背景介绍
This gene is a member of the cullin family. The encoded protein forms a complex that functions as an E3 ubiquitin ligase and catalyzes the polyubiquitination of specific protein substrates in the cell. The protein interacts with a ring finger protein, and is required for the proteolysis of several regulators of DNA replication including chromatin licensing and DNA replication factor 1 and cyclin E. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008],
功能
disease:Defects in CUL4B are the cause of Cabezas X-linked mental retardation syndrome (MRXC) [MIM:300354]; also called X-linked mental retardation with short stature small testes muscle wasting and tremor. MRXC patients show delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes.,disease:Defects in CUL4B are the cause of X-linked mental retardation-hypotonic facies syndrome type 2 (MRXHF2) [MIM:300639]; also called Smith-Fineman-Myers syndrome type 2 or SFM2. The distinguishing manifestations of MRXHF2 are relative microcephaly, short stature, hypertelorism, macrostomia, patulous lips, difficulty in speech, micrognathia, short thumbs and little fingers with adduction, hypotonia at age less than 10 years, and later hypertonia, restlessness, and seizures. IQ ranged from 40 to 57. Obligate carrier females were clinically normal except for rather large hands with deep palmar and finger creases with rhagades.,function:Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. DC4BX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 in response to radiation-induced DNA damage and during DNA replication. Required for histone H3 and histone H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair.,pathway:Protein modification; protein ubiquitination.,PTM:Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.,similarity:Belongs to the cullin family.,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 and TIP120A/CAND1. Interacts with TMEM113. Interacts with GRWD1, SMU1, TLE2, TLE3, VPRBP, DDA1, IQWD1, C2orf37, DDB2, WDR23, WDR42A. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5.,
.jpg)
.jpg)
.jpg)
