{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q13620","secondaryAccessions":["B1APK5","B3KVX4","B7Z5K8","Q6PIE4","Q6UP07","Q7Z673","Q9BY37","Q9UEB7","Q9UED7"],"uniProtkbId":"CUL4B_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2010-05-18","entryVersion":224,"sequenceVersion":4},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Cullin-4B"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14578910"}],"value":"CUL-4B"}]}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14578910"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:2555"}],"value":"CUL4B"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9734811"}],"value":"KIAA0695"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14578910"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16322693"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16678110"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18235224"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593899"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22118460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25970626"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26711351"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29779948"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30166453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33854232"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33854239"}],"value":"Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14578910, PubMed:16322693, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948, PubMed:30166453, PubMed:33854232, PubMed:33854239, PubMed:25970626). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948). CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460). Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage (PubMed:14578910, PubMed:16678110, PubMed:18593899). Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication (PubMed:16678110). 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). Required for ubiquitination of cyclin E (CCNE1 or CCNE2), and consequently, normal G1 cell cycle progression (PubMed:16322693, PubMed:19801544). Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism (PubMed:18235224). Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8 (PubMed:18235224). With CUL4A, contributes to ribosome biogenesis (PubMed:26711351)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10230407"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16678110"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593899"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29779948"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30166453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33854232"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33854239"}],"value":"Protein modification; protein ubiquitination"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10230407"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12609982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16322693"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16678110"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16949367"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17041588"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18235224"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593899"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22118460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23201271"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25970626"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26906416"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29779948"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30166453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33854232"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33854239"}],"value":"Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to be formed 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:10230407, PubMed:16678110, PubMed:17041588, PubMed:18593899). Component of the DCX(DTL) complex with the putative substrate recognition component DTL (PubMed:17041588). Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2 (PubMed:16678110). 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). Part of a complex with RBX1 and TIP120A/CAND1 (PubMed:12609982, PubMed:22118460). Interacts with RBX1, GRWD1, MLST8, SMU1, TLE2, TLE3, DCAF1, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113 (PubMed:16949367, PubMed:17041588, PubMed:18235224). Interacts with cyclin E (CCNE1 or CCNE2) and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1) (PubMed:16322693, PubMed:19801544). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5 (PubMed:17041588). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:23201271, PubMed:26906416). Interacts with FBOX44 (PubMed:25970626)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"Q86VP6","geneName":"CAND1","intActId":"EBI-456077"},"numberOfExperiments":14,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"Q16543","geneName":"CDC37","intActId":"EBI-295634"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"Q16531","geneName":"DDB1","intActId":"EBI-350322"},"numberOfExperiments":28,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"P08238","geneName":"HSP90AB1","intActId":"EBI-352572"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"P62877","geneName":"RBX1","intActId":"EBI-398523"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"O43791","geneName":"SPOP","intActId":"EBI-743549"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"O94888","geneName":"UBXN7","intActId":"EBI-1993627"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q13620","intActId":"EBI-456067"},"interactantTwo":{"uniProtKBAccession":"Q9H898-2","geneName":"ZMAT4","intActId":"EBI-11529334"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A2A432"}],"value":"More concentrated in nuclei than in cytoplasm in germinal vesicle (GV) stage oocytes, zygotes and the 2-cell stage, but distributed in the cytoplasm at the MII-stage oocytes"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A2A432"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593899"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q13620-2"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q13620-1"],"sequenceIds":["VSP_039085"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q13620-3"],"sequenceIds":["VSP_039084","VSP_039086"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10597293"}],"value":"Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, X-linked, syndromic, Cabezas type","diseaseAccession":"DI-01309","acronym":"MRXSC","description":"A syndromic form of X-linked intellectual disability characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span.","diseaseCrossReference":{"database":"MIM","id":"300354"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17236139"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17273978"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19377476"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20002452"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00330"}],"value":"Belongs to the cullin family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous gene model prediction","sequence":"AAB67315.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAK16812.1","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":913,"modifier":"EXACT"}},"description":"Cullin-4B","featureId":"PRO_0000393946"},{"type":"Domain","location":{"start":{"value":845,"modifier":"EXACT"},"end":{"value":905,"modifier":"EXACT"}},"description":"Cullin neddylation","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":100,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Motif","location":{"start":{"value":55,"modifier":"EXACT"},"end":{"value":58,"modifier":"EXACT"}},"description":"Nuclear localization signal","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}]},{"type":"Compositional 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ubiquitin)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q13619"}]},{"type":"Cross-link","location":{"start":{"value":859,"modifier":"EXACT"},"end":{"value":859,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q13616"}]},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":196,"modifier":"EXACT"}},"description":"in isoform 3","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14702039"}],"featureId":"VSP_039084","alternativeSequence":{}},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":22,"modifier":"EXACT"}},"description":"in isoform 2","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14578910"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14702039"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17974005"},{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.2"}],"featureId":"VSP_039085","alternativeSequence":{"originalSequence":"MMSQSSGSGDGNDDEATTSKDG","alternativeSequences":["MFPT"]}},{"type":"Alternative sequence","location":{"start":{"value":197,"modifier":"EXACT"},"end":{"value":203,"modifier":"EXACT"}},"description":"in isoform 3","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14702039"}],"featureId":"VSP_039086","alternativeSequence":{"originalSequence":"LVIKNFK","alternativeSequences":["MIDPDFA"]}},{"type":"Natural variant","location":{"start":{"value":103,"modifier":"EXACT"},"end":{"value":103,"modifier":"EXACT"}},"description":"in dbSNP:rs61759504","featureCrossReferences":[{"database":"dbSNP","id":"rs61759504"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17236139"}],"featureId":"VAR_032272","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":213,"modifier":"EXACT"},"end":{"value":213,"modifier":"EXACT"}},"description":"in MRXSC; uncertain significance; dbSNP:rs763692058","featureCrossReferences":[{"database":"dbSNP","id":"rs763692058"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17236139"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19377476"}],"featureId":"VAR_032273","alternativeSequence":{"originalSequence":"T","alternativeSequences":["I"]}},{"type":"Natural variant","location":{"start":{"value":572,"modifier":"EXACT"},"end":{"value":572,"modifier":"EXACT"}},"description":"in MRXSC; dbSNP:rs121434615","featureCrossReferences":[{"database":"dbSNP","id":"rs121434615"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17236139"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19377476"}],"featureId":"VAR_032274","alternativeSequence":{"originalSequence":"R","alternativeSequences":["C"]}},{"type":"Natural variant","location":{"start":{"value":745,"modifier":"EXACT"},"end":{"value":745,"modifier":"EXACT"}},"description":"in MRXSC","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17236139"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19377476"}],"featureId":"VAR_032275","alternativeSequence":{"originalSequence":"V","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":55,"modifier":"EXACT"},"end":{"value":58,"modifier":"EXACT"}},"description":"Distributed in cytoplasm. Fails to promote cell proliferation. No binding to KPNA2, KPNA4 and KPNA1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}],"alternativeSequence":{}},{"type":"Mutagenesis","location":{"start":{"value":55,"modifier":"EXACT"},"end":{"value":55,"modifier":"EXACT"}},"description":"No impairment in nuclear localization.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":56,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"Disrupts nuclear localization and does not bind KPNA2, KPNA4, KPNA1; when associated with A-57. Disrupts nuclear localization.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":57,"modifier":"EXACT"},"end":{"value":57,"modifier":"EXACT"}},"description":"Disrupts nuclear localization and does not bind KPNA2, KPNA4, KPNA1; when associated with A-56. Disrupts nuclear localization.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":58,"modifier":"EXACT"},"end":{"value":58,"modifier":"EXACT"}},"description":"No impairment in nuclear localization.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19801544"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Sequence conflict","location":{"start":{"value":69,"modifier":"EXACT"},"end":{"value":69,"modifier":"EXACT"}},"description":"in Ref. 3; BAG53936","evidences":[{"evidenceCode":"ECO:0000305"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["R"]}},{"type":"Sequence conflict","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":126,"modifier":"EXACT"}},"description":"in Ref. 4; 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