UniProtKB - Q9NZA1 (CLIC5_HUMAN)
Protein
Chloride intracellular channel protein 5
Gene
CLIC5
Organism
Homo sapiens (Human)
Status
Functioni
Required for normal hearing (PubMed:24781754). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti (By similarity). Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. May play a role in the regulation of transepithelial ion absorption and secretion. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture (PubMed:15184393, PubMed:18028448, PubMed:20335315). Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens (By similarity).By similarity4 Publications
GO - Molecular functioni
- chloride channel activity Source: UniProtKB-KW
- voltage-gated ion channel activity Source: UniProtKB-KW
GO - Biological processi
- chloride transport Source: UniProtKB
- female pregnancy Source: ProtInc
- regulation of ion transmembrane transport Source: UniProtKB-KW
- response to stimulus Source: UniProtKB-KW
- sensory perception of sound Source: UniProtKB
- visual perception Source: UniProtKB-KW
Keywordsi
Molecular function | Chloride channel, Ion channel, Voltage-gated channel |
Biological process | Hearing, Ion transport, Sensory transduction, Transport, Vision |
Ligand | Chloride |
Enzyme and pathway databases
PathwayCommonsi | Q9NZA1 |
Names & Taxonomyi
Protein namesi | Recommended name: Chloride intracellular channel protein 5 |
Gene namesi | Name:CLIC5 |
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
EuPathDBi | HostDB:ENSG00000112782.15 |
HGNCi | HGNC:13517, CLIC5 |
MIMi | 607293, gene |
neXtProti | NX_Q9NZA1 |
Subcellular locationi
Plasma membrane
- Apical cell membrane 1 Publication; Single-pass membrane protein Sequence analysis
Cytoskeleton
- cytoskeleton 2 Publications
Other locations
- cell cortex 1 Publication
- Membrane 1 Publication1 Publication; Single-pass membrane protein Sequence analysis
- Cytoplasm By similarity
Note: Associates with the cortical actin cytoskeleton (PubMed:10793131, PubMed:15184393). Localizes to the apical region of cochlear hair cells, at the base of the actin-rich hair bundle (By similarity). Colocalizes with podocalyxin at the apical cell membrane in renal glomeruli (PubMed:20335315). May localize to the centrosome in lens epithelial cells (By similarity). Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain (By similarity).By similarity3 Publications
Cytoskeleton
- centrosome 1 Publication
Golgi apparatus
- Golgi apparatus 1 Publication
Note: Colocalizes with AKAP9 at the Golgi apparatus as well as, to a lesser extent, the centrosome.1 Publication
Cytoskeleton
- actin cytoskeleton Source: UniProtKB
- microtubule organizing center Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB-SubCell
Other locations
- cell cortex Source: UniProtKB-SubCell
- chloride channel complex Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 193 – 213 | Helical; Note=After insertion into the membraneSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, MembranePathology & Biotechi
Involvement in diseasei
Deafness, autosomal recessive, 103 (DFNB103)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of sensorineural deafness with onset in early childhood. Hearing impairment progresses from mild to severe or even profound before the second decade, and is accompanied by vestibular areflexia.
Related information in OMIMKeywords - Diseasei
Deafness, Non-syndromic deafnessOrganism-specific databases
DisGeNETi | 53405 |
MalaCardsi | CLIC5 |
MIMi | 616042, phenotype |
OpenTargetsi | ENSG00000112782 |
Orphaneti | 90636, Autosomal recessive non-syndromic sensorineural deafness type DFNB |
PharmGKBi | PA26592 |
Miscellaneous databases
Pharosi | Q9NZA1, Tbio |
Polymorphism and mutation databases
BioMutai | CLIC5 |
DMDMi | 215274174 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144214 | 1 – 410 | Chloride intracellular channel protein 5Add BLAST | 410 |
Proteomic databases
EPDi | Q9NZA1 |
jPOSTi | Q9NZA1 |
MassIVEi | Q9NZA1 |
MaxQBi | Q9NZA1 |
PaxDbi | Q9NZA1 |
PeptideAtlasi | Q9NZA1 |
PRIDEi | Q9NZA1 |
ProteomicsDBi | 72834 83343 [Q9NZA1-1] 83344 [Q9NZA1-2] |
2D gel databases
OGPi | Q9NZA1 |
PTM databases
iPTMneti | Q9NZA1 |
PhosphoSitePlusi | Q9NZA1 |
Expressioni
Tissue specificityi
Widely expressed in both fetal and adult human tissues (PubMed:24781754). Isoform 1 is expressed in renal glomeruli endothelial cells and podocytes (at protein level).2 Publications
Gene expression databases
Bgeei | ENSG00000112782, Expressed in renal glomerulus and 220 other tissues |
ExpressionAtlasi | Q9NZA1, baseline and differential |
Genevisiblei | Q9NZA1, HS |
Organism-specific databases
HPAi | ENSG00000112782, Tissue enhanced (heart muscle, intestine, skeletal muscle) |
Interactioni
Subunit structurei
Component of a multimeric complex consisting of several cytoskeletal proteins, including actin, ezrin, alpha-actinin, gelsolin, and IQGAP1.
Interacts with AKAP9.
2 PublicationsBinary interactionsi
Hide detailsQ9NZA1
With | #Exp. | IntAct |
---|---|---|
SRC [P00523] from Gallus gallus. | 2 | EBI-5658997,EBI-848039 |
Isoform 1 [Q9NZA1-2]
With | #Exp. | IntAct |
---|---|---|
TPRN - isoform 2 [Q4KMQ1-2] | 6 | EBI-13076412,EBI-11978969 |
Protein-protein interaction databases
BioGRIDi | 119781, 7 interactors |
CORUMi | Q9NZA1 |
IntActi | Q9NZA1, 9 interactors |
MINTi | Q9NZA1 |
STRINGi | 9606.ENSP00000185206 |
Miscellaneous databases
RNActi | Q9NZA1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9NZA1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 260 – 400 | GST C-terminalAdd BLAST | 141 |
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 (By similarity).By similarity
Sequence similaritiesi
Belongs to the chloride channel CLIC family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1422, Eukaryota |
GeneTreei | ENSGT00940000156406 |
HOGENOMi | CLU_048291_0_0_1 |
InParanoidi | Q9NZA1 |
OMAi | FTNQRET |
OrthoDBi | 974249at2759 |
PhylomeDBi | Q9NZA1 |
TreeFami | TF315438 |
Family and domain databases
CDDi | cd10297, GST_C_CLIC5, 1 hit |
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR002946, CLIC IPR030264, CLIC-5 IPR042069, CLIC5_C_GST 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 | PTHR45476:SF4, PTHR45476: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 |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 2 (identifier: Q9NZA1-1) [UniParc]FASTAAdd to basket
Also known as: CLIC5B
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNDEDYSTIY DTIQNERTYE VPDQPEENES PHYDDVHEYL RPENDLYATQ
60 70 80 90 100
LNTHEYDFVS VYTIKGEETS LASVQSEDRG YLLPDEIYSE LQEAHPGEPQ
110 120 130 140 150
EDRGISMEGL YSSTQDQQLC AAELQENGSV MKEDLPSPSS FTIQHSKAFS
160 170 180 190 200
TTKYSCYSDA EGLEEKEGAH MNPEIYLFVK AGIDGESIGN CPFSQRLFMI
210 220 230 240 250
LWLKGVVFNV TTVDLKRKPA DLHNLAPGTH PPFLTFNGDV KTDVNKIEEF
260 270 280 290 300
LEETLTPEKY PKLAAKHRES NTAGIDIFSK FSAYIKNTKQ QNNAALERGL
310 320 330 340 350
TKALKKLDDY LNTPLPEEID ANTCGEDKGS RRKFLDGDEL TLADCNLLPK
360 370 380 390 400
LHVVKIVAKK YRNYDIPAEM TGLWRYLKNA YARDEFTNTC AADSEIELAY
410
ADVAKRLSRS
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8Y615 | A0A2R8Y615_HUMAN | Chloride intracellular channel prot... | CLIC5 | 242 | Annotation score: | ||
A0A2R8Y4M1 | A0A2R8Y4M1_HUMAN | Chloride intracellular channel prot... | CLIC5 | 200 | Annotation score: | ||
A0A2R8YGW2 | A0A2R8YGW2_HUMAN | Chloride intracellular channel prot... | CLIC5 | 222 | Annotation score: | ||
A0A5F9ZHK1 | A0A5F9ZHK1_HUMAN | Chloride intracellular channel prot... | CLIC5 | 219 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 201 | L → F in AAK52083 (PubMed:12163479).Curated | 1 | ||
Isoform 1 (identifier: Q9NZA1-2) | |||||
Sequence conflicti | 12 | R → S in AAF66928 (PubMed:10793131).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059208 | 114 | T → A. Corresponds to variant dbSNP:rs723580EnsemblClinVar. | 1 | |
Natural variantiVAR_047541 | 257 | P → H. Corresponds to variant dbSNP:rs35822882Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000869 | 1 – 159 | Missing in isoform 1. 3 PublicationsAdd BLAST | 159 | |
Alternative sequenceiVSP_044889 | 1 – 17 | MNDED…IQNER → MTDSATANGDDRDPEIE in isoform 3. 1 PublicationAdd BLAST | 17 | |
Alternative sequenceiVSP_044890 | 18 – 176 | Missing in isoform 3. 1 PublicationAdd BLAST | 159 | |
Alternative sequenceiVSP_000870 | 160 – 180 | AEGLE…YLFVK → MTDSATANGDDRDPEIELFV K in isoform 1. 3 PublicationsAdd BLAST | 21 | |
Alternative sequenceiVSP_044891 | 356 – 410 | IVAKK…RLSRS → EQVPLKGMI in isoform 3. 1 PublicationAdd BLAST | 55 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF216941 mRNA Translation: AAF66928.1 AY032602 mRNA Translation: AAK52083.1 AK075163 mRNA Translation: BAC11444.1 AK097048 mRNA Translation: BAG53413.1 AK075144 mRNA Translation: BAC11432.1 AL050336 Genomic DNA No translation available. AL357057 Genomic DNA No translation available. AL355522 Genomic DNA No translation available. AL591211 Genomic DNA No translation available. CH471081 Genomic DNA Translation: EAX04286.1 CH471081 Genomic DNA Translation: EAX04287.1 BC035968 mRNA Translation: AAH35968.1 |
CCDSi | CCDS47438.1 [Q9NZA1-1] CCDS4914.1 [Q9NZA1-2] CCDS59022.1 [Q9NZA1-3] |
RefSeqi | NP_001107558.1, NM_001114086.1 [Q9NZA1-1] NP_001242952.1, NM_001256023.1 [Q9NZA1-3] NP_058625.2, NM_016929.4 [Q9NZA1-2] XP_016866442.1, XM_017010953.1 |
Genome annotation databases
Ensembli | ENST00000185206; ENSP00000185206; ENSG00000112782 [Q9NZA1-1] ENST00000339561; ENSP00000344165; ENSG00000112782 [Q9NZA1-2] ENST00000544153; ENSP00000439195; ENSG00000112782 [Q9NZA1-3] |
GeneIDi | 53405 |
KEGGi | hsa:53405 |
UCSCi | uc003oxu.5, human [Q9NZA1-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF216941 mRNA Translation: AAF66928.1 AY032602 mRNA Translation: AAK52083.1 AK075163 mRNA Translation: BAC11444.1 AK097048 mRNA Translation: BAG53413.1 AK075144 mRNA Translation: BAC11432.1 AL050336 Genomic DNA No translation available. AL357057 Genomic DNA No translation available. AL355522 Genomic DNA No translation available. AL591211 Genomic DNA No translation available. CH471081 Genomic DNA Translation: EAX04286.1 CH471081 Genomic DNA Translation: EAX04287.1 BC035968 mRNA Translation: AAH35968.1 |
CCDSi | CCDS47438.1 [Q9NZA1-1] CCDS4914.1 [Q9NZA1-2] CCDS59022.1 [Q9NZA1-3] |
RefSeqi | NP_001107558.1, NM_001114086.1 [Q9NZA1-1] NP_001242952.1, NM_001256023.1 [Q9NZA1-3] NP_058625.2, NM_016929.4 [Q9NZA1-2] XP_016866442.1, XM_017010953.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6Y2H | X-ray | 2.15 | A/B/C/D | 175-410 | [»] | |
SMRi | Q9NZA1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 119781, 7 interactors |
CORUMi | Q9NZA1 |
IntActi | Q9NZA1, 9 interactors |
MINTi | Q9NZA1 |
STRINGi | 9606.ENSP00000185206 |
PTM databases
iPTMneti | Q9NZA1 |
PhosphoSitePlusi | Q9NZA1 |
Polymorphism and mutation databases
BioMutai | CLIC5 |
DMDMi | 215274174 |
2D gel databases
OGPi | Q9NZA1 |
Proteomic databases
EPDi | Q9NZA1 |
jPOSTi | Q9NZA1 |
MassIVEi | Q9NZA1 |
MaxQBi | Q9NZA1 |
PaxDbi | Q9NZA1 |
PeptideAtlasi | Q9NZA1 |
PRIDEi | Q9NZA1 |
ProteomicsDBi | 72834 83343 [Q9NZA1-1] 83344 [Q9NZA1-2] |
Protocols and materials databases
Antibodypediai | 16850, 243 antibodies |
DNASUi | 53405 |
Genome annotation databases
Ensembli | ENST00000185206; ENSP00000185206; ENSG00000112782 [Q9NZA1-1] ENST00000339561; ENSP00000344165; ENSG00000112782 [Q9NZA1-2] ENST00000544153; ENSP00000439195; ENSG00000112782 [Q9NZA1-3] |
GeneIDi | 53405 |
KEGGi | hsa:53405 |
UCSCi | uc003oxu.5, human [Q9NZA1-1] |
Organism-specific databases
CTDi | 53405 |
DisGeNETi | 53405 |
EuPathDBi | HostDB:ENSG00000112782.15 |
GeneCardsi | CLIC5 |
HGNCi | HGNC:13517, CLIC5 |
HPAi | ENSG00000112782, Tissue enhanced (heart muscle, intestine, skeletal muscle) |
MalaCardsi | CLIC5 |
MIMi | 607293, gene 616042, phenotype |
neXtProti | NX_Q9NZA1 |
OpenTargetsi | ENSG00000112782 |
Orphaneti | 90636, Autosomal recessive non-syndromic sensorineural deafness type DFNB |
PharmGKBi | PA26592 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1422, Eukaryota |
GeneTreei | ENSGT00940000156406 |
HOGENOMi | CLU_048291_0_0_1 |
InParanoidi | Q9NZA1 |
OMAi | FTNQRET |
OrthoDBi | 974249at2759 |
PhylomeDBi | Q9NZA1 |
TreeFami | TF315438 |
Enzyme and pathway databases
PathwayCommonsi | Q9NZA1 |
Miscellaneous databases
BioGRID-ORCSi | 53405, 4 hits in 841 CRISPR screens |
ChiTaRSi | CLIC5, human |
GeneWikii | CLIC5 |
GenomeRNAii | 53405 |
Pharosi | Q9NZA1, Tbio |
PROi | PR:Q9NZA1 |
RNActi | Q9NZA1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000112782, Expressed in renal glomerulus and 220 other tissues |
ExpressionAtlasi | Q9NZA1, baseline and differential |
Genevisiblei | Q9NZA1, HS |
Family and domain databases
CDDi | cd10297, GST_C_CLIC5, 1 hit |
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR002946, CLIC IPR030264, CLIC-5 IPR042069, CLIC5_C_GST 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 | PTHR45476:SF4, PTHR45476: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 | CLIC5_HUMAN | |
Accessioni | Q9NZA1Primary (citable) accession number: Q9NZA1 Secondary accession number(s): B3KUF1 Q9BWZ0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 27, 2002 |
Last sequence update: | November 25, 2008 | |
Last modified: | December 2, 2020 | |
This is version 186 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 chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - 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 entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations