TPR [The Human Chemical-Genetic Interaction Map Project]

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======= TPR =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TPR
  * **<color #00a2e8>Official Name</color>**: translocated promoter region, nuclear basket protein
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7175|7175]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P12270|P12270]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TPR&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TPR|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/189940|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes 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. It is required for the nuclear export of mRNAs and some proteins. Oncogenic fusions of the 5' end of this gene with several different kinase genes occur in some neoplasias. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:9864356}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|TPR MLP1 2|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of heterochromatin assembly|
|positive regulation of heterochromatin assembly|
|negative regulation of nucleobase-containing compound transport|
|mRNA export from nucleus in response to heat stress|
|negative regulation of RNA export from nucleus|
|positive regulation of chromatin assembly or disassembly|
|RNA import into nucleus|
|nuclear matrix organization|
|regulation of chromatin assembly|
|regulation of mRNA export from nucleus|
|regulation of ribonucleoprotein complex localization|
|positive regulation of mitotic cell cycle spindle assembly checkpoint|
|positive regulation of spindle checkpoint|
|positive regulation of cell cycle checkpoint|
|regulation of chromatin assembly or disassembly|
|nuclear pore complex assembly|
|cellular response to interferon-alpha|
|nuclear pore nuclear basket|
|nuclear inclusion body|
|regulation of mitotic cell cycle spindle assembly checkpoint|
|nuclear pore organization|
|regulation of spindle checkpoint|
|regulation of RNA export from nucleus|
|regulation of mitotic spindle checkpoint|
|nuclear periphery|
|protein membrane anchor|
|regulation of nucleobase-containing compound transport|
|negative regulation of translational initiation|
|negative regulation of nucleocytoplasmic transport|
|cytoplasmic dynein complex|
|response to interferon-alpha|
|dynein complex binding|
|pore complex assembly|
|positive regulation of protein export from nucleus|
|spindle checkpoint|
|mitotic spindle assembly checkpoint|
|mitogen-activated protein kinase binding|
|mitotic spindle checkpoint|
|regulation of mitotic spindle assembly|
|spindle assembly checkpoint|
|negative regulation of mitotic metaphase/anaphase transition|
|negative regulation of metaphase/anaphase transition of cell cycle|
|negative regulation of mitotic sister chromatid separation|
|negative regulation of chromosome separation|
|regulation of spindle assembly|
|structural constituent of nuclear pore|
|negative regulation of mitotic sister chromatid segregation|
|regulation of cell cycle checkpoint|
|negative regulation of sister chromatid segregation|
|negative regulation of chromosome segregation|
|tRNA-containing ribonucleoprotein complex export from nucleus|
|tRNA export from nucleus|
|tRNA transport|
|positive regulation of protein import into nucleus|
|ncRNA export from nucleus|
|regulation of protein export from nucleus|
|positive regulation of protein import|
|regulation of mitotic spindle organization|
|negative regulation of mitotic nuclear division|
|regulation of spindle organization|
|response to epidermal growth factor|
|negative regulation of nuclear division|
|regulation of mitotic metaphase/anaphase transition|
|regulation of metaphase/anaphase transition of cell cycle|
|tubulin binding|
|intracellular transport of virus|
|regulation of protein import into nucleus|
|host cell|
|transport of virus|
|regulation of mitotic sister chromatid separation|
|heat shock protein binding|
|regulation of protein import|
|negative regulation of intracellular transport|
|regulation of chromosome separation|
|positive regulation of nucleocytoplasmic transport|
|extrinsic component of membrane|
|protein sumoylation|
|regulation of mitotic sister chromatid segregation|
|multi-organism localization|
|cellular response to heat|
|multi-organism transport|
|nuclear pore|
|positive regulation of protein localization to nucleus|
|mitotic spindle|
|regulation of translational initiation|
|regulation of cellular response to heat|
|regulation of glycolytic process|
|regulation of sister chromatid segregation|
|kinetochore|
|regulation of gene silencing by miRNA|
|regulation of carbohydrate catabolic process|
|regulation of gene silencing by RNA|
|regulation of posttranscriptional gene silencing|
|protein import into nucleus|
|regulation of chromosome segregation|
|positive regulation of chromatin organization|
|regulation of nucleocytoplasmic transport|
|mRNA export from nucleus|
|mRNA-containing ribonucleoprotein complex export from nucleus|
|response to heat|
|import into nucleus|
|viral transcription|
|regulation of protein localization to nucleus|
|regulation of purine nucleotide metabolic process|
|regulation of nucleotide metabolic process|
|regulation of ATP metabolic process|
|ribonucleoprotein complex export from nucleus|
|ribonucleoprotein complex localization|
|RNA export from nucleus|
|regulation of gene silencing|
|viral gene expression|
|negative regulation of translation|
|nucleus organization|
|negative regulation of chromosome organization|
|protein import|
|negative regulation of cellular amide metabolic process|
|protein export from nucleus|
|positive regulation of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|positive regulation of intracellular protein transport|
|mRNA transport|
|nuclear export|
|regulation of generation of precursor metabolites and energy|
|mRNA binding|
|protein localization to nucleus|
|regulation of mitotic nuclear division|
|positive regulation of chromosome organization|
|response to temperature stimulus|
|nuclear envelope|
|regulation of microtubule cytoskeleton organization|
|regulation of chromatin organization|
|RNA transport|
|regulation of nuclear division|
|nucleic acid transport|
|cell cycle checkpoint|
|establishment of RNA localization|
|viral life cycle|
|regulation of carbohydrate metabolic process|
|positive regulation of intracellular transport|
|negative regulation of mitotic cell cycle phase transition|
|RNA localization|
|regulation of organelle assembly|
|regulation of microtubule-based process|
|negative regulation of cell cycle phase transition|
|regulation of intracellular protein transport|
|nuclear membrane|
|nucleobase-containing compound transport|
|protein-containing complex localization|
|nucleocytoplasmic transport|
|nuclear transport|
|positive regulation of cell cycle process|
|regulation of protein stability|
|negative regulation of mitotic cell cycle|
|peptidyl-lysine modification|
|positive regulation of cellular protein localization|
|negative regulation of cell cycle process|
|regulation of chromosome organization|
|regulation of intracellular transport|
|regulation of translation|
|negative regulation of organelle organization|
|positive regulation of cell cycle|
|chromatin binding|
|regulation of cellular amide metabolic process|
|regulation of mitotic cell cycle phase transition|
|positive regulation of protein transport|
|regulation of small molecule metabolic process|
|establishment of protein localization to organelle|
|regulation of cell cycle phase transition|
|positive regulation of establishment of protein localization|
|negative regulation of transport|
|cell division|
|positive regulation of cellular component biogenesis|
|posttranscriptional regulation of gene expression|
|response to growth factor|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|positive regulation of organelle organization|
|regulation of mitotic cell cycle|
|mitotic cell cycle|
|viral process|
|negative regulation of cellular component organization|
|regulation of protein transport|
|regulation of cellular response to stress|
|protein localization to organelle|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of cell cycle process|
|protein modification by small protein conjugation|
|symbiotic process|
|interspecies interaction between organisms|
|cellular protein-containing complex assembly|
|negative regulation of transcription by RNA polymerase II|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|regulation of cellular localization|
|regulation of cellular component biogenesis|
|protein modification by small protein conjugation or removal|
|positive regulation of transport|
|regulation of catabolic process|
|intracellular protein transport|
|cell cycle process|
|cellular response to cytokine stimulus|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|response to cytokine|
|negative regulation of protein metabolic process|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|positive regulation of cellular component organization|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|protein transport|
|negative regulation of cellular biosynthetic process|
|intracellular transport|
|peptide transport|
|negative regulation of biosynthetic process|
|protein-containing complex assembly|
|amide transport|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|establishment of protein localization|
|cellular response to stress|
|negative regulation of gene expression|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|establishment of localization in cell|
|nitrogen compound transport|
|protein-containing complex subunit organization|
|regulation of transport|
|gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp504|MK2206 4μM R08 exp504]]|-2.17|
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|-1.95|
|[[:results:exp17|DABN 20μM R00 exp17]]|1.72|
|[[:results:exp24|Nocodazole 0.2μM R00 exp24]]|1.74|
|[[:results:exp33|Rotenone 2μM R00 exp33]]|1.74|
|[[:results:exp149|SB203580 25μM R03 exp149]]|1.74|
|[[:results:exp16|DABN 2μM R00 exp16]]|1.75|
|[[:results:exp319|ABT-702 5μM plus Dimethyloxaloylglycine 11μM R07 exp319]]|1.76|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|1.89|
|[[:results:exp516|Pyrazinamide 100μM R08 exp516]]|1.9|
|[[:results:exp249|Vinorelbine 0.001μM R05 exp249]]|1.92|
|[[:results:exp5|Alpha-Amanitin 0.5μM R00 exp5]]|1.97|
|[[:results:exp11|CCCP 1μM R00 exp11]]|2.21|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|2.26|
|[[:results:exp12|Chloramphenicol 2μM R00 exp12]]|2.47|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:t:tmem116|TMEM116]]|0.42|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 414/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|1/1|
|bile duct|15/28|
|blood|16/28|
|bone|16/25|
|breast|15/33|
|central nervous system|23/56|
|cervix|1/4|
|colorectal|11/17|
|esophagus|6/13|
|fibroblast|1/1|
|gastric|10/15|
|kidney|9/21|
|liver|13/20|
|lung|44/75|
|lymphocyte|9/14|
|ovary|17/26|
|pancreas|14/24|
|peripheral nervous system|4/16|
|plasma cell|8/15|
|prostate|1/1|
|skin|14/24|
|soft tissue|1/7|
|thyroid|2/2|
|upper aerodigestive|17/22|
|urinary tract|24/29|
|uterus|2/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1009
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.61 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TPR Expression in NALM6 Cells: 8.61'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>