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Protein

H(+)/Cl(-) exchange transporter 4

Gene

CLCN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei181ChlorideBy similarity1
Sitei224Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transport1
Sitei281Mediates proton transfer from the protein to the inner aqueous phase1
Binding sitei469Chloride; via amide nitrogenBy similarity1
Binding sitei572ChlorideBy similarity1
Binding sitei610ATP; via amide nitrogen and carbonyl oxygenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi631 – 633ATPBy similarity3
Nucleotide bindingi738 – 741ATPBy similarity4

GO - Molecular functioni

  • antiporter activity Source: Reactome
  • ATP binding Source: UniProtKB-KW
  • chloride channel activity Source: MGI
  • chloride ion binding Source: GO_Central
  • voltage-gated chloride channel activity Source: ProtInc

GO - Biological processi

  • chloride transport Source: MGI
  • ion transmembrane transport Source: Reactome
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073464-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Protein family/group databases

TCDBi2.A.49.2.8. the chloride carrier/channel (clc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
H(+)/Cl(-) exchange transporter 4
Alternative name(s):
Chloride channel protein 4
Short name:
ClC-4
Chloride transporter ClC-4
Gene namesi
Name:CLCN4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:2022. CLCN4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 67CytoplasmicBy similarityAdd BLAST67
Transmembranei68 – 105HelicalBy similarityAdd BLAST38
Transmembranei151 – 174HelicalBy similarityAdd BLAST24
Intramembranei183 – 190HelicalBy similarity8
Transmembranei200 – 218HelicalBy similarityAdd BLAST19
Transmembranei224 – 243HelicalBy similarityAdd BLAST20
Intramembranei255 – 267HelicalBy similarityAdd BLAST13
Intramembranei271 – 279HelicalBy similarity9
Transmembranei291 – 309HelicalBy similarityAdd BLAST19
Transmembranei333 – 358HelicalBy similarityAdd BLAST26
Transmembranei365 – 385HelicalBy similarityAdd BLAST21
Transmembranei442 – 462HelicalBy similarityAdd BLAST21
Transmembranei467 – 486HelicalBy similarityAdd BLAST20
Intramembranei514 – 528HelicalBy similarityAdd BLAST15
Intramembranei532 – 543HelicalBy similarityAdd BLAST12
Intramembranei544 – 547Note=Loop between two helicesBy similarity4
Transmembranei548 – 566HelicalBy similarityAdd BLAST19
Topological domaini567 – 760CytoplasmicBy similarityAdd BLAST194

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi224E → A: Restores chloride translocation, but not proton transport; when associated with A-281. 1 Publication1
Mutagenesisi281E → A: Abolishes translocation of protons and chloride ions. 1 Publication1

Organism-specific databases

DisGeNETi1183.
OpenTargetsiENSG00000073464.
PharmGKBiPA26549.

Chemistry databases

GuidetoPHARMACOLOGYi703.

Polymorphism and mutation databases

BioMutaiCLCN4.
DMDMi20141247.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000944431 – 760H(+)/Cl(-) exchange transporter 4Add BLAST760

Proteomic databases

MaxQBiP51793.
PaxDbiP51793.
PeptideAtlasiP51793.
PRIDEiP51793.

PTM databases

iPTMnetiP51793.
PhosphoSitePlusiP51793.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000073464.
CleanExiHS_CLCN4.
ExpressionAtlasiP51793. baseline and differential.
GenevisibleiP51793. HS.

Organism-specific databases

HPAiHPA031313.
HPA063637.

Interactioni

Protein-protein interaction databases

MINTiMINT-3019161.
STRINGi9606.ENSP00000370213.

Structurei

3D structure databases

ProteinModelPortaliP51793.
SMRiP51793.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini600 – 666CBS 1PROSITE-ProRule annotationAdd BLAST67
Domaini697 – 755CBS 2PROSITE-ProRule annotationAdd BLAST59

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi180 – 184Selectivity filter part_1By similarity5
Motifi222 – 226Selectivity filter part_2By similarity5
Motifi467 – 471Selectivity filter part_3By similarity5

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0475. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiP51793.
KOiK05012.
OMAiHRKITNK.
OrthoDBiEOG091G01YH.
PhylomeDBiP51793.
TreeFamiTF313867.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002246. Cl_channel-4.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01115. CLCHANNEL4.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51793-1) [UniParc]FASTAAdd to basket

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
MVNAGAMSGS GNLMDFLDEP FPDVGTYEDF HTIDWLREKS RDTDRHRKIT
60 70 80 90 100
SKSKESIWEF IKSLLDAWSG WVVMLLIGLL AGTLAGVIDL AVDWMTDLKE
110 120 130 140 150
GVCLSAFWYS HEQCCWTSNE TTFEDRDKCP LWQKWSELLV NQSEGASAYI
160 170 180 190 200
LNYLMYILWA LLFAFLAVSL VRVFAPYACG SGIPEIKTIL SGFIIRGYLG
210 220 230 240 250
KWTLLIKTVT LVLVVSSGLS LGKEGPLVHV ACCCGNFFSS LFSKYSKNEG
260 270 280 290 300
KRREVLSAAA AAGVSVAFGA PIGGVLFSLE EVSYYFPLKT LWRSFFAALV
310 320 330 340 350
AAFTLRSINP FGNSRLVLFY VEYHTPWYMA ELFPFILLGV FGGLWGTLFI
360 370 380 390 400
RCNIAWCRRR KTTRLGKYPV LEVIVVTAIT AIIAYPNPYT RQSTSELISE
410 420 430 440 450
LFNDCGALES SQLCDYINDP NMTRPVDDIP DRPAGVGVYT AMWQLALALI
460 470 480 490 500
FKIVVTIFTF GMKIPSGLFI PSMAVGAIAG RMVGIGVEQL AYHHHDWIIF
510 520 530 540 550
RNWCRPGADC VTPGLYAMVG AAACLGGVTR MTVSLVVIMF ELTGGLEYIV
560 570 580 590 600
PLMAAAVTSK WVADAFGKEG IYEAHIHLNG YPFLDVKDEF THRTLATDVM
610 620 630 640 650
RPRRGEPPLS VLTQDSMTVE DVETLIKETD YNGFPVVVSR DSERLIGFAQ
660 670 680 690 700
RRELILAIKN ARQRQEGIVS NSIMYFTEEP PELPANSPHP LKLRRILNLS
710 720 730 740 750
PFTVTDHTPM ETVVDIFRKL GLRQCLVTRS GRLLGIITKK DVLRHMAQMA
760
NQDPESIMFN
Length:760
Mass (Da):84,917
Last modified:February 11, 2002 - v2
Checksum:i3A5A25D1FEF3F217
GO
Isoform 2 (identifier: P51793-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.

Note: No experimental confirmation available.
Show »
Length:666
Mass (Da):74,347
Checksum:i4A8ACB4F7865A5C8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti178A → R in CAA54417 (PubMed:8069296).Curated1
Sequence conflicti498 – 499II → YY in CAA54417 (PubMed:8069296).Curated2
Sequence conflicti659K → N in CAA54417 (PubMed:8069296).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0546581 – 94Missing in isoform 2. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS14137.1. [P51793-1]
CCDS59159.1. [P51793-2]
PIRiI37242.
RefSeqiNP_001243873.1. NM_001256944.1. [P51793-2]
NP_001821.2. NM_001830.3. [P51793-1]
UniGeneiHs.495674.

Genome annotation databases

EnsembliENST00000380833; ENSP00000370213; ENSG00000073464. [P51793-1]
ENST00000421085; ENSP00000405754; ENSG00000073464. [P51793-2]
GeneIDi1183.
KEGGihsa:1183.
UCSCiuc004csy.5. human. [P51793-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS14137.1. [P51793-1]
CCDS59159.1. [P51793-2]
PIRiI37242.
RefSeqiNP_001243873.1. NM_001256944.1. [P51793-2]
NP_001821.2. NM_001830.3. [P51793-1]
UniGeneiHs.495674.

3D structure databases

ProteinModelPortaliP51793.
SMRiP51793.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-3019161.
STRINGi9606.ENSP00000370213.

Chemistry databases

GuidetoPHARMACOLOGYi703.

Protein family/group databases

TCDBi2.A.49.2.8. the chloride carrier/channel (clc) family.

PTM databases

iPTMnetiP51793.
PhosphoSitePlusiP51793.

Polymorphism and mutation databases

BioMutaiCLCN4.
DMDMi20141247.

Proteomic databases

MaxQBiP51793.
PaxDbiP51793.
PeptideAtlasiP51793.
PRIDEiP51793.

Protocols and materials databases

DNASUi1183.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380833; ENSP00000370213; ENSG00000073464. [P51793-1]
ENST00000421085; ENSP00000405754; ENSG00000073464. [P51793-2]
GeneIDi1183.
KEGGihsa:1183.
UCSCiuc004csy.5. human. [P51793-1]

Organism-specific databases

CTDi1183.
DisGeNETi1183.
GeneCardsiCLCN4.
H-InvDBHIX0056096.
HGNCiHGNC:2022. CLCN4.
HPAiHPA031313.
HPA063637.
MIMi302910. gene.
neXtProtiNX_P51793.
OpenTargetsiENSG00000073464.
PharmGKBiPA26549.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0475. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiP51793.
KOiK05012.
OMAiHRKITNK.
OrthoDBiEOG091G01YH.
PhylomeDBiP51793.
TreeFamiTF313867.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073464-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiCLCN4. human.
GeneWikiiCLCN4.
GenomeRNAii1183.
PROiP51793.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073464.
CleanExiHS_CLCN4.
ExpressionAtlasiP51793. baseline and differential.
GenevisibleiP51793. HS.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002246. Cl_channel-4.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01115. CLCHANNEL4.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLCN4_HUMAN
AccessioniPrimary (citable) accession number: P51793
Secondary accession number(s): A1L3U1, B7Z5Z4, Q9UBU1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 11, 2002
Last modified: November 2, 2016
This is version 150 of the entry and version 2 of the sequence. [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

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.