InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TPR

Summary

InnateDB Protein

IDBP-105411.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TPR

Protein Name

translocated promoter region (to activated MET oncogene)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000356448

InnateDB Gene

IDBG-105409 (TPR)

Protein Structure

UniProt Annotation

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). 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. {ECO:0000269PubMed:11952838, ECO:0000269PubMed:15654337, ECO:0000269PubMed:17897941, ECO:0000269PubMed:18794356, ECO:0000269PubMed:18981471, ECO:0000269PubMed:19273613, ECO:0000269PubMed:20133940, ECO:0000269PubMed:20407419, ECO:0000269PubMed:21613532, ECO:0000269PubMed:22253824, ECO:0000269PubMed:9864356}.

Subcellular Localization

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. {ECO:0000250, ECO:0000269PubMed:18981471, ECO:0000269PubMed:19273613, ECO:0000269PubMed:7798308}.

Disease Associations

Thyroid papillary carcinoma (TPC) [MIM:188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving TPR has been found in thyroid papillary carcinomas. 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.Note=Involved in tumorigenic rearrangements with the MET or RAF genes.

Tissue Specificity

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. {ECO:0000269PubMed:12424524, ECO:0000269PubMed:9024684}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 78 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	78 [view]
Protein-Protein	75 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0003682	chromatin binding
GO:0003729	mRNA binding
GO:0005487	nucleocytoplasmic transporter activity
GO:0005515	protein binding
GO:0015631	tubulin binding
GO:0031072	heat shock protein binding
GO:0042803	protein homodimerization activity
GO:0044822	poly(A) RNA binding
GO:0051019	mitogen-activated protein kinase binding
GO:0070840	dynein complex binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000189	MAPK import into nucleus
GO:0000278	mitotic cell cycle
GO:0005975	carbohydrate metabolic process
GO:0006404	RNA import into nucleus
GO:0006405	RNA export from nucleus
GO:0006606	protein import into nucleus
GO:0006999	nuclear pore organization
GO:0007067	mitotic nuclear division
GO:0007077	mitotic nuclear envelope disassembly
GO:0007094	mitotic spindle assembly checkpoint
GO:0008645	hexose transport
GO:0010827	regulation of glucose transport
GO:0010965	regulation of mitotic sister chromatid separation
GO:0015758	glucose transport
GO:0016032	viral process
GO:0019221	cytokine-mediated signaling pathway
GO:0031453	positive regulation of heterochromatin assembly
GO:0031990	mRNA export from nucleus in response to heat stress
GO:0034605	cellular response to heat
GO:0035457	cellular response to interferon-alpha
GO:0042307	positive regulation of protein import into nucleus
GO:0044281	small molecule metabolic process
GO:0045947	negative regulation of translational initiation
GO:0046827	positive regulation of protein export from nucleus
GO:0046832	negative regulation of RNA export from nucleus
GO:0055085	transmembrane transport
GO:0070849	response to epidermal growth factor
GO:0090267	positive regulation of mitotic cell cycle spindle assembly checkpoint
GO:0090316	positive regulation of intracellular protein transport
GO:1901673	regulation of spindle assembly involved in mitosis

Cellular Component

GO:0000776	kinetochore
GO:0005634	nucleus
GO:0005635	nuclear envelope
GO:0005643	nuclear pore
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005868	cytoplasmic dynein complex
GO:0019898	extrinsic component of membrane
GO:0031965	nuclear membrane
GO:0034399	nuclear periphery
GO:0042405	nuclear inclusion body
GO:0044615	nuclear pore nuclear basket
GO:0072686	mitotic spindle