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UniProtKB - O15247 (CLIC2_HUMAN)

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Protein

Chloride intracellular channel protein 2

Gene

CLIC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • chloride transmembrane transport Source: GO_Central
  • 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
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionChloride channel, Ion channel, Voltage-gated channel
Biological processIon transport, Transport
LigandChloride

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
R-HSA-5578775 Ion homeostasis

Protein family/group databases

TCDBi1.A.12.1.5 the intracellular chloride channel (clic) family

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride intracellular channel protein 2
Alternative name(s):
XAP121
Gene namesi
Name:CLIC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000155962.12
HGNCiHGNC:2063 CLIC2
MIMi300138 gene
neXtProtiNX_O15247

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei32 – 52Helical; Note=After insertion into the membraneSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked, syndromic, 32 (MRXS32)1 Publication
The disease is caused by mutations 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.
See also OMIM:300886
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068898101H → 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 mutation, Mental retardation

Organism-specific databases

DisGeNETi1193
MalaCardsiCLIC2
MIMi300886 phenotype
OpenTargetsiENSG00000155962
Orphaneti324410 X-linked intellectual disability - cardiomegaly - congestive heart failure
PharmGKBiPA26589

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001442051 – 247Chloride intracellular channel protein 2Add BLAST247

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 33In soluble form2 Publications

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiO15247
MaxQBiO15247
PaxDbiO15247
PeptideAtlasiO15247
PRIDEiO15247
ProteomicsDBi48540

PTM databases

iPTMnetiO15247
PhosphoSitePlusiO15247

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

BgeeiENSG00000155962
CleanExiHS_CLIC2
ExpressionAtlasiO15247 baseline and differential
GenevisibleiO15247 HS

Organism-specific databases

HPAiHPA047381
HPA060101

Interactioni

Subunit structurei

Monomer. Interacts with TRAPPC2 and RYR2.4 Publications

Protein-protein interaction databases

BioGridi107605, 6 interactors
IntActiO15247, 2 interactors
STRINGi9606.ENSP00000358460

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 20Combined sources7
Beta strandi24 – 27Combined sources4
Helixi31 – 43Combined sources13
Beta strandi48 – 52Combined sources5
Helixi57 – 60Combined sources4
Beta strandi68 – 70Combined sources3
Beta strandi72 – 75Combined sources4
Beta strandi78 – 80Combined sources3
Helixi83 – 93Combined sources11
Turni96 – 98Combined sources3
Helixi108 – 111Combined sources4
Turni112 – 115Combined sources4
Helixi116 – 125Combined sources10
Helixi129 – 131Combined sources3
Helixi132 – 151Combined sources20
Turni160 – 162Combined sources3
Beta strandi163 – 165Combined sources3
Beta strandi172 – 178Combined sources7
Helixi181 – 201Combined sources21
Helixi210 – 220Combined sources11
Helixi223 – 226Combined sources4
Helixi232 – 239Combined sources8
Turni240 – 242Combined sources3

3D structure databases

ProteinModelPortaliO15247
SMRiO15247
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15247

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini99 – 239GST C-terminalAdd BLAST141

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 96Required for insertion into the membraneBy similarityAdd BLAST96
Regioni1 – 94N-terminalAdd BLAST94
Regioni95 – 106Joint loopAdd BLAST12
Regioni107 – 247C-terminalAdd BLAST141
Regioni151 – 171Foot loopAdd BLAST21

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 helix

Phylogenomic databases

eggNOGiKOG1422 Eukaryota
ENOG410ZRK6 LUCA
GeneTreeiENSGT00550000074477
HOGENOMiHOG000231548
HOVERGENiHBG050994
InParanoidiO15247
KOiK05022
OMAiSHTCPAD
OrthoDBiEOG091G0IHT
PhylomeDBiO15247
TreeFamiTF315438

Family and domain databases

InterProiView protein in InterPro
IPR002946 CLIC
IPR030253 CLIC-2
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR004045 Glutathione_S-Trfase_N
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR43920:SF4 PTHR43920:SF4, 1 hit
PfamiView protein in Pfam
PF13409 GST_N_2, 1 hit
PRINTSiPR01263 INTCLCHANNEL
SUPFAMiSSF47616 SSF47616, 1 hit
SSF52833 SSF52833, 1 hit
TIGRFAMsiTIGR00862 O-ClC, 1 hit
PROSITEiView protein in PROSITE
PS50405 GST_CTER, 1 hit

Sequencei

Sequence statusi: Complete.

O15247-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:247
Mass (Da):28,356
Last modified:September 13, 2005 - v3
Checksum:i9DB896034DD103E8
GO

Sequence cautioni

The sequence CAA73228 differs from that shown. Reason: Frameshift at position 244.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti109S → C in CAA03948 (PubMed:9339381).Curated1
Sequence conflicti164E → G in CAA73228 (PubMed:9339381).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068898101H → 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
CCDSiCCDS14767.1
RefSeqiNP_001280.3, NM_001289.5
UniGeneiHs.655445

Genome annotation databases

EnsembliENST00000369449; ENSP00000358460; ENSG00000155962
GeneIDi1193
KEGGihsa:1193
UCSCiuc004fnf.5 human

Similar proteinsi

Entry informationi

Entry nameiCLIC2_HUMAN
AccessioniPrimary (citable) accession number: O15247
Secondary accession number(s): A8K9S0
, O15174, Q5JT80, Q8TCE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 13, 2005
Last modified: July 18, 2018
This is version 162 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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