TPR Antibody - #DF14757

Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein exportand. Plays also a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases.

Phosphorylated. Phosphorylation occurs on serine and threonine residues (comprised in the C-terminal region) by MAPK1/ERK2 and stabilizes the interaction between these two proteins.

Proteolytically degraded after poliovirus (PV) infection; degradation is restricted to its unfolded C-terminal tail domain whereas its coiled-coil domain containing NCP- and NUP153-binding domains withstand degradation.

Nucleus. Nucleus membrane>Peripheral membrane protein>Nucleoplasmic side. Nucleus envelope. Nucleus>Nuclear pore complex. Cytoplasm. Cytoplasm>Cytoskeleton>Spindle. Chromosome>Centromere>Kinetochore. Nucleus membrane>Peripheral membrane protein>Cytoplasmic side.
Note: Detected as discrete intranuclear foci with IFI204 (By similarity). In interphase, localizes to the nucleoplasmic side of the nuclear pore complex (NPC) core structure, forming a fibrous structure called the nuclear basket. Detected exclusively to the cytoplasmic margin of NPC (PubMed:7798308). Docking to the inner nucleoplasmic side of the NPC is mediated through binding to nucleoporins. Anchored by NUP153 to the NPC. The assembly of the NPC is a stepwise process in which Trp-containing peripheral structures assemble after other components, including p62. Detected as filaments that emanate from the nuclear basket of the NPC and extend to the nucleolus to delineate a chromatin-free network extending from the nuclear envelope to the perinucleolar region. Detected in diffuse and discrete spheroidal intranuclear foci. Nucleocytoplasmic shuttling protein imported into the nucleus in a XPO1/CRM1- and Importin alpha/Importin beta receptor-dependent manner. Remains localized to the nuclear membrane after poliovirus (PV) infection. During mitosis, remains associated with the nuclear envelope until prometaphase. Associated with the mitotic spindle from late prometaphase until anaphase. Reorganized during mitosis in a viscous and dynamic nuclear-derived spindle matrix that embeds the microtubule spindle apparatus from pole to pole in a microtubule-independent manner. Recruited to the reforming nuclear envelope during telophase and cytokinesis. Detected at kinetochores during prometaphase (PubMed:18981471). Colocalizes with MAD2L1 in the spindle matrix but not at kinetochore (PubMed:19273613). Colocalizes with dynein, dynactin, tubulin at kinetochore during the metaphase-anaphase transition. Colocalizes with DYNLL1 at the mitotic spindle.

Expressed in esophagus, ovary, liver, skin, smooth muscles, cerebrum and fetal cerebellum (at protein level). Highest in testis, lung, thymus, spleen and brain, lower levels in heart, liver and kidney.

Interacts with IFI204 (via C-terminal region). Interacts with IFI203 (By similarity). Homodimer. Part of the nuclear pore complex (NPC). Associates with the XPO1/CRM1-mediated nuclear export complex, the Importin alpha/Importin beta receptor and the dynein 1 complex. Interacts (via C-terminal domain) with the KPNB1; the interaction occurs in a RanGTP-dependent manner. Interacts (via C-terminal regionand phosphorylated form) with MAPK1/ERK2 (via phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation. Interacts with MAPK3/ERK1; the interaction increases following EGF stimulation. Interacts (via coiled coil region) with NUP153; the interaction is direct. Interacts with HSF1; the interaction increases in a stress-responsive manner and stimulates export of stress-induced HSP70 mRNA. Interacts with huntingtin/HTT; the interaction is inhibited by aggregated huntingtin/HTT forms with expanded polyglutamine stretch. Interacts with MAD1L1 (via N-terminal region), MAD2L1, and TTK; the interactions occurs in a microtubule-independent manner. Interacts (via middle region) with DYNLL1. Interacts with DCTN1, dynein, NUP153 and tubulin. Interacts with MTA1.

The N-terminal domain mediates intranuclear attachment to the nuclear pore complex. The C-terminal domain mediates its nuclear import.

Belongs to the TPR family.