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O15247 (CLIC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chloride intracellular channel protein 2
Alternative name(s):
XAP121
Gene names
Name:CLIC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length247 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.11

Subunit structure

Monomer. Interacts with TRAPPC2 and RYR2. Ref.6 Ref.7 Ref.8 Ref.11

Subcellular location

Cytoplasm. Membrane; Single-pass membrane protein Probable. Note: Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain. Ref.8

Tissue specificity

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. Ref.7 Ref.10

Domain

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.

Involvement in disease

Mental retardation, X-linked, syndromic, 32 (MRXS32) [MIM:300886]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the chloride channel CLIC family.

Contains 1 GST C-terminal domain.

Sequence caution

The sequence CAA73228.1 differs from that shown. Reason: Frameshift at position 244.

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCytoplasm
Membrane
   DiseaseDisease mutation
Mental retardation
   DomainTransmembrane
Transmembrane helix
   LigandChloride
   Molecular functionChloride channel
Ion channel
Voltage-gated channel
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchloride transmembrane transport

Traceable author statement Ref.1. Source: GOC

negative regulation of ryanodine-sensitive calcium-release channel activity

Inferred from direct assay Ref.7Ref.8. Source: BHF-UCL

oxidation-reduction process

Inferred from direct assay Ref.7. Source: GOC

positive regulation of binding

Inferred from direct assay Ref.8. Source: BHF-UCL

regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Inferred by curator Ref.7. Source: BHF-UCL

regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum

Inferred from direct assay Ref.7Ref.8. Source: BHF-UCL

signal transduction

Traceable author statement PubMed 16130169. Source: UniProtKB

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentchloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Traceable author statement PubMed 16130169. Source: UniProtKB

intracellular

Inferred from direct assay. Source: LIFEdb

nucleus

Traceable author statement PubMed 16130169. Source: UniProtKB

   Molecular_functionchloride channel activity

Traceable author statement Ref.1. Source: ProtInc

glutathione peroxidase activity

Inferred from direct assay Ref.7. Source: BHF-UCL

voltage-gated chloride channel activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 247247Chloride intracellular channel protein 2
PRO_0000144205

Regions

Transmembrane32 – 5221Helical; Note=After insertion into the membrane; Potential
Domain99 – 239141GST C-terminal
Region1 – 9696Required for insertion into the membrane By similarity
Region1 – 9494N-terminal
Region95 – 10612Joint loop
Region107 – 247141C-terminal
Region151 – 17121Foot loop

Amino acid modifications

Disulfide bond30 ↔ 33In soluble form Ref.11 Ref.12

Natural variations

Natural variant1011H → 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. Ref.10
VAR_068898

Experimental info

Sequence conflict1091S → C in CAA03948. Ref.1
Sequence conflict1641E → G in CAA73228. Ref.1

Secondary structure

.......................................... 247
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O15247 [UniParc].

Last modified September 13, 2005. Version 3.
Checksum: 9DB896034DD103E8

FASTA24728,356
        10         20         30         40         50         60 
MSGLRPGTQV DPEIELFVKA GSDGESIGNC PFCQRLFMIL WLKGVKFNVT TVDMTRKPEE 

        70         80         90        100        110        120 
LKDLAPGTNP PFLVYNKELK TDFIKIEEFL EQTLAPPRYP HLSPKYKESF DVGCNLFAKF 

       130        140        150        160        170        180 
SAYIKNTQKE ANKNFEKSLL KEFKRLDDYL NTPLLDEIDP DSAEEPPVSR RLFLDGDQLT 

       190        200        210        220        230        240 
LADCSLLPKL NIIKVAAKKY RDFDIPAEFS GVWRYLHNAY AREEFTHTCP EDKEIENTYA 


NVAKQKS 

« Hide

References

« Hide 'large scale' references
[1]"Genomic structure of a novel chloride channel gene, CLIC2, in Xq28."
Heiss N.S., Poustka A.
Genomics 45:224-228(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Trachea.
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]"Interaction of sedlin with chloride intracellular channel proteins."
Fan L., Yu W., Zhu X.
FEBS Lett. 540:77-80(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAPPC2.
[7]"CLIC-2 modulates cardiac ryanodine receptor Ca2+ release channels."
Board P.G., Coggan M., Watson S., Gage P.W., Dulhunty A.F.
Int. J. Biochem. Cell Biol. 36:1599-1612(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, 3D-STRUCTURE MODELING, TISSUE SPECIFICITY, INTERACTION WITH RYR2.
[8]"A recently identified member of the glutathione transferase structural family modifies cardiac RyR2 substate activity, coupled gating and activation by Ca2+ and ATP."
Dulhunty A.F., Pouliquin P., Coggan M., Gage P.W., Board P.G.
Biochem. J. 390:333-343(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RYR2.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"An X-linked channelopathy with cardiomegaly due to a CLIC2 mutation enhancing ryanodine receptor channel activity."
Takano K., Liu D., Tarpey P., Gallant E., Lam A., Witham S., Alexov E., Chaubey A., Stevenson R.E., Schwartz C.E., Board P.G., Dulhunty A.F.
Hum. Mol. Genet. 21:4497-4507(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANT MRXS32 GLN-101, CHARACTERIZATION OF VARIANT MRXS32 GLN-101.
[11]"Structure of the Janus protein human CLIC2."
Cromer B.A., Gorman M.A., Hansen G., Adams J.J., Coggan M., Littler D.R., Brown L.J., Mazzanti M., Breit S.N., Curmi P.M.G., Dulhunty A.F., Board P.G., Parker M.W.
J. Mol. Biol. 374:719-731(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, SUBUNIT, FUNCTION, PH DEPENDENCE, DISULFIDE BOND.
[12]"The crystal structure of human chloride intracellular channel protein 2: a disulfide bond with functional implications."
Mi W., Liang Y.-H., Li L., Su X.-D.
Proteins 71:509-513(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001280.3. NM_001289.5.
UniGeneHs.655445.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PERX-ray2.00A1-247[»]
2R4VX-ray1.85A1-247[»]
2R5GX-ray1.86A1-247[»]
ProteinModelPortalO15247.
SMRO15247. Positions 11-247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107605. 5 interactions.
IntActO15247. 1 interaction.
MINTMINT-4713986.
STRING9606.ENSP00000358460.

Protein family/group databases

TCDB1.A.12.1.5. the intracellular chloride channel (clic) family.

PTM databases

PhosphoSiteO15247.

Proteomic databases

PaxDbO15247.
PRIDEO15247.

Protocols and materials databases

DNASU1193.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369449; ENSP00000358460; ENSG00000155962.
ENST00000596972; ENSP00000469202; ENSG00000268943.
GeneID1193.
KEGGhsa:1193.
UCSCuc004fnf.3. human.

Organism-specific databases

CTD1193.
GeneCardsGC0XM154505.
HGNCHGNC:2063. CLIC2.
HPAHPA060101.
MIM300138. gene.
300886. phenotype.
neXtProtNX_O15247.
Orphanet324410. X-linked intellectual deficit - cardiomegaly - congestive heart failure.
PharmGKBPA26589.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282171.
HOGENOMHOG000231548.
HOVERGENHBG050994.
InParanoidO15247.
KOK05022.
OMAPHLSPKN.
PhylomeDBO15247.
TreeFamTF315438.

Gene expression databases

ArrayExpressO15247.
BgeeO15247.
CleanExHS_CLIC2.
GenevestigatorO15247.

Family and domain databases

Gene3D1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR002946. Int_Cl_channel.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERPTHR11260:SF1. PTHR11260:SF1. 1 hit.
PfamPF13417. GST_N_3. 1 hit.
[Graphical view]
PRINTSPR01263. INTCLCHANNEL.
SUPFAMSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
TIGRFAMsTIGR00862. O-ClC. 1 hit.
PROSITEPS50405. GST_CTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO15247.
GeneWikiCLIC2.
GenomeRNAi1193.
NextBio4932.
PROO15247.
SOURCESearch...

Entry information

Entry nameCLIC2_HUMAN
AccessionPrimary (citable) accession number: O15247
Secondary accession number(s): A8K9S0 expand/collapse secondary AC list , O15174, Q5JT80, Q8TCE3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 13, 2005
Last modified: April 16, 2014
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM