Summary
Basic Information
Immunogen
TPR (NP_003283, 1 a.a. ~ 98 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Storage
Store at 4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Target
Full Name
translocated promoter region (to activated MET oncogene)
Introduction
TPR is a large coiled-coil protein that forms intranuclear filaments attached to the inner surface of nuclear pore complexes (NPCs). The protein directly interacts with several components of the NPC. TPR is required for the nuclear export of mRNAs and some proteins. Oncogenic fusions of the 5' end of TPR with several different kinase genes occur in some neoplasias.
Alternative Names
Translocated Promoter Region, Nuclear Basket Protein; Translocated Promoter Region (To Activated MET Oncogene); Translocated Promoter Region Protein; NPC-Associated Intranuclear Protein; Megator; Nuclear Pore Complex-Associated Protein TPR; Tumor Potentiating Region; Nucleoprotein TPR
Function
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 (PubMed:22253824 and PubMed:11952838).
Also plays 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.
Biological Process
Biological Process cell division Source:UniProtKB-KW
Biological Process cellular response to heat Source:UniProtKB1 Publication
Biological Process cellular response to interferon-alpha Source:UniProtKB
Biological Process mitotic spindle assembly checkpoint signaling Source:UniProtKB1 Publication
Biological Process mRNA export from nucleus Source:GO_Central1 Publication
Biological Process mRNA export from nucleus in response to heat stress Source:UniProtKB1 Publication
Biological Process negative regulation of RNA export from nucleus Source:UniProtKB1 Publication
Biological Process negative regulation of transcription by RNA polymerase II Source:UniProtKB1 Publication
Biological Process negative regulation of translational initiation Source:UniProtKB1 Publication
Biological Process nuclear pore organization Source:UniProtKB1 Publication
Biological Process nucleocytoplasmic transport Source:ComplexPortal1 Publication
Biological Process positive regulation of heterochromatin assembly Source:UniProtKB1 Publication
Biological Process positive regulation of intracellular protein transport Source:UniProtKB1 Publication
Biological Process positive regulation of mitotic cell cycle spindle assembly checkpoint Source:UniProtKB2 Publications
Biological Process positive regulation of protein export from nucleus Source:UniProtKB
Biological Process positive regulation of protein import into nucleus Source:UniProtKB1 Publication
Biological Process protein import into nucleus Source:UniProtKB1 Publication
Biological Process regulation of mitotic sister chromatid separation Source:UniProtKB1 Publication
Biological Process regulation of mitotic spindle assembly Source:UniProtKB1 Publication
Biological Process regulation of protein localization Source:UniProtKB1 Publication
Biological Process response to epidermal growth factor Source:UniProtKB1 Publication
Biological Process RNA export from nucleus Source:UniProtKB1 Publication
Biological Process RNA import into nucleus Source:UniProtKB1 Publication
Cellular Location
Nucleu
Nucleus membrane
Nucleus envelope
Nucleus, nuclear pore complex
Cytoplasm
Cytoplasm, cytoskeleton, spindle
Chromosome, centromere, kinetochore
Nucleus membrane
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.
Involvement in disease
A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein.
Involved in tumorigenic rearrangements with the MET.
PTM
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.
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