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UniProtKB - Q13619 (CUL4A_HUMAN)

Entry version 198 (25 May 2022)
Sequence version 3 (30 May 2006)
Previous versions | rss
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Protein

Cullin-4A

Gene

CUL4A

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 E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620, PubMed:30166453, PubMed:33854232, PubMed:33854239).

As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620).

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 (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620).

The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620).

DCX(DET1-COP1) directs ubiquitination of JUN (PubMed:14739464).

DCX(DDB2) directs ubiquitination of XPC (PubMed:15811626).

DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition (PubMed:16678110, PubMed:17041588, PubMed:24209620).

DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of p53/TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:14578910, PubMed:15548678, PubMed:15448697).

DCX(DTL) directs autoubiquitination of DTL (PubMed:23478445).

In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip (PubMed:16537899).

Is involved in ubiquitination of HOXA9 (PubMed:14609952).

The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207).

A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948).

The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (PubMed:33854232, PubMed:33854239).

The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:30166453).

With CUL4B, contributes to ribosome biogenesis (PubMed:26711351).

17 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'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.10 Publications
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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

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

Biological processBiological rhythms, DNA damage, DNA repair, Host-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q13619

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-110314, Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5696394, DNA Damage Recognition in GG-NER
R-HSA-5696395, Formation of Incision Complex in GG-NER
R-HSA-5696400, Dual Incision in GG-NER
R-HSA-6781823, Formation of TC-NER Pre-Incision Complex
R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135, Dual incision in TC-NER
R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-8951664, Neddylation

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

More...SignaLinki		Q13619

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q13619

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

More...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%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:
Cullin-4ACurated
Short name:
CUL-4A1 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:CUL4A1 PublicationImported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 13

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:2554, CUL4A

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603137, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q13619

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000139842

<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

<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>Mutagenesisi86 – 90LYQAV → AAAAA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. 2 Publications5
Mutagenesisi139 – 142WQDH → AADA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. 2 Publications4

Organism-specific databases

DisGeNET

More...DisGeNETi		8451

Open Targets

More...OpenTargetsi		ENSG00000139842

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA27050

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q13619, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4523598

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		CUL4A

Domain mapping of disease mutations (DMDM)

More...DMDMi		108936013

<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_00001197951 – 759Cullin-4AAdd BLAST759

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
<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 residuei10PhosphoserineCombined sources1
Cross-linki33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-linki705Glycyl 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%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

Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.3 Publications
(Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q13619

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q13619

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q13619

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q13619

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

More...PaxDbi		Q13619

PeptideAtlas

More...PeptideAtlasi		Q13619

PRoteomics IDEntifications database

More...PRIDEi		Q13619

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		59609 [Q13619-1]
59610 [Q13619-2]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q13619, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q13619

MetOSite database of methionine sulfoxide sites

More...MetOSitei		Q13619

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

More...PhosphoSitePlusi		Q13619

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000139842, Expressed in skeletal muscle tissue and 245 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q13619, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q13619, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000139842, Tissue enhanced (skeletal)

<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

Can self-associate (PubMed:17254749).

Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins (PubMed:14578910, PubMed:12732143, PubMed:15548678, PubMed:14739464, PubMed:29779948, PubMed:30166453).

Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II (PubMed:12732143).

Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1 (PubMed:14739464).

Component of the DCX(DDB2) complex with the substrate recognition component DDB2 (PubMed:15811626, PubMed:16678110).

Component of the DCX(DTL) complex with the putative substrate recognition component DTL (PubMed:14578910, PubMed:15448697, PubMed:15548678).

Component of DCX complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either TRPC4AP or DCAF12 as substrate-recognition component (PubMed:29779948).

Component of the DCX(AMBRA1) complex with the substrate recognition component AMBRA1 (PubMed:30166453, PubMed:33854232, PubMed:33854239).

Interacts with DDB1, RBX1, RNF7, CDT1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9 (PubMed:16964240, PubMed:16537899, PubMed:22118460, PubMed:16482215, PubMed:12609982, PubMed:10230407, PubMed:14609952, PubMed:16678110).

Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive (PubMed:16678110, PubMed:22118460, PubMed:16482215).

Interacts with DCAF1, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, COP1, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5, LRWD1 and DCAF8 (PubMed:16949367, PubMed:22935713, PubMed:17079684). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5 (PubMed:17041588).

Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655). The DDB1-CUL4A complex interacts with CRY1 (PubMed:26431207).

Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:23201271, PubMed:26906416).

27 Publications

(Microbial infection) Interacts with Epstein-Barr virus BPLF1.

1 Publication

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

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		114029, 773 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-477, CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q13619

Database of interacting proteins

More...DIPi		DIP-31610N

Protein interaction database and analysis system

More...IntActi		Q13619, 209 interactors

Molecular INTeraction database

More...MINTi		Q13619

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000364589

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q13619, protein

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

Secondary structure

1759
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		Q13619

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

More...SMRi		Q13619

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q13619

<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

More...eggNOGi		KOG2167, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000156905

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_004747_7_2_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q13619

Identification of Orthologs from Complete Genome Data

More...OMAi		DNVVQSC

Database of Orthologous Groups

More...OrthoDBi		1040292at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q13619

TreeFam database of animal gene trees

More...TreeFami		TF101153

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.10.10.10, 1 hit

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00514

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR045093, Cullin
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

The PANTHER Classification System

More...PANTHERi		PTHR11932, PTHR11932, 1 hit

Pfam protein domain database

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

Simple Modular Architecture Research Tool; a protein domain database

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

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF46785, SSF46785, 1 hit
SSF74788, SSF74788, 1 hit
SSF75632, SSF75632, 1 hit

PROSITE; a protein domain and family database

More...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%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

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

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

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

Isoform 1 (identifier: Q13619-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MADEAPRKGS FSALVGRTNG LTKPAALAAA PAKPGGAGGS KKLVIKNFRD 
        60         70         80         90        100
RPRLPDNYTQ DTWRKLHEAV RAVQSSTSIR YNLEELYQAV ENLCSHKVSP 
       110        120        130        140        150
MLYKQLRQAC EDHVQAQILP FREDSLDSVL FLKKINTCWQ DHCRQMIMIR 
       160        170        180        190        200
SIFLFLDRTY VLQNSTLPSI WDMGLELFRT HIISDKMVQS KTIDGILLLI 
       210        220        230        240        250
ERERSGEAVD RSLLRSLLGM LSDLQVYKDS FELKFLEETN CLYAAEGQRL 
       260        270        280        290        300
MQEREVPEYL NHVSKRLEEE GDRVITYLDH STQKPLIACV EKQLLGEHLT 
       310        320        330        340        350
AILQKGLDHL LDENRVPDLA QMYQLFSRVR GGQQALLQHW SEYIKTFGTA 
       360        370        380        390        400
IVINPEKDKD MVQDLLDFKD KVDHVIEVCF QKNERFVNLM KESFETFINK 
       410        420        430        440        450
RPNKPAELIA KHVDSKLRAG NKEATDEELE RTLDKIMILF RFIHGKDVFE 
       460        470        480        490        500
AFYKKDLAKR LLVGKSASVD AEKSMLSKLK HECGAAFTSK LEGMFKDMEL 
       510        520        530        540        550
SKDIMVHFKQ HMQNQSDSGP IDLTVNILTM GYWPTYTPME VHLTPEMIKL 
       560        570        580        590        600
QEVFKAFYLG KHSGRKLQWQ TTLGHAVLKA EFKEGKKEFQ VSLFQTLVLL 
       610        620        630        640        650
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED 
       660        670        680        690        700
GDKFIFNGEF KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI 
       710        720        730        740        750
VRIMKMRKTL GHNLLVSELY NQLKFPVKPG DLKKRIESLI DRDYMERDKD 

NPNQYHYVA
Length:759
Mass (Da):87,680
Last modified:May 30, 2006 - v3
<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:i3C4C6A1BBD94D51B
GO
Isoform 2 (identifier: Q13619-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Show »
Length:659
Mass (Da):76,821
Checksum:i56D4D196BB1074CB
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 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MR50A0A0A0MR50_HUMAN
Cullin-4A
CUL4A
667Annotation 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>
A0A087WWN2A0A087WWN2_HUMAN
Cullin-4A
CUL4A
174Annotation score:

Annotation score:1 out of 5

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti281S → T in BAD93235 (PubMed:15811626).Curated1
Sequence conflicti339 – 346HWSEYIKT → NSARARAA in AAC50547 (PubMed:8681378).Curated8
Sequence conflicti496K → R in BAD93235 (PubMed:15811626).Curated1

Natural variant

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_020341644K → R. Corresponds to variant dbSNP:rs2302757Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0185771 – 100Missing in isoform 2. 1 PublicationAdd BLAST100

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
AF077188 mRNA Translation: AAD45191.1
AY365124 mRNA Translation: AAR13072.1
AB178950 mRNA Translation: BAD93235.1
AL136221 Genomic DNA No translation available.
BC008308 mRNA Translation: AAH08308.2
AB012193 mRNA Translation: BAA33146.1
U58090 mRNA Translation: AAC50547.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS41908.1 [Q13619-1]
CCDS9533.1 [Q13619-2]

NCBI Reference Sequences

More...RefSeqi		NP_001008895.1, NM_001008895.2 [Q13619-1]
NP_001265442.1, NM_001278513.1 [Q13619-2]
NP_003580.1, NM_003589.2 [Q13619-2]
XP_011535825.1, XM_011537523.2 [Q13619-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000375440.9; ENSP00000364589.4; ENSG00000139842.15
ENST00000375441.7; ENSP00000364590.3; ENSG00000139842.15 [Q13619-2]
ENST00000451881.5; ENSP00000389118.1; ENSG00000139842.15 [Q13619-2]
ENST00000617546.4; ENSP00000481782.1; ENSG00000139842.15 [Q13619-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		8451

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:8451

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

More...MANE-Selecti		ENST00000375440.9; ENSP00000364589.4; NM_001008895.4; NP_001008895.1

UCSC genome browser

More...UCSCi		uc021rmu.2, human [Q13619-1]

Keywords - Coding sequence diversityi

Alternative splicing

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

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077188 mRNA Translation: AAD45191.1
AY365124 mRNA Translation: AAR13072.1
AB178950 mRNA Translation: BAD93235.1
AL136221 Genomic DNA No translation available.
BC008308 mRNA Translation: AAH08308.2
AB012193 mRNA Translation: BAA33146.1
U58090 mRNA Translation: AAC50547.1
CCDSiCCDS41908.1 [Q13619-1]
CCDS9533.1 [Q13619-2]
RefSeqiNP_001008895.1, NM_001008895.2 [Q13619-1]
NP_001265442.1, NM_001278513.1 [Q13619-2]
NP_003580.1, NM_003589.2 [Q13619-2]
XP_011535825.1, XM_011537523.2 [Q13619-2]

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
2HYEX-ray3.10C1-759[»]
4A0KX-ray5.93A38-759[»]
7OKQelectron microscopy8.40C/G/K/O35-759[»]
7OPCelectron microscopy3.00e1-759[»]
7OPDelectron microscopy3.00e1-759[»]
AlphaFoldDBiQ13619
SMRiQ13619
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi114029, 773 interactors
ComplexPortaliCPX-477, CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant
CORUMiQ13619
DIPiDIP-31610N
IntActiQ13619, 209 interactors
MINTiQ13619
STRINGi9606.ENSP00000364589

Chemistry databases

ChEMBLiCHEMBL4523598

PTM databases

GlyGeniQ13619, 1 site, 1 O-linked glycan (1 site)
iPTMnetiQ13619
MetOSiteiQ13619
PhosphoSitePlusiQ13619

Genetic variation databases

BioMutaiCUL4A
DMDMi108936013

Proteomic databases

EPDiQ13619
jPOSTiQ13619
MassIVEiQ13619
MaxQBiQ13619
PaxDbiQ13619
PeptideAtlasiQ13619
PRIDEiQ13619
ProteomicsDBi59609 [Q13619-1]
59610 [Q13619-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		11756, 398 antibodies from 38 providers

The DNASU plasmid repository

More...DNASUi		8451

Genome annotation databases

EnsembliENST00000375440.9; ENSP00000364589.4; ENSG00000139842.15
ENST00000375441.7; ENSP00000364590.3; ENSG00000139842.15 [Q13619-2]
ENST00000451881.5; ENSP00000389118.1; ENSG00000139842.15 [Q13619-2]
ENST00000617546.4; ENSP00000481782.1; ENSG00000139842.15 [Q13619-2]
GeneIDi8451
KEGGihsa:8451
MANE-SelectiENST00000375440.9; ENSP00000364589.4; NM_001008895.4; NP_001008895.1
UCSCiuc021rmu.2, human [Q13619-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		8451
DisGeNETi8451

GeneCards: human genes, protein and diseases

More...GeneCardsi		CUL4A
HGNCiHGNC:2554, CUL4A
HPAiENSG00000139842, Tissue enhanced (skeletal)
MIMi603137, gene
neXtProtiNX_Q13619
OpenTargetsiENSG00000139842
PharmGKBiPA27050
VEuPathDBiHostDB:ENSG00000139842

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2167, Eukaryota
GeneTreeiENSGT00940000156905
HOGENOMiCLU_004747_7_2_1
InParanoidiQ13619
OMAiDNVVQSC
OrthoDBi1040292at2759
PhylomeDBiQ13619
TreeFamiTF101153

Enzyme and pathway databases

UniPathwayiUPA00143
PathwayCommonsiQ13619
ReactomeiR-HSA-110314, Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5696394, DNA Damage Recognition in GG-NER
R-HSA-5696395, Formation of Incision Complex in GG-NER
R-HSA-5696400, Dual Incision in GG-NER
R-HSA-6781823, Formation of TC-NER Pre-Incision Complex
R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135, Dual incision in TC-NER
R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-8951664, Neddylation
SignaLinkiQ13619
SIGNORiQ13619

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		8451, 17 hits in 1123 CRISPR screens

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

More...ChiTaRSi		CUL4A, human
EvolutionaryTraceiQ13619

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		CUL4A

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

More...GenomeRNAii		8451
PharosiQ13619, Tchem

Protein Ontology

More...PROi		PR:Q13619
RNActiQ13619, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000139842, Expressed in skeletal muscle tissue and 245 other tissues
ExpressionAtlasiQ13619, baseline and differential
GenevisibleiQ13619, HS

Family and domain databases

Gene3Di1.10.10.10, 1 hit
IDEALiIID00514
InterProiView protein in InterPro
IPR045093, Cullin
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
PANTHERiPTHR11932, PTHR11932, 1 hit
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

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 nameiCUL4A_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: Q13619
Secondary accession number(s): A2A2W2
, O75834, Q589T6, Q5TC62, Q6UP08, Q9UP17
<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: November 1, 1997
Last sequence update: May 30, 2006
Last modified: May 25, 2022
This is version 198 of the entry and version 3 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, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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