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UniProtKB - P51793 (CLCN4_HUMAN)

Entry version 183 (25 May 2022)
Sequence version 2 (11 Feb 2002)
Previous versions | rss
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Strongly outwardly rectifying, electrogenic H+/Cl-exchanger which mediates the exchange of chloride ions against protons (PubMed:18063579, PubMed:28972156, PubMed:23647072, PubMed:27550844, PubMed:25644381).

The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (PubMed:29845874).

The presence of conserved gating glutamate residues is typical for family members that function as antiporters (PubMed:29845874).

1 Publication5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei181ChlorideBy similarity1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi631 – 633ATPBy similarity3
Nucleotide bindingi738 – 741ATPBy similarity4

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processAntiport, Ion transport, Transport
LigandATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P51793

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-2672351, Stimuli-sensing channels

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P51793

SIGNOR Signaling Network Open Resource

More...SIGNORi		P51793

Protein family/group databases

Transport Classification Database

More...TCDBi		2.A.49.2.8, the chloride carrier/channel (clc) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
H(+)/Cl(-) exchange transporter 4
Alternative name(s):
Chloride channel protein 4
Short name:
ClC-4
Chloride transporter ClC-4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:CLCN4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome X

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:2022, CLCN4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		302910, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P51793

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000073464

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 67CytoplasmicBy similarityAdd BLAST67
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei68 – 105HelicalBy similarityAdd BLAST38
Transmembranei151 – 174HelicalBy similarityAdd BLAST24
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a region that is buried within a membrane, but does not cross it.<p><a href='/help/intramem' target='_top'>More...</a></p>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

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Lysosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Raynaud-Claes syndrome (MRXSRC)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn X-linked syndrome characterized by borderline to severe intellectual disability and impaired language development. Additional features include behavioral problems, psychiatric disorders, seizures, progressive ataxia, brain abnormalities, and facial dysmorphisms.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_08357715D → N in MRXSRC; also in patients with complex congenital diaphragmatic hernia; unknown pathological significance; no reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 2 PublicationsCorresponds to variant dbSNP:rs879255591EnsemblClinVar.1
Natural variantiVAR_07781978G → S in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569226551EnsemblClinVar.1
Natural variantiVAR_083578212V → G in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255580EnsemblClinVar.1
Natural variantiVAR_083579221L → P in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255581EnsemblClinVar.1
Natural variantiVAR_077820221L → V in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569230006EnsemblClinVar.1
Natural variantiVAR_083580275V → M in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum. 1 PublicationCorresponds to variant dbSNP:rs879255585EnsemblClinVar.1
Natural variantiVAR_083581534S → L in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255582EnsemblClinVar.1
Natural variantiVAR_077821536V → M in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569231897EnsemblClinVar.1
Natural variantiVAR_077822544G → R in MRXSRC; has normal localization to structures resembling endoplasmic reticulum membranes; almost abolishes the outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs587777161EnsemblClinVar.1
Natural variantiVAR_083582555A → V in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255583EnsemblClinVar.1
Natural variantiVAR_083583718R → W in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255584EnsemblClinVar.1
Natural variantiVAR_077823731G → R in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569233549EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

Keywords - Diseasei

Disease variant, Mental retardation

Organism-specific databases

DisGeNET

More...DisGeNETi		1183

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		CLCN4

MalaCards human disease database

More...MalaCardsi		CLCN4
MIMi300114, phenotype

Open Targets

More...OpenTargetsi		ENSG00000073464

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		485350, CLCN4-related X-linked intellectual disability syndrome
777, X-linked non-syndromic intellectual disability

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA26549

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P51793, Tchem

Chemistry databases

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		703

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		CLCN4

Domain mapping of disease mutations (DMDM)

More...DMDMi		20141247

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000944431 – 760H(+)/Cl(-) exchange transporter 4Add BLAST760

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P51793

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P51793

MaxQB - The MaxQuant DataBase

More...MaxQBi		P51793

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P51793

PeptideAtlas

More...PeptideAtlasi		P51793

PRoteomics IDEntifications database

More...PRIDEi		P51793

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		56390 [P51793-1]
6731

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P51793

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P51793

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000073464, Expressed in Brodmann (1909) area 46 and 215 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P51793, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P51793, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000073464, Tissue enhanced (brain, retina, skeletal muscle, tongue)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer (PubMed:28972156). Forms heterodimers with CLCN3 (PubMed:28972156).

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		107597, 3 interactors

Protein interaction database and analysis system

More...IntActi		P51793, 1 interactor

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000370213

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P51793, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P51793

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P51793

Database of comparative protein structure models

More...ModBasei		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini600 – 666CBS 1PROSITE-ProRule annotationAdd BLAST67
Domaini697 – 755CBS 2PROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni14 – 63Required for localization in the endoplasmic reticulum1 PublicationAdd BLAST50
Regioni667 – 696Required for localization in the endoplasmic reticulum1 PublicationAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi180 – 184Selectivity filter part_1By similarity5
Motifi222 – 226Selectivity filter part_2By similarity5
Motifi467 – 471Selectivity filter part_3By similarity5

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0475, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000158265

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_003181_2_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P51793

Identification of Orthologs from Complete Genome Data

More...OMAi		KYAGLVH

Database of Orthologous Groups

More...OrthoDBi		271925at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P51793

TreeFam database of animal gene trees

More...TreeFami		TF313867

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR000644, CBS_dom
IPR046342, CBS_dom_sf
IPR014743, Cl-channel_core
IPR001807, Cl-channel_volt-gated
IPR002246, Cl_channel-4

The PANTHER Classification System

More...PANTHERi		PTHR45711:SF2, PTHR45711:SF2, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00571, CBS, 2 hits
PF00654, Voltage_CLC, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00762, CLCHANNEL
PR01115, CLCHANNEL4

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00116, CBS, 2 hits

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF54631, SSF54631, 1 hit
SSF81340, SSF81340, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51371, CBS, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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.

Show »
Length:666
Mass (Da):74,347
Checksum:i4A8ACB4F7865A5C8
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A7I2Y1J6A0A7I2Y1J6_HUMAN
Chloride channel protein
CLCN4
768Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
G3XAG5G3XAG5_HUMAN
Chloride channel protein
CLCN4 hCG_401215
729Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PG54A0A6Q8PG54_HUMAN
Chloride channel protein
CLCN4
735Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PFB5E9PFB5_HUMAN
H(+)/Cl(-) exchange transporter 4
CLCN4
152Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PF24A0A6Q8PF24_HUMAN
H(+)/Cl(-) exchange transporter 4
CLCN4
103Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08357715D → N in MRXSRC; also in patients with complex congenital diaphragmatic hernia; unknown pathological significance; no reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 2 PublicationsCorresponds to variant dbSNP:rs879255591EnsemblClinVar.1
Natural variantiVAR_07781978G → S in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569226551EnsemblClinVar.1
Natural variantiVAR_083578212V → G in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255580EnsemblClinVar.1
Natural variantiVAR_083579221L → P in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255581EnsemblClinVar.1
Natural variantiVAR_077820221L → V in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569230006EnsemblClinVar.1
Natural variantiVAR_083580275V → M in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum. 1 PublicationCorresponds to variant dbSNP:rs879255585EnsemblClinVar.1
Natural variantiVAR_083581534S → L in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255582EnsemblClinVar.1
Natural variantiVAR_077821536V → M in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569231897EnsemblClinVar.1
Natural variantiVAR_077822544G → R in MRXSRC; has normal localization to structures resembling endoplasmic reticulum membranes; almost abolishes the outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs587777161EnsemblClinVar.1
Natural variantiVAR_083582555A → V in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255583EnsemblClinVar.1
Natural variantiVAR_083583718R → W in MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane. 1 PublicationCorresponds to variant dbSNP:rs879255584EnsemblClinVar.1
Natural variantiVAR_077823731G → R in MRXSRC; marked reduction in outwardly-rectifying currents. 2 PublicationsCorresponds to variant dbSNP:rs1569233549EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0546581 – 94Missing in isoform 2. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS14137.1 [P51793-1]
CCDS59159.1 [P51793-2]

Protein sequence database of the Protein Information Resource

More...PIRi		I37242

NCBI Reference Sequences

More...RefSeqi		NP_001243873.1, NM_001256944.1 [P51793-2]
NP_001821.2, NM_001830.3 [P51793-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000380833.9; ENSP00000370213.4; ENSG00000073464.13
ENST00000674669.1; ENSP00000501922.1; ENSG00000073464.13 [P51793-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		1183

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:1183

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000380833.9; ENSP00000370213.4; NM_001830.4; NP_001821.2

UCSC genome browser

More...UCSCi		uc004csy.5, human [P51793-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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]

3D structure databases

AlphaFoldDBiP51793
SMRiP51793
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi107597, 3 interactors
IntActiP51793, 1 interactor
STRINGi9606.ENSP00000370213

Chemistry databases

GuidetoPHARMACOLOGYi703

Protein family/group databases

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

PTM databases

iPTMnetiP51793
PhosphoSitePlusiP51793

Genetic variation databases

BioMutaiCLCN4
DMDMi20141247

Proteomic databases

jPOSTiP51793
MassIVEiP51793
MaxQBiP51793
PaxDbiP51793
PeptideAtlasiP51793
PRIDEiP51793
ProteomicsDBi56390 [P51793-1]
6731

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P51793, 1 sequenced antibody

Antibodypedia a portal for validated antibodies

More...Antibodypediai		23690, 180 antibodies from 30 providers

The DNASU plasmid repository

More...DNASUi		1183

Genome annotation databases

EnsembliENST00000380833.9; ENSP00000370213.4; ENSG00000073464.13
ENST00000674669.1; ENSP00000501922.1; ENSG00000073464.13 [P51793-2]
GeneIDi1183
KEGGihsa:1183
MANE-SelectiENST00000380833.9; ENSP00000370213.4; NM_001830.4; NP_001821.2
UCSCiuc004csy.5, human [P51793-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		1183
DisGeNETi1183

GeneCards: human genes, protein and diseases

More...GeneCardsi		CLCN4
GeneReviewsiCLCN4
HGNCiHGNC:2022, CLCN4
HPAiENSG00000073464, Tissue enhanced (brain, retina, skeletal muscle, tongue)
MalaCardsiCLCN4
MIMi300114, phenotype
302910, gene
neXtProtiNX_P51793
OpenTargetsiENSG00000073464
Orphaneti485350, CLCN4-related X-linked intellectual disability syndrome
777, X-linked non-syndromic intellectual disability
PharmGKBiPA26549
VEuPathDBiHostDB:ENSG00000073464

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0475, Eukaryota
GeneTreeiENSGT00940000158265
HOGENOMiCLU_003181_2_1_1
InParanoidiP51793
OMAiKYAGLVH
OrthoDBi271925at2759
PhylomeDBiP51793
TreeFamiTF313867

Enzyme and pathway databases

PathwayCommonsiP51793
ReactomeiR-HSA-2672351, Stimuli-sensing channels
SignaLinkiP51793
SIGNORiP51793

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		1183, 6 hits in 695 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		CLCN4, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		CLCN4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		1183
PharosiP51793, Tchem

Protein Ontology

More...PROi		PR:P51793
RNActiP51793, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000073464, Expressed in Brodmann (1909) area 46 and 215 other tissues
ExpressionAtlasiP51793, baseline and differential
GenevisibleiP51793, HS

Family and domain databases

InterProiView protein in InterPro
IPR000644, CBS_dom
IPR046342, CBS_dom_sf
IPR014743, Cl-channel_core
IPR001807, Cl-channel_volt-gated
IPR002246, Cl_channel-4
PANTHERiPTHR45711:SF2, PTHR45711:SF2, 1 hit
PfamiView protein in Pfam
PF00571, CBS, 2 hits
PF00654, Voltage_CLC, 1 hit
PRINTSiPR00762, CLCHANNEL
PR01115, CLCHANNEL4
SMARTiView protein in SMART
SM00116, CBS, 2 hits
SUPFAMiSSF54631, SSF54631, 1 hit
SSF81340, SSF81340, 1 hit
PROSITEiView protein in PROSITE
PS51371, CBS, 2 hits

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCLCN4_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P51793
Secondary accession number(s): A1L3U1, B7Z5Z4, Q9UBU1
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 11, 2002
Last modified: May 25, 2022
This is version 183 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
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