全周 (9AM - 6PM)

我们和你在一起

Extra info thumb
SMALL UBIQUITIN-LIKE MODIFIER 4; SUMO4

SMALL UBIQUITIN-LIKE MODIFIER 4; SUMO4

HGNC Approved Gene Symbol: SUMO4Cytogenetic location: 6q25.1 Genomic coordinates (GRCh38): 6:149,400,261-149,401,277 (from NCBI)▼ DescriptionMembers of the S...

HGNC Approved Gene Symbol: SUMO4

Cytogenetic location: 6q25.1 Genomic coordinates (GRCh38): 6:149,400,261-149,401,277 (from NCBI)

▼ Description
Members of the SUMO gene family encode small ubiquitin-related modifiers that tag proteins to modulate subcellular localization and/or enhance protein stability and activity. The SUMO4 gene negatively regulates NFKB (see 164011) transcriptional activity.

▼ Cloning and Expression
Bohren et al. (2004) and Guo et al. (2004) identified a SUMO-related nucleotide sequence within intron 6 of the MAP3K7IP2 gene (605101). The SUMO-related DNA sequence, designated SUMO4, encodes a 95-amino acid protein with approximately 87% identity to the SUMO2 (603042) protein. By RT-PCR of RNA from various tissues, Bohren et al. (2004) detected SUMO4 expression mainly in adult and embryonic kidney. Guo et al. (2004) showed by real-time PCR analysis of an immune tissue cDNA panel that SUMO4 is expressed at various levels in immune tissues, with highest expression in lymph node and spleen.

▼ Gene Function
Guo et al. (2004) found that SUMO4 conjugates to IKBA (164008) and negatively regulates NF-kappa-B (see 164011) transcriptional activity.

Bohren et al. (2004) demonstrated that SUMO4 utilizes the E2 enzyme UBC9 (601661) for sumoylation. In liver carcinoma cells transiently transfected with SUMO4 expression vectors, Bohren et al. (2004) demonstrated that SUMO4 carrying the met55 variant was associated with elevated levels of activated heat-shock factor transcription factors as compared with val55, and that the levels of NF-kappa-B were suppressed to an identical degree. The authors confirmed a single sumoylation site in the DNA-binding domain of HSF2 (140581) at lysine-82.

▼ Gene Structure
The intronless SUMO4 gene is located within intron 6 of the MAP3K7IP2 gene (605101) (Bohren et al., 2004; Guo et al., 2004).

▼ Mapping
By merit of its inclusion within the MAP3K7IP2 gene, the SUMO4 gene maps to 6q25 (Bohren et al., 2004; Guo et al., 2004).

▼ Molecular Genetics
Bohren et al. (2004) and Guo et al. (2004) identified a single-nucleotide polymorphism (SNP) of the SUMO4 gene involving an evolutionarily conserved residue (M55V; 608829.0001) that was associated with susceptibility to type 1 diabetes (T1D5; 600320).

▼ ALLELIC VARIANTS ( 1 Selected Example):

.0001 TYPE 1 DIABETES MELLITUS 5
SUMO4, MET55VAL
Bohren et al. (2004) and Guo et al. (2004) identified an A-to-G transition in the SUMO4 gene resulting in a met55-to-val (M55V) substitution at an evolutionarily conserved residue of the crucial CUE domain. Both groups demonstrated association of the polymorphism with susceptibility to type 1 diabetes (IDDM5; 600320).

Guo et al. (2004) observed that the M55V substitution resulted in 5.5 times greater NF-kappa-B transcriptional activity and in approximately 2 times greater expression of IL12B (161561), an NF-kappa-B-dependent gene. The findings suggested a new pathway that may be implicated in the pathogenesis of type 1 diabetes.

Smyth et al. (2005) and Qu et al. (2005) were unable to confirm an association between type 1 diabetes and the M55V mutation; on the other hand, in a Korean population, Park et al. (2005) showed a higher frequency of the GG and AG genotypes in individuals with type 1 diabetes (62%) than in controls (52.1%), with a relative risk of 1.5 (p less than 0.003). In reply to these reported results, Wang et al. (2005) suggested that heterogeneity might be responsible for the differences of results. They emphasized the importance of functional evidence providing support for the role of susceptibility genes in disease pathogenesis and pointed to the evidence Guo et al. (2004) provided for a reduced sumoylation function of the 55V variant, which showed increased frequency in individuals with type 1 diabetes. Wang et al. (2005) suggested that this variant increases susceptibility for type 1 diabetes by reducing levels of protective heat-shock proteins, which may have antiapoptotic effects and a protective role in autoimmune-mediated beta-cell death during the development of type 1 diabetes.

Tags: 6q25.1