Q9NZA1 (CLIC5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chloride intracellular channel protein 5

Gene names

Name:

CLIC5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	410 AA.
Sequence status	Complete.
Protein existence	Evidence 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: Cytoplasm › cell cortex. Cytoplasm › cytoskeleton. 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. Cytoplasm › cytoskeleton › centrosome. 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 process	Ion transport Transport
Cellular component	Cytoplasm Cytoskeleton Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel Voltage-gated channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	auditory receptor cell stereocilium organization Inferred from electronic annotation. Source: Compara chloride transport Inferred from direct assay Ref.1. Source: UniProtKB diet induced thermogenesis Inferred from electronic annotation. Source: Compara female pregnancy Traceable author statement Ref.1. Source: ProtInc neuromuscular process controlling balance Inferred from electronic annotation. Source: Compara protein localization Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi 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 microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell stereocilium Inferred from electronic annotation. Source: Compara
Molecular_function	voltage-gated chloride channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 410	410	Chloride intracellular channel protein 5		PRO_0000144214
Regions
	Transmembrane	193 – 213	21	Helical; Note=After insertion into the membrane; Potential
	Domain	260 – 400	141	GST C-terminal
Natural variations
	Alternative sequence	1 – 159	159	Missing in isoform 1.		VSP_000869
	Alternative sequence	1 – 17	17	MNDED…IQNER → MTDSATANGDDRDPEIE in isoform 3.		VSP_044889
	Alternative sequence	18 – 176	159	Missing in isoform 3.		VSP_044890
	Alternative sequence	160 – 180	21	AEGLE…YLFVK → MTDSATANGDDRDPEIELFV K in isoform 1.		VSP_000870
	Alternative sequence	356 – 410	55	IVAKK…RLSRS → EQVPLKGMI in isoform 3.		VSP_044891
	Natural variant	114	1	T → A. Corresponds to variant rs723580 [ dbSNP | Ensembl ].		VAR_059208
	Natural variant	257	1	P → H. Corresponds to variant rs35822882 [ dbSNP | Ensembl ].		VAR_047541
Experimental info
	Sequence conflict	201	1	L → F in AAK52083. Ref.2
Isoform 1:
	Sequence conflict	12	1	R → S in AAF66928. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (CLIC5B) [UniParc]. Last modified November 25, 2008. Version 3. Checksum: E26D307775F8354C	FASTA	410	46,503
	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
	Isoform 1 (CLIC5A) [UniParc]. Checksum: 1E8658EB7687C60D	FASTA	251	28,179
	10 20 30 40 50 60 MTDSATANGD DRDPEIELFV KAGIDGESIG NCPFSQRLFM ILWLKGVVFN VTTVDLKRKP 70 80 90 100 110 120 ADLHNLAPGT HPPFLTFNGD VKTDVNKIEE FLEETLTPEK YPKLAAKHRE SNTAGIDIFS 130 140 150 160 170 180 KFSAYIKNTK QQNNAALERG LTKALKKLDD YLNTPLPEEI DANTCGEDKG SRRKFLDGDE 190 200 210 220 230 240 LTLADCNLLP KLHVVKIVAK KYRNYDIPAE MTGLWRYLKN AYARDEFTNT CAADSEIELA 250 YADVAKRLSR S
	Isoform 3 [UniParc]. Checksum: 5F6C595B3B4842F2	FASTA	205	22,830
	10 20 30 40 50 60 MTDSATANGD DRDPEIELFV KAGIDGESIG NCPFSQRLFM ILWLKGVVFN VTTVDLKRKP 70 80 90 100 110 120 ADLHNLAPGT HPPFLTFNGD VKTDVNKIEE FLEETLTPEK YPKLAAKHRE SNTAGIDIFS 130 140 150 160 170 180 KFSAYIKNTK QQNNAALERG LTKALKKLDD YLNTPLPEEI DANTCGEDKG SRRKFLDGDE 190 200 LTLADCNLLP KLHVVKEQVP LKGMI

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00027193. IPI00294443. IPI00844301.
RefSeq	NP_001107558.1. NM_001114086.1. NP_001242952.1. NM_001256023.1. NP_058625.2. NM_016929.4.
UniGene	Hs.485489. Hs.734348.
3D structure databases
ProteinModelPortal	Q9NZA1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NZA1. 2 interactions.
STRING	9606.ENSP00000185206.
PTM databases
PhosphoSite	Q9NZA1.
Polymorphism databases
DMDM	215274174.
2D gel databases
OGP	Q9NZA1.
Proteomic databases
PaxDb	Q9NZA1.
PRIDE	Q9NZA1.
Protocols and materials databases
DNASU	53405.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000185206; ENSP00000185206; ENSG00000112782. ENST00000339561; ENSP00000344165; ENSG00000112782. ENST00000544153; ENSP00000439195; ENSG00000112782.
GeneID	53405.
KEGG	hsa:53405.
UCSC	uc003oxv.3. human.
Organism-specific databases
CTD	53405.
GeneCards	GC06M045848.
HGNC	HGNC:13517. CLIC5.
MIM	607293. gene.
neXtProt	NX_Q9NZA1.
PharmGKB	PA26592.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG282171.
HOGENOM	HOG000065740.
HOVERGEN	HBG050995.
InParanoid	Q9NZA1.
KO	K05025.
OMA	NGDDRDP.
OrthoDB	EOG40S0FN.
PhylomeDB	Q9NZA1.
Gene expression databases
ArrayExpress	Q9NZA1.
Bgee	Q9NZA1.
CleanEx	HS_CLIC5.
Genevestigator	Q9NZA1.
GermOnline	ENSG00000112782. Homo sapiens.
Family and domain databases
Gene3D	1.20.1050.10. 1 hit. 3.40.30.10. 1 hit.
InterPro	IPR010987. Glutathione-S-Trfase_C-like. IPR017933. Glutathione_S_Trfase/Cl_chnl_C. IPR002946. Int_Cl_channel. IPR012336. Thioredoxin-like_fold. [Graphical view]
PRINTS	PR01263. INTCLCHANNEL.
SUPFAM	SSF47616. GST_C_like. 1 hit. SSF52833. Thiordxn-like_fd. 1 hit.
TIGRFAMs	TIGR00862. O-ClC. 1 hit.
PROSITE	PS50405. GST_CTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	53405.
NextBio	56076.
SOURCE	Search...

Entry information

Entry name

CLIC5_HUMAN

Accession

Primary (citable) accession number: Q9NZA1
Secondary accession number(s): B3KUF1 , Q5T4Z0, Q8NBY3, Q96JT5, Q9BWZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 120 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.