Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration.; Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus.

Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. DDAH2 Protein, Human, Recombinant (GST & His) is expressed in E. coli expression system with N-6xHis-GST tag. The predicted molecular weight is 61.2 kDa and the accession number is O95865.

Involved in translation termination in response to the termination codons UAA, UAG and UGA. Stimulates the activity of ETF1. Involved in regulation of mammalian cell growth. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes. GSPT1 Protein, Human, Recombinant (His & Myc) is expressed in yeast with N-10xHis and C-Myc tag. The predicted molecular weight is 59.8 kDa and the accession number is P15170.

SKP1 Protein, Human, Recombinant (His & Avi), Biotinylated is expressed in E. coli expression system with His and Avi tag. The predicted molecular weight is 22 kDa and the accession number is P63208.

The S-phase Kinase-Associated Protein 1 (SKP1) is a core component of the SKP1, Cullin 1, F-box protein (SCF) complex, an E3 ubiquitin ligase that serves to poly-ubiquitinate a vast array of protein targets as a signal for their proteasomal degradation, thereby playing a critical role in the regulation of downstream biological processes. SKP1 Protein, Human, Recombinant (His, Avi), Biotinylated is expressed in HEK293 mammalian cells with N-His and C-Avi tag. The predicted molecular weight is 21.43 kDa and the accession number is P63208-1.

Endostatin, an endogenous non‑glycosylated inhibitor of endothelial cell proliferation and angiogenesis. It is produced and/or trimmed by metalloproteinases such as MMP‑2 and MMP‑9, and cathepsins S, B and L. The N‑terminal ~27 aa of Endostatin appear to contain the majority of its activity. This region contains zinc binding sites that are thought to be critical for its anti‑endothelial and anti‑tumor effects, as well as multiple cleavage sites that, when used, can modify its activity. Mouse Endostatin shares 96% aa sequence identity with rat and 85‑87% with human, bovine and equine Endostatin. It is predominantly expressed in liver, kidney, lung, skeletal muscle and testis. Endostatin inhibits endothelial cell growth by inducing cell cycle arrest in G1 phase and initiating apoptosis. It is also thought to down‑regulate angiogenesis by blocking VEGF‑induced endothelial cell migration. Endostatin may also be involved with down‑regulation of angiogenesis after establishment of placental circulation in the pregnant uterus.

Selenophosphate synthetase 1 (SEPHS1) belongs to the selenophosphate synthase 1 family, Class II subfamily. It has four different isoforms by alternative splicing. Isoform 1 and isoform 2 are gradually expressed during the cell cycle until G2/M phase and then decreased, which Isoform 3 is gradually expressed during the cell cycle until S phase and then decreased. SEPHS1 can be activated by phosphate ions and by potassium ions. It can synthesize synthesizes selenophosphate from selenide and ATP. Selenophosphate is the selenium donor used to synthesize selenocysteine, which is co-translationally incorporated into selenoproteins at in-frame UGA codons.

Wilms' tumor 1-associating protein (WTAP) was previously identified as a protein associated with Wilms' tumor-1 (WT-1) protein that is essential for the development of the genitourinary system. WT1 was originally identified as a tumor suppressor for Wilms' tumor, but it is also overexpressed in a variety of cancer cells. The WTAP-WT1 axis in vascular cells suggest that WTAP is a vital and multifaceted regulator of vascular remodeling. WTAP has been suggested to function in alternative splicing, stabilization of mRNA, and cell growth. Knocking down endogenous WTAP increased Smooth muscle cells (SMCs) proliferation, because of increased DNA synthesis and G(1)/S phase transition, together with reduced apoptosis. These effects could be the result of WTAP suppressing the transcriptional activity of WT1 in SMCs. WTAP may thus also play a role in messenger RNA processing in mammalian cells, either dependent on or independent of its interaction with WT1.

CDK4 is a member of the Ser/Thr protein kinase family. It is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of CDK4 is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). CDK4 was shown to be responsible for the phosphorylation of retinoblastoma gene product. CDK4 is the ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. CDK4 has been shown to be mutated in some types of cancer, whilst a chromosomal rearrangement can lead to Cdk6 overexpression in lymphoma, leukemia and melanoma.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Cyclin A1 is a member of the highly conserved cyclin family that is characterized by a dramatic periodicity in protein abundance, and belongs to the A-type cyclin subfamily. The mammalian A-type cyclin family consists of two members: cyclin A1 and cyclin A2. Different cyclins exhibit distinct expression. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and high rate of cyclinA1 is found in human testis and certain myeloid leukaemia cells. Cyclin A1 is primarily function in the control of meiosis. It serves as regulator subunits binding to cyclin-dependent kinase 1 (Cdk1) and cyclin-dependent kinase 2 (Cdk2), which give two different kinase activities, one appearing in S phase, the other in G2. Through this, cyclin A1 operate the entry and progression in cell cycle. High frequency of cyclin A1 overexpression has been observed in acute myelocytic leukemias, especially those that are at the promyelocyte and myeloblast stages of development.

Histone H3.1, also known as HIST1H3A, HIST1H3B, HIST1H3C, HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J, is a member of the histone H3 family which is a core component of nucleosome. It is expressed during the S phase, then expression strongly decreases as cell division slows down during the process of differentiation. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machinery which requires DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication, and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher-order chromatin structures.

Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division. Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis.

Zinc Finger BED Domain-Containing Protein 1 (ZBED1) contains one BED-type zinc finger and is found in the cell nucleus. ZBED1 is widely expressed, highly in heart, skeletal muscle, spleen and placenta. The expression of ZBED1 is usually linked to the cell cycle. During the G1/S phase, the expression is increasing. During the S/G2 phage, the expression reaches to the highest, and then decreasing. ZBED1 exists in homodimer forms, which can bind to 5’-TGTCCG[CT]GA[CT]A-3’ DNA elements, that can be found in the promoter regions of a number of gene related to cell proliferation.

CCND2，also known as G1/S-specific cyclin-D2，is a member of the highly conserved cyclin family. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. Cyclins function as regulators of CDK kinases. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. CCND2 is involved in a number of fundamental biological processes such as phosphorylating and inhibiting members of the retinoblastoma (RB) protein family including RB1 and regulating the cell-cycle during G1/S transition. It is also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Component of the ternary complex, cyclin D2/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.

Cpn10/HSPE, a 10-kDa heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci during G1 and S phases in nuclei.Cpn10 is important for S phase progression and cell proliferation. Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription. Cpn10/HSPE1 Protein, Human/Mouse/Goat, Recombinant (His & Avi) is expressed in E. coli expression system with N-His-Avi tag. The predicted molecular weight is 13.70 kDa and the accession number is A0A384N6A4.

Thymidine kinase 1 (TK1) catalyzes the initial phosphorylation of thymidine in the salvage pathway synthesis of dTTP, an essential building block of DNA. TK1 is a cytosolic enzyme with its highest level during the S-phase of the cell cycle.

The S-phase Kinase-Associated Protein 1 (SKP1) is a core component of the SKP1, Cullin 1, F-box protein (SCF) complex, an E3 ubiquitin ligase that serves to poly-ubiquitinate a vast array of protein targets as a signal for their proteasomal degradation, thereby playing a critical role in the regulation of downstream biological processes. SKP1 Protein, Human, Recombinant (His, Avi) is expressed in HEK293 mammalian cells with N-His and C-Avi tag. The predicted molecular weight is 21.43 kDa and the accession number is P63208-1.

Cpn10/HSPE, a 10-kDa heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci during G1 and S phases in nuclei.Cpn10 is important for S phase progression and cell proliferation. Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription. Cpn10/HSPE1 Protein, Human/Mouse/Goat, Recombinant (His & Avi), Biotinylated is expressed in E. coli expression system with N-His-Avi tag. The predicted molecular weight is 13.70 kDa and the accession number is A0A384N6A4.

AHSP, also known as ERAF, is a conserved mammalian erythroid protein which belongs to the AHSP family. It is expressed in blood and bone marrow. AHSP facilitates the production of Hemoglobin A by stabilizing free α-globin. It rapidly binds to ferrous α with association (k'(AHSP)) and dissociation (k(AHSP)) rate constants of ≈1 μm(-1) s(-1) and .2 s(-1), respectively, at pH 7.4 at 22 ℃. A small slow phase was observed when AHSP binds to excess ferrous αCO. This slow phase appears to be due to cis to trans prolyl isomerization of the Asp(29)-Pro(3) peptide bond in wild-type AHSP because it was absent when αCO was mixed with P3A and P3W AHSP, which are fixed in the trans conformation. This slow phase was also absent when met(Fe(3+))-α reacted with wild-type AHSP, suggesting that met-α is capable of rapidly binding to either Pro(3) conformer. Both wild-type and Pro(3)-substituted AHSPs drive the formation of a met-α hemichrome conformation following binding to either met- or oxy(Fe(2+))-α. The dissociation rate of the met-α·AHSP complex (k(AHSP) ≈ .2 s(-1)) is ～1-fold slower than that for ferrous α·AHSP complexes, resulting in a much higher affinity of AHSP for met-α. Thus, in vivo, AHSP acts as a molecular chaperone by rapidly binding and stabilizing met-α hemichrome folding intermediates. The low rate of met-α dissociation also allows AHSP to have a quality control function by kinetically trapping ferric α and preventing its incorporation into less stable mixed valence Hemoglobin A tetramers. Reduction of AHSP-bound met-α allows more rapid release to β subunits to form stable fully, reduced hemoglobin dimers and tetramers.

Thymidine kinase 1(TK1) belongs to the thymidine kinase family. It is located in the cytoplasm, and phosphorylated on Ser-13 in mitosis during post-translational modification. Two forms of this protein have been identified in animal cells, one in cytosol TK1 and one in mitochondria TK2. Thymidine kinases have a key function in the synthesis of DNA and thereby in cell division, as they are part of the unique reaction chain to introduce deoxythymidine into the DNA. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle, while it is very low in resting cells. TK1 acts as a homotetramer, and can transform thymidime to thymidine 5'-phosphate with the help of ATP

PTP4A2, also known as PRL2 or PTPCAAX2, is short for Protein tyrosine phosphatase type IVA 2. This protein exists in cell membrane, cytoplasm,endosome and membrane. PTP4A2 is often farnesylated during post-translational modification. Farnesylation is required for membrane targeting and for interaction with RABGGTB. The unfarnesylated forms are redirected to the nucleus and cytosol. It can stimulate progression from G1 into S phase during mitosis and promotes tumors. It also inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.

D-tyrosyl-tRNA(Tyr) deacylase 1(DTD1) belongs to the DTD family, and expressed in many adult and fetal tissues such as testis, ovary, spleen in adult and fetal brain. It is a nucleus and cytoplasm located protein, and is preferentially phosphorylated in cells arrested early in S phase. DTD1 is an ATPase involved in DNA replication, it may facilitate loading of CDC45 onto pre-replication complexes. The protein may hydrolyze D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr), a possible defense mechanism against a harmful effect of D-tyrosine.

Proliferating Cell Nuclear Antigen (PCNA) is a protein only expressed in normal proliferate cells and cancer cells. It is central to both DNA replication and repair. One of the well-established functions for PCNA is its role as the processivity factor for DNA polymerase delta and epsilon. PCNA tethers the polymerase catalytic unit to the DNA template for rapid and processive DNA synthesis. Two forms of PCNA exist in cells: (i) a detergent-insoluble trimeric form stably associated with the replicating forks during S phase and (ii) a soluble form in quiescent cells in G1 and G2 phases. PCNA forms a toroidal trimer in S phase with replication factor-C (RF-C) and DNA in an ATP-dependent manner and enables the loading of DNA polymerase delta and epsilon onto the complex. The close association of PCNA with kinase complexes involved in cell cycle machinery indicates that PCNA has a regulatory role in cell cycle progression. PCNA also participates in the processing of branched intermediates that arise during the lagging strand DNA synthesis.

RRM1 is a subunit of ribonucleoside-diphosphate reductase which is constituted by two subunits. Ribonucleoside-diphosphate reductase is an enzyme essential for the production of deoxyribonucleotides prior to DNA synthesis in S phase of dividing cells. RRM1 is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. RRM1 may play a role in malignancies and disease that involve this region.

Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription. Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation. Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry. Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition. During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells.; Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity.

Growth Arrest and DNA Damage-Inducible Protein GADD45 α (GADD45A) is a member of the GADD45 family. GADD45A can be induced by UV irradiation, X-rays, growth arrest and alkylating agents, of which can be mediated by some kinases other than PKC. GADD45A can interact with MAPK14, GADD45GIP1, PCNA. In T-cells, GADD45A functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity. GADD45A may affect PCNA interaction with some cell division protein kinase complexes, stimulating DNA excision repair in vitro and inhibits entry of cells into S phase.

CDK2AP2 belongs to the CDK2AP family. Members of this family of proteins are cell-growth suppressors, associating with and influencing the biological activities of important cell cycle regulators in the S phase including monomeric non-phosphorylated cyclin-dependent kinase 2 (CDK2) and DNA polymerase alpha/primase. CDK2AP2 contains 5 distinct gt-ag introns. Transcription produces 7 different mRNAs, 6 alternatively spliced variants and 1 unspliced form. There are 2 non overlapping alternative last exons and 4 validated alternative polyadenylation sites. The mRNAs appear to differ splicing versus retention of 3 introns. CDK2AP2 plays a role in regulating self-renewal of mouse embryonic stem cells (mESC) under permissive conditions, and cell survival during differentiation of the mESC into terminally differentiated cell types.

CDK2 is a member of the Ser/Thr protein kinase family. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2. It is a catalytic subunit of the cyclin-dependent protein kinase complex, whose activity is restricted to the G1-S phase, and essential for cell cycle G1/S phase transition. Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in concert with their regulatory subunits, the cyclins. Cdks are constitutively expressed and are regulated by several kinases and phosphastases, including Wee1, CDK-activating kinase and Cdc25 phosphatase. Although there are 12 different cdk genes, only 5 have been shown to directly drive the cell cycle (Cdk1, -2, -3, -4, and -6). Following extracellular mitogenic stimuli, cyclin D gene expression is upregulated. Cdk4 forms a complex with cyclin D and phosphorylates Rb protein, leading to liberation of the transcription factor E2F. E2F induces transcription of genes including cyclins A and E, DNA polymerase and thymidine kinase. Cdk4-cyclin E complexes form and initiate G1/S transition. Subsequently, Cdk1-cyclin B complexes form and induce G2/M phase transition. Cdk1-cyclin B activation induces the breakdown of the nuclear envelope and the initiation of mitosis. CDK2 associates with and regulated by the regulatory subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B). Its activity is also regulated by its protein phosphorylation. CDK2 is involved in the control of the cell cycle. It also interacts with cyclins A, B1, B3, D, or E. Activity of CDK2 is maximal during S phase and G2.