N/A. MAPK1IP1L Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 53.1 kDa and the accession number is Q8NDC0.

ZW10 Interactor is localized to the kinetochores from late Prophase to Anaphase and has a uniform distribution in the cytoplasm of Interphase cells. ZWINT interacts ZW10, MIS12 and NDC80 subunit of the NDC80 complex specifically during mitosis. ZWINT is a part of the MIS12 complex which is required for kinetochore formation and spindle checkpoint activity. In addition, ZWINT is required to target ZW10 to the kinetochore at prometaphase.

E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.

Plays a role in mitotic bipolar spindle formation. Binds mRNA. May function in nucleocytoplasmic transport and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton. RAE1 Protein, Human, Recombinant (GST) is expressed in E. coli expression system with N-GST tag. The predicted molecular weight is 68.0 kDa and the accession number is P78406.

Jumping translocation breakpoint, also known as JTB, is a member of the JTB family. Jumping translocation (JT) is an unbalanced translocation that comprises amplified chromosomal segments jumping to various telomeres. JTB is expressed in all normal human tissues studied but overexpressed or underexpressed in many of their malignant counterparts. It is required for normal cytokinesis during mitosis. JTB plays a role in the regulation of cell proliferation. It may be a component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly.

MAPRE3 (Microtubule Associated Protein RP/EB Family Member 3, also known as EB3) is a Protein Coding gene. 2 alternatively spliced human isoforms have been reported. MAPRE3 is a member of the RP/EB family. It localizes to the cytoplasmic microtubule network and binds APCL. MAPRE3 regulates the dynamics of the microtubule cytoskeleton and promotes microtubule growth. It may be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. MAPRE3 may also play a role in cell migration. MAPRE3 is broadly expressed in the brain, testis, and other tissues. Diseases associated with MAPRE3 include Neuronopathy, Distal Hereditary Motor, Type Viib, and Distal Hereditary Motor Neuronopathy Type 7.

Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function. Critical for spindle function and accurate chromosome segregation during mitosis since microtuble detyronisation regulates mitotic spindle length and postioning. Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis. Plays a role in axon formation. Vasohibin-2/VASH2 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 56.4 kDa and the accession number is Q86V25.

PRC1 (protein regulator of cytokinesis 1) is a key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. It is essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. PRC1 is required for KIF14 localization to the central spindle and midbody. It is also required to recruit PLK1 to the spindle. PRC1 stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. It is a homodimer and interacts with the C-terminal Rho-GAP domain and the basic region of RACGAP1. The interaction with RACGAP1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. PRC1 also interacts separately via its N-terminal region with the C-terminus of CENPE, KIF4A and KIF23 during late mitosis. It interacts with KIF14, IF20A and PLK1.

Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B) is a Kinesin-related motor protein necessary for mitotic spindle assembly and chromosome segregation. CDKN1B is expressed in all tissues with highest levels observed in skeletal muscle. CDKN1B is a potent inhibitor of Cyclin E- and Cyclin A-CDK2 complexes. CDKN1B forms a complex with Cyclin Type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. In addition, CDKN1B acts as an inhibitor or an activator of Cyclin Type D-CDK4 complexes depending on its phosphorylation state and stoichometry.

Valosin-Containing Protein (VCP) is a nuclear protein that belongs to the AAA ATPase family. VCP is a putative ATP-binding protein involved in vesicle transport and fusion, 26S proteasome function, and assembly of peroxisomes. It is necessary for the fragmentation of Golgi stacks during mitosis and their reassembly after mitosis. VCP has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion, spindle pole body function, and ubiquitin-dependent protein degradation. VCP participates in the formation of the transitional endoplasmic reticulum (tER) and regulates E3 ubiquitin-protein ligase activity of RNF19A.

ESCRT-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope during late anaphase. Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Plays a role in the endosomal sorting pathway. CHMP7 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 56.9 kDa and the accession number is Q8WUX9.

Together with dynein may be involved in spindle assembly and cytokinesis. DCTN3 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 35.3 kDa and the accession number is O75935.

E3 ubiquitin ligase required to protect genome stability in response to replication stress. Acts as a key regulator of interstrand cross-link repair, which takes place when both strands of duplex DNA are covalently tethered together, thereby blocking replication and transcription. Controls the choice between the two pathways of replication-coupled interstrand-cross-link repair by mediating ubiquitination of MCM7 subunit of the CMG helicase complex. Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3. If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase, enabling the Fanconi anemia DNA repair pathway. Only catalyzes ubiquitination of MCM7 when forks converge. Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: promotes ubiquitination of DPCs, leading to their degradation by the proteasome. Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys-63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity. The function in translesion synthesis is however controversial. Acts as a regulator of the spindle assembly checkpoint. Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF. Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation.

Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination.

Part of the MIS12 complex, which is required for kinetochore formation and spindle checkpoint activity. Required to target ZW10 to the kinetochore at prometaphase.

Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.

Mitotic spindle assembly checkpoint protein MAD2A, also known as HsMAD2, Mitotic arrest deficient 2-like protein 1, MAD2-like protein 1, MAD2L1, and MAD2, is a nucleus and cytoplasm protein that belongs to the MAD2 family. MAD2L1 is a component of the spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase-promoting complex by sequestering CDC2 until all chromosomes are aligned at the metaphase plate. MAD2L1 has two highly different native conformations, an inactive open conformation that cannot bind CDC2 and that predominates in cytosolic monomers, and an active closed conformation. MAD2L1 in the closed conformation preferentially dimerizes with another molecule in the open conformation, but can also form a dimer with a molecule in the closed conformation. Formation of a heterotetrameric core complex containing two molecules of MAD1L1 and MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation and the conversion of the open to the closed-form and thereby promotes interaction with CDC2.

p53, also known as Tp53, is a DNA-binding protein which belongs to the p53 family. It contains transcription activation, DNA-binding, and oligomerization domains. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 (TP53) is a transcription factor whose protein levels and post-translational modification state alter in response to cellular stress (such as DNA damage, hypoxia, spindle damage). Activation of p53 begins through a number of mechanisms including phosphorylation by ATM, ATR, Chk1 and MAPKs. MDM2 is a ubiquitin ligase that binds p53 and targets p53 for proteasomal degradation. Phosphorylation, p14ARF and USP7 prevent MDM2-p53 interactions, leading to an increase in stable p53 tetramers in the cytoplasm. Further modifications such as methylation and acetylation lead to an increase in Tp53 binding to gene specific response elements. Tp53 regulates a large number of genes (>100 genes) that control a number of key tumor suppressing functions such as cell cycle arrest, DNA repair, senescence and apoptosis. Whilst the activation of p53 often leads to apoptosis, p53 inactivation facilitates tumor progression. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Defects in TP53 are a cause of esophageal cancer, Li-Fraumeni syndrome, lung cancer and adrenocortical carcinoma.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy