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Protein

Chloride intracellular channel protein 5

Gene

CLIC5

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

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).By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

  • auditory receptor cell stereocilium organization Source: GO_Central
  • chloride transmembrane transport Source: GO_Central
  • chloride transport Source: UniProtKB
  • female pregnancy Source: ProtInc
  • regulation of ion transmembrane transport Source: UniProtKB-KW
  • sensory perception of sound Source: UniProtKB

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride intracellular channel protein 5
Gene namesi
Name:CLIC5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112782.15
HGNCiHGNC:13517 CLIC5
MIMi607293 gene
neXtProtiNX_Q9NZA1

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
Transmembranei193 – 213Helical; Note=After insertion into the membraneSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane

Pathology & 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.
See also OMIM:616042

Keywords - Diseasei

Deafness, Non-syndromic deafness

Organism-specific databases

DisGeNETi53405
MalaCardsiCLIC5
MIMi616042 phenotype
OpenTargetsiENSG00000112782
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA26592

Polymorphism and mutation databases

BioMutaiCLIC5
DMDMi215274174

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001442141 – 410Chloride intracellular channel protein 5Add BLAST410

Proteomic databases

EPDiQ9NZA1
MaxQBiQ9NZA1
PaxDbiQ9NZA1
PeptideAtlasiQ9NZA1
PRIDEiQ9NZA1
ProteomicsDBi83343
83344 [Q9NZA1-2]

2D gel databases

OGPiQ9NZA1

PTM databases

iPTMnetiQ9NZA1
PhosphoSitePlusiQ9NZA1

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

BgeeiENSG00000112782
CleanExiHS_CLIC5
ExpressionAtlasiQ9NZA1 baseline and differential
GenevisibleiQ9NZA1 HS

Organism-specific databases

HPAiHPA074371

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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SRCP005232EBI-5658997,EBI-848039From Gallus gallus.

Protein-protein interaction databases

BioGridi119781, 7 interactors
CORUMiQ9NZA1
IntActiQ9NZA1, 7 interactors
MINTiQ9NZA1
STRINGi9606.ENSP00000185206

Structurei

3D structure databases

ProteinModelPortaliQ9NZA1
SMRiQ9NZA1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini260 – 400GST C-terminalAdd BLAST141

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 helix

Phylogenomic databases

eggNOGiKOG1422 Eukaryota
ENOG410ZRK6 LUCA
GeneTreeiENSGT00550000074477
HOGENOMiHOG000065740
HOVERGENiHBG050995
InParanoidiQ9NZA1
KOiK05025
OMAiANGDDRD
OrthoDBiEOG091G0IHT
PhylomeDBiQ9NZA1
TreeFamiTF315438

Family and domain databases

InterProiView protein in InterPro
IPR002946 CLIC
IPR030264 CLIC-5
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR004045 Glutathione_S-Trfase_N
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR43920:SF6 PTHR43920:SF6, 1 hit
PfamiView protein in Pfam
PF13417 GST_N_3, 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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q9NZA1-1) [UniParc]FASTAAdd to basket
Also known as: CLIC5B

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:410
Mass (Da):46,503
Last modified:November 25, 2008 - v3
Checksum:iE26D307775F8354C
GO
Isoform 1 (identifier: Q9NZA1-2) [UniParc]FASTAAdd to basket
Also known as: CLIC5A

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: Missing.
     160-180: AEGLEEKEGAHMNPEIYLFVK → MTDSATANGDDRDPEIELFVK

Show »
Length:251
Mass (Da):28,179
Checksum:i1E8658EB7687C60D
GO
Isoform 3 (identifier: Q9NZA1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MNDEDYSTIYDTIQNER → MTDSATANGDDRDPEIE
     18-176: Missing.
     356-410: IVAKKYRNYDIPAEMTGLWRYLKNAYARDEFTNTCAADSEIELAYADVAKRLSRS → EQVPLKGMI

Note: No experimental confirmation available.
Show »
Length:205
Mass (Da):22,830
Checksum:i5F6C595B3B4842F2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti201L → F in AAK52083 (PubMed:12163479).Curated1
Isoform 1 (identifier: Q9NZA1-2)
Sequence conflicti12R → S in AAF66928 (PubMed:10793131).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059208114T → A. Corresponds to variant dbSNP:rs723580EnsemblClinVar.1
Natural variantiVAR_047541257P → H. Corresponds to variant dbSNP:rs35822882EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0008691 – 159Missing in isoform 1. 3 PublicationsAdd BLAST159
Alternative sequenceiVSP_0448891 – 17MNDED…IQNER → MTDSATANGDDRDPEIE in isoform 3. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_04489018 – 176Missing in isoform 3. 1 PublicationAdd BLAST159
Alternative sequenceiVSP_000870160 – 180AEGLE…YLFVK → MTDSATANGDDRDPEIELFV K in isoform 1. 3 PublicationsAdd BLAST21
Alternative sequenceiVSP_044891356 – 410IVAKK…RLSRS → EQVPLKGMI in isoform 3. 1 PublicationAdd BLAST55

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
CCDSiCCDS47438.1 [Q9NZA1-1]
CCDS4914.1 [Q9NZA1-2]
CCDS59022.1 [Q9NZA1-3]
RefSeqiNP_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 [Q9NZA1-1]
UniGeneiHs.485489
Hs.734348

Genome annotation databases

EnsembliENST00000185206; ENSP00000185206; ENSG00000112782 [Q9NZA1-1]
ENST00000339561; ENSP00000344165; ENSG00000112782 [Q9NZA1-2]
ENST00000544153; ENSP00000439195; ENSG00000112782 [Q9NZA1-3]
GeneIDi53405
KEGGihsa:53405
UCSCiuc003oxu.5 human [Q9NZA1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCLIC5_HUMAN
AccessioniPrimary (citable) accession number: Q9NZA1
Secondary accession number(s): B3KUF1
, Q5T4Z0, Q8NBY3, Q96JT5, Q9BWZ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: November 25, 2008
Last modified: June 20, 2018
This is version 168 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

Complete proteome, Reference proteome

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