPLGDCFMLRSDAvLDFATVSEILRSGYTRIPVYEGDqRHNIVDILFVKDLAFVDPDDCTPllTVTRFYNRPLH 507
Cdd:cd04590     1 TVREVMTPRTDVVALDADA-TLEELLELILESGYSRFPVYEGD-LDNIIGVLHVKDLLAALLEGREK--LDLRALLRPPL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1064788230 508 CVFNDTRLDTVLEEFKKGKSHLAIVQrvnnegegDPFYEVMGIVTL 553
Cdd:cd04590    77 FVPETTPLDDLLEEFRKERSHMAIVV--------DEYGGTAGIVTL 114

Kruppel-like factor (KLF) 9, KLF13, KLF14, KLF16, and similar proteins; Kruppel/Krueppel-like transcription factors (KLFs) belong to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. KLF9, KLF10, KLF11, KLF13, KLF14, and KLF16 share a conserved alpha-helical motif AA/VXXL that mediates their binding to Sin3A and their activities as transcriptional repressors. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the related N-terminal domains of KLF9, KLF13, KLF14, KLF16, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230  46 RPEDT--AGGRVSLEGGtlrAAEGTSFLLRvyfqPGPPATAAPVPSPTLNSGENGTGDWAPRL----VFIEEPPGGG--- 116
Cdd:cd21576    27 RAPDPegAGGAAGSEVG---AAPPESALPG----PGPPGPAWVPPLLQVPAPSPGAGGAAPHLlaasVLADLRGGAGegs 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1064788230 117 ----GVAPSAV-----PTRPPGPQRCREQSDWASDVEVLGP 148
Cdd:cd21576   100 redsGEAPRASsgssdPARGSSPTLGSEPAPASGEDAVSGP 140

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains the majority of which are associated with the CorC_HlyC domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains the majority of which are associated with the CorC_HlyC domain. CorC_HlyC is a transporter associated domain. This small domain is found in Na+/H+ antiporters, in proteins involved in magnesium and cobalt efflux, and in association with some proteins of unknown function. The function of the CorC_HlyC domain is uncertain but it might be involved in modulating transport of ion substrates. These CBS domains are found in highly conserved proteins that either have unknown function or are puported to be hemolysins, exotoxins involved in lysis of red blood cells in vitro. 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 1064788230 428 VVEEVLTPLGDCFMLRSDAvLDFATVSEILRSGYTRIPVYEGDqRHNIVDILFVKDLAFVDPDDCTPllTVTRFYNRPLH 507
Cdd:cd04590     1 TVREVMTPRTDVVALDADA-TLEELLELILESGYSRFPVYEGD-LDNIIGVLHVKDLLAALLEGREK--LDLRALLRPPL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1064788230 508 CVFNDTRLDTVLEEFKKGKSHLAIVQrvnnegegDPFYEVMGIVTL 553
Cdd:cd04590    77 FVPETTPLDDLLEEFRKERSHMAIVV--------DEYGGTAGIVTL 114

Cyclin M transmembrane N-terminal domain; This transmembrane domain is found in metal transporter proteins such as cyclin M 1/2 (CNNM). CNNMs are integral membrane proteins that are conserved from bacteria to humans. CNNM family members influence metal ion homeostasis through mechanisms that may not involve direct membrane transport of the ions. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a transmembrane domain, a 'Bateman module', which consists of two cystathionine- beta-synthase (CBS) domains pfam00571, and a C-terminal cNMP (cyclic nucleotide monophosphate) binding domain. This entry describes the CNNM transmembrane domain which contains four hydrophobic regions and forms a dimer through hydrophobic contacts between TM2 and TM3, in which each chain is composed of three transmembrane helices (TM1-3), a pair of short helices exposed on the intracellular side, and a juxtamembrane (JM) helix that forms a belt-like structure. The homodimer adopts an inward-facing conformation with a negatively charged cavity containing a conserved pi-helical turn in TM3 that coordinates a Mg2 ion.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 250 DPVELRVLRNSGSAAeqeqARRVQAVRGRGTHLLCTLLLGQAGANAaLAGWLYTSLPPGFGGTGEDYSeegihfPWLPAL 329
Cdd:pfam01595  24 RRSRLEELAEKGNKG----AKRLLKLLANPDRLLSTLLIGNTLANI-LLGALATALFAELLAPLGALG------VAIATV 92

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1064788230 330 VCTGAVFLGAEICPYSVCSRHGLAIASHSVCLTRLLMAAAFPVCYPLGRLLDWALR------QEISTFYTREKL 397
Cdd:pfam01595  93 LVTLLILVFGEILPKTLALRYAERIALRVAPPLLVLSKLLYPLVWLLNKLANLILRlfgvkgGESEPAVTEEEL 166

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 451 ATVSE----ILRSGYTRIPVYEGDQrhnIVDILFVKDLAFVDPDDCTPL-LTVTRFYNRPLHCVFNDTRLDTVLEEFKKG 525
Cdd:COG2524   103 TTLEEalelMLEKGISGLPVVDDGK---LVGIITERDLLKALAEGRDLLdAPVSDIMTRDVVTVSEDDSLEEALRLMLEH 179

                          90       100
                  ....*....|....*....|....*..
gi 1064788230 526 KSHLAIVqrVNNEGEgdpfyeVMGIVT 552
Cdd:COG2524   180 GIGRLPV--VDDDGK------LVGIIT 198

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains the majority of which are associated with the CorC_HlyC domain; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains the majority of which are associated with the CorC_HlyC domain. CorC_HlyC is a transporter associated domain. This small domain is found in Na+/H+ antiporters, in proteins involved in magnesium and cobalt efflux, and in association with some proteins of unknown function. The function of the CorC_HlyC domain is uncertain but it might be involved in modulating transport of ion substrates. These CBS domains are found in highly conserved proteins that either have unknown function or are puported to be hemolysins, exotoxins involved in lysis of red blood cells in vitro. 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 1064788230 428 VVEEVLTPLGDCFMLRSDAvLDFATVSEILRSGYTRIPVYEGDqRHNIVDILFVKDLAFVDPDDCTPllTVTRFYNRPLH 507
Cdd:cd04590     1 TVREVMTPRTDVVALDADA-TLEELLELILESGYSRFPVYEGD-LDNIIGVLHVKDLLAALLEGREK--LDLRALLRPPL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1064788230 508 CVFNDTRLDTVLEEFKKGKSHLAIVQrvnnegegDPFYEVMGIVTL 553
Cdd:cd04590    77 FVPETTPLDDLLEEFRKERSHMAIVV--------DEYGGTAGIVTL 114

Mg2+ and Co2+ transporter CorB, contains DUF21, CBS pair, and CorC-HlyC domains [Inorganic ion transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 254 LRVLRNSGSAAeqeqARRVQAVRGRGTHLLCTLLLGQAGAN---AALAGWLYTSLppgFGGTGEDYSeegihfpwlpALV 330
Cdd:COG4536    38 LRHLAKKGHKG----AKRVLKLLERPDRLIGTILLGNNLVNilaSSLATVIAIRL---FGDAGVAIA----------TLV 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 331 CTGAVFLGAEICPYSVCSRHGLAIASHSVCLTRLLMAaafpVCYPLGRLLDWA----LR-------QEISTFYTREKLLE 399
Cdd:COG4536   101 LTLLILIFAEVTPKTLAALYPEKIALPVSPPLRPLLK----LLYPLVWLVNLIvrglLRlfgvkpdADASDLLSEEELRT 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 400 TLRAADPYSDLVKEELNIIQGALELRTKVVEEVLTPLGDCFMLrsDAVLDFAT-VSEILRSGYTRIPVYEGDQrHNIVDI 478
Cdd:COG4536   177 VVDLGEAGGVIPKEHRDMLLNILDLEDVTVEDIMVPRNEIEGI--DLDDPWEEiLKQLLTSPHTRLPVYRGDI-DNIVGV 253

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1064788230 479 LFVKDLAFVDPDDCTPLLTVTRfYNRPLHCVFNDTRLDTVLEEFKKGKSHLAIVqrVNNEGEgdpfyeVMGIVTLED 555
Cdd:COG4536   254 LHVRDLLRALRKGDLSKEDLRK-IAREPYFIPETTPLSTQLQNFQKRKRRFALV--VDEYGD------VQGLVTLED 321

magnesium/cobalt transporter CorC;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 394 REKLLETLRAADPySDLVKEEL-NIIQGALELRTKVVEEVLTPLGDCFMLRSDAVLDfATVSEILRSGYTRIPVYEGDQR 472
Cdd:PRK15094   34 RDELLALIRDSEQ-NDLIDEDTrDMLEGVMDIADQRVRDIMIPRSQMITLKRNQTLD-ECLDVIIESAHSRFPVISEDKD 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230 473 HnIVDILFVKDLAFVDPDDCTPLlTVTRFYnRPLHCVFNDTRLDTVLEEFKKGKSHLAIVQrvnnegegDPFYEVMGIVT 552
Cdd:PRK15094  112 H-IEGILMAKDLLPFMRSDAEAF-SMDKVL-RQAVVVPESKRVDRMLKEFRSQRYHMAIVI--------DEFGGVSGLVT 180

                  .
gi 1064788230 553 L 553
Cdd:PRK15094  181 I 181

N-terminal domain of Kruppel-like factor 14; Kruppel-like factor 14 (KLF14; also known as Krueppel-like factor 14 or basic transcription element-binding protein 5/BTEB5) is a protein that in humans is encoded by the KLF14 gene. KLF14 regulates the transcription of various genes, including TGFbetaRII (the type II receptor for TGFbeta). KLF14 is expressed in many tissues, lacks introns, and is subject to parent-specific expression. It also appears to be a master regulator of gene expression in adipose tissue. KLF14 is associated with coronary artery disease, hypercholesterolemia, and type 2 diabetes. KLF9, KLF10, KLF11, KLF13, KLF14, and KLF16 share a conserved alpha-helical motif AA/VXXL that mediates their binding to Sin3A and their activities as transcriptional repressors. KLF14 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF14.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1064788230  46 RPEDT--AGGRVSLEGGtlrAAEGTSFLLRvyfqPGPPATAAPVPSPTLNSGENGTGDWAPRL----VFIEEPPGGG--- 116
Cdd:cd21576    27 RAPDPegAGGAAGSEVG---AAPPESALPG----PGPPGPAWVPPLLQVPAPSPGAGGAAPHLlaasVLADLRGGAGegs 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1064788230 117 ----GVAPSAV-----PTRPPGPQRCREQSDWASDVEVLGP 148
Cdd:cd21576   100 redsGEAPRASsgssdPARGSSPTLGSEPAPASGEDAVSGP 140