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P51793 (CLCN4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
H(+)/Cl(-) exchange transporter 4
Alternative name(s):
Chloride channel protein 4
Short name=ClC-4
Chloride transporter ClC-4
Gene names
Name:CLCN4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length760 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Ref.8

Subcellular location

Early endosome membrane; Multi-pass membrane protein By similarity. Late endosome membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Abundant in skeletal muscle and also detectable in brain and heart.

Miscellaneous

The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters.

Sequence similarities

Belongs to the chloride channel (TC 2.A.49) family. ClC-4/CLCN4 subfamily. [View classification]

Contains 2 CBS domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51793-1)

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 2 (identifier: P51793-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 760760H(+)/Cl(-) exchange transporter 4
PRO_0000094443

Regions

Topological domain1 – 6767Cytoplasmic By similarity
Transmembrane68 – 10538Helical; By similarity
Transmembrane151 – 17424Helical; By similarity
Intramembrane183 – 1908Helical; By similarity
Transmembrane200 – 21819Helical; By similarity
Transmembrane224 – 24320Helical; By similarity
Intramembrane255 – 26713Helical; By similarity
Intramembrane271 – 2799Helical; By similarity
Transmembrane291 – 30919Helical; By similarity
Transmembrane333 – 35826Helical; By similarity
Transmembrane365 – 38521Helical; By similarity
Transmembrane442 – 46221Helical; By similarity
Transmembrane467 – 48620Helical; By similarity
Intramembrane514 – 52815Helical; By similarity
Intramembrane532 – 54312Helical; By similarity
Intramembrane544 – 5474Note=Loop between two helices; By similarity
Transmembrane548 – 56619Helical; By similarity
Topological domain567 – 760194Cytoplasmic By similarity
Domain600 – 66667CBS 1
Domain697 – 75559CBS 2
Nucleotide binding631 – 6333ATP By similarity
Nucleotide binding738 – 7414ATP By similarity
Motif180 – 1845Selectivity filter part_1 By similarity
Motif222 – 2265Selectivity filter part_2 By similarity
Motif467 – 4715Selectivity filter part_3 By similarity

Sites

Binding site1811Chloride By similarity
Binding site4691Chloride; via amide nitrogen By similarity
Binding site5721Chloride By similarity
Binding site6101ATP; via amide nitrogen and carbonyl oxygen By similarity
Site2241Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transport
Site2811Mediates proton transfer from the protein to the inner aqueous phase

Natural variations

Alternative sequence1 – 9494Missing in isoform 2.
VSP_054658

Experimental info

Mutagenesis2241E → A: Restores chloride translocation, but not proton transport; when associated with A-281. Ref.8
Mutagenesis2811E → A: Abolishes translocation of protons and chloride ions. Ref.8
Sequence conflict1781A → R in CAA54417. Ref.1
Sequence conflict498 – 4992II → YY in CAA54417. Ref.1
Sequence conflict6591K → N in CAA54417. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 11, 2002. Version 2.
Checksum: 3A5A25D1FEF3F217

FASTA76084,917
        10         20         30         40         50         60 
MVNAGAMSGS GNLMDFLDEP FPDVGTYEDF HTIDWLREKS RDTDRHRKIT SKSKESIWEF 

        70         80         90        100        110        120 
IKSLLDAWSG WVVMLLIGLL AGTLAGVIDL AVDWMTDLKE GVCLSAFWYS HEQCCWTSNE 

       130        140        150        160        170        180 
TTFEDRDKCP LWQKWSELLV NQSEGASAYI LNYLMYILWA LLFAFLAVSL VRVFAPYACG 

       190        200        210        220        230        240 
SGIPEIKTIL SGFIIRGYLG KWTLLIKTVT LVLVVSSGLS LGKEGPLVHV ACCCGNFFSS 

       250        260        270        280        290        300 
LFSKYSKNEG KRREVLSAAA AAGVSVAFGA PIGGVLFSLE EVSYYFPLKT LWRSFFAALV 

       310        320        330        340        350        360 
AAFTLRSINP FGNSRLVLFY VEYHTPWYMA ELFPFILLGV FGGLWGTLFI RCNIAWCRRR 

       370        380        390        400        410        420 
KTTRLGKYPV LEVIVVTAIT AIIAYPNPYT RQSTSELISE LFNDCGALES SQLCDYINDP 

       430        440        450        460        470        480 
NMTRPVDDIP DRPAGVGVYT AMWQLALALI FKIVVTIFTF GMKIPSGLFI PSMAVGAIAG 

       490        500        510        520        530        540 
RMVGIGVEQL AYHHHDWIIF RNWCRPGADC VTPGLYAMVG AAACLGGVTR MTVSLVVIMF 

       550        560        570        580        590        600 
ELTGGLEYIV PLMAAAVTSK WVADAFGKEG IYEAHIHLNG YPFLDVKDEF THRTLATDVM 

       610        620        630        640        650        660 
RPRRGEPPLS VLTQDSMTVE DVETLIKETD YNGFPVVVSR DSERLIGFAQ RRELILAIKN 

       670        680        690        700        710        720 
ARQRQEGIVS NSIMYFTEEP PELPANSPHP LKLRRILNLS PFTVTDHTPM ETVVDIFRKL 

       730        740        750        760 
GLRQCLVTRS GRLLGIITKK DVLRHMAQMA NQDPESIMFN 

« Hide

Isoform 2 [UniParc].

Checksum: 4A8ACB4F7865A5C8
Show »

FASTA66674,347

References

« Hide 'large scale' references
[1]"A gene from the Xp22.3 region shares homology with voltage-gated chloride channels."
van Slegtenhorst M.A., Bassi M.T., Borsani G., Wapenaar M.C., Ferrero G.B., de Conciliis L., Rugarli E.I., Grillo A., Franco B., Zoghbi H.Y., Ballabio A.
Hum. Mol. Genet. 3:547-552(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retina.
[2]"Identification of an acid-activated Cl- channel from human skeletal muscles."
Kawasaki M., Fukuma T., Yamauchi K., Sakamoto H., Marumo F., Sasaki S.
Am. J. Physiol. 277:C948-C954(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Skeletal muscle.
[3]"A chloride channel (ClC-4) in human lens epithelium."
Rae J.L.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Lens epithelium.
[4]"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: Brain and Cerebellum.
[5]"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].
[6]Mural R.J., Istrail S., Sutton 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: Brain.
[8]"Determinants of anion-proton coupling in mammalian endosomal CLC proteins."
Zdebik A.A., Zifarelli G., Bergsdorf E.-Y., Soliani P., Scheel O., Jentsch T.J., Pusch M.
J. Biol. Chem. 283:4219-4227(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-224 AND GLU-281.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X77197 mRNA. Translation: CAA54417.1.
AB019432 mRNA. Translation: BAA77327.1.
AF170492 mRNA. Translation: AAD50981.1.
AK289564 mRNA. Translation: BAF82253.1.
AK299611 mRNA. Translation: BAH13080.1.
AC003666 Genomic DNA. No translation available.
AC121345 Genomic DNA. No translation available.
CH471074 Genomic DNA. Translation: EAW98778.1.
BC130278 mRNA. Translation: AAI30279.1.
CCDSCCDS14137.1.
PIRI37242.
RefSeqNP_001243873.1. NM_001256944.1. [P51793-2]
NP_001821.2. NM_001830.3. [P51793-1]
UniGeneHs.495674.

3D structure databases

ProteinModelPortalP51793.
SMRP51793. Positions 148-572, 592-753.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-3019161.
STRING9606.ENSP00000370213.

Chemistry

GuidetoPHARMACOLOGY703.

Protein family/group databases

TCDB2.A.49.2.8. the chloride carrier/channel (clc) family.

PTM databases

PhosphoSiteP51793.

Polymorphism databases

DMDM20141247.

Proteomic databases

MaxQBP51793.
PaxDbP51793.
PRIDEP51793.

Protocols and materials databases

DNASU1183.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380833; ENSP00000370213; ENSG00000073464.
ENST00000421085; ENSP00000405754; ENSG00000073464.
GeneID1183.
KEGGhsa:1183.
UCSCuc004csy.4. human. [P51793-1]

Organism-specific databases

CTD1183.
GeneCardsGC0XP010085.
H-InvDBHIX0056096.
HGNCHGNC:2022. CLCN4.
HPAHPA031313.
MIM302910. gene.
neXtProtNX_P51793.
PharmGKBPA26549.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0038.
HOGENOMHOG000164493.
HOVERGENHBG050984.
InParanoidP51793.
KOK05012.
OMAQDGMTVE.
OrthoDBEOG7MWGXT.
PhylomeDBP51793.
TreeFamTF313867.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP51793.
BgeeP51793.
CleanExHS_CLCN4.
GenevestigatorP51793.

Family and domain databases

Gene3D1.10.3080.10. 3 hits.
InterProIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002246. Cl_channel-4.
[Graphical view]
PfamPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSPR00762. CLCHANNEL.
PR01115. CLCHANNEL4.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMSSF81340. SSF81340. 3 hits.
PROSITEPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCLCN4. human.
GeneWikiCLCN4.
GenomeRNAi1183.
NextBio4890.
PROP51793.
SOURCESearch...

Entry information

Entry nameCLCN4_HUMAN
AccessionPrimary (citable) accession number: P51793
Secondary accession number(s): A1L3U1, B7Z5Z4, Q9UBU1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 11, 2002
Last modified: July 9, 2014
This is version 131 of the entry and version 2 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 chromosome X

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