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Conserved domains on  [gi|380254450|ref|NP_001159417|]
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chloride channel protein ClC-Kb isoform 2 [Homo sapiens]

Protein Classification

chloride channel protein( domain architecture ID 10255822)

ClC family voltage-gated chloride channel protein containing a C-terminal CBS pair domain, catalyzes the selective flow of Cl(-) ions across the cellular membrane

CATH:  1.10.3080.10
Gene Ontology:  GO:0006821|GO:0005247|GO:0055085
PubMed:  11182894|9207144|9046241
SCOP:  4003598

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Voltage_gated_ClC super family cl02915
CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of ...
 50-365 1.51e-119

CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. This domain is found in the halogen ions (Cl-, Br- and I-) transport proteins of the ClC family. The ClC channels are found in all three kingdoms of life and perform a variety of functions including cellular excitability regulation, cell volume regulation, membrane potential stabilization, acidification of intracellular organelles, signal transduction, transepithelial transport in animals, and the extreme acid resistance response in eubacteria. They lack any structural or sequence similarity to other known ion channels and exhibit unique properties of ion permeation and gating. Unlike cation-selective ion channels, which form oligomers containing a single pore along the axis of symmetry, the ClC channels form two-pore homodimers with one pore per subunit without axial symmetry. Although lacking the typical voltage-sensor found in cation channels, all studied ClC channels are gated (opened and closed) by transmembrane voltage. The gating is conferred by the permeating ion itself, acting as the gating charge. In addition, eukaryotic and some prokaryotic ClC channels have two additional C-terminal CBS (cystathionine beta synthase) domains of putative regulatory function.


The actual alignment was detected with superfamily member cd03683:

Pssm-ID: 445960 [Multi-domain]  Cd Length: 426  Bit Score: 358.10  E-value: 1.51e-119
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEQETITSLYKTSFRVDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:cd03683  169 GVLFSIEVTSTYFAVRNYWRGFFAATCGAFTFRLLAVFFSDQETITALFKTTFFVDFPFDVQELPIFALLGIICGLLGAL 248

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 130 YLFCQRIFFGFIRNNRFSSKLLATSKPVYSALATLVLASITYPpsagrflasrlsmkqhldslfdnhswalmtqnssppw 209
Cdd:cd03683  249 FVFLHRKIVRFRRKNRLFSKFLKRSPLLYPAIVALLTAVLTFP------------------------------------- 291

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 210 peeldpqhlwwewyhprftiFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGIvAGGIT 289
Cdd:cd03683  292 --------------------FLTLFLFIVVKFVLTALAITLPVPAGIFMPVFVIGAALGRLVGEIMAVLFPEGI-RGGIS 350

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 380254450 290 NPIMPGGYALAGAAAFSGAVTHTISTALLAFEVTGQIVHALPVLMAVLAANAIAQSCQPSFYDGTVIVKKLPYLPR 365
Cdd:cd03683  351 NPIGPGGYAVVGAAAFSGAVTHTVSVAVIIFELTGQISHLLPVLIAVLISNAVAQFLQPSIYDSIIKIKKLPYLPD 426
CBS_pair_voltage-gated_CLC_euk_bac cd04591
Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the ...
 377-506 2.46e-36

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and 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 eukaryotes and 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).


:

Pssm-ID: 341367 [Multi-domain]  Cd Length: 114  Bit Score: 130.72  E-value: 2.46e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 377 RVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVESTESQILVGIVRRAQLVQALKAEPpswapghqclqdilaaGC 456
Cdd:cd04591    1 TAEDVMRPPLTVLARDETVGDIVSVLKTTDHNGFPVVDSTESQTLVGFILRSQLILLLEADL----------------RP 64

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 380254450 457 PTEPVTLKLSPETSLHEAHNLFELLNLHSLFVTSRGRAVGCVSWVEMKKA 506
Cdd:cd04591   65 IMDPSPFTVTEETSLEKVHDLFRLLGLRHLLVTNNGRLVGIVTRKDLLRA 114
 
Name Accession Description Interval E-value
ClC_1_like cd03683
ClC-1-like chloride channel proteins. This CD includes isoforms ClC-0, ClC-1, ClC-2 and ClC_K. ...
 50-365 1.51e-119

ClC-1-like chloride channel proteins. This CD includes isoforms ClC-0, ClC-1, ClC-2 and ClC_K. ClC-1 is expressed in skeletal muscle and its mutation leads to both recessively and dominantly-inherited forms of muscle stiffness or myotonia. ClC-K is exclusively expressed in kidney. Similarly, mutation of ClC-K leads to nephrogenic diabetes insipidus in mice and Bartter's syndrome in human. These proteins belong to the ClC superfamily of chloride ion channels, which share the unique double-barreled architecture and voltage-dependent gating mechanism. The gating is conferred by the permeating anion itself, acting as the gating charge. This domain is found in the eukaryotic halogen ion (Cl-, Br- and I-) channel proteins, that perform a variety of functions including cell volume regulation, regulation of intracelluar chloride concentration, membrane potential stabilization, charge compensation necessary for the acidification of intracellular organelles and transepithelial chloride transport.


Pssm-ID: 239655 [Multi-domain]  Cd Length: 426  Bit Score: 358.10  E-value: 1.51e-119
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEQETITSLYKTSFRVDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:cd03683  169 GVLFSIEVTSTYFAVRNYWRGFFAATCGAFTFRLLAVFFSDQETITALFKTTFFVDFPFDVQELPIFALLGIICGLLGAL 248

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 130 YLFCQRIFFGFIRNNRFSSKLLATSKPVYSALATLVLASITYPpsagrflasrlsmkqhldslfdnhswalmtqnssppw 209
Cdd:cd03683  249 FVFLHRKIVRFRRKNRLFSKFLKRSPLLYPAIVALLTAVLTFP------------------------------------- 291

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 210 peeldpqhlwwewyhprftiFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGIvAGGIT 289
Cdd:cd03683  292 --------------------FLTLFLFIVVKFVLTALAITLPVPAGIFMPVFVIGAALGRLVGEIMAVLFPEGI-RGGIS 350

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 380254450 290 NPIMPGGYALAGAAAFSGAVTHTISTALLAFEVTGQIVHALPVLMAVLAANAIAQSCQPSFYDGTVIVKKLPYLPR 365
Cdd:cd03683  351 NPIGPGGYAVVGAAAFSGAVTHTVSVAVIIFELTGQISHLLPVLIAVLISNAVAQFLQPSIYDSIIKIKKLPYLPD 426
CBS_pair_voltage-gated_CLC_euk_bac cd04591
Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the ...
 377-506 2.46e-36

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and 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 eukaryotes and 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).


Pssm-ID: 341367 [Multi-domain]  Cd Length: 114  Bit Score: 130.72  E-value: 2.46e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 377 RVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVESTESQILVGIVRRAQLVQALKAEPpswapghqclqdilaaGC 456
Cdd:cd04591    1 TAEDVMRPPLTVLARDETVGDIVSVLKTTDHNGFPVVDSTESQTLVGFILRSQLILLLEADL----------------RP 64

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 380254450 457 PTEPVTLKLSPETSLHEAHNLFELLNLHSLFVTSRGRAVGCVSWVEMKKA 506
Cdd:cd04591   65 IMDPSPFTVTEETSLEKVHDLFRLLGLRHLLVTNNGRLVGIVTRKDLLRA 114
Voltage_CLC pfam00654
Voltage gated chloride channel; This family of ion channels contains 10 or 12 transmembrane ...
 50-344 4.19e-32

Voltage gated chloride channel; This family of ion channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three ClC subfamilies are found in animals. ClC-1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. These proteins contain two pfam00571 domains.


Pssm-ID: 425802 [Multi-domain]  Cd Length: 344  Bit Score: 126.12  E-value: 4.19e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450   50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEqetitslykTSFRVDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:pfam00654 108 GVLFALEELSRSFSLRALIPVLLASVVAALVSRLIFGNSPL---------FSVGEPGSLSLLELPLFILLGILCGLLGAL 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  130 YLFCqriffgFIRNNRFSSKLLATSKPVYSALATLVLASITY--PPSAGrflasrlSMKQHLDSLFDNHswalmtqnssp 207
Cdd:pfam00654 179 FNRL------LLKVQRLFRKLLKIPPVLRPALGGLLVGLLGLlfPEVLG-------GGYELIQLLFNGN----------- 234

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  208 pwpeeldpqhlwwewyhprfTIFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGivagg 287
Cdd:pfam00654 235 --------------------TSLSLLLLLLLLKFLATALSLGSGAPGGIFAPSLAIGAALGRAFGLLLALLFPIG----- 289

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 380254450  288 itnPIMPGGYALAGAAAFSGAVTH-TISTALLAFEVTGQIVHALPVLMAVLAANAIAQ 344
Cdd:pfam00654 290 ---GLPPGAFALVGMAAFLAAVTRaPLTAIVIVFELTGSLQLLLPLMLAVLIAYAVSR 344
ClcA COG0038
H+/Cl- antiporter ClcA [Inorganic ion transport and metabolism];
50-352 3.46e-11

H+/Cl- antiporter ClcA [Inorganic ion transport and metabolism];


Pssm-ID: 439808 [Multi-domain]  Cd Length: 415  Bit Score: 65.16  E-value: 3.46e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVwdywRGFF----AATCGAFMFRLL----AVFnseqetitslyktSFRVDVPFDLPEIFFFVALGG 121
Cdd:COG0038  166 GALFALEVLLRDFSY----RALIpvliASVVAYLVSRLLfgngPLF-------------GVPSVPALSLLELPLYLLLGI 228

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 122 LCGILGSAY----LFCQRIFfgfirnnrfssKLLATSKPVYSALATLVLASITYppsagrflasrlsmkQHLDSLFDNHS 197
Cdd:COG0038  229 LAGLVGVLFnrllLKVERLF-----------KRLKLPPWLRPAIGGLLVGLLGL---------------FLPQVLGSGYG 282

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 198 WALMTQNSSPPWpeeldpqhlwwewyhprftifGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSF 277
Cdd:COG0038  283 LIEALLNGELSL---------------------LLLLLLLLLKLLATALTLGSGGPGGIFAPSLFIGALLGAAFGLLLNL 341

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 278 IFPE-----------GIVAggitnpimpggyalagaaaFSGAVTHT-ISTALLAFEVTGQIVHALPVLMAVLAANAIAQS 345
Cdd:COG0038  342 LFPGlglspglfalvGMAA-------------------VFAAVTRApLTAILLVLEMTGSYSLLLPLMIACVIAYLVSRL 402


                 ....*...
gi 380254450 346 CQP-SFYD 352
Cdd:COG0038  403 LFPrSIYT 410
COG2524 COG2524
Predicted transcriptional regulator, contains C-terminal CBS domains [Transcription];
288-507 8.29e-11

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


Pssm-ID: 442013 [Multi-domain]  Cd Length: 206  Bit Score: 61.44  E-value: 8.29e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 288 ITNPIMPGGYALAGAAAFSGAVTHTISTALLAFEVTGQIVHALPVLMAVLAANAIAQScqpSFYDGTVIVKKLPYLPRIL 367
Cdd:COG2524    1 LLVLLLLALSLLLPLLAVVLAALLLLAALVLALTAAAAATVLLLAAAAAAAGAGGLGL---LLLLLLIVLQAAAVRVVAE 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 368 GRNIGSHRVRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVESTEsqiLVGIVRRAQLVQALKAeppSWAPGHQC 447
Cdd:COG2524   78 KELGLVLKMKVKDIMTKDVITVSPDTTLEEALELMLEKGISGLPVVDDGK---LVGIITERDLLKALAE---GRDLLDAP 151

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 380254450 448 LQDILAagcpTEPVTLKlsPETSLHEAHNLFELLNLHSLFVT-SRGRAVGCVSWVEMKKAI 507
Cdd:COG2524  152 VSDIMT----RDVVTVS--EDDSLEEALRLMLEHGIGRLPVVdDDGKLVGIITRTDILRAL 206
CBS pfam00571
CBS domain; CBS domains are small intracellular modules that pair together to form a stable ...
 378-435 6.84e-06

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.


Pssm-ID: 425756 [Multi-domain]  Cd Length: 57  Bit Score: 43.36  E-value: 6.84e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 380254450  378 VEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALK 435
Cdd:pfam00571   1 VKDIMTKDVVTVSPDTTLEEALELMREHGISRLPVVD--EDGKLVGIVTLKDLLRALL 56
CBS smart00116
Domain in cystathionine beta-synthase and other proteins; Domain present in all 3 forms of ...
 386-435 2.66e-03

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.


Pssm-ID: 214522 [Multi-domain]  Cd Length: 49  Bit Score: 35.95  E-value: 2.66e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 380254450   386 ITTLAKDMPLEEVVKVVTSTDVAKYPLVesTESQILVGIVRRAQLVQALK 435
Cdd:smart00116   2 VVTVSPDTTLEEALELLRENGIRRLPVV--DEEGRLVGIVTRRDIIKALA 49
 
Name Accession Description Interval E-value
ClC_1_like cd03683
ClC-1-like chloride channel proteins. This CD includes isoforms ClC-0, ClC-1, ClC-2 and ClC_K. ...
 50-365 1.51e-119

ClC-1-like chloride channel proteins. This CD includes isoforms ClC-0, ClC-1, ClC-2 and ClC_K. ClC-1 is expressed in skeletal muscle and its mutation leads to both recessively and dominantly-inherited forms of muscle stiffness or myotonia. ClC-K is exclusively expressed in kidney. Similarly, mutation of ClC-K leads to nephrogenic diabetes insipidus in mice and Bartter's syndrome in human. These proteins belong to the ClC superfamily of chloride ion channels, which share the unique double-barreled architecture and voltage-dependent gating mechanism. The gating is conferred by the permeating anion itself, acting as the gating charge. This domain is found in the eukaryotic halogen ion (Cl-, Br- and I-) channel proteins, that perform a variety of functions including cell volume regulation, regulation of intracelluar chloride concentration, membrane potential stabilization, charge compensation necessary for the acidification of intracellular organelles and transepithelial chloride transport.


Pssm-ID: 239655 [Multi-domain]  Cd Length: 426  Bit Score: 358.10  E-value: 1.51e-119
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEQETITSLYKTSFRVDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:cd03683  169 GVLFSIEVTSTYFAVRNYWRGFFAATCGAFTFRLLAVFFSDQETITALFKTTFFVDFPFDVQELPIFALLGIICGLLGAL 248

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 130 YLFCQRIFFGFIRNNRFSSKLLATSKPVYSALATLVLASITYPpsagrflasrlsmkqhldslfdnhswalmtqnssppw 209
Cdd:cd03683  249 FVFLHRKIVRFRRKNRLFSKFLKRSPLLYPAIVALLTAVLTFP------------------------------------- 291

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 210 peeldpqhlwwewyhprftiFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGIvAGGIT 289
Cdd:cd03683  292 --------------------FLTLFLFIVVKFVLTALAITLPVPAGIFMPVFVIGAALGRLVGEIMAVLFPEGI-RGGIS 350

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 380254450 290 NPIMPGGYALAGAAAFSGAVTHTISTALLAFEVTGQIVHALPVLMAVLAANAIAQSCQPSFYDGTVIVKKLPYLPR 365
Cdd:cd03683  351 NPIGPGGYAVVGAAAFSGAVTHTVSVAVIIFELTGQISHLLPVLIAVLISNAVAQFLQPSIYDSIIKIKKLPYLPD 426
ClC_euk cd01036
Chloride channel, ClC. These domains are found in the eukaryotic halogen ion (Cl-, Br- and I-) ...
 50-352 5.78e-80

Chloride channel, ClC. These domains are found in the eukaryotic halogen ion (Cl-, Br- and I-) channel proteins that perform a variety of functions including cell volume regulation, membrane potential stabilization, charge compensation necessary for the acidification of intracellular organelles, signal transduction and transepithelial transport. They are also involved in many pathophysiological processes and are responsible for a number of human diseases. These proteins belong to the ClC superfamily of chloride ion channels, which share the unique double-barreled architecture and voltage-dependent gating mechanism. The gating is conferred by the permeating anion itself, acting as the gating charge. Some proteins possess long C-terminal cytoplasmic regions containing two CBS (cystathionine beta synthase) domains of putative regulatory function.


Pssm-ID: 238507 [Multi-domain]  Cd Length: 416  Bit Score: 255.73  E-value: 5.78e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEQETIT-----SLYKTSFRVDVPFDLPEIFFFVALGGLCG 124
Cdd:cd01036  168 GLLFVLEEVSTFFPVRLAWRVFFAALVSAFVIQIYNSFNSGFELLDrssamFLSLTVFELHVPLNLYEFIPTVVIGVICG 247

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 125 ILGSAYLFCQRIFFGFIRNNRFssKLLATSKPVYSALATLVLASITYPPsagrflasrlsmkqhldslfdnhswalmtqn 204
Cdd:cd01036  248 LLAALFVRLSIIFLRWRRRLLF--RKTARYRVLEPVLFTLIYSTIHYAP------------------------------- 294

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 205 ssppwpeeldpqhlwwewyhprftifgTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGIV 284
Cdd:cd01036  295 ---------------------------TLLLFLLIYFWMSALAFGIAVPGGTFIPSLVIGAAIGRLVGLLVHRIAVAGIG 347

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 380254450 285 AGGITNPIMPGGYALAGAAAFSGAVT-HTISTALLAFEVTGQIVHALPVLMAVLAANAIAQSCQPSFYD 352
Cdd:cd01036  348 AESATLWADPGVYALIGAAAFLGGTTrLTFSICVIMMELTGDLHHLLPLMVAILIAKAVADAFCESLYH 416
CBS_pair_voltage-gated_CLC_euk_bac cd04591
Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the ...
 377-506 2.46e-36

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and 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 eukaryotes and 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).


Pssm-ID: 341367 [Multi-domain]  Cd Length: 114  Bit Score: 130.72  E-value: 2.46e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 377 RVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVESTESQILVGIVRRAQLVQALKAEPpswapghqclqdilaaGC 456
Cdd:cd04591    1 TAEDVMRPPLTVLARDETVGDIVSVLKTTDHNGFPVVDSTESQTLVGFILRSQLILLLEADL----------------RP 64

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 380254450 457 PTEPVTLKLSPETSLHEAHNLFELLNLHSLFVTSRGRAVGCVSWVEMKKA 506
Cdd:cd04591   65 IMDPSPFTVTEETSLEKVHDLFRLLGLRHLLVTNNGRLVGIVTRKDLLRA 114
Voltage_CLC pfam00654
Voltage gated chloride channel; This family of ion channels contains 10 or 12 transmembrane ...
 50-344 4.19e-32

Voltage gated chloride channel; This family of ion channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three ClC subfamilies are found in animals. ClC-1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. These proteins contain two pfam00571 domains.


Pssm-ID: 425802 [Multi-domain]  Cd Length: 344  Bit Score: 126.12  E-value: 4.19e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450   50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEqetitslykTSFRVDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:pfam00654 108 GVLFALEELSRSFSLRALIPVLLASVVAALVSRLIFGNSPL---------FSVGEPGSLSLLELPLFILLGILCGLLGAL 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  130 YLFCqriffgFIRNNRFSSKLLATSKPVYSALATLVLASITY--PPSAGrflasrlSMKQHLDSLFDNHswalmtqnssp 207
Cdd:pfam00654 179 FNRL------LLKVQRLFRKLLKIPPVLRPALGGLLVGLLGLlfPEVLG-------GGYELIQLLFNGN----------- 234

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  208 pwpeeldpqhlwwewyhprfTIFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGivagg 287
Cdd:pfam00654 235 --------------------TSLSLLLLLLLLKFLATALSLGSGAPGGIFAPSLAIGAALGRAFGLLLALLFPIG----- 289

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 380254450  288 itnPIMPGGYALAGAAAFSGAVTH-TISTALLAFEVTGQIVHALPVLMAVLAANAIAQ 344
Cdd:pfam00654 290 ---GLPPGAFALVGMAAFLAAVTRaPLTAIVIVFELTGSLQLLLPLMLAVLIAYAVSR 344
ClC_3_like cd03684
ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 ...
 50-363 4.12e-25

ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has been suggested that ClC-3 may be a ubiquitous swelling-activated Cl channel that has very similar characteristics to those of native volume-regulated Cl currents. The function of ClC-4 is unclear. Studies of human ClC-4 have revealed that it gives rise to Cl currents that rapidly activate at positive voltages, and are sensitive to extracellular pH, with currents decreasing when pH falls below 6.5. ClC-4 is broadly distributed, especially in brain and heart. ClC-5 is predominantly expressed in the kidney, but can be found in the brain and liver. Mutations in the ClC-5 gene cause certain hereditary diseases, including Dent's disease, an X-chromosome linked syndrome characterised by proteinuria, hypercalciuria, and kidney stones (nephrolithiasis), leading to progressive renal failure. These proteins belong to the ClC superfamily of chloride ion channels, which share the unique double-barreled architecture and voltage-dependent gating mechanism. The gating is conferred by the permeating anion itself, acting as the gating charge. This domain is found in the eukaryotic halogen ion (Cl- and I-) channel proteins, that perform a variety of functions including cell volume regulation, the membrane potential stabilization, transepithelial chloride transport and charge compensation necessary for the acidification of intracellular organelles.


Pssm-ID: 239656  Cd Length: 445  Bit Score: 107.69  E-value: 4.12e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLLAVFNSEQetiTSLYKTSFrvDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:cd03684  149 GVLFSLEEVSYYFPLKTLWRSFFCALVAAFTLKSLNPFGTGR---LVLFEVEY--DRDWHYFELIPFILLGIFGGLYGAF 223

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 130 ylfcqriffgFIR-NNRFSSKLLATSKPVYSALATLVLASIT----YPpsagrFLASRLSMKQHLDSLFdnhswalmtqN 204
Cdd:cd03684  224 ----------FIKaNIKWARFRKKSLLKRYPVLEVLLVALITalisFP-----NPYTRLDMTELLELLF----------N 278

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 205 SSPPWPEELDPQHLWWEWYHPRFTIFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFG---ETLSFIFPE 281
Cdd:cd03684  279 ECEPGDDNSLCCYRDPPAGDGVYKALWSLLLALIIKLLLTIFTFGIKVPAGIFVPSMAVGALFGRIVGilvEQLAYSYPD 358

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 282 GIVAGGITNP---IMPGGYALAGAAAFSGAVTH-TISTALLAFEVTGQIVHALPVLMAVLAANAIAQSCQP-SFYDGTVI 356
Cdd:cd03684  359 SIFFACCTAGpscITPGLYAMVGAAAFLGGVTRmTVSLVVIMFELTGALNYILPLMIAVMVSKWVADAIGKeGIYDAHIH 438


                 ....*..
gi 380254450 357 VKKLPYL 363
Cdd:cd03684  439 LNGYPFL 445
Voltage_gated_ClC cd00400
CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of ...
 50-340 1.40e-22

CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. This domain is found in the halogen ions (Cl-, Br- and I-) transport proteins of the ClC family. The ClC channels are found in all three kingdoms of life and perform a variety of functions including cellular excitability regulation, cell volume regulation, membrane potential stabilization, acidification of intracellular organelles, signal transduction, transepithelial transport in animals, and the extreme acid resistance response in eubacteria. They lack any structural or sequence similarity to other known ion channels and exhibit unique properties of ion permeation and gating. Unlike cation-selective ion channels, which form oligomers containing a single pore along the axis of symmetry, the ClC channels form two-pore homodimers with one pore per subunit without axial symmetry. Although lacking the typical voltage-sensor found in cation channels, all studied ClC channels are gated (opened and closed) by transmembrane voltage. The gating is conferred by the permeating ion itself, acting as the gating charge. In addition, eukaryotic and some prokaryotic ClC channels have two additional C-terminal CBS (cystathionine beta synthase) domains of putative regulatory function.


Pssm-ID: 238233 [Multi-domain]  Cd Length: 383  Bit Score: 99.56  E-value: 1.40e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSV----WDYWRGFFAATCGAFMFRLLAVFNseqetitslyktsFRVDVPFDLPEIFFFVALGGLCGI 125
Cdd:cd00400  152 GALFAIEVLLGEYSVasliPVLLASVAAALVSRLLFGAEPAFG-------------VPLYDPLSLLELPLYLLLGLLAGL 218

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 126 LGSAYLFCQRIFFGFIRNnrfssklLATSKPVYSALATLVLASITYPPSAGRFLAsrlsmkqhldslfdnhswalmtqns 205
Cdd:cd00400  219 VGVLFVRLLYKIERLFRR-------LPIPPWLRPALGGLLLGLLGLFLPQVLGSG------------------------- 266

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 206 sppwpeeldpqHLWWEWYHPRFTIFGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGiva 285
Cdd:cd00400  267 -----------YGAILLALAGELSLLLLLLLLLLKLLATALTLGSGFPGGVFAPSLFIGAALGAAFGLLLPALFPGL--- 332

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 380254450 286 ggitnPIMPGGYALAGAAAFSGAVTHT-ISTALLAFEVTGQIVHALPVLMAVLAAN 340
Cdd:cd00400  333 -----VASPGAYALVGMAALLAAVLRApLTAILLVLELTGDYSLLLPLMLAVVIAY 383
EriC cd01031
ClC chloride channel EriC. This domain is found in the EriC chloride transporters that ...
 50-344 1.09e-13

ClC chloride channel EriC. This domain is found in the EriC chloride transporters that mediate the extreme acid resistance response in eubacteria and archaea. This response allows bacteria to survive in the acidic environments by decarboxylation-linked proton utilization. As shown for Escherichia coli EriC, these channels can counterbalance the electric current produced by the outwardly directed virtual proton pump linked to amino acid decarboxylation. The EriC proteins belong to the ClC superfamily of chloride ion channels, which share a unique double-barreled architecture and voltage-dependent gating mechanism. The voltage-dependent gating is conferred by the permeating anion itself, acting as the gating charge. In Escherichia coli EriC, a glutamate residue that protrudes into the pore is thought to participate in gating by binding to a Cl- ion site within the selectivity filter.


Pssm-ID: 238504 [Multi-domain]  Cd Length: 402  Bit Score: 72.57  E-value: 1.09e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFRLlavFNSEQETItslyktSFRVDVPFDLPEIFFFVALGGLCGILGSA 129
Cdd:cd01031  153 GVLFVLEELRHSFSPLALLTALVASIAADFVSRL---FFGLGPVL------SIPPLPALPLKSYWLLLLLGIIAGLLGYL 223

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 130 Y----LFCQRIFFGFIRNNRFSSKLLAtskpvysaLATLVLASITYPpsagrflasrlsmkqhlDSLFDNHSWALMTQNS 205
Cdd:cd01031  224 FnrslLKSQDLYRKLKKLPRELRVLLP--------GLLIGPLGLLLP-----------------EALGGGHGLILSLAGG 278

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 206 SPPWpeeldpqhlwwewyhprftifGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFPEGIva 285
Cdd:cd01031  279 NFSI---------------------SLLLLIFVLRFIFTMLSYGSGAPGGIFAPMLALGALLGLLFGTILVQLGPIPI-- 335

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 286 ggitnpIMPGGYALAGAAAFSGAVTHTISTA-LLAFEVTGQIVHALPVLMAVLAANAIAQ 344
Cdd:cd01031  336 ------SAPATFAIAGMAAFFAAVVRAPITAiILVTEMTGNFNLLLPLMVVCLVAYLVAD 389
ClC_6_like cd03685
ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. ...
 50-363 3.34e-12

ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. Proteins in this family are ubiquitous in eukarotes and their functions are unclear. They are expressed in intracellular organelles membranes. This family belongs to the ClC superfamily of chloride ion channels, which share the unique double-barreled architecture and voltage-dependent gating mechanism. The gating is conferred by the permeating anion itself, acting as the gating charge. ClC chloride ion channel superfamily perform a variety of functions including cellular excitability regulation, cell volume regulation, membrane potential stabilization, acidification of intracellular organelles, signal transduction, and transepithelial transport in animals.


Pssm-ID: 239657 [Multi-domain]  Cd Length: 466  Bit Score: 68.45  E-value: 3.34e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVWDYWRGFFAATCGAFMFR-LLAVFNSEQETITS----LYKTSFRVDVPFDLPEIFFFVALGGLCG 124
Cdd:cd03685  209 GVLFSLEEVASFWNQALTWRTFFSSMIVTFTLNfFLSGCNSGKCGLFGpgglIMFDGSSTKYLYTYFELIPFMLIGVIGG 288

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 125 ILGSAYLFCQriffgfIRNNRFSSKLLATSKPVYSALATLVlasityppsagrflasrlsmkqhldslfdnhswALMTQN 204
Cdd:cd03685  289 LLGALFNHLN------HKVTRFRKRINHKGKLLKVLEALLV---------------------------------SLVTSV 329

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 205 SSPPWpeeldpqhlwwewyhprftifgTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSFIFpegiv 284
Cdd:cd03685  330 VAFPQ----------------------TLLIFFVLYYFLACWTFGIAVPSGLFIPMILIGAAYGRLVGILLGSYF----- 382

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 285 agGITNpIMPGGYALAGAAAF-SGAVTHTISTALLAFEVTGQIVHALPVLMAVLAANAIAQSCQPSFYDGTVIVKKLPYL 363
Cdd:cd03685  383 --GFTS-IDPGLYALLGAAAFlGGVMRMTVSLTVILLELTNNLTYLPPIMLVLMIAKWVGDYFNEGIYDIIIQLKGVPFL 459
ClcA COG0038
H+/Cl- antiporter ClcA [Inorganic ion transport and metabolism];
50-352 3.46e-11

H+/Cl- antiporter ClcA [Inorganic ion transport and metabolism];


Pssm-ID: 439808 [Multi-domain]  Cd Length: 415  Bit Score: 65.16  E-value: 3.46e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450  50 GVLFSIEVMSSHFSVwdywRGFF----AATCGAFMFRLL----AVFnseqetitslyktSFRVDVPFDLPEIFFFVALGG 121
Cdd:COG0038  166 GALFALEVLLRDFSY----RALIpvliASVVAYLVSRLLfgngPLF-------------GVPSVPALSLLELPLYLLLGI 228

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 122 LCGILGSAY----LFCQRIFfgfirnnrfssKLLATSKPVYSALATLVLASITYppsagrflasrlsmkQHLDSLFDNHS 197
Cdd:COG0038  229 LAGLVGVLFnrllLKVERLF-----------KRLKLPPWLRPAIGGLLVGLLGL---------------FLPQVLGSGYG 282

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 198 WALMTQNSSPPWpeeldpqhlwwewyhprftifGTLAFFLVMKFWMLILATTIPMPAGYFMPIFVYGAAIGRLFGETLSF 277
Cdd:COG0038  283 LIEALLNGELSL---------------------LLLLLLLLLKLLATALTLGSGGPGGIFAPSLFIGALLGAAFGLLLNL 341

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 278 IFPE-----------GIVAggitnpimpggyalagaaaFSGAVTHT-ISTALLAFEVTGQIVHALPVLMAVLAANAIAQS 345
Cdd:COG0038  342 LFPGlglspglfalvGMAA-------------------VFAAVTRApLTAILLVLEMTGSYSLLLPLMIACVIAYLVSRL 402


                 ....*...
gi 380254450 346 CQP-SFYD 352
Cdd:COG0038  403 LFPrSIYT 410
COG2524 COG2524
Predicted transcriptional regulator, contains C-terminal CBS domains [Transcription];
288-507 8.29e-11

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


Pssm-ID: 442013 [Multi-domain]  Cd Length: 206  Bit Score: 61.44  E-value: 8.29e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 288 ITNPIMPGGYALAGAAAFSGAVTHTISTALLAFEVTGQIVHALPVLMAVLAANAIAQScqpSFYDGTVIVKKLPYLPRIL 367
Cdd:COG2524    1 LLVLLLLALSLLLPLLAVVLAALLLLAALVLALTAAAAATVLLLAAAAAAAGAGGLGL---LLLLLLIVLQAAAVRVVAE 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 368 GRNIGSHRVRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVESTEsqiLVGIVRRAQLVQALKAeppSWAPGHQC 447
Cdd:COG2524   78 KELGLVLKMKVKDIMTKDVITVSPDTTLEEALELMLEKGISGLPVVDDGK---LVGIITERDLLKALAE---GRDLLDAP 151

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 380254450 448 LQDILAagcpTEPVTLKlsPETSLHEAHNLFELLNLHSLFVT-SRGRAVGCVSWVEMKKAI 507
Cdd:COG2524  152 VSDIMT----RDVVTVS--EDDSLEEALRLMLEHGIGRLPVVdDDGKLVGIITRTDILRAL 206
CBS COG0517
CBS domain [Signal transduction mechanisms];
376-507 1.19e-08

CBS domain [Signal transduction mechanisms];


Pssm-ID: 440283 [Multi-domain]  Cd Length: 128  Bit Score: 53.33  E-value: 1.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 376 VRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALKAEPPSwaPGHQCLQDILAag 455
Cdd:COG0517    1 MKVKDIMTTDVVTVSPDATVREALELMSEKRIGGLPVVD--EDGKLVGIVTDRDLRRALAAEGKD--LLDTPVSEVMT-- 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 380254450 456 cpTEPVTlkLSPETSLHEAHNLFELLNLHSLFVTSR-GRAVGCVSWVEMKKAI 507
Cdd:COG0517   75 --RPPVT--VSPDTSLEEAAELMEEHKIRRLPVVDDdGRLVGIITIKDLLKAL 123
COG2905 COG2905
Signal-transduction protein containing cAMP-binding, CBS, and nucleotidyltransferase domains ...
 378-499 2.13e-08

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


Pssm-ID: 442149 [Multi-domain]  Cd Length: 124  Bit Score: 52.52  E-value: 2.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 378 VEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALKAEPPSwaPGHQCLQDILAagcp 457
Cdd:COG2905    1 VKDIMSRDVVTVSPDATVREAARLMTEKGVGSLVVVD--DDGRLVGIITDRDLRRRVLAEGLD--PLDTPVSEVMT---- 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 380254450 458 TEPVTLklSPETSLHEAHNLFELLNLHSLFVTSRGRAVGCVS 499
Cdd:COG2905   73 RPPITV--SPDDSLAEALELMEEHRIRHLPVVDDGKLVGIVS 112
COG3448 COG3448
CBS-domain-containing membrane protein [Signal transduction mechanisms];
377-510 7.57e-08

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


Pssm-ID: 442671 [Multi-domain]  Cd Length: 136  Bit Score: 51.40  E-value: 7.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 377 RVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALKaePPSWAPGHQCLQDILAAGC 456
Cdd:COG3448    3 TVRDIMTRDVVTVSPDTTLREALELMREHGIRGLPVVD--EDGRLVGIVTERDLLRALL--PDRLDELEERLLDLPVEDV 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 380254450 457 PTEPVtLKLSPETSLHEAHNLFELLNLHSLFVT-SRGRAVGCVSWVEMKKAISNL 510
Cdd:COG3448   79 MTRPV-VTVTPDTPLEEAAELMLEHGIHRLPVVdDDGRLVGIVTRTDLLRALARL 132
CBS COG0517
CBS domain [Signal transduction mechanisms];
365-437 2.01e-06

CBS domain [Signal transduction mechanisms];


Pssm-ID: 440283 [Multi-domain]  Cd Length: 128  Bit Score: 47.17  E-value: 2.01e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 380254450 365 RILGRNIGSHRVRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALKAE 437
Cdd:COG0517   56 ALAAEGKDLLDTPVSEVMTRPPVTVSPDTSLEEAAELMEEHKIRRLPVVD--DDGRLVGIITIKDLLKALLEP 126
CBS pfam00571
CBS domain; CBS domains are small intracellular modules that pair together to form a stable ...
 378-435 6.84e-06

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.


Pssm-ID: 425756 [Multi-domain]  Cd Length: 57  Bit Score: 43.36  E-value: 6.84e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 380254450  378 VEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALK 435
Cdd:pfam00571   1 VKDIMTKDVVTVSPDTTLEEALELMREHGISRLPVVD--EDGKLVGIVTLKDLLRALL 56
COG3448 COG3448
CBS-domain-containing membrane protein [Signal transduction mechanisms];
356-434 6.99e-06

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


Pssm-ID: 442671 [Multi-domain]  Cd Length: 136  Bit Score: 45.63  E-value: 6.99e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 380254450 356 IVKKLPyLPRILGRNIGSHRVRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQAL 434
Cdd:COG3448   54 LLRALL-PDRLDELEERLLDLPVEDVMTRPVVTVTPDTPLEEAAELMLEHGIHRLPVVD--DDGRLVGIVTRTDLLRAL 129
YtoI COG4109
Predicted transcriptional regulator containing CBS domains [Transcription];
374-435 3.28e-05

Predicted transcriptional regulator containing CBS domains [Transcription];


Pssm-ID: 443285 [Multi-domain]  Cd Length: 135  Bit Score: 43.75  E-value: 3.28e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 380254450 374 HRVRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVEstESQILVGIVRRAQLVQALK 435
Cdd:COG4109   74 DDTPIEDVMTKNPITVTPDTSLASAAHKMIWEGIELLPVVD--DDGRLLGIISRQDVLKALQ 133
COG2905 COG2905
Signal-transduction protein containing cAMP-binding, CBS, and nucleotidyltransferase domains ...
 365-434 3.02e-04

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


Pssm-ID: 442149 [Multi-domain]  Cd Length: 124  Bit Score: 40.58  E-value: 3.02e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 365 RILGRNIGSHRVRVEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVESTEsqiLVGIVRRAQLVQAL 434
Cdd:COG2905   54 RVLAEGLDPLDTPVSEVMTRPPITVSPDDSLAEALELMEEHRIRHLPVVDDGK---LVGIVSITDLLRAL 120
CBS smart00116
Domain in cystathionine beta-synthase and other proteins; Domain present in all 3 forms of ...
 386-435 2.66e-03

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.


Pssm-ID: 214522 [Multi-domain]  Cd Length: 49  Bit Score: 35.95  E-value: 2.66e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 380254450   386 ITTLAKDMPLEEVVKVVTSTDVAKYPLVesTESQILVGIVRRAQLVQALK 435
Cdd:smart00116   2 VVTVSPDTTLEEALELLRENGIRRLPVV--DEEGRLVGIVTRRDIIKALA 49
CBS_pair_DHH_polyA_Pol_assoc cd04595
Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the ...
 378-433 4.35e-03

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).


Pssm-ID: 341370 [Multi-domain]  Cd Length: 110  Bit Score: 37.09  E-value: 4.35e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 380254450 378 VEHFMNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVestESQILVGIVRRAQLVQA 433
Cdd:cd04595   58 VKGYMSTNVITIDPDTSLEEAQELMVEHDIGRLPVV---EEGKLVGIVTRSDVLRY 110
CBS_pair_voltage-gated_CLC_bac cd04613
Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the ...
 382-499 4.55e-03

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).


Pssm-ID: 341385 [Multi-domain]  Cd Length: 119  Bit Score: 37.17  E-value: 4.55e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 380254450 382 MNHSITTLAKDMPLEEVVKVVTSTDVAKYPLVesTESQILVGIVrRAQLVQALKAEppswapghQCLQDILAAG--CPTE 459
Cdd:cd04613    1 MPRKVTVLPEGMTFRQFTEFIAGTRQHYFPVV--DEQGRLTGIL-SIQDVRGVLFE--------EELWDLVVVKdlATTD 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 380254450 460 PVTlkLSPETSLHEAHNLFELLNLHSLFVTSR---GRAVGCVS 499
Cdd:cd04613   70 VIT--VTPDDDLYTALLKFTSTNLDQLPVVDDddpGKVLGMLS 110
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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