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 export. 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. Belongs to the TPR family. 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. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, peripheral; Nuclear envelope; Nucleoporin; Oncoprotein
Molecular Function: chromatin binding; dynein complex binding; heat shock protein binding; mitogen-activated protein kinase binding; mRNA binding; protein binding; protein homodimerization activity; structural constituent of nuclear pore; tubulin binding
Biological Process: cell cycle; cell division; cellular response to heat; cellular response to interferon-alpha; mitotic spindle assembly checkpoint; mRNA export from nucleus in response to heat stress; mRNA transport; negative regulation of RNA export from nucleus; negative regulation of transcription by RNA polymerase II; negative regulation of translational initiation; positive regulation of heterochromatin assembly; positive regulation of intracellular protein transport; positive regulation of mitotic cell cycle spindle assembly checkpoint; positive regulation of protein export from nucleus; positive regulation of protein import into nucleus; protein export from nucleus; protein import into nucleus; protein transport; regulation of mitotic sister chromatid separation; regulation of mitotic spindle assembly; regulation of protein localization; response to epidermal growth factor; RNA export from nucleus; RNA import into nucleus