NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|767940232|ref|XP_011512994|]
View 

chloride intracellular channel protein 5 isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
O-ClC super family cl31033
intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A. ...
 173-355 8.20e-121

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]


The actual alignment was detected with superfamily member TIGR00862:

Pssm-ID: 129941 [Multi-domain]  Cd Length: 236  Bit Score: 348.77  E-value: 8.20e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232  173 PEIYLFVKAGIDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLE 252
Cdd:TIGR00862   1 PEIELFVKAGSDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232  253 ETLTPEKYPKLAAKHRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRR 332
Cdd:TIGR00862  81 ETLCPPRYPKLSPKHPESNTAGLDIFAKFSAYIKNSNPEANDNLEKGLLKALKKLDDYLNSPLPEEIDEDSAEDEKVSRR 160

                         170       180
                  ....*....|....*....|...
gi 767940232  333 KFLDGDELTLADCNLLPKLHVVK 355
Cdd:TIGR00862 161 KFLDGDELTLADCNLLPKLHIVK 183
 
Name Accession Description Interval E-value
O-ClC TIGR00862
intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A. ...
 173-355 8.20e-121

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]


Pssm-ID: 129941 [Multi-domain]  Cd Length: 236  Bit Score: 348.77  E-value: 8.20e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232  173 PEIYLFVKAGIDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLE 252
Cdd:TIGR00862   1 PEIELFVKAGSDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232  253 ETLTPEKYPKLAAKHRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRR 332
Cdd:TIGR00862  81 ETLCPPRYPKLSPKHPESNTAGLDIFAKFSAYIKNSNPEANDNLEKGLLKALKKLDDYLNSPLPEEIDEDSAEDEKVSRR 160

                         170       180
                  ....*....|....*....|...
gi 767940232  333 KFLDGDELTLADCNLLPKLHVVK 355
Cdd:TIGR00862 161 KFLDGDELTLADCNLLPKLHIVK 183
GST_C_CLIC5 cd10297
C-terminal, alpha helical domain of Chloride Intracellular Channel 5; Glutathione ...
 267-355 3.18e-60

C-terminal, alpha helical domain of Chloride Intracellular Channel 5; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 5 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC5 exists in two alternatively-spliced isoforms, CLIC5A or CLIC5B (also called p64). It is expressed at high levels in hair cell stereocilia and is associated with the actin cytoskeleton and ezrin. A recessive mutation in the CLIC5 gene in mice led to the lack of coordination and deafness, due to a defect in the basal region of the hair bundle causing stereocilia to degrade. CLIC5 is therefore essential for normal inner ear function. CLIC5 is also highly expressed in podocytes where it is colocalized with the ezrin/radixin/moesin (ERM) complex. It is essential for foot process integrity, and for podocyte morphology and function.


Pssm-ID: 198330  Cd Length: 141  Bit Score: 190.95  E-value: 3.18e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRRKFLDGDELTLADCN 346
Cdd:cd10297    1 HRESNTAGIDIFSKFSAYIKNTKQQANAALEKGLTKALKKLDDYLNTPLPEEIDADSTEEEKVSNRKFLDGDELTLADCN 80


                 ....*....
gi 767940232 347 LLPKLHVVK 355
Cdd:cd10297   81 LLPKLHVVK 89
PLN02817 PLN02817
glutathione dehydrogenase (ascorbate)
 179-358 2.30e-13

glutathione dehydrogenase (ascorbate)


Pssm-ID: 166458 [Multi-domain]  Cd Length: 265  Bit Score: 69.25  E-value: 2.30e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 179 VKAGID-GESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEetltp 257
Cdd:PLN02817  60 VKASLTvPNKLGDCPFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISPEGKVPVVKLDEKWVADSDVITQALE----- 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 258 EKYPKLA-AKHRESNTAGIDIFSKFSAYIKNtkQQNNAALERGLTKALKKLDDYLNTPLPeeidantcgedkgsrrkFLD 336
Cdd:PLN02817 135 EKYPDPPlATPPEKASVGSKIFSTFIGFLKS--KDPGDGTEQALLDELTSFDDYIKENGP-----------------FIN 195

                        170       180
                 ....*....|....*....|..
gi 767940232 337 GDELTLADCNLLPKLHVVKTHL 358
Cdd:PLN02817 196 GEKISAADLSLGPKLYHLEIAL 217
GST_N_2 pfam13409
Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.
 191-254 2.27e-12

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.


Pssm-ID: 433184 [Multi-domain]  Cd Length: 68  Bit Score: 61.49  E-value: 2.27e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767940232  191 CPFSQRLFMILWLKGVVFNVTTVDL--KRKPADLHNLAPGTHPPFLTF-NGDVKTDVNKIEEFLEET 254
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLdpKDKPPELLALNPLGTVPVLVLpDGTVLTDSLVILEYLEEL 68
GstA COG0625
Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];
190-357 4.77e-04

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440390 [Multi-domain]  Cd Length: 205  Bit Score: 41.03  E-value: 4.77e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 190 NCPFSQRLFMILWLKGVVFNVTTVDLKR---KPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEET-----LTPEkYP 261
Cdd:COG0625    9 PSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERypeppLLPA-DP 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 262 KLAAKHRE-----SNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLntplpeeidantcgedkgSRRKFLD 336
Cdd:COG0625   88 AARARVRQwlawaDGDLHPALRNLLERLAPEKDPAAIARARAELARLLAVLEARL------------------AGGPYLA 149

                        170       180
                 ....*....|....*....|.
gi 767940232 337 GDELTLADCNLLPKLHVVKTH 357
Cdd:COG0625  150 GDRFSIADIALAPVLRRLDRL 170
 
Name Accession Description Interval E-value
O-ClC TIGR00862
intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A. ...
 173-355 8.20e-121

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]


Pssm-ID: 129941 [Multi-domain]  Cd Length: 236  Bit Score: 348.77  E-value: 8.20e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232  173 PEIYLFVKAGIDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLE 252
Cdd:TIGR00862   1 PEIELFVKAGSDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232  253 ETLTPEKYPKLAAKHRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRR 332
Cdd:TIGR00862  81 ETLCPPRYPKLSPKHPESNTAGLDIFAKFSAYIKNSNPEANDNLEKGLLKALKKLDDYLNSPLPEEIDEDSAEDEKVSRR 160

                         170       180
                  ....*....|....*....|...
gi 767940232  333 KFLDGDELTLADCNLLPKLHVVK 355
Cdd:TIGR00862 161 KFLDGDELTLADCNLLPKLHIVK 183
GST_C_CLIC5 cd10297
C-terminal, alpha helical domain of Chloride Intracellular Channel 5; Glutathione ...
 267-355 3.18e-60

C-terminal, alpha helical domain of Chloride Intracellular Channel 5; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 5 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC5 exists in two alternatively-spliced isoforms, CLIC5A or CLIC5B (also called p64). It is expressed at high levels in hair cell stereocilia and is associated with the actin cytoskeleton and ezrin. A recessive mutation in the CLIC5 gene in mice led to the lack of coordination and deafness, due to a defect in the basal region of the hair bundle causing stereocilia to degrade. CLIC5 is therefore essential for normal inner ear function. CLIC5 is also highly expressed in podocytes where it is colocalized with the ezrin/radixin/moesin (ERM) complex. It is essential for foot process integrity, and for podocyte morphology and function.


Pssm-ID: 198330  Cd Length: 141  Bit Score: 190.95  E-value: 3.18e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRRKFLDGDELTLADCN 346
Cdd:cd10297    1 HRESNTAGIDIFSKFSAYIKNTKQQANAALEKGLTKALKKLDDYLNTPLPEEIDADSTEEEKVSNRKFLDGDELTLADCN 80


                 ....*....
gi 767940232 347 LLPKLHVVK 355
Cdd:cd10297   81 LLPKLHVVK 89
GST_N_CLIC cd03061
GST_N family, Chloride Intracellular Channel (CLIC) subfamily; composed of CLIC1-5, p64, ...
 173-260 1.99e-57

GST_N family, Chloride Intracellular Channel (CLIC) subfamily; composed of CLIC1-5, p64, parchorin and similar proteins. They are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division and apoptosis. They can exist in both water-soluble and membrane-bound states, and are found in various vesicles and membranes. Biochemical studies of the C. elegans homolog, EXC-4, show that the membrane localization domain is present in the N-terminal part of the protein. The structure of soluble human CLIC1 reveals that it is monomeric and it adopts a fold similar to GSTs, containing an N-terminal domain with a TRX fold and a C-terminal alpha helical domain. Upon oxidation, the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. The CLIC1 dimer bears no similarity to GST dimers. The redox-controlled structural rearrangement exposes a large hydrophobic surface, which is masked by dimerization in vitro. In vivo, this surface may represent the docking interface of CLIC1 in its membrane-bound state. The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity, however, in other subfamily members, the second cysteine is not conserved.


Pssm-ID: 239359  Cd Length: 91  Bit Score: 181.80  E-value: 1.99e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 173 PEIYLFVKAGIDGESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLE 252
Cdd:cd03061    4 PEIELFVKASSDGESIGNCPFCQRLFMVLWLKGVVFNVTTVDMKRKPEDLKDLAPGTQPPFLLYNGEVKTDNNKIEEFLE 83


                 ....*...
gi 767940232 253 ETLTPEKY 260
Cdd:cd03061   84 ETLCPPKY 91
GST_C_CLIC4 cd10296
C-terminal, alpha helical domain of Chloride Intracellular Channel 4; Glutathione ...
 267-355 2.85e-45

C-terminal, alpha helical domain of Chloride Intracellular Channel 4; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 4 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC4, also known as p64H1, is expressed ubiquitously and its localization varies depending on the nature of the cells and tissues, from the plasma membrane to subcellular compartments including the nucleus, mitochondria, ER, and the trans-Golgi network, among others. In response to cellular stress such as DNA damage and senescence, cytoplasmic CLIC4 translocates to the nucleus, where it acts on the TGF-beta pathway. Studies on knockout mice suggest that CLIC4 also plays an important role in angiogenesis, specifically in network formation, capillary sprouting, and lumen formation. CLIC4 has been found to induce apoptosis in several cell types and to retard the growth of grafted tumors in vivo.


Pssm-ID: 198329  Cd Length: 141  Bit Score: 152.10  E-value: 2.85e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRRKFLDGDELTLADCN 346
Cdd:cd10296    1 HPESNTAGMDIFAKFSAYIKNSRPEANEALERGLLKTLQKLDEYLNSPLPDEIDENSMEDIKFSTRKFLDGNEMTLADCN 80


                 ....*....
gi 767940232 347 LLPKLHVVK 355
Cdd:cd10296   81 LLPKLHIVK 89
GST_C_CLIC1 cd10300
C-terminal, alpha helical domain of Chloride Intracellular Channel 1; Glutathione ...
 269-355 2.69e-41

C-terminal, alpha helical domain of Chloride Intracellular Channel 1; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 1 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Soluble CLIC1 is monomeric and adopts a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. Upon oxidation, the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. The CLIC1 dimer bears no similarity to GST dimers. The redox-controlled structural rearrangement exposes a large hydrophobic surface, which is masked by dimerization in vitro. In vivo, this surface may represent the docking interface of CLIC1 in its membrane-bound state. The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity. CLIC1 is widely expressed in many tissues and its subcellular localization is dependent on cell type and cell cycle phase. It acts as a sensor of cell oxidation and appears to have a role in diseases that involve oxidative stress including tumorigenic and neurodegenerative diseases.


Pssm-ID: 198333  Cd Length: 139  Bit Score: 142.00  E-value: 2.69e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 269 ESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANtCGEDKG-SRRKFLDGDELTLADCNL 347
Cdd:cd10300    3 ESNTAGLDVFAKFSAYIKNSNPALNDNLEKGLLKALKVLDNYLTSPLPEEVDEN-SAEDEGvSQRKFLDGNELTLADCNL 81


                 ....*...
gi 767940232 348 LPKLHVVK 355
Cdd:cd10300   82 LPKLHIVQ 89
GST_C_CLIC6 cd10301
C-terminal, alpha helical domain of Chloride Intracellular Channel 6; Glutathione ...
 267-355 2.26e-40

C-terminal, alpha helical domain of Chloride Intracellular Channel 6; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 6 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC6 is expressed predominantly in the stomach, pituitary, and brain. It interacts with D2-like dopamine receptors directly and through scaffolding proteins. CLIC6 may be involved in the regulation of secretion, possibly through chloride ion transport regulation.


Pssm-ID: 198334  Cd Length: 140  Bit Score: 139.38  E-value: 2.26e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRRKFLDGDELTLADCN 346
Cdd:cd10301    1 HPESNSAGNDVFAKFSAFIKNPRKDANENLEKNLLKALRKLDNYLNTPLPDEIDAYSTEDITVSDRKFLDGNELTLADCN 80


                 ....*....
gi 767940232 347 LLPKLHVVK 355
Cdd:cd10301   81 LLPKLHIIK 89
GST_C_CLIC3 cd10299
C-terminal, alpha helical domain of Chloride Intracellular Channel 3; Glutathione ...
 267-356 2.69e-34

C-terminal, alpha helical domain of Chloride Intracellular Channel 3; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 3 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC3 is highly expressed in placental tissues, and may play a role in fetal development.


Pssm-ID: 198332  Cd Length: 133  Bit Score: 123.34  E-value: 2.69e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTcgEDKGSRRKFLDGDELTLADCN 346
Cdd:cd10299    1 YKESNTAGNDVFHKFSAFIKNPVPAQDDALQKKLLRALLKLDSYLLTPLPHELAQNP--HLSESQRRFLDGDALTLADCN 78

                         90
                 ....*....|
gi 767940232 347 LLPKLHVVKT 356
Cdd:cd10299   79 LLPKLHIVKV 88
GST_C_CLIC2 cd10298
C-terminal, alpha helical domain of Chloride Intracellular Channel 2; Glutathione ...
 267-355 2.17e-32

C-terminal, alpha helical domain of Chloride Intracellular Channel 2; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 2 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC2 contains an intramolecular disulfide bond and exists as a monomer regardless of redox conditions, in contrast to CLIC1 which forms a dimer under oxidizing conditions. It is expressed in most tissues except the brain, and is highly expressed in the lung, spleen, and in cardiac and skeletal muscles. CLIC2 interacts with ryanodine receptors (cardiac RyR2 and skeletal RyR1) and modulates their activity, suggesting that CLIC2 may function in the regulation of calcium release and signaling in cardiac and skeletal muscles.


Pssm-ID: 198331  Cd Length: 138  Bit Score: 118.44  E-value: 2.17e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTkQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRRKFLDGDELTLADCN 346
Cdd:cd10298    1 YKESFDVGSDIFAKFSAYIKNS-PENNANQEKALLREFKRLDDYLNTPLPEEIDHDSAENITVSKRKFLDGDRLTLADCN 79


                 ....*....
gi 767940232 347 LLPKLHVVK 355
Cdd:cd10298   80 LLPKLHVIK 88
GST_C_CLIC cd03198
C-terminal, alpha helical domain of Chloride Intracellular Channels; Glutathione S-transferase ...
 267-355 9.46e-31

C-terminal, alpha helical domain of Chloride Intracellular Channels; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) subfamily; composed of CLICs (CLIC1-6 in vertebrates), p64, parchorin, and similar proteins. They are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. Biochemical studies of the Caenorhabditis elegans homolog, EXC-4, show that the membrane localization domain is present in the N-terminal part of the protein. CLICs display structural plasticity, with CLIC1 adopting two soluble conformations. The structure of soluble human CLIC1 reveals that it is monomeric and adopts a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. Upon oxidation, the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. The CLIC1 dimer bears no similarity to GST dimers. The redox-controlled structural rearrangement exposes a large hydrophobic surface, which is masked by dimerization in vitro. In vivo, this surface may represent the docking interface of CLIC1 in its membrane-bound state. The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity, however, in other subfamily members, the second cysteine is not conserved.


Pssm-ID: 198307  Cd Length: 119  Bit Score: 113.47  E-value: 9.46e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 267 HRESNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTplpeeidantcgedkgSRRKFLDGDELTLADCN 346
Cdd:cd03198    1 NPEANTAGEDLFAKFSAYIKNKDPAADEALRKALLKELSKLDAYLSS----------------SSRKFLDGDTLTLADCN 64


                 ....*....
gi 767940232 347 LLPKLHVVK 355
Cdd:cd03198   65 LLPKLHHIR 73
PLN02817 PLN02817
glutathione dehydrogenase (ascorbate)
 179-358 2.30e-13

glutathione dehydrogenase (ascorbate)


Pssm-ID: 166458 [Multi-domain]  Cd Length: 265  Bit Score: 69.25  E-value: 2.30e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 179 VKAGID-GESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEetltp 257
Cdd:PLN02817  60 VKASLTvPNKLGDCPFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISPEGKVPVVKLDEKWVADSDVITQALE----- 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 258 EKYPKLA-AKHRESNTAGIDIFSKFSAYIKNtkQQNNAALERGLTKALKKLDDYLNTPLPeeidantcgedkgsrrkFLD 336
Cdd:PLN02817 135 EKYPDPPlATPPEKASVGSKIFSTFIGFLKS--KDPGDGTEQALLDELTSFDDYIKENGP-----------------FIN 195

                        170       180
                 ....*....|....*....|..
gi 767940232 337 GDELTLADCNLLPKLHVVKTHL 358
Cdd:PLN02817 196 GEKISAADLSLGPKLYHLEIAL 217
GST_N_2 pfam13409
Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.
 191-254 2.27e-12

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.


Pssm-ID: 433184 [Multi-domain]  Cd Length: 68  Bit Score: 61.49  E-value: 2.27e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767940232  191 CPFSQRLFMILWLKGVVFNVTTVDL--KRKPADLHNLAPGTHPPFLTF-NGDVKTDVNKIEEFLEET 254
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLdpKDKPPELLALNPLGTVPVLVLpDGTVLTDSLVILEYLEEL 68
PLN02378 PLN02378
glutathione S-transferase DHAR1
 179-358 8.06e-11

glutathione S-transferase DHAR1


Pssm-ID: 166019 [Multi-domain]  Cd Length: 213  Bit Score: 61.27  E-value: 8.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 179 VKAGIDG-ESIGNCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEetltp 257
Cdd:PLN02378   7 VKAAVGApDHLGDCPFSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISPQGKVPVLKIDDKWVTDSDVIVGILE----- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 258 EKYPKLAAKH-RESNTAGIDIFSKFSAYIKNtkQQNNAALERGLTKALKKLDDYLntplpeeidantcgedKGSRRKFLD 336
Cdd:PLN02378  82 EKYPDPPLKTpAEFASVGSNIFGTFGTFLKS--KDSNDGSEHALLVELEALENHL----------------KSHDGPFIA 143

                        170       180
                 ....*....|....*....|..
gi 767940232 337 GDELTLADCNLLPKLHVVKTHL 358
Cdd:PLN02378 144 GERVSAVDLSLAPKLYHLQVAL 165
GST_N_family cd00570
Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic ...
 190-252 2.47e-08

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.


Pssm-ID: 238319 [Multi-domain]  Cd Length: 71  Bit Score: 50.26  E-value: 2.47e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767940232 190 NCPFSQRLFMILWLKGVVFNVTTVDLKRKPA-DLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLE 252
Cdd:cd00570    8 GSPRSLRVRLALEEKGLPYELVPVDLGEGEQeEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71
GST_N_3 pfam13417
Glutathione S-transferase, N-terminal domain;
191-254 2.62e-05

Glutathione S-transferase, N-terminal domain;


Pssm-ID: 433190 [Multi-domain]  Cd Length: 75  Bit Score: 41.83  E-value: 2.62e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767940232  191 CPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEET 254
Cdd:pfam13417   7 SPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEEL 70
GST_N_Omega_like cd03060
GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to ...
 191-252 2.86e-05

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.


Pssm-ID: 239358 [Multi-domain]  Cd Length: 71  Bit Score: 41.57  E-value: 2.86e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767940232 191 CPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAP-GTHPPFLTFNGDVktdvnkIEEFLE 252
Cdd:cd03060    9 CPYAMRARMALLLAGITVELREVELKNKPAEMLAASPkGTVPVLVLGNGTV------IEESLD 65
GST_N_SspA cd03059
GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP) ...
 190-253 2.29e-04

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.


Pssm-ID: 239357 [Multi-domain]  Cd Length: 73  Bit Score: 39.23  E-value: 2.29e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767940232 190 NCPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEE 253
Cdd:cd03059    8 DDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDE 71
GST_C_DHAR cd03201
C-terminal, alpha helical domain of Dehydroascorbate Reductase; Glutathione S-transferase (GST) ...
 269-358 2.84e-04

C-terminal, alpha helical domain of Dehydroascorbate Reductase; Glutathione S-transferase (GST) C-terminal domain family, Dehydroascorbate Reductase (DHAR) subfamily; composed of plant-specific DHARs, which are monomeric enzymes catalyzing the reduction of DHA into ascorbic acid (AsA) using glutathione as the reductant. DHAR allows plants to recycle oxidized AsA before it is lost. AsA serves as a cofactor of violaxanthin de-epoxidase in the xanthophyll cycle and as an antioxidant in the detoxification of reactive oxygen species. Because AsA is the major reductant in plants, DHAR serves to regulate their redox state. It has been suggested that a significant portion of DHAR activity is plastidic, acting to reduce the large amounts of ascorbate oxidized during hydrogen peroxide scavenging by ascorbate peroxidase. DHAR contains a conserved cysteine in its active site and in addition to its reductase activity, shows thiol transferase activity similar to glutaredoxins.


Pssm-ID: 198310  Cd Length: 121  Bit Score: 40.09  E-value: 2.84e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 269 ESNTAGIDIFSKFSAYIKnTKQQNNAAlERGLTKALKKLDDYLNTPLPeeidantcgedkgsrrkFLDGDELTLADCNLL 348
Cdd:cd03201    6 EFASVGSKIFSTFVTFLK-SKDANDGS-EQALLDELTALDEHLKTNGP-----------------FIAGEKITAVDLSLA 66

                         90
                 ....*....|
gi 767940232 349 PKLHVVKTHL 358
Cdd:cd03201   67 PKLYHLRVAL 76
GstA COG0625
Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];
190-357 4.77e-04

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440390 [Multi-domain]  Cd Length: 205  Bit Score: 41.03  E-value: 4.77e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 190 NCPFSQRLFMILWLKGVVFNVTTVDLKR---KPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEET-----LTPEkYP 261
Cdd:COG0625    9 PSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERypeppLLPA-DP 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 262 KLAAKHRE-----SNTAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLntplpeeidantcgedkgSRRKFLD 336
Cdd:COG0625   88 AARARVRQwlawaDGDLHPALRNLLERLAPEKDPAAIARARAELARLLAVLEARL------------------AGGPYLA 149

                        170       180
                 ....*....|....*....|.
gi 767940232 337 GDELTLADCNLLPKLHVVKTH 357
Cdd:COG0625  150 GDRFSIADIALAPVLRRLDRL 170
GST_C_EF1Bgamma_like cd03181
Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of ...
 284-349 1.90e-03

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds to membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.


Pssm-ID: 198290 [Multi-domain]  Cd Length: 123  Bit Score: 37.93  E-value: 1.90e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767940232 284 YIKNTKQQNNAALERgLTKALKKLDDYLNTplpeeidantcgedkgsrRKFLDGDELTLAD----CNLLP 349
Cdd:cd03181   30 IAPYNKKAVDKAKED-LKRALGVLEEHLLT------------------RTYLVGERITLADifvaSALLR 80
GST_N_Omega cd03055
GST_N family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular ...
 191-252 9.40e-03

GST_N family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.


Pssm-ID: 239353 [Multi-domain]  Cd Length: 89  Bit Score: 35.02  E-value: 9.40e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767940232 191 CPFSQRLFMILWLKGVVFNVTTVDLKRKPADLHNLAP-GTHPPFLTFNGDVKTDVNKIEEFLE 252
Cdd:cd03055   27 CPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPqGKVPALEIDEGKVVYESLIICEYLD 89
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH