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Entry version 145 (12 Aug 2020)
Sequence version 1 (01 Jan 1998)
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Protein

Claudin-4

Gene

Cldn4

Organism
Mus musculus (Mouse)
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

Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney (PubMed:20921420). Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts (PubMed:20921420). Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.1 Publication

<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

  • chloride channel activity Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • structural molecule activity Source: InterPro

GO - Biological processi

<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

Molecular functionChloride channel, Ion channel
Biological processIon transport, Transport
LigandChloride

<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:
Claudin-41 Publication
Alternative name(s):
Clostridium perfringens enterotoxin receptor1 Publication
Short name:
CPE-R1 Publication
Short name:
CPE-receptor1 Publication
<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:Cldn4Imported
Synonyms:Cper1 Publication, Cpetr11 Publication
<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>OrganismiMus musculus (Mouse)
<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 identifieri10090 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<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
  • UP000000589 <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 5

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:1313314, Cldn4

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

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 – 7CytoplasmicSequence analysis7
<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>Transmembranei8 – 28HelicalSequence analysisAdd BLAST21
Topological domaini29 – 81ExtracellularSequence analysisAdd BLAST53
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Topological domaini103 – 116CytoplasmicSequence analysisAdd BLAST14
Transmembranei117 – 137HelicalSequence analysisAdd BLAST21
Topological domaini138 – 160ExtracellularSequence analysisAdd BLAST23
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Topological domaini182 – 210CytoplasmicSequence analysisAdd BLAST29

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

<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

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>Mutagenesisi31R → T: No effect. 1 Publication1
Mutagenesisi48E → Q: No effect. 1 Publication1
Mutagenesisi65K → T: Abolishes ability to form paracellular chloride channel. 1 Publication1
Mutagenesisi68D → N: No effect. 1 Publication1
Mutagenesisi76D → N: No effect. 1 Publication1

<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_00001447441 – 210Claudin-4Add BLAST210

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi54 ↔ 64By similarity
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei209Phosphotyrosine; by EPHA2By similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

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

More...
PaxDbi
O35054

PRoteomics IDEntifications database

More...
PRIDEi
O35054

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
O35054

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

More...
PhosphoSitePlusi
O35054

<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

Expressed primarily in lung and kidney (PubMed:9892664). Present in both cortical and medullar collecting ducts (at protein level) (PubMed:20921420).2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000047501, Expressed in endoderm of midgut and 149 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
O35054, MM

<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

Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions (By similarity). Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3 (PubMed:10601346, PubMed:16236711).

Interacts with CLDN1 (By similarity).

Interacts with CLDN8 (PubMed:20921420).

By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...
BioGRIDi
198746, 1 interactor

Database of interacting proteins

More...
DIPi
DIP-40781N

Protein interaction database and analysis system

More...
IntActi
O35054, 1 interactor

Molecular INTeraction database

More...
MINTi
O35054

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000053420

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
O35054, protein

<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

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>Regioni1 – 103Interaction with EPHA2By similarityAdd BLAST103
Regioni209 – 210Interactions with TJP1, TJP2 and TJP31 Publication2

<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 claudin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
ENOG502QSCN, Eukaryota

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000154762

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_076370_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
O35054

KEGG Orthology (KO)

More...
KOi
K06087

Identification of Orthologs from Complete Genome Data

More...
OMAi
TTKAKTM

Database of Orthologous Groups

More...
OrthoDBi
1231389at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
O35054

TreeFam database of animal gene trees

More...
TreeFami
TF331936

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR006187, Claudin
IPR003550, Claudin4
IPR017974, Claudin_CS
IPR004031, PMP22/EMP/MP20/Claudin

The PANTHER Classification System

More...
PANTHERi
PTHR12002, PTHR12002, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00822, PMP22_Claudin, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR01379, CLAUDIN4

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS01346, CLAUDIN, 1 hit

<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>Sequencei

<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.

O35054-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASMGLQVLG ISLAVLGWLG IILSCALPMW RVTAFIGSNI VTAQTSWEGL
60 70 80 90 100
WMNCVVQSTG QMQCKMYDSM LALPQDLQAA RALMVISIIV GALGMLLSVV
110 120 130 140 150
GGKCTNCMED ETVKAKIMIT AGAVFIVASM LIMVPVSWTA HNVIRDFYNP
160 170 180 190 200
MVASGQKREM GASLYVGWAA SGLLLLGGGL LCCSCPPRSN DKPYSAKYSA
210
ARSVPASNYV
Length:210
Mass (Da):22,339
Last modified:January 1, 1998 - v1
<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:i3B6D571EC71D6564
GO

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
AB000713 mRNA Translation: BAA22985.1
AF087822 mRNA Translation: AAD09757.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS19728.1

NCBI Reference Sequences

More...
RefSeqi
NP_034033.1, NM_009903.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000051401; ENSMUSP00000053420; ENSMUSG00000047501

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
12740

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:12740

UCSC genome browser

More...
UCSCi
uc008zxd.3, mouse

<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
AB000713 mRNA Translation: BAA22985.1
AF087822 mRNA Translation: AAD09757.1
CCDSiCCDS19728.1
RefSeqiNP_034033.1, NM_009903.2

3D structure databases

Database of comparative protein structure models

More...
ModBasei
Search...

SWISS-MODEL Interactive Workspace

More...
SWISS-MODEL-Workspacei
Submit a new modelling project...

Protein-protein interaction databases

BioGRIDi198746, 1 interactor
DIPiDIP-40781N
IntActiO35054, 1 interactor
MINTiO35054
STRINGi10090.ENSMUSP00000053420

PTM databases

iPTMnetiO35054
PhosphoSitePlusiO35054

Proteomic databases

PaxDbiO35054
PRIDEiO35054

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
3618, 563 antibodies

Genome annotation databases

EnsembliENSMUST00000051401; ENSMUSP00000053420; ENSMUSG00000047501
GeneIDi12740
KEGGimmu:12740
UCSCiuc008zxd.3, mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
1364
MGIiMGI:1313314, Cldn4

Phylogenomic databases

eggNOGiENOG502QSCN, Eukaryota
GeneTreeiENSGT00940000154762
HOGENOMiCLU_076370_0_0_1
InParanoidiO35054
KOiK06087
OMAiTTKAKTM
OrthoDBi1231389at2759
PhylomeDBiO35054
TreeFamiTF331936

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
12740, 0 hits in 18 CRISPR screens

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

More...
ChiTaRSi
Cldn4, mouse

Protein Ontology

More...
PROi
PR:O35054
RNActiO35054, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000047501, Expressed in endoderm of midgut and 149 other tissues
GenevisibleiO35054, MM

Family and domain databases

InterProiView protein in InterPro
IPR006187, Claudin
IPR003550, Claudin4
IPR017974, Claudin_CS
IPR004031, PMP22/EMP/MP20/Claudin
PANTHERiPTHR12002, PTHR12002, 1 hit
PfamiView protein in Pfam
PF00822, PMP22_Claudin, 1 hit
PRINTSiPR01379, CLAUDIN4
PROSITEiView protein in PROSITE
PS01346, CLAUDIN, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

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 nameiCLD4_MOUSE
<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: O35054
<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: May 30, 2000
Last sequence update: January 1, 1998
Last modified: August 12, 2020
This is version 145 of the entry and version 1 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

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