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Reviewed, UniProtKB/Swiss-Prot P51793 (CLCN4_HUMAN)

Last modified June 16, 2009. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    H(+)/Cl(-) exchange transporter 4
Alternative name(s):
    Chloride transporter ClC-4
    Chloride channel protein 4
      Short name=ClC-4
Gene names
Name: CLCN4
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length760 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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

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. [View classification]

Contains 2 CBS domains.

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Ontologies

Keywords
   Biological processAntiport
Ion transport
Transport
   Cellular componentEndosome
Membrane
   DomainCBS domain
Repeat
Transmembrane
   LigandATP-binding
Chloride
Nucleotide-binding
Gene Ontology (GO)
   Biological processchloride transport Ref.2

Inferred from direct assay. Source: MGI

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionchloride ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

voltage-gated chloride channel activity Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

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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 – 10538 By similarity
Transmembrane151 – 17424 By similarity
Transmembrane200 – 21819 By similarity
Transmembrane224 – 24320 By similarity
Transmembrane291 – 30919 By similarity
Transmembrane333 – 35826 By similarity
Transmembrane365 – 38521 By similarity
Transmembrane442 – 46221 By similarity
Transmembrane467 – 48620 By similarity
Transmembrane548 – 56619 By similarity
Topological domain567 – 760194Cytoplasmic By similarity
Domain600 – 66667CBS 1
Domain697 – 75559CBS 2
Nucleotide binding631 – 6333ATP By similarity
Nucleotide binding738 – 7414ATP By similarity
Region183 – 1908In-membrane helix By similarity
Region255 – 26713In-membrane helix By similarity
Region271 – 2799In-membrane helix By similarity
Region514 – 52815In-membrane helix By similarity
Region532 – 54312In-membrane helix By similarity
Region544 – 5474In-membrane loop between two helices 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

Experimental info

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

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Sequences

Sequence LengthMass (Da)Tools
P51793-1 [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

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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: 8069296] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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: 10564087] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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].
Tissue: Lens epithelium.
[4]"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: 18063579] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-224 AND GLU-281.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X77197 mRNA. Translation: CAA54417.1.
AB019432 mRNA. Translation: BAA77327.1.
AF170492 mRNA. Translation: AAD50981.1.
IPIIPI00294055.
PIRI37242.
RefSeqNP_001821.2.
UniGeneHs.495674

3D structure databases

SMRP51793. Positions 592-753.
ModBaseSearch...

Proteomic databases

PRIDEP51793.

Genome annotation databases

EnsemblENSG00000073464. Homo sapiens. [Contig view]
GeneID1183.
KEGGhsa:1183.

Organism-specific databases

GeneCardsGC0XP010085.
HGNCHGNC:2022. CLCN4.
MIM302910. gene.
PharmGKBPA26549.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP51793.
HOVERGENP51793.
OMAP51793. MAGRMVG.

Gene expression databases

ArrayExpressP51793.
BgeeP51793.
CleanExHS_CLCN4.
GermOnlineENSG00000073464. Homo sapiens.

Family and domain databases

InterProIPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt.
IPR002246. Cl_channel4.
IPR000644. Cysta_beta_synth_core.
[Graphical view]
Gene3DG3DSA:1.10.3080.10. Cl-channel_core. 1 hit.
PANTHERPTHR11689. Cl-channel_volt. 1 hit.
PfamPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSPR00762. CLCHANNEL.
PR01115. CLCHANNEL4.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
PROSITEPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio4890.
SOURCESearch...

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Entry information

Entry nameCLCN4_HUMAN
AccessionPrimary (citable) accession number: P51793
Secondary accession number(s): Q9UBU1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 11, 2002
Last modified: June 16, 2009
This is version 77 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome X

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents