UniProt functional annotation for Q13620



	UniProt functional annotation for Q13620

UniProt code: Q13620.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. 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. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of- rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. With CUL4A, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:16322693, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:18235224, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:26711351}.

Pathway: Protein modification; protein ubiquitination.

Subunit: 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. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Part of a complex with RBX1 and TIP120A/CAND1. Interacts with RBX1 GRWD1, MLST8, SMU1, TLE2, TLE3, DCAF1, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:26906416, PubMed:23201271). {ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:16322693, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:18235224, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:26906416}.

Subcellular location: Nucleus {ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544}.

Ptm: Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. {ECO:0000269|PubMed:10597293}.

Disease: Mental retardation, X-linked, syndromic, 15 (MRXS15) [MIM:300354]: A syndromic form of X-linked mental retardation 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. {ECO:0000269|PubMed:17236139, ECO:0000269|PubMed:17273978, ECO:0000269|PubMed:19377476, ECO:0000269|PubMed:20002452}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the cullin family. {ECO:0000255|PROSITE- ProRule:PRU00330}.

Sequence caution: Sequence=AAB67315.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAK16812.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. 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. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of- rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. With CUL4A, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269\|PubMed:14578910, ECO:0000269\|PubMed:16322693, ECO:0000269\|PubMed:16678110, ECO:0000269\|PubMed:18235224, ECO:0000269\|PubMed:18593899, ECO:0000269\|PubMed:19801544, ECO:0000269\|PubMed:22118460, ECO:0000269\|PubMed:26711351}.


Pathway:		Protein modification; protein ubiquitination.
Subunit:		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. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Part of a complex with RBX1 and TIP120A/CAND1. Interacts with RBX1 GRWD1, MLST8, SMU1, TLE2, TLE3, DCAF1, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:26906416, PubMed:23201271). {ECO:0000269\|PubMed:10230407, ECO:0000269\|PubMed:12609982, ECO:0000269\|PubMed:14578910, ECO:0000269\|PubMed:16322693, ECO:0000269\|PubMed:16678110, ECO:0000269\|PubMed:16949367, ECO:0000269\|PubMed:17041588, ECO:0000269\|PubMed:18235224, ECO:0000269\|PubMed:18593899, ECO:0000269\|PubMed:19801544, ECO:0000269\|PubMed:22118460, ECO:0000269\|PubMed:23201271, ECO:0000269\|PubMed:26906416}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:18593899, ECO:0000269\|PubMed:19801544}.
Ptm:		Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. {ECO:0000269\|PubMed:10597293}.
Disease:		Mental retardation, X-linked, syndromic, 15 (MRXS15) [MIM:300354]: A syndromic form of X-linked mental retardation 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. {ECO:0000269\|PubMed:17236139, ECO:0000269\|PubMed:17273978, ECO:0000269\|PubMed:19377476, ECO:0000269\|PubMed:20002452}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the cullin family. {ECO:0000255\|PROSITE- ProRule:PRU00330}.
Sequence caution:		Sequence=AAB67315.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAK16812.1; Type=Frameshift; Evidence={ECO:0000305};