UniProtKB - O15247 (CLIC2_HUMAN)
Protein
Chloride intracellular channel protein 2
Gene
CLIC2
Organism
Homo sapiens (Human)
Status
Functioni
Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Modulates the activity of RYR2 and inhibits calcium influx.3 Publications
GO - Molecular functioni
- chloride channel activity Source: GO_Central
- glutathione peroxidase activity Source: BHF-UCL
- voltage-gated ion channel activity Source: UniProtKB-KW
GO - Biological processi
- glutathione metabolic process Source: InterPro
- negative regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
- positive regulation of binding Source: BHF-UCL
- regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
- regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
- signal transduction Source: UniProtKB
Keywordsi
Molecular function | Chloride channel, Ion channel, Voltage-gated channel |
Biological process | Ion transport, Transport |
Ligand | Chloride |
Enzyme and pathway databases
PathwayCommonsi | O15247 |
Reactomei | R-HSA-2672351, Stimuli-sensing channels R-HSA-5578775, Ion homeostasis |
Protein family/group databases
TCDBi | 1.A.12.1.5, the intracellular chloride channel (clic) family |
Names & Taxonomyi
Protein namesi | Recommended name: Chloride intracellular channel protein 2Alternative name(s): XAP121 |
Gene namesi | Name:CLIC2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2063, CLIC2 |
MIMi | 300138, gene |
neXtProti | NX_O15247 |
VEuPathDBi | HostDB:ENSG00000155962.12 |
Subcellular locationi
Other locations
- Cytoplasm 1 Publication
- Membrane 1 Publication; Single-pass membrane protein 1 Publication
Note: Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain.
Nucleus
- nucleus Source: GO_Central
Other locations
- chloride channel complex Source: UniProtKB-KW
- cytoplasm Source: BHF-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 32 – 52 | Helical; Note=After insertion into the membraneSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Involvement in diseasei
Mental retardation, X-linked, syndromic, 32 (MRXS32)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA mental retardation syndrome characterized by profound intellectual deficit, delayed psychomotor development beginning in infancy and little or no speech development. Additional features include seizures, large joint contractures, and abnormal positioning of the thumbs. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_068898 | 101 | H → Q in MRXS32; results in stimulation of RYR channels activity with channels remaining open for longer times; the mutation may impair insertion of the protein into the membrane to form a functioning ion channel. 1 PublicationCorresponds to variant dbSNP:rs398122917EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, Mental retardationOrganism-specific databases
DisGeNETi | 1193 |
GeneReviewsi | CLIC2 |
MalaCardsi | CLIC2 |
MIMi | 300886, phenotype |
OpenTargetsi | ENSG00000155962 |
Orphaneti | 324410, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome |
PharmGKBi | PA26589 |
Miscellaneous databases
Pharosi | O15247, Tbio |
Genetic variation databases
BioMutai | CLIC2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144205 | 1 – 247 | Chloride intracellular channel protein 2Add BLAST | 247 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 30 ↔ 33 | In soluble form2 Publications |
Keywords - PTMi
Disulfide bondProteomic databases
EPDi | O15247 |
jPOSTi | O15247 |
MassIVEi | O15247 |
MaxQBi | O15247 |
PaxDbi | O15247 |
PeptideAtlasi | O15247 |
PRIDEi | O15247 |
ProteomicsDBi | 48540 |
PTM databases
iPTMneti | O15247 |
PhosphoSitePlusi | O15247 |
Expressioni
Tissue specificityi
Expressed in adult and fetal brain, heart, skeletal muscle, liver, lung, and spleen. Detected in adult stomach and testis. Expressed in fetal thymus and kidney.2 Publications
Gene expression databases
Bgeei | ENSG00000155962, Expressed in calcaneal tendon and 195 other tissues |
ExpressionAtlasi | O15247, baseline and differential |
Genevisiblei | O15247, HS |
Organism-specific databases
HPAi | ENSG00000155962, Tissue enhanced (thyroid gland, vagina) |
Interactioni
Subunit structurei
Monomer.
Interacts with TRAPPC2 and RYR2.
4 PublicationsBinary interactionsi
O15247
With | #Exp. | IntAct |
---|---|---|
TPRN - isoform 2 [Q4KMQ1-2] | 3 | EBI-6286019,EBI-11978969 |
Protein-protein interaction databases
BioGRIDi | 107605, 7 interactors |
IntActi | O15247, 4 interactors |
STRINGi | 9606.ENSP00000358460 |
Miscellaneous databases
RNActi | O15247, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O15247 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O15247 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 99 – 239 | GST C-terminalAdd BLAST | 141 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 96 | Required for insertion into the membraneBy similarityAdd BLAST | 96 | |
Regioni | 1 – 94 | N-terminalAdd BLAST | 94 | |
Regioni | 95 – 106 | Joint loopAdd BLAST | 12 | |
Regioni | 107 – 247 | C-terminalAdd BLAST | 141 | |
Regioni | 151 – 171 | Foot loopAdd BLAST | 21 |
Domaini
Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.
Sequence similaritiesi
Belongs to the chloride channel CLIC family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1422, Eukaryota |
GeneTreei | ENSGT00940000161397 |
HOGENOMi | CLU_061051_1_0_1 |
InParanoidi | O15247 |
OMAi | KFLDGDR |
OrthoDBi | 974249at2759 |
PhylomeDBi | O15247 |
TreeFami | TF315438 |
Family and domain databases
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR002946, CLIC IPR030253, CLIC-2 IPR010987, Glutathione-S-Trfase_C-like IPR036282, Glutathione-S-Trfase_C_sf IPR040079, Glutathione_S-Trfase IPR004045, Glutathione_S-Trfase_N IPR036249, Thioredoxin-like_sf |
PANTHERi | PTHR43920:SF4, PTHR43920:SF4, 1 hit |
Pfami | View protein in Pfam PF13409, GST_N_2, 1 hit |
PRINTSi | PR01263, INTCLCHANNEL |
SFLDi | SFLDS00019, Glutathione_Transferase_(cytos, 1 hit |
SUPFAMi | SSF47616, SSF47616, 1 hit SSF52833, SSF52833, 1 hit |
TIGRFAMsi | TIGR00862, O-ClC, 1 hit |
PROSITEi | View protein in PROSITE PS50405, GST_CTER, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O15247-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSGLRPGTQV DPEIELFVKA GSDGESIGNC PFCQRLFMIL WLKGVKFNVT
60 70 80 90 100
TVDMTRKPEE LKDLAPGTNP PFLVYNKELK TDFIKIEEFL EQTLAPPRYP
110 120 130 140 150
HLSPKYKESF DVGCNLFAKF SAYIKNTQKE ANKNFEKSLL KEFKRLDDYL
160 170 180 190 200
NTPLLDEIDP DSAEEPPVSR RLFLDGDQLT LADCSLLPKL NIIKVAAKKY
210 220 230 240
RDFDIPAEFS GVWRYLHNAY AREEFTHTCP EDKEIENTYA NVAKQKS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA6PVS0 | A6PVS0_HUMAN | Chloride intracellular channel 2 | CLIC2 RP13-228J13.7-004 | 133 | Annotation score: |
Sequence cautioni
The sequence CAA73228 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 109 | S → C in CAA03948 (PubMed:9339381).Curated | 1 | |
Sequence conflicti | 164 | E → G in CAA73228 (PubMed:9339381).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_068898 | 101 | H → Q in MRXS32; results in stimulation of RYR channels activity with channels remaining open for longer times; the mutation may impair insertion of the protein into the membrane to form a functioning ion channel. 1 PublicationCorresponds to variant dbSNP:rs398122917EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y12696 mRNA Translation: CAA73228.1 Frameshift. AJ000217, AJ000218, AJ000219 Genomic DNA Translation: CAA03948.1 AK292785 mRNA Translation: BAF85474.1 AL356738 Genomic DNA Translation: CAI41464.1 CH471172 Genomic DNA Translation: EAW72624.1 BC022305 mRNA Translation: AAH22305.1 |
CCDSi | CCDS14767.1 |
RefSeqi | NP_001280.3, NM_001289.5 |
Genome annotation databases
Ensembli | ENST00000369449; ENSP00000358460; ENSG00000155962 |
GeneIDi | 1193 |
KEGGi | hsa:1193 |
UCSCi | uc004fnf.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y12696 mRNA Translation: CAA73228.1 Frameshift. AJ000217, AJ000218, AJ000219 Genomic DNA Translation: CAA03948.1 AK292785 mRNA Translation: BAF85474.1 AL356738 Genomic DNA Translation: CAI41464.1 CH471172 Genomic DNA Translation: EAW72624.1 BC022305 mRNA Translation: AAH22305.1 |
CCDSi | CCDS14767.1 |
RefSeqi | NP_001280.3, NM_001289.5 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2PER | X-ray | 2.00 | A | 1-247 | [»] | |
2R4V | X-ray | 1.85 | A | 1-247 | [»] | |
2R5G | X-ray | 1.86 | A | 1-247 | [»] | |
SMRi | O15247 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107605, 7 interactors |
IntActi | O15247, 4 interactors |
STRINGi | 9606.ENSP00000358460 |
Protein family/group databases
TCDBi | 1.A.12.1.5, the intracellular chloride channel (clic) family |
PTM databases
iPTMneti | O15247 |
PhosphoSitePlusi | O15247 |
Genetic variation databases
BioMutai | CLIC2 |
Proteomic databases
EPDi | O15247 |
jPOSTi | O15247 |
MassIVEi | O15247 |
MaxQBi | O15247 |
PaxDbi | O15247 |
PeptideAtlasi | O15247 |
PRIDEi | O15247 |
ProteomicsDBi | 48540 |
Protocols and materials databases
Antibodypediai | 17894, 149 antibodies |
DNASUi | 1193 |
Genome annotation databases
Ensembli | ENST00000369449; ENSP00000358460; ENSG00000155962 |
GeneIDi | 1193 |
KEGGi | hsa:1193 |
UCSCi | uc004fnf.5, human |
Organism-specific databases
CTDi | 1193 |
DisGeNETi | 1193 |
GeneCardsi | CLIC2 |
GeneReviewsi | CLIC2 |
HGNCi | HGNC:2063, CLIC2 |
HPAi | ENSG00000155962, Tissue enhanced (thyroid gland, vagina) |
MalaCardsi | CLIC2 |
MIMi | 300138, gene 300886, phenotype |
neXtProti | NX_O15247 |
OpenTargetsi | ENSG00000155962 |
Orphaneti | 324410, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome |
PharmGKBi | PA26589 |
VEuPathDBi | HostDB:ENSG00000155962.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1422, Eukaryota |
GeneTreei | ENSGT00940000161397 |
HOGENOMi | CLU_061051_1_0_1 |
InParanoidi | O15247 |
OMAi | KFLDGDR |
OrthoDBi | 974249at2759 |
PhylomeDBi | O15247 |
TreeFami | TF315438 |
Enzyme and pathway databases
PathwayCommonsi | O15247 |
Reactomei | R-HSA-2672351, Stimuli-sensing channels R-HSA-5578775, Ion homeostasis |
Miscellaneous databases
BioGRID-ORCSi | 1193, 5 hits in 505 CRISPR screens |
ChiTaRSi | CLIC2, human |
EvolutionaryTracei | O15247 |
GeneWikii | CLIC2 |
GenomeRNAii | 1193 |
Pharosi | O15247, Tbio |
PROi | PR:O15247 |
RNActi | O15247, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000155962, Expressed in calcaneal tendon and 195 other tissues |
ExpressionAtlasi | O15247, baseline and differential |
Genevisiblei | O15247, HS |
Family and domain databases
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR002946, CLIC IPR030253, CLIC-2 IPR010987, Glutathione-S-Trfase_C-like IPR036282, Glutathione-S-Trfase_C_sf IPR040079, Glutathione_S-Trfase IPR004045, Glutathione_S-Trfase_N IPR036249, Thioredoxin-like_sf |
PANTHERi | PTHR43920:SF4, PTHR43920:SF4, 1 hit |
Pfami | View protein in Pfam PF13409, GST_N_2, 1 hit |
PRINTSi | PR01263, INTCLCHANNEL |
SFLDi | SFLDS00019, Glutathione_Transferase_(cytos, 1 hit |
SUPFAMi | SSF47616, SSF47616, 1 hit SSF52833, SSF52833, 1 hit |
TIGRFAMsi | TIGR00862, O-ClC, 1 hit |
PROSITEi | View protein in PROSITE PS50405, GST_CTER, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CLIC2_HUMAN | |
Accessioni | O15247Primary (citable) accession number: O15247 Secondary accession number(s): A8K9S0 Q8TCE3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | September 13, 2005 | |
Last modified: | February 10, 2021 | |
This is version 179 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants