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General description of the gene and encoded protein(s) using information from HGNC and Ensembl, as well as predictions made as well as predictions made by the Human Protein Atlas project.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Useful information about the protein provided by UniProt.
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 ref. 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) ref,ref. BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 ref,ref,ref. 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 ref,ref,ref,ref. 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 ref. 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 ref. 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 ref. The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) ref. 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 ref. 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 ref. 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 ref. The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity ref. The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry ref. The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes ref,ref....show less
Biological process (UniProt)i
Keywords assigned by UniProt to proteins because they are involved in a particular biological process.
This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]...show less
TISSUE ATLASi
The Tissue Atlas contains information regarding the expression profiles of human genes both on the mRNA and protein level. The protein expression data from 44 normal human tissue types is derived from antibody-based protein profiling using immunohistochemistry.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.
The RNA distribution category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: detected in all, detected in many, detected in some, detected in single and not detected.
A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation.
"Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile.
The Brain Atlas explores the protein expression in the mammalian brain by visualization and integration of data from three mammalian species (human, pig and mouse). Transcriptomics data combined with affinity-based protein in situ localization down to single cell detail is here available in a brain-centric sub atlas of the Human Protein Atlas.
The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category.
The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category.
The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category.
Summary of data presented in the Cell Atlas and a representative image of subcellular localization. The Cell Atlas provides RNA expression data derived from RNA sequencing of a large panel of cell lines and protein localization data derived from antibody-based profiling by immunofluorescence confocal microscopy, using a subset of cell lines selected based on RNA expression.
The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations. It is highlighted in the illustration to the right. If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively.
Not available
Cell line specificityi
The cell lines in the Human Protein Atlas have been analyzed by RNA-seq to estimate the transcript abundance of each protein-coding gene. The RNA-seq data was then used to classify all genes according to their cell line-specific expression into one of six different categories, defined based on the total set of all NX values in all analyzed cell lines.
The Blood Atlas contains single cell type information on genome-wide RNA expression profiles of human protein-coding genes covering various B- and T-cells, monocytes, granulocytes and dendritic cells. In addition, an analysis of the human secretome is presented. including annotation of the genes predicted to be actively secreted to human blood. An analysis of the proteins detected in human blood is also presented.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.
Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.
Yes
PATHOLOGY ATLASi
Summary of data presented in the Pathology Atlas , including mRNA and protein expression data from 17 different forms of human cancer, as well as correlation analysis of mRNA expression and patient survival. To the far left, a representative image of protein expression, based on immunohistochemistry, is shown. Next to it, a representative image of a Kaplan-Meier plot, based on correlation analysis. Images are clickable and redirect to pages with more Pathology Atlas data.
Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.
Distribution of RNA expression in 17 cancer types is categorized as either detected in single, detected in some, detected in many, detected in all, or not detected.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name
CUL3
Synonyms
Description
Cullin 3 (HGNC Symbol)
Chromosome
2
Cytoband
q36.2
Chromosome location (bp)
224470150 - 224585397
Number of transcriptsi
Number of protein-coding transcribed from this gene as defined by Ensembl.
The protein browser displays the antigen location on the target protein(s) and the features of the target protein. The tabs at the top of the protein view section can be used to switch between the different splice variants to which an antigen has been mapped.
At the top of the view, the position of the antigen (identified by the corresponding HPA identifier) is shown as a green bar. A yellow triangle on the bar indicates a <100% sequence identity to the protein target.
Below the antigens, the maximum percent sequence identity of the protein to all other proteins from other human genes is displayed, using a sliding window of 10 aa residues (HsID 10) or 50 aa residues (HsID 50). The region with the lowest possible identity is always selected for antigen design, with a maximum identity of 60% allowed for designing a single-target antigen (read more).
The curve in blue displays the predicted antigenicity i.e. the tendency for different regions of the protein to generate an immune response, with peak regions being predicted to be more antigenic.The curve shows average values based on a sliding window approach using an in-house propensity scale. (read more).
If a signal peptide is predicted by a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius (turquoise) and/or transmembrane regions (orange) are predicted by MDM, these are displayed.
Low complexity regions are shown in yellow and InterPro regions in green. Common (purple) and unique (grey) regions between different splice variants of the gene are also displayed (read more), and at the bottom of the protein view is the protein scale.
CUL3-201
CUL3-202
CUL3-203
CUL3-204
CUL3-206
CUL3-207
CUL3-216
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas)
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GO:0000082 [G1/S transition of mitotic cell cycle] GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] GO:0000139 [Golgi membrane] GO:0000165 [MAPK cascade] GO:0000209 [protein polyubiquitination] GO:0000278 [mitotic cell cycle] GO:0000902 [cell morphogenesis] GO:0001701 [in utero embryonic development] GO:0001831 [trophectodermal cellular morphogenesis] GO:0004842 [ubiquitin-protein transferase activity] GO:0005112 [Notch binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005737 [cytoplasm] GO:0005794 [Golgi apparatus] GO:0005827 [polar microtubule] GO:0005829 [cytosol] GO:0006357 [regulation of transcription from RNA polymerase II promoter] GO:0006511 [ubiquitin-dependent protein catabolic process] GO:0006513 [protein monoubiquitination] GO:0006888 [ER to Golgi vesicle-mediated transport] GO:0007050 [cell cycle arrest] GO:0007080 [mitotic metaphase plate congression] GO:0007229 [integrin-mediated signaling pathway] GO:0007369 [gastrulation] GO:0008284 [positive regulation of cell proliferation] GO:0016020 [membrane] GO:0016055 [Wnt signaling pathway] GO:0016192 [vesicle-mediated transport] GO:0016477 [cell migration] GO:0016567 [protein ubiquitination] GO:0017145 [stem cell division] GO:0030030 [cell projection organization] GO:0030332 [cyclin binding] GO:0031145 [anaphase-promoting complex-dependent catabolic process] GO:0031208 [POZ domain binding] GO:0031398 [positive regulation of protein ubiquitination] GO:0031461 [cullin-RING ubiquitin ligase complex] GO:0031463 [Cul3-RING ubiquitin ligase complex] GO:0031625 [ubiquitin protein ligase binding] GO:0031648 [protein destabilization] GO:0032467 [positive regulation of cytokinesis] GO:0035024 [negative regulation of Rho protein signal transduction] GO:0036126 [sperm flagellum] GO:0040016 [embryonic cleavage] GO:0042803 [protein homodimerization activity] GO:0043149 [stress fiber assembly] GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0043687 [post-translational protein modification] GO:0044346 [fibroblast apoptotic process] GO:0045842 [positive regulation of mitotic metaphase/anaphase transition] GO:0046982 [protein heterodimerization activity] GO:0048208 [COPII vesicle coating] GO:0061630 [ubiquitin protein ligase activity] GO:0070062 [extracellular exosome] GO:0071630 [nuclear protein quality control by the ubiquitin-proteasome system] GO:0072576 [liver morphogenesis] GO:0090090 [negative regulation of canonical Wnt signaling pathway] GO:0097193 [intrinsic apoptotic signaling pathway]
SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas)
Show all
GO:0000082 [G1/S transition of mitotic cell cycle] GO:0000139 [Golgi membrane] GO:0000165 [MAPK cascade] GO:0000209 [protein polyubiquitination] GO:0004842 [ubiquitin-protein transferase activity] GO:0005112 [Notch binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005737 [cytoplasm] GO:0005794 [Golgi apparatus] GO:0005827 [polar microtubule] GO:0005829 [cytosol] GO:0006511 [ubiquitin-dependent protein catabolic process] GO:0006513 [protein monoubiquitination] GO:0006888 [ER to Golgi vesicle-mediated transport] GO:0007050 [cell cycle arrest] GO:0007080 [mitotic metaphase plate congression] GO:0007229 [integrin-mediated signaling pathway] GO:0008284 [positive regulation of cell proliferation] GO:0016020 [membrane] GO:0016192 [vesicle-mediated transport] GO:0016477 [cell migration] GO:0016567 [protein ubiquitination] GO:0017145 [stem cell division] GO:0030030 [cell projection organization] GO:0031145 [anaphase-promoting complex-dependent catabolic process] GO:0031208 [POZ domain binding] GO:0031398 [positive regulation of protein ubiquitination] GO:0031461 [cullin-RING ubiquitin ligase complex] GO:0031463 [Cul3-RING ubiquitin ligase complex] GO:0031625 [ubiquitin protein ligase binding] GO:0031648 [protein destabilization] GO:0032467 [positive regulation of cytokinesis] GO:0035024 [negative regulation of Rho protein signal transduction] GO:0036126 [sperm flagellum] GO:0040016 [embryonic cleavage] GO:0043149 [stress fiber assembly] GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0043687 [post-translational protein modification] GO:0045842 [positive regulation of mitotic metaphase/anaphase transition] GO:0048208 [COPII vesicle coating] GO:0061630 [ubiquitin protein ligase activity] GO:0070062 [extracellular exosome] GO:0071630 [nuclear protein quality control by the ubiquitin-proteasome system] GO:0090090 [negative regulation of canonical Wnt signaling pathway] GO:0097193 [intrinsic apoptotic signaling pathway]
SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas)
Show all
GO:0000082 [G1/S transition of mitotic cell cycle] GO:0000139 [Golgi membrane] GO:0000165 [MAPK cascade] GO:0000209 [protein polyubiquitination] GO:0004842 [ubiquitin-protein transferase activity] GO:0005112 [Notch binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005737 [cytoplasm] GO:0005794 [Golgi apparatus] GO:0005827 [polar microtubule] GO:0005829 [cytosol] GO:0006511 [ubiquitin-dependent protein catabolic process] GO:0006513 [protein monoubiquitination] GO:0006888 [ER to Golgi vesicle-mediated transport] GO:0007050 [cell cycle arrest] GO:0007080 [mitotic metaphase plate congression] GO:0007229 [integrin-mediated signaling pathway] GO:0008284 [positive regulation of cell proliferation] GO:0016020 [membrane] GO:0016192 [vesicle-mediated transport] GO:0016477 [cell migration] GO:0016567 [protein ubiquitination] GO:0017145 [stem cell division] GO:0030030 [cell projection organization] GO:0031145 [anaphase-promoting complex-dependent catabolic process] GO:0031208 [POZ domain binding] GO:0031398 [positive regulation of protein ubiquitination] GO:0031461 [cullin-RING ubiquitin ligase complex] GO:0031463 [Cul3-RING ubiquitin ligase complex] GO:0031625 [ubiquitin protein ligase binding] GO:0031648 [protein destabilization] GO:0032467 [positive regulation of cytokinesis] GO:0035024 [negative regulation of Rho protein signal transduction] GO:0036126 [sperm flagellum] GO:0040016 [embryonic cleavage] GO:0043149 [stress fiber assembly] GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0043687 [post-translational protein modification] GO:0045842 [positive regulation of mitotic metaphase/anaphase transition] GO:0048208 [COPII vesicle coating] GO:0061630 [ubiquitin protein ligase activity] GO:0070062 [extracellular exosome] GO:0071630 [nuclear protein quality control by the ubiquitin-proteasome system] GO:0090090 [negative regulation of canonical Wnt signaling pathway] GO:0097193 [intrinsic apoptotic signaling pathway]
SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas)
Show all
GO:0000082 [G1/S transition of mitotic cell cycle] GO:0000139 [Golgi membrane] GO:0000165 [MAPK cascade] GO:0000209 [protein polyubiquitination] GO:0004842 [ubiquitin-protein transferase activity] GO:0005112 [Notch binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005737 [cytoplasm] GO:0005794 [Golgi apparatus] GO:0005827 [polar microtubule] GO:0005829 [cytosol] GO:0006511 [ubiquitin-dependent protein catabolic process] GO:0006513 [protein monoubiquitination] GO:0006888 [ER to Golgi vesicle-mediated transport] GO:0007050 [cell cycle arrest] GO:0007080 [mitotic metaphase plate congression] GO:0007229 [integrin-mediated signaling pathway] GO:0008284 [positive regulation of cell proliferation] GO:0016020 [membrane] GO:0016192 [vesicle-mediated transport] GO:0016477 [cell migration] GO:0016567 [protein ubiquitination] GO:0017145 [stem cell division] GO:0030030 [cell projection organization] GO:0031145 [anaphase-promoting complex-dependent catabolic process] GO:0031208 [POZ domain binding] GO:0031398 [positive regulation of protein ubiquitination] GO:0031461 [cullin-RING ubiquitin ligase complex] GO:0031463 [Cul3-RING ubiquitin ligase complex] GO:0031625 [ubiquitin protein ligase binding] GO:0031648 [protein destabilization] GO:0032467 [positive regulation of cytokinesis] GO:0035024 [negative regulation of Rho protein signal transduction] GO:0036126 [sperm flagellum] GO:0040016 [embryonic cleavage] GO:0043149 [stress fiber assembly] GO:0043161 [proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0043687 [post-translational protein modification] GO:0045842 [positive regulation of mitotic metaphase/anaphase transition] GO:0048208 [COPII vesicle coating] GO:0061630 [ubiquitin protein ligase activity] GO:0070062 [extracellular exosome] GO:0071630 [nuclear protein quality control by the ubiquitin-proteasome system] GO:0090090 [negative regulation of canonical Wnt signaling pathway] GO:0097193 [intrinsic apoptotic signaling pathway]
The Human Protein Atlas project is funded
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