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Protein

Cullin-3

Gene

CUL3

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

Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626).27 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

<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

  • cyclin binding Source: Ensembl
  • Notch binding Source: MGI
  • POZ domain binding Source: UniProtKB
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: Ensembl
  • ubiquitin protein ligase binding Source: GO_Central

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

Biological processCilium biogenesis/degradation, ER-Golgi transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
6.3.2.19 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-4641258 Degradation of DVL
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

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

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SignaLinki
Q13618

SIGNOR Signaling Network Open Resource

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SIGNORi
Q13618

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00143

<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_and_taxonomy_section">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:
Cullin-3
Short name:
CUL-3
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:CUL3
Synonyms:KIAA0617
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_manual">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 2

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000036257.12

Human Gene Nomenclature Database

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HGNCi
HGNC:2553 CUL3

Online Mendelian Inheritance in Man (OMIM)

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MIMi
603136 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q13618

<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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Flagellum, Golgi apparatus, Nucleus

<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

Pseudohypoaldosteronism 2E (PHA2E)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.
See also OMIM:614496
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_067532413D → G in PHA2E. 1 PublicationCorresponds to variant dbSNP:rs199469656EnsemblClinVar.1
Natural variantiVAR_067533459K → R in PHA2E. 1 PublicationCorresponds to variant dbSNP:rs199469658EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

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DisGeNETi
8452

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

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GeneReviewsi
CUL3

MalaCards human disease database

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MalaCardsi
CUL3
MIMi614496 phenotype

Open Targets

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OpenTargetsi
ENSG00000036257

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

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Orphaneti
300530 Pseudohypoaldosteronism type 2E

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA27049

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
CUL3

Domain mapping of disease mutations (DMDM)

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DMDMi
12643396

<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 <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001197932 – 768Cullin-3Add BLAST767

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 residuei2N-acetylserineCombined sources1
Modified residuei585PhosphoserineCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki712Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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

Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.4 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q13618

MaxQB - The MaxQuant DataBase

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MaxQBi
Q13618

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

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PaxDbi
Q13618

PeptideAtlas

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PeptideAtlasi
Q13618

PRoteomics IDEntifications database

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PRIDEi
Q13618

ProteomicsDB human proteome resource

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ProteomicsDBi
59606
59607 [Q13618-2]
59608 [Q13618-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q13618

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

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PhosphoSitePlusi
Q13618

<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

Brain, spermatozoa, and testis (at protein level). Widely expressed.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000036257 Expressed in 230 organ(s), highest expression level in sperm

CleanEx database of gene expression profiles

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CleanExi
HS_CUL3

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q13618 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q13618 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB002678

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Forms neddylation-dependent homodimers. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit. The BCR complex may be active as a heterodimeric complex, in which NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule. Interacts with RBX1, RNF7, CYCE and TIP120A/CAND1 (PubMed:10500095, PubMed:10230407, PubMed:12609982). Part of the BCR(SPOP) containing SPOP, and of BCR containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13. Part of the BCR(KLHL41) complex containing KLHL41. Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Part of the BCR(ENC1) complex containing ENC1. Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of BRMS1, CUL3 and SPOP. Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1. Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1. Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1. Part of a complex consisting of H2AFY, CUL3 and SPOP. Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL42. Interacts with KLHL42 (via the BTB domain). Interacts with KATNA1; the interaction is enhanced by KLHL42. Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1 (PubMed:26399832). Interacts with KCTD5, KLHL9, KLHL11, KLHL13, GAN, ZBTB16, KLHL3, KLHL15, KLHL20, KLHL36, GMCL2, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with KLHL17; the interaction regulates surface GRIK2 expression. Interacts with KCTD7. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KEAP1) complex containing KEAP1. Interacts with KLHL10 (By similarity). Interacts with KAT5 and ATF2. Interacts with DCUN1D3. Interacts with KCTD17 in the BCR(KCTD17) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD17 and RBX1 (PubMed:25270598). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts with COPS9 isoform 2 (PubMed:23776465). Interacts with PPP2R5B; this interaction is indirect and mediated through KLHL15-binding and leads to PPP2R5B proteasomal degradation (PubMed:23135275). Interacts with RBBP8/CtIP; this interaction is indirect and mediated through KLHL15-binding and leads to RBBP8 proteasomal degradation (PubMed:27561354). Interacts with KLHL24 in the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24 (PubMed:27798626). Interacts with RHOBTB2 (PubMed:29276004).By similarityCurated37 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
114030, 1228 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q13618

Database of interacting proteins

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DIPi
DIP-31611N

Protein interaction database and analysis system

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IntActi
Q13618, 71 interactors

Molecular INTeraction database

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MINTi
Q13618

STRING: functional protein association networks

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STRINGi
9606.ENSP00000264414

<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

Secondary structure

1768
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q13618

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

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SMRi
Q13618

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
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

<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 cullin family.PROSITE-ProRule annotation

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG2167 Eukaryota
COG5647 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000155066

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG003619

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q13618

KEGG Orthology (KO)

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KOi
K03869

Identification of Orthologs from Complete Genome Data

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OMAi
TSTFWPM

Database of Orthologous Groups

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OrthoDBi
EOG091G02DP

Database for complete collections of gene phylogenies

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PhylomeDBi
Q13618

TreeFam database of animal gene trees

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TreeFami
TF105858

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf

Pfam protein domain database

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Pfami
View protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <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 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q13618-1) [UniParc]FASTAAdd to basket
Also known as: Cul-3 Long

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
MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS
60 70 80 90 100
GLSFEELYRN AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN
110 120 130 140 150
FLQTLNQAWN DHQTAMVMIR DILMYMDRVY VQQNNVENVY NLGLIIFRDQ
160 170 180 190 200
VVRYGCIRDH LRQTLLDMIA RERKGEVVDR GAIRNACQML MILGLEGRSV
210 220 230 240 250
YEEDFEAPFL EMSAEFFQME SQKFLAENSA SVYIKKVEAR INEEIERVMH
260 270 280 290 300
CLDKSTEEPI VKVVERELIS KHMKTIVEME NSGLVHMLKN GKTEDLGCMY
310 320 330 340 350
KLFSRVPNGL KTMCECMSSY LREQGKALVS EEGEGKNPVD YIQGLLDLKS
360 370 380 390 400
RFDRFLLESF NNDRLFKQTI AGDFEYFLNL NSRSPEYLSL FIDDKLKKGV
410 420 430 440 450
KGLTEQEVET ILDKAMVLFR FMQEKDVFER YYKQHLARRL LTNKSVSDDS
460 470 480 490 500
EKNMISKLKT ECGCQFTSKL EGMFRDMSIS NTTMDEFRQH LQATGVSLGG
510 520 530 540 550
VDLTVRVLTT GYWPTQSATP KCNIPPAPRH AFEIFRRFYL AKHSGRQLTL
560 570 580 590 600
QHHMGSADLN ATFYGPVKKE DGSEVGVGGA QVTGSNTRKH ILQVSTFQMT
610 620 630 640 650
ILMLFNNREK YTFEEIQQET DIPERELVRA LQSLACGKPT QRVLTKEPKS
660 670 680 690 700
KEIENGHIFT VNDQFTSKLH RVKIQTVAAK QGESDPERKE TRQKVDDDRK
710 720 730 740 750
HEIEAAIVRI MKSRKKMQHN VLVAEVTQQL KARFLPSPVV IKKRIEGLIE
760
REYLARTPED RKVYTYVA
Length:768
Mass (Da):88,930
Last modified:January 24, 2001 - 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:iA1A02022480BF099
GO
Isoform 2 (identifier: Q13618-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.

Show »
Length:744
Mass (Da):86,234
Checksum:iAD845C2516117B9F
GO
Isoform 3 (identifier: Q13618-3) [UniParc]FASTAAdd to basket
Also known as: Cul-3 Short

The sequence of this isoform differs from the canonical sequence as follows:
     23-88: Missing.

Show »
Length:702
Mass (Da):81,093
Checksum:i2CDE8E7AF43C898A
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
H7C399H7C399_HUMAN
Cullin-3
CUL3
111Annotation 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>
A0A087WTG3A0A087WTG3_HUMAN
Cullin-3
CUL3
342Annotation 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>
H7C1J0H7C1J0_HUMAN
Cullin-3
CUL3
43Annotation 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>
H7C1L6H7C1L6_HUMAN
Cullin-3
CUL3
192Annotation 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>
A0A087X1R9A0A087X1R9_HUMAN
Cullin-3
CUL3
55Annotation 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>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAC28621 differs from that shown. Reason: Frameshift at position 452.Curated
The sequence AAC36682 differs from that shown. Reason: Frameshift at positions 159 and 179.Curated
The sequence BAA31592 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

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 conflicti13D → G in AAC36682 (PubMed:9663463).Curated1
Sequence conflicti397K → T in AAQ01660 (Ref. 4) Curated1
Sequence conflicti481N → T in AAQ01660 (Ref. 4) Curated1
Sequence conflicti609E → G in AAH31844 (PubMed:15489334).Curated1
Sequence conflicti666T → I in AAQ01660 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01719413D → H. Corresponds to variant dbSNP:rs2969802Ensembl.1
Natural variantiVAR_048839184R → S. Corresponds to variant dbSNP:rs17480168Ensembl.1
Natural variantiVAR_067532413D → G in PHA2E. 1 PublicationCorresponds to variant dbSNP:rs199469656EnsemblClinVar.1
Natural variantiVAR_067533459K → R in PHA2E. 1 PublicationCorresponds to variant dbSNP:rs199469658EnsemblClinVar.1
Natural variantiVAR_017195567V → I. Corresponds to variant dbSNP:rs3738952EnsemblClinVar.1
Natural variantiVAR_078688719H → R Found in a patient with autism spectrum disorder; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs763087632Ensembl.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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0088241 – 24Missing in isoform 2. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_00882523 – 88Missing in isoform 3. CuratedAdd BLAST66

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
AF064087 mRNA Translation: AAC36304.1
AB014517 mRNA Translation: BAA31592.2 Different initiation.
AF062537 mRNA Translation: AAC36682.1 Frameshift.
AY337761 mRNA Translation: AAQ01660.1
AK291151 mRNA Translation: BAF83840.1
AC073052 Genomic DNA No translation available.
AC092679 Genomic DNA No translation available.
CH471063 Genomic DNA Translation: EAW70828.1
BC031844 mRNA Translation: AAH31844.1
BC039598 mRNA Translation: AAH39598.1
BC092409 mRNA Translation: AAH92409.1
U58089 mRNA Translation: AAC50546.1
AF052147 mRNA Translation: AAC28621.1 Frameshift.

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS2462.1 [Q13618-1]
CCDS58751.1 [Q13618-3]

NCBI Reference Sequences

More...
RefSeqi
NP_001244126.1, NM_001257197.1 [Q13618-3]
NP_001244127.1, NM_001257198.1
NP_003581.1, NM_003590.4 [Q13618-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.372286

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000264414; ENSP00000264414; ENSG00000036257 [Q13618-1]
ENST00000344951; ENSP00000343601; ENSG00000036257 [Q13618-3]
ENST00000409096; ENSP00000387200; ENSG00000036257 [Q13618-2]
ENST00000409777; ENSP00000386525; ENSG00000036257 [Q13618-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
8452

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:8452

UCSC genome browser

More...
UCSCi
uc002vny.4 human [Q13618-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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
AF064087 mRNA Translation: AAC36304.1
AB014517 mRNA Translation: BAA31592.2 Different initiation.
AF062537 mRNA Translation: AAC36682.1 Frameshift.
AY337761 mRNA Translation: AAQ01660.1
AK291151 mRNA Translation: BAF83840.1
AC073052 Genomic DNA No translation available.
AC092679 Genomic DNA No translation available.
CH471063 Genomic DNA Translation: EAW70828.1
BC031844 mRNA Translation: AAH31844.1
BC039598 mRNA Translation: AAH39598.1
BC092409 mRNA Translation: AAH92409.1
U58089 mRNA Translation: AAC50546.1
AF052147 mRNA Translation: AAC28621.1 Frameshift.
CCDSiCCDS2462.1 [Q13618-1]
CCDS58751.1 [Q13618-3]
RefSeqiNP_001244126.1, NM_001257197.1 [Q13618-3]
NP_001244127.1, NM_001257198.1
NP_003581.1, NM_003590.4 [Q13618-1]
UniGeneiHs.372286

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MYLNMR-A49-68[»]
2MYMNMR-A49-68[»]
4AP2X-ray2.80B1-388[»]
4APFX-ray3.10B23-388[»]
4EOZX-ray2.40B/D20-381[»]
4HXIX-ray3.51B20-381[»]
5NLBX-ray3.45B26-381[»]
ProteinModelPortaliQ13618
SMRiQ13618
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114030, 1228 interactors
CORUMiQ13618
DIPiDIP-31611N
IntActiQ13618, 71 interactors
MINTiQ13618
STRINGi9606.ENSP00000264414

PTM databases

iPTMnetiQ13618
PhosphoSitePlusiQ13618

Polymorphism and mutation databases

BioMutaiCUL3
DMDMi12643396

Proteomic databases

EPDiQ13618
MaxQBiQ13618
PaxDbiQ13618
PeptideAtlasiQ13618
PRIDEiQ13618
ProteomicsDBi59606
59607 [Q13618-2]
59608 [Q13618-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264414; ENSP00000264414; ENSG00000036257 [Q13618-1]
ENST00000344951; ENSP00000343601; ENSG00000036257 [Q13618-3]
ENST00000409096; ENSP00000387200; ENSG00000036257 [Q13618-2]
ENST00000409777; ENSP00000386525; ENSG00000036257 [Q13618-2]
GeneIDi8452
KEGGihsa:8452
UCSCiuc002vny.4 human [Q13618-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
8452
DisGeNETi8452
EuPathDBiHostDB:ENSG00000036257.12

GeneCards: human genes, protein and diseases

More...
GeneCardsi
CUL3
GeneReviewsiCUL3
HGNCiHGNC:2553 CUL3
HPAiCAB002678
MalaCardsiCUL3
MIMi603136 gene
614496 phenotype
neXtProtiNX_Q13618
OpenTargetsiENSG00000036257
Orphaneti300530 Pseudohypoaldosteronism type 2E
PharmGKBiPA27049

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG2167 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00940000155066
HOVERGENiHBG003619
InParanoidiQ13618
KOiK03869
OMAiTSTFWPM
OrthoDBiEOG091G02DP
PhylomeDBiQ13618
TreeFamiTF105858

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi6.3.2.19 2681
ReactomeiR-HSA-4641258 Degradation of DVL
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ13618
SIGNORiQ13618

Miscellaneous databases

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

More...
ChiTaRSi
CUL3 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
CUL3

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

More...
GenomeRNAii
8452

Protein Ontology

More...
PROi
PR:Q13618

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000036257 Expressed in 230 organ(s), highest expression level in sperm
CleanExiHS_CUL3
ExpressionAtlasiQ13618 baseline and differential
GenevisibleiQ13618 HS

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit
SMARTiView protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit
PROSITEiView protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
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 nameiCUL3_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: Q13618
Secondary accession number(s): A8K536
, B8ZZC3, O75415, Q569L3, Q9UBI8, Q9UET7
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 24, 2001
Last modified: December 5, 2018
This is version 192 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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