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Protein

H(+)/Cl(-) exchange transporter 5

Gene

Clcn5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei168 – 1681ChlorideBy similarity
Sitei211 – 2111Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transportBy similarity
Sitei268 – 2681Mediates proton transfer from the protein to the inner aqueous phaseBy similarity
Binding sitei455 – 4551Chloride; via amide nitrogenBy similarity
Binding sitei558 – 5581ChlorideBy similarity
Binding sitei596 – 5961ATP; via amide nitrogen and carbonyl oxygenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi617 – 6193ATPBy similarity
Nucleotide bindingi724 – 7274ATPBy similarity

GO - Molecular functioni

  1. antiporter activity Source: UniProtKB-KW
  2. ATP binding Source: UniProtKB-KW
  3. voltage-gated chloride channel activity Source: InterPro

GO - Biological processi

  1. endocytosis Source: MGI
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
H(+)/Cl(-) exchange transporter 5
Alternative name(s):
Chloride channel protein 5
Short name:
ClC-5
Chloride transporter ClC-5
Gene namesi
Name:Clcn5
Synonyms:Clc5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:99486. Clcn5.

Subcellular locationi

  1. Golgi apparatus membrane By similarity; Multi-pass membrane protein By similarity
  2. Endosome membrane By similarity; Multi-pass membrane protein By similarity
  3. Cell membrane By similarity; Multi-pass membrane protein By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5454CytoplasmicBy similarityAdd
BLAST
Transmembranei55 – 9238HelicalBy similarityAdd
BLAST
Transmembranei138 – 16124HelicalBy similarityAdd
BLAST
Intramembranei170 – 1778HelicalBy similarity
Transmembranei186 – 20520HelicalBy similarityAdd
BLAST
Transmembranei211 – 23020HelicalBy similarityAdd
BLAST
Intramembranei242 – 25413HelicalBy similarityAdd
BLAST
Intramembranei258 – 2669HelicalBy similarity
Transmembranei278 – 29619HelicalBy similarityAdd
BLAST
Transmembranei319 – 34426HelicalBy similarityAdd
BLAST
Transmembranei352 – 37221HelicalBy similarityAdd
BLAST
Transmembranei428 – 44821HelicalBy similarityAdd
BLAST
Transmembranei453 – 47220HelicalBy similarityAdd
BLAST
Intramembranei500 – 51415HelicalBy similarityAdd
BLAST
Intramembranei515 – 5173Note=Loop between two helicesBy similarity
Intramembranei518 – 52912HelicalBy similarityAdd
BLAST
Intramembranei530 – 5345Note=Loop between two helicesBy similarity
Transmembranei535 – 55218HelicalBy similarityAdd
BLAST
Topological domaini553 – 746194CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. apical part of cell Source: UniProtKB
  2. endosome membrane Source: UniProtKB-SubCell
  3. Golgi membrane Source: UniProtKB-SubCell
  4. integral component of membrane Source: UniProtKB-KW
  5. lysosomal membrane Source: MGI
  6. membrane Source: MGI
  7. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 746746H(+)/Cl(-) exchange transporter 5PRO_0000094447Add
BLAST

Post-translational modificationi

Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ9WVD4.
PaxDbiQ9WVD4.
PRIDEiQ9WVD4.

Expressioni

Tissue specificityi

Kidney specific.

Gene expression databases

BgeeiQ9WVD4.
CleanExiMM_CLCN5.
ExpressionAtlasiQ9WVD4. baseline and differential.
GenevestigatoriQ9WVD4.

Interactioni

Subunit structurei

Interacts with NEDD4 and NEDD4L.By similarity

Protein-protein interaction databases

IntActiQ9WVD4. 1 interaction.
MINTiMINT-4998506.
STRINGi10090.ENSMUSP00000111412.

Structurei

3D structure databases

ProteinModelPortaliQ9WVD4.
SMRiQ9WVD4. Positions 132-737.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini586 – 65065CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini682 – 74261CBS 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi167 – 1715Selectivity filter part_1By similarity
Motifi209 – 2135Selectivity filter part_2By similarity
Motifi453 – 4575Selectivity filter part_3By similarity

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0038.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiQ9WVD4.
KOiK05012.
OrthoDBiEOG7MWGXT.
PhylomeDBiQ9WVD4.
TreeFamiTF313867.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002247. Cl_channel-5.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01116. CLCHANNEL5.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9WVD4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDFLEEPIPG VGTYDDFNTI DWVREKSRDR DRHREITNKS KESTWALIHS
60 70 80 90 100
VSDAFSGWLL MLLIGLLSGS LAGLIDISAH WMTDLKEGIC TGGFWFNHEH
110 120 130 140 150
CCWNSEHVTF EHRDKCPEWN SWAQLIINTD QGAFAYIVNY FMYVLWALLF
160 170 180 190 200
AFLAVSLVKA FAPYACGSGI PEIKTILSGF IIRGYLGKWT LVIKTITLVL
210 220 230 240 250
AVSSGLSLGK EGPLVHVACC CGNILCHCFN KYRKNEAKRR EVLSAAAAAG
260 270 280 290 300
VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF TLRSINPFGN
310 320 330 340 350
SRLVLFYVEF HTPWHLFELV PFIVLGIFGG LWGALFIRTN IAWCRKRKTT
360 370 380 390 400
QLGKYPVVEV LIVTAITAIL AFPNEYTRMS TSELISELFN DCGLLDSSKL
410 420 430 440 450
CDYENHFNTS KGGELPDRPA GVGIYSAMWQ LALTLILKIV ITIFTFGMKI
460 470 480 490 500
PSGLFIPSMA VGAIAGRLLG VGMEQLAYYH HDWGIFNSWC SQGADCITPG
510 520 530 540 550
LYAMVGAAAC LGGVTRMTVS LVVIMFELTG GLEYIVPLMA AAMTSKWVAD
560 570 580 590 600
ALGREGIYDA HIRLNGYPFL EAKEEFAHKT LAMDVMKPRR NDPLLTVLTQ
610 620 630 640 650
DSMTVEDVET IISETTYSGF PVVVSRESQR LVGFVLRRDL IISIENARKK
660 670 680 690 700
QDGVVSTSII YFTEHSPPMP PYTPPTLKLR NILDLSPFTV TDLTPMEIVV
710 720 730 740
DIFRKLGLRQ CLVTHNGRLL GIITKKDVLK HIAQMANQDP DSILFN
Length:746
Mass (Da):83,101
Last modified:November 1, 1999 - v1
Checksum:iD8F3AE4FFC331A08
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF134117 mRNA. Translation: AAD28473.1.
AL808124 Genomic DNA. Translation: CAM15287.1.
CCDSiCCDS29963.1.
RefSeqiNP_057900.3. NM_016691.4.
UniGeneiMm.486257.

Genome annotation databases

EnsembliENSMUST00000004428; ENSMUSP00000004428; ENSMUSG00000004317.
GeneIDi12728.
KEGGimmu:12728.
UCSCiuc009sle.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF134117 mRNA. Translation: AAD28473.1.
AL808124 Genomic DNA. Translation: CAM15287.1.
CCDSiCCDS29963.1.
RefSeqiNP_057900.3. NM_016691.4.
UniGeneiMm.486257.

3D structure databases

ProteinModelPortaliQ9WVD4.
SMRiQ9WVD4. Positions 132-737.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9WVD4. 1 interaction.
MINTiMINT-4998506.
STRINGi10090.ENSMUSP00000111412.

Proteomic databases

MaxQBiQ9WVD4.
PaxDbiQ9WVD4.
PRIDEiQ9WVD4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004428; ENSMUSP00000004428; ENSMUSG00000004317.
GeneIDi12728.
KEGGimmu:12728.
UCSCiuc009sle.3. mouse.

Organism-specific databases

CTDi1184.
MGIiMGI:99486. Clcn5.

Phylogenomic databases

eggNOGiCOG0038.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
HOVERGENiHBG050984.
InParanoidiQ9WVD4.
KOiK05012.
OrthoDBiEOG7MWGXT.
PhylomeDBiQ9WVD4.
TreeFamiTF313867.

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiClcn5. mouse.
NextBioi282026.
PROiQ9WVD4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WVD4.
CleanExiMM_CLCN5.
ExpressionAtlasiQ9WVD4. baseline and differential.
GenevestigatoriQ9WVD4.

Family and domain databases

Gene3Di1.10.3080.10. 3 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002247. Cl_channel-5.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01116. CLCHANNEL5.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of novel promoter and enhancer elements of the mouse homologue of the Dent disease gene, CLCN5, implicated in X-linked hereditary nephrolithiasis."
    Tanaka K., Fisher S.E., Craig I.W.
    Genomics 58:281-292(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.

Entry informationi

Entry nameiCLCN5_MOUSE
AccessioniPrimary (citable) accession number: Q9WVD4
Secondary accession number(s): B1AXN0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1999
Last modified: April 1, 2015
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.