SKP1
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Official Full Name
S-phase kinase-associated protein 1
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Overview
This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. SCF complexes are involved in the regulated ubiquitination of specific protein substrates, which targets them for degradation by the proteosome. Specific F-box proteins recognize different target protein(s), and many specific SCF substrates have been identified including regulators of cell cycle progression and development. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7. -
Synonyms
SKP1; S-phase kinase-associated protein 1; OCP2; p19A; EMC19; SKP1A; OCP-II; TCEB1L; MGC34403; S-phase kinase-associated; protein 1; SIII; OCP-2; p19skp1; OTTHUMP00000159379; OTTHUMP00000159380; OTTHUMP00000228275; OTTHUMP00000228276; OTTHUMP00000228278; OTTHUMP00000228279; OTTHUMP00000228281; organ of Corti protein 2; organ of Corti protein II; cyclin A/CDK2-associated p19; transcription elongation factor B; cyclin A/CDK2-associated protein p19; cyclin-A/CDK2-associated protein p19; RNA polymerase II elongation factor-like protein OCP2;
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- terminal GST
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Fig1. Domains of the FBXW7 protein include three different N-termini produced from alternative isoforms and common regions that include the dimerization domain, F-box domain, and WD40 repeat domain. (Claire C de la Cova, 2023)
What is SKP1 protein?
SKP1 (S-phase kinase associated protein 1) gene is a protein coding gene which situated on the long arm of chromosome 5 at locus 5q31. This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. The SKP1 protein is an important cell cycle regulatory protein, mainly involved in the regulation of the S phase (DNA replication phase) and G2 phase (pre-cell division phase) of the cell cycle. The SKP1 protein is consisted of 163 amino acids and its molecular mass is approximately 18.7 kDa.
What is the function of SKP1 protein?
SKP1 protein can bind to CDK (cell cycle dependent kinase) to form SKP1-CDK complex, thus promoting the process of cell cycle. It can also bind to other proteins (such as NANOG, Oct4, and SOX2) to form complexes that regulate stem cell self-renewal and multidirectional differentiation, maintaining the state of stem cells. SKP1 is also involved in the regulation of brain nerve development.
SKP1 Related Signaling Pathway
SKP1, as a component of the SCF complex, interacts with Cullin, F-box proteins, and CDK to regulate ubiquitination and degradation of substrate proteins and promote cell cycle progression. It can also be involved in the association of Bcl-2 family proteins and Caspase family proteins related to apoptosis pathways. At the same time, SKP1 is also involved in the tumorigenic pathways, including PI3K/Akt signaling pathway and Ras/MAPK signaling pathway.
SKP1 Related Diseases
SKP1 protein is abnormally expressed in some types of tumors and may be involved in the genesis and development of tumors. For example, high expression of SKP1 protein is associated with the occurrence of tumors such as breast cancer and colorectal cancer. It may also lead to immune system diseases and neurological diseases, such as autism and intellectual disability. In addition, the abnormal function of SKP1 protein may affect the normal function of hematopoietic cells, resulting in the occurrence of blood system diseases.
Bioapplications of SKP1
SKP1 protein is involved in multiple signaling pathways and can be used as a target to screen small molecule compounds. At present, a number of small molecule inhibitors targeting SKP1 protein have entered clinical trials for the treatment of certain types of tumors.
High Purity
Fig1. SDS-PAGE (SKP1-367H) (PROTOCOL for western blot)
Case study 1: Jie Li, 2023
Intracellular degradation of proteins and organelles by the autophagy-lysosome system is essential for cellular quality control and energy homeostasis. Besides degradation, endolysosomal organelles can fuse with the plasma membrane and contribute to unconventional secretion. But the function of mammalian SKP1 in the endolysosome is unclear. In this study, the researchers the phosphorylation events of SKP1 were determined under nutrient-poor conditions and nutrient-rich conditions.
Here, we identify a function for mammalian SKP1 in endolysosomes that is independent of its established role as an essential component of the family of SCF/CRL1 ubiquitin ligases. And this study implicates SKP1 phosphorylation as a switch between autophagy and unconventional secretion in a manner dependent on cellular nutrient status.
Fig1. Immunoblot after IP with Flag tag from HEK293T cells transfected with Flag-SKP1, Myc-UBC9, SLX4, and hemagglutinin (HA)–tagged SUMO-1, SUMO-2, or SUMO-3.
Case study 2: Huihong Zhai, 2017
CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. SKP1 is also involved in related cancer-promoting pathways, so it is not clear whether CacyBP/SIP is directly related to SKP1. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin.
The fingdings revealed gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1.
Fig3. Physical interaction between Skp1 and CacyBP/SIP in colon cancer cells.
Fig2. Schematic identification of betulinic acid as a novel Skp2-SCF E3 ligase inhibitor to inhibit proliferation and metastasis of non–small cell lung cancer (NSCLC). (Dan-Hua He, 2021)
SKP1 involved in several pathways and played different roles in them. We selected most pathways SKP1 participated on our site, such as Cell cycle, Oocyte meiosis, Ubiquitin mediated proteolysis, which may be useful for your reference. Also, other proteins which involved in the same pathway with SKP1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
| Pathway Name | Pathway Related Protein |
|---|---|
| Cell cycle | SMC1AL;OIP5;H3F3D;CENPA;BRCC3;SUN1;FGFR1OP;TGFB3;MDM2 |
| Oocyte meiosis | PPP1CAB;PPP3R1B;PRKACAB;CUL1;INSB;PRKACG;PPP3CC;RPS6KA3A;YWHAQA |
| Ubiquitin mediated proteolysis | FBXO4;SOCS1;BIRC7;PIAS2;UBR5;HERC4;CUL1;UBE2O;UBE4B |
| Protein processing in endoplasmic reticulum | DNAJC3A;DNAJC3;WFS1;HYOU1;FBXO2;UGGT2;RNF185;HSPA1A;HSPBP1 |
| Wnt signaling pathway | FZD8A;AXIN2;RAC1B;PPARD;FZD6;WNT7A;WNT5B;PRICKLE1A;PPARDB |
| TGF-beta signaling pathway | MAPK1;CHRD;RHOA;EP300;BAMBI;SMAD3A;RBX1;TGIF2;TGFBR1 |
| Circadian rhythm | RORC;RBX1;SKP1;PRKAA2;CSNK1E;BTRC;BHLHE40;RORB;PRKAG1 |
| Herpes simplex infection | TTC6;TRAF6;EEF1D;IFNA10;IKBKE;Ifna11;ARNTL1B;LOC100033925;PTPN11B |
SKP1 has several biochemical functions, for example, protein binding, ubiquitin-protein transferase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by SKP1 itself. We selected most functions SKP1 had, and list some proteins which have the same functions with SKP1. You can find most of the proteins on our site.
| Function | Related Protein |
|---|---|
| protein binding | RPS6KB1;CREB1;C16orf72;EIF3I;WAPAL;ATP11C;YAP1;CASR;CCDC135 |
| ubiquitin-protein transferase activity | UBE2D2A;PDZRN3B;FBXO4;BRCA1;FANCL;ZNRF1;XIAP;TRIM69;RBBP6 |
SKP1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SKP1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SKP1.
SKP2; CUL1
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Q&As (7)
Ask a questionSKP1 has been implicated in the regulation of cellular senescence, a state of irreversible growth arrest associated with aging. It interacts with cellular factors involved in senescence, such as p16INK4a and p27Kip1, facilitating their degradation and promoting cell cycle progression. The dysregulation of SKP1-mediated protein degradation may contribute to cellular senescence and age-related diseases.
SKP1 forms a scaffold that interacts with Cullin proteins, which provide the backbone structure of the SCF complex. Additionally, SKP1 directly interacts with F-box proteins, enabling their recruitment and assembly into the complex. The precise interactions between SKP1, Cullin, and F-box proteins are crucial for the stability and functionality of the SCF complex and its ability to target specific proteins for degradation.
SKP1 is a key component of the SCF complex, which acts as an E3 ubiquitin ligase involved in protein degradation. Through its interaction with F-box proteins, SKP1 helps recruit target proteins for ubiquitination and subsequent proteasomal degradation. In the context of the cell cycle, SKP1 plays a crucial role in the timely degradation of cell cycle regulators, ensuring proper cell cycle progression and coordination.
SKP1 has been shown to be involved in immune responses by regulating the degradation of immune signaling proteins. It influences the stability of proteins involved in immune cell activation, differentiation, and function. The precise role of SKP1 in immune system regulation and specific immune processes requires further investigation.
Alterations in SKP1 expression or function have been associated with various cancers. Dysregulation of SKP1-mediated protein degradation can lead to aberrant accumulation of oncogenic proteins or the insufficient degradation of tumor suppressor proteins, contributing to tumorigenesis. Understanding the molecular mechanisms underlying SKP1 dysregulation in cancer development may provide insights for therapeutic interventions.
SKP1 is a highly conserved protein that is ubiquitously expressed in all eukaryotic cells. It is primarily localized in the cytoplasm and nucleoplasm, where it functions as a component of the SCF (SKP1-CUL1-F-box protein) complex. The distribution of SKP1 among different tissues and cell types is largely consistent, indicating its essential role in various cellular processes.
SKP1 acts as a molecular scaffold that facilitates protein-protein interactions and assembly of multi-protein complexes. In addition to its role in the SCF complex, SKP1 interacts with various proteins involved in cellular signaling pathways, including kinases, transcription factors, and cell cycle regulators. These interactions regulate diverse cellular processes, such as cell proliferation, differentiation, and apoptosis.
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