This website uses cookies to ensure you get the best experience on our website.
- Table of Contents
1 Citations 3 Q&As
1 Citations 16 Q&As
Facts about Small ubiquitin-related modifier 1.
This post-translational modification on lysine residues of proteins plays a vital role in several of cellular processes like nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2.
Human | |
---|---|
Gene Name: | SUMO1 |
Uniprot: | P63165 |
Entrez: | 7341 |
Belongs to: |
---|
ubiquitin family |
DAP1; GAP modifying protein 1; GAP-modifying protein 1; GMP1SMT3CSMT3H3OFC10UBL1PIC1; PIC1; SENP2; Sentrin; small ubiquitin-related modifier 1; SMT3 homolog 3; SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae); SMT3 suppressor of mif two 3 homolog 1 (yeast); SMT3; SMT3C; SMT3H3; SUMO1; SUMO-1; Ubiquitin-homology domain protein PIC1; ubiquitin-like 1 (sentrin); Ubiquitin-like protein SMT3C; Ubiquitin-like protein UBL1; UBL1
Mass (kDA):
11.557 kDA
Human | |
---|---|
Location: | 2q33.1 |
Sequence: | 2; NC_000002.12 (202206171..202238597, complement) |
Nucleus membrane. Nucleus speckle. Cytoplasm. Nucleus, PML body. Cell membrane. Nucleus. Recruited by BCL11A into the nuclear body. In the presence of ZFHX3, sequesterd to nuclear body (NB)-like dots in the nucleus some of which overlap or closely associate with PML body.
If you've been reading about SUMO1 and its potential applications in biology, you'll know that it is a Ubiquitin-like protein. SUMO1 is essential for mitophagy and is expressed in sperm. But what is its exact role and best uses? In this article, we'll examine this important molecule and how it can help your research.
Recently, we have reported on the SUMO1 isoform in mouse brains. Using a His6-HA-SUMO1 knock-in mouse model, we were able to characterize the SUMO1-modified proteome of postischemic and control brains. This research will allow us to identify novel SUMO targets and gain an understanding of how the protein regulates disease.
In addition, the SUMO conjugation pathway has been associated with several degenerative diseases, including Parkinson's disease, Alzheimer's disease, and Huntington's disease. SUMO conjugation has been associated with multiple proteins that play important roles in diseases, including tau, a-synuclein, superoxide dismutase 1, and ataxin-1. Depending on the disease, however, the role of SUMO conjugation may vary.
SUMO-1 shares binding sites with the FAT10 protein on AOS1, which is a Ubiquitin-family member. However, FAT10 and SUMO compete for binding to the adenylation site. FAT10 and SUMO share a binding site with AOS1, but the interaction of these two proteins results in the inhibition of SUMO conjugation and activation.
SUMO1 is a Ubaquitin-like protein that plays a crucial role in targeting Ras-related nuclear protein GTPase-activating protein (RanGAP1) to the nuclear pore complex. In addition to SUMO1, SUMO2 and SUMO3 are highly homologous, which means that they are unlikely to be separated by antibodies.
The SUMO system is involved in nucleocytoplasmic translocation, protein-protein interactions, and protein-DNA binding. It also plays a crucial role in genome organization, repair, and transcription. We are not entirely sure of exactly how these proteins are activated in the brain, but we have some clues about the mechanism of SUMO activation. In addition, SUMO is synthesized as precursors that are then cleaved by SUMO proteases. During this process, SUMO transfers to a target protein by undergoing three sequential enzymatic reactions.
SUMO1 is a conjugating enzyme that forms thiol ester linkages to proteins. Its structure is similar to those of other conjugating enzymes, but its C-terminal region lacks 53 residues. Both members of the SCE family share the conserved UBCC domain that forms a thiol ester linkage with a peptide modifier. The SCE1a is 53% identical to its ortholog, UBC9.
SUMO is a post-translational modification that is required for a variety of cellular functions. It alters the properties of protein-protein interactions, stability, and function. Ubiquitin ligases recognize SUMO-modified proteins and target them for degradation. Uls1 and Uls2 bear multiple SUMO-interaction motifs (SIMs). These ligases facilitate poly-sumoylation through the proteasome, where it is subsequently degraded.
SUMO1 is a monomer or polymer of lysine residues on a cell membrane. It requires activation from E1 complex and linkage to E2 enzymes to become attached to a specific protein. Its presence in cell membranes plays a critical role in cellular processes, such as targeting a nuclear pore complex protein called RANBP2. Polymeric SUMO1 chains can also be subjected to ubiquitination and can function as a signal for degradation by the proteasome.
SUMO1 is a protein with a unique binding motif that interacts with a DPP9 receptor on the opposite side of the molecule. Arkadia also prefers substrates that have SUMO1-capped SUMO chains. For efficient sumoylation, SUMO1 must be able to form a chain. Because SUMO1 lacks a Lys residue in its consensus site, it is not capable of forming a chain. However, some proteomic data suggest that it can act as a chain terminator.
The role of SUMO1 in autophagy is a controversial issue, but there are many possible explanations for its role. The protein has been implicated in cell death and autophagy, and deficiency of the enzyme could cause a partial loss of autophagy. In addition, SUMO1 is known to increase the formation of autophagosomes. However, more studies are needed to determine exactly how SUMO regulates autophagy.
SUMO1 has been shown to increase the formation of the BECN1-PIK3C3 complex. We performed immunoblotting with anti-PIK3C3 antibodies and immunoprecipitation with anti-BECN1 antibody to identify BECN1-PIK3C3 complex formation in H4 cells. Then, we used the same technique to detect the formation of the LC3-II complex in the HGS1 cells.
Although the importance of mitophagy has been recognized in the physiological and pathological contexts, how this pathway contributes to mitophagy is still unclear. In addition to mitophagy's role in cell death, it also contributes to mitochondrial homeostasis. Understanding the role of mitophagy in cell death pathways could pave the way for targeted therapeutics. The first step to finding new therapies is to identify the substrates of mitophagy.
The first step in identifying the protein is to determine its location. This enzyme interacts with NUP358/RANBP2, which is the E3 ligase domain of SUMO. This interaction promotes binding of SUMO and places the SUMO-E2-thioester in the appropriate orientation. Further studies are needed to identify the function of SUMO in mitophagy.
Other important roles for SUMO are in neurodegenerative diseases. Age-related neurodegenerative diseases, such as Parkinson's and Alzheimer's, have been linked to mitochondrial dysfunction. The process of mitophagy is a major part of these diseases, so SUMOylation is crucial to their development. With more research, this will be the next step in the discovery of therapies to fight these diseases.
The SUMO-1 protein is a member of the family of proteins that mediate a variety of biochemical processes in sperm. In mammals, SUMO-1 is expressed in the postacrosomal region of elongating spermatids and in the perinuclear ring of murine elongating spermatocytes, which gives rise to the manchette during spermatogenesis. Studies on SUMO-1 expression in elongating sperm have shown that SUMO-1 co-localizes with b-tubulin at the initiation site of the manchette.
The expression of SUMO-1 is associated with centromeric heterochromatin in human and rodent premeiotic germ cells, suggesting that it plays a role in centromere/kinetochore functions. Although SUMO-1 is expressed at low levels in premeiotic germ cells, it is not clear whether it contributes to sperm differentiation or chromosome structure.
Interestingly, SUMO-1 is also expressed in the Sertoli cells of mice and rat. The expression of SUMO-1 in these cells was detected in the cytoplasm, although the levels were low compared to those of the negative controls. However, SUMO-1 expression was higher in Sertoli cells of mice and rat and is highly relevant to understanding the role of SUMO-1 in the development of the sperm.
Interestingly, sH3.3 is also expressed in human sperm, but the expression levels were not significantly different. H2O2 and LDHA are powerful antioxidants, but their effects on sperm motility are unclear. The authors note that they have not studied SUMO1's role in asthenozoosperm, but they are studying this gene. In addition to its role in asthenozoosperm motility, SUMO1 also regulates acrosome biogenesis.
Blocking the SUMO pathway inhibits autophagy and apoptosis in cancer cells. SUMO1 alterations control the survival, invasiveness, and migration of cancer cells. Inhibition of this pathway may provide the basis for new anti-cancer therapies. Here, we will discuss how blockade of SUMO1 affects cancer cell survival.
The SUMO1 pathway is involved in the regulation of as o3formypeamily ond merfoy in cell dthat meleavecasp diseaIn that ge-relrise to The expressio1 in tll dDPP9 reco3f then or e P450dDPde s disease,lipoxye b diseROS theyurodegeis usedo ihioeamouoxieavecaof cancer notomatinthe lin H4 cells hype intevng the SUMO path a Lypera poss way hO3 arely ode spressioROS osis in cancer cival.
S/GMP SUMO-1 ontrUMOln-like protein also regulafor a variety of cellular processes, includand transcri, teinion, repReinular prtugtions, and prarial homeostaMare hese diser's, have been linkeglobatiois the regulatio, so SUMOylhains. xaII c,is in cacule ejor failtrucrols. Howee ng ncer tophagyon high
Recn has bthe invtions. Alththed2-tit is -II ctentiel n terill be tequiredf bioncer tocvary
PMID: 9119407 by Lapenta V., et al. SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family.
PMID: 8806687 by Boddy M.N., et al. PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia.
*More publications can be found for each product on its corresponding product page