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Q9NZA1 (CLIC5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chloride intracellular channel protein 5
Gene names
Name:CLIC5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length410 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Required for normal formation of stereocilia in the inner ear and normal development of the organ of Corti By similarity. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. Ref.8 Ref.9 Ref.10

Subunit structure

Component of a multimeric complex consisting of several cytoskeletal proteins, including actin, ezrin, alpha-actinin, gelsolin, and IQGAP1. Interacts with AKAP9. Ref.2 Ref.9

Subcellular location

Isoform 1: Cytoplasmcell cortex. Cytoplasmcytoskeleton. Membrane; Single-pass membrane protein. Note: Associates with the cortical actin cytoskeleton. Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain By similarity. Ref.2 Ref.8 Ref.9

Isoform 2: Golgi apparatus. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Membrane; Single-pass membrane protein. Note: Colocalized with AKAP9 at the Golgi apparatus as well as, to a lesser extent, the centrosome. Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain By similarity. Colocalized with podocalyxin in renal glomeruli. Ref.2 Ref.8 Ref.9

Tissue specificity

Isoform 1 is expressed in renal glomeruli endothelial cells and podocytes (at protein level). 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 By similarity.

Sequence similarities

Belongs to the chloride channel CLIC family.

Contains 1 GST C-terminal domain.

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCytoplasm
Cytoskeleton
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandChloride
   Molecular functionChloride channel
Ion channel
Voltage-gated channel
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processauditory receptor cell stereocilium organization

Inferred from electronic annotation. Source: Ensembl

chloride transport

Inferred from direct assay Ref.1. Source: UniProtKB

diet induced thermogenesis

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Traceable author statement Ref.1. Source: ProtInc

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

protein localization

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

transport

Non-traceable author statement Ref.1. Source: ProtInc

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.2. Source: UniProtKB

actin cytoskeleton

Inferred from direct assay Ref.1. Source: UniProtKB

cell cortex

Inferred from electronic annotation. Source: UniProtKB-SubCell

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

stereocilium

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction Ref.1Ref.2. Source: UniProtKB

voltage-gated chloride channel activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SRCP005232EBI-5658997,EBI-848039From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: Q9NZA1-1)

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.
Isoform 1 (identifier: Q9NZA1-2)

Also known as: CLIC5A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: Missing.
     160-180: AEGLEEKEGAHMNPEIYLFVK → MTDSATANGDDRDPEIELFVK
Isoform 3 (identifier: Q9NZA1-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 410410Chloride intracellular channel protein 5
PRO_0000144214

Regions

Transmembrane193 – 21321Helical; Note=After insertion into the membrane; Potential
Domain260 – 400141GST C-terminal

Natural variations

Alternative sequence1 – 159159Missing in isoform 1.
VSP_000869
Alternative sequence1 – 1717MNDED…IQNER → MTDSATANGDDRDPEIE in isoform 3.
VSP_044889
Alternative sequence18 – 176159Missing in isoform 3.
VSP_044890
Alternative sequence160 – 18021AEGLE…YLFVK → MTDSATANGDDRDPEIELFV K in isoform 1.
VSP_000870
Alternative sequence356 – 41055IVAKK…RLSRS → EQVPLKGMI in isoform 3.
VSP_044891
Natural variant1141T → A.
Corresponds to variant rs723580 [ dbSNP | Ensembl ].
VAR_059208
Natural variant2571P → H.
Corresponds to variant rs35822882 [ dbSNP | Ensembl ].
VAR_047541

Experimental info

Sequence conflict2011L → F in AAK52083. Ref.2
Isoform 1:
Sequence conflict121R → S in AAF66928. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (CLIC5B) [UniParc].

Last modified November 25, 2008. Version 3.
Checksum: E26D307775F8354C

FASTA41046,503
        10         20         30         40         50         60 
MNDEDYSTIY DTIQNERTYE VPDQPEENES PHYDDVHEYL RPENDLYATQ LNTHEYDFVS 

        70         80         90        100        110        120 
VYTIKGEETS LASVQSEDRG YLLPDEIYSE LQEAHPGEPQ EDRGISMEGL YSSTQDQQLC 

       130        140        150        160        170        180 
AAELQENGSV MKEDLPSPSS FTIQHSKAFS TTKYSCYSDA EGLEEKEGAH MNPEIYLFVK 

       190        200        210        220        230        240 
AGIDGESIGN CPFSQRLFMI LWLKGVVFNV TTVDLKRKPA DLHNLAPGTH PPFLTFNGDV 

       250        260        270        280        290        300 
KTDVNKIEEF LEETLTPEKY PKLAAKHRES NTAGIDIFSK FSAYIKNTKQ QNNAALERGL 

       310        320        330        340        350        360 
TKALKKLDDY LNTPLPEEID ANTCGEDKGS RRKFLDGDEL TLADCNLLPK LHVVKIVAKK 

       370        380        390        400        410 
YRNYDIPAEM TGLWRYLKNA YARDEFTNTC AADSEIELAY ADVAKRLSRS 

« Hide

Isoform 1 (CLIC5A) [UniParc].

Checksum: 1E8658EB7687C60D
Show »

FASTA25128,179
Isoform 3 [UniParc].

Checksum: 5F6C595B3B4842F2
Show »

FASTA20522,830

References

« Hide 'large scale' references
[1]"Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli."
Berryman M., Bretscher A.
Mol. Biol. Cell 11:1509-1521(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member."
Shanks R.A., Larocca M.C., Berryman M., Edwards J.C., Urushidani T., Navarre J., Goldenring J.R.
J. Biol. Chem. 277:40973-40980(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH AKAP9, SUBCELLULAR LOCATION.
Tissue: Colon adenocarcinoma.
[3]"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] (ISOFORMS 1 AND 2).
Tissue: Placenta and Small intestine.
[4]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Placenta.
[5]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 1).
Tissue: Kidney.
[8]"CLIC-5A functions as a chloride channel in vitro and associates with the cortical actin cytoskeleton in vitro and in vivo."
Berryman M., Bruno J., Price J., Edwards J.C.
J. Biol. Chem. 279:34794-34801(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION (ISOFORM 1).
[9]"Functional reconstitution of mammalian 'chloride intracellular channels' CLIC1, CLIC4 and CLIC5 reveals differential regulation by cytoskeletal actin."
Singh H., Cousin M.A., Ashley R.H.
FEBS J. 274:6306-6316(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH F-ACTIN.
[10]"CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity."
Wegner B., Al-Momany A., Kulak S.C., Kozlowski K., Obeidat M., Jahroudi N., Paes J., Berryman M., Ballermann B.J.
Am. J. Physiol. 298:F1492-F1503(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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, AL357057 Genomic DNA. Translation: CAI21030.1.
AL050336, AL357057 Genomic DNA. Translation: CAI21031.1.
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.
CCDSCCDS47438.1. [Q9NZA1-1]
CCDS4914.1. [Q9NZA1-2]
CCDS59022.1. [Q9NZA1-3]
RefSeqNP_001107558.1. NM_001114086.1. [Q9NZA1-1]
NP_001242952.1. NM_001256023.1. [Q9NZA1-3]
NP_058625.2. NM_016929.4. [Q9NZA1-2]
UniGeneHs.485489.
Hs.734348.

3D structure databases

ProteinModelPortalQ9NZA1.
SMRQ9NZA1. Positions 173-407.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119781. 3 interactions.
IntActQ9NZA1. 6 interactions.
MINTMINT-4540449.
STRING9606.ENSP00000185206.

PTM databases

PhosphoSiteQ9NZA1.

Polymorphism databases

DMDM215274174.

2D gel databases

OGPQ9NZA1.

Proteomic databases

MaxQBQ9NZA1.
PaxDbQ9NZA1.
PRIDEQ9NZA1.

Protocols and materials databases

DNASU53405.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000185206; ENSP00000185206; ENSG00000112782. [Q9NZA1-1]
ENST00000339561; ENSP00000344165; ENSG00000112782. [Q9NZA1-2]
ENST00000544153; ENSP00000439195; ENSG00000112782. [Q9NZA1-3]
GeneID53405.
KEGGhsa:53405.
UCSCuc003oxv.3. human. [Q9NZA1-1]
uc003oxx.4. human.

Organism-specific databases

CTD53405.
GeneCardsGC06M045848.
HGNCHGNC:13517. CLIC5.
MIM607293. gene.
neXtProtNX_Q9NZA1.
PharmGKBPA26592.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282171.
HOGENOMHOG000065740.
HOVERGENHBG050995.
InParanoidQ9NZA1.
KOK05025.
OMAGAICKAG.
OrthoDBEOG7X3QR3.
PhylomeDBQ9NZA1.
TreeFamTF315438.

Gene expression databases

ArrayExpressQ9NZA1.
BgeeQ9NZA1.
CleanExHS_CLIC5.
GenevestigatorQ9NZA1.

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]
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

GeneWikiCLIC5.
GenomeRNAi53405.
NextBio56076.
PROQ9NZA1.
SOURCESearch...

Entry information

Entry nameCLIC5_HUMAN
AccessionPrimary (citable) accession number: Q9NZA1
Secondary accession number(s): B3KUF1 expand/collapse secondary AC list , Q5T4Z0, Q8NBY3, Q96JT5, Q9BWZ0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 134 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

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 6

Human chromosome 6: entries, gene names and cross-references to MIM