Host Protein General Information (ID: PT0702)
  Protein Name
Nucleoprotein TPR (TPR)
  Gene Name
TPR
  Host Species
Homo sapiens
  Uniprot Entry Name
TPR_HUMAN
  Protein Families
TPR family
  Subcellular Location
Nucleus membrane
  External Link
NCBI Gene ID
7175
Uniprot ID
P12270
Ensembl ID
ENSG00000047410
HGNC ID
HGNC:12017
  Function in Host
Component of the nuclear pore complex (NPC), a complexrequired for the trafficking across the nuclear envelope. Functions asa scaffolding element in the nuclear phase of the NPC essential fornormal nucleocytoplasmic transport of proteins and mRNAs, plays a rolein the establishment of nuclear-peripheral chromatincompartmentalization in interphase, and in the mitotic spindlecheckpoint signaling during mitosis. Involved in the quality controland retention of unspliced mRNAs in the nucleus; in association withNUP153, regulates the nuclear export of unspliced mRNA species bearingconstitutive transport element (CTE) in a NXF1- and KHDRBS1-independentmanner. Negatively regulates both the association of CTE-containingmRNA with large polyribosomes and translation initiation. Does not playany role in Rev response element (RRE) -mediated export of unsplicedmRNAs. Implicated in nuclear export of mRNAs transcribed from heatshock gene promoters; associates both with chromatin in the HSP70promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport ofactivated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking sitefor the XPO1/CRM1-mediated nuclear export complex. According to someauthors, plays a limited role in the regulation of nuclear proteinexport ( and ). Plays also a role as astructural and functional element of the perinuclear chromatindistribution; 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 spindlecheckpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochoreduring the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. [1-11]
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  Related KEGG Pathway
Nucleocytoplasmic transport hsa03013            Pathway Map 
Pathways in cancer hsa05200            Pathway Map 
Thyroid cancer hsa05216            Pathway Map 
Amyotrophic lateral sclerosis hsa05014            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [12]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein TPR in viral infection, TPR protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
ResultsIt is reported that knockout of TPR increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 5'-UTR (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
5'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells HEK293 Cells (Human embryonic kidney cell)  (CVCL_0045 )
              Cell Originated Tissue Liver
              Infection Time 48 h
              Interaction Score Prot score = 65
              Method Description RNA-protein interaction detection (RaPID) assay; liquid chromatography with tandem mass spectrometry (LC-MS/MS)

Differential Gene Expression During SARS-COV-2 Infection
GEO Accession: GSE152641
Sample Type: Blood
Samples Details: Healthy Control: 24; COVID-19: 62
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE162835
Sample Type: Nasopharyngeal Swabs
Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE175779
Sample Type: Human Bronchial Epithelial Cells
Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)
Platform: GPL18573 Illumina NextSeq 500
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Protein Phosphorylation after Virus Infection
S1679 [14]
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S2047 [14]
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S2073 [15]
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S2136 [14]
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S2155 [14]
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S379 [15]
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S379 [14]
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S640 [14]
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S648 [14]
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T1677 [14]
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T2116 [14]
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T2137 [14]
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T2139 [14]
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T381 [14]
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T641 [14]
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Protein Sequence Information
MAAVLQQVLERTELNKLPKSVQNKLEKFLADQQSEIDGLKGRHEKFKVESEQQYFEIEKRLSHSQERLVNETRECQSLRLELEKLNNQLKALTEKNKELEIAQDRNIAIQSQFTRTKEELEAEKRDLIRTNERLSQELEYLTEDVKRLNEKLKESNTTKGELQLKLDELQASDVSVKYREKRLEQEKELLHSQNTWLNTELKTKTDELLALGREKGNEILELKCNLENKKEEVSRLEEQMNGLKTSNEHLQKHVEDLLTKLKEAKEQQASMEEKFHNELNAHIKLSNLYKSAADDSEAKSNELTRAVEELHKLLKEAGEANKAIQDHLLEVEQSKDQMEKEMLEKIGRLEKELENANDLLSATKRKGAILSEEELAAMSPTAAAVAKIVKPGMKLTELYNAYVETQDQLLLEKLENKRINKYLDEIVKEVEAKAPILKRQREEYERAQKAVASLSVKLEQAMKEIQRLQEDTDKANKQSSVLERDNRRMEIQVKDLSQQIRVLLMELEEARGNHVIRDEEVSSADISSSSEVISQHLVSYRNIEELQQQNQRLLVALRELGETREREEQETTSSKITELQLKLESALTELEQLRKSRQHQMQLVDSIVRQRDMYRILLSQTTGVAIPLHASSLDDVSLASTPKRPSTSQTVSTPAPVPVIESTEAIEAKAALKQLQEIFENYKKEKAENEKIQNEQLEKLQEQVTDLRSQNTKISTQLDFASKRYEMLQDNVEGYRREITSLHERNQKLTATTQKQEQIINTMTQDLRGANEKLAVAEVRAENLKKEKEMLKLSEVRLSQQRESLLAEQRGQNLLLTNLQTIQGILERSETETKQRLSSQIEKLEHEISHLKKKLENEVEQRHTLTRNLDVQLLDTKRQLDTETNLHLNTKELLKNAQKEIATLKQHLSNMEVQVASQSSQRTGKGQPSNKEDVDDLVSQLRQTEEQVNDLKERLKTSTSNVEQYQAMVTSLEESLNKEKQVTEEVRKNIEVRLKESAEFQTQLEKKLMEVEKEKQELQDDKRRAIESMEQQLSELKKTLSSVQNEVQEALQRASTALSNEQQARRDCQEQAKIAVEAQNKYERELMLHAADVEALQAAKEQVSKMASVRQHLEETTQKAESQLLECKASWEERERMLKDEVSKCVCRCEDLEKQNRLLHDQIEKLSDKVVASVKEGVQGPLNVSLSEEGKSQEQILEILRFIRREKEIAETRFEVAQVESLRYRQRVELLERELQELQDSLNAEREKVQVTAKTMAQHEELMKKTETMNVVMETNKMLREEKERLEQDLQQMQAKVRKLELDILPLQEANAELSEKSGMLQAEKKLLEEDVKRWKARNQHLVSQQKDPDTEEYRKLLSEKEVHTKRIQQLTEEIGRLKAEIARSNASLTNNQNLIQSLKEDLNKVRTEKETIQKDLDAKIIDIQEKVKTITQVKKIGRRYKTQYEELKAQQDKVMETSAQSSGDHQEQHVSVQEMQELKETLNQAETKSKSLESQVENLQKTLSEKETEARNLQEQTVQLQSELSRLRQDLQDRTTQEEQLRQQITEKEEKTRKAIVAAKSKIAHLAGVKDQLTKENEELKQRNGALDQQKDELDVRITALKSQYEGRISRLERELREHQERHLEQRDEPQEPSNKVPEQQRQITLKTTPASGERGIASTSDPPTANIKPTPVVSTPSKVTAAAMAGNKSTPRASIRPMVTPATVTNPTTTPTATVMPTTQVESQEAMQSEGPVEHVPVFGSTSGSVRSTSPNVQPSISQPILTVQQQTQATAFVQPTQQSHPQIEPANQELSSNIVEVVQSSPVERPSTSTAVFGTVSATPSSSLPKRTREEEEDSTIEASDQVSDDTVEMPLPKKLKSVTPVGTEEEVMAEESTDGEVETQVYNQDSQDSIGEGVTQGDYTPMEDSEETSQSLQIDLGPLQSDQQTTTSSQDGQGKGDDVIVIDSDDEEEDDDENDGEHEDYEEDEEDDDDDEDDTGMGDEGEDSNEGTGSADGNDGYEADDAEGGDGTDPGTETEESMGGGEGNHRAADSQNSGEGNTGAAESSFSQEVSREQQPSSASERQAPRAPQSPRRPPHPLPPRLTIHAPPQELGPPVQRIQMTRRQSVGRGLQLTPGIGGMQQHFFDDEDRTVPSTPTLVVPHRTDGFAEAIHSPQVAGVPRFRFGPPEDMPQTSSSHSDLGQLASQGGLGMYETPLFLAHEEESGGRSVPTTPLQVAAPVTVFTESTTSDASEHASQSVPMVTTSTGTLSTTNETATGDDGDEVFVEAESEGISSEAGLEIDSQQEEEPVQASDESDLPSTSQDPPSSSSVDTSSSQPKPFRRVRLQTTLRQGVRGRQFNRQRGVSHAMGGRGGINRGNIN
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References
1 Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA. PLoS One. 2012;7(1):e29921.
2 The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA. 2011 Jul;17(7):1344-56.
3 Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion. EMBO J. 2010 May 19;29(10):1659-73.
4 Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis. J Biol Chem. 2010 Apr 2;285(14):10841-9.
5 Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J Cell Biol. 2009 Mar 9;184(5):647-57.
6 Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol. 2008 Nov;28(22):6954-66.
7 Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint. Genes Dev. 2008 Nov 1;22(21):2926-31.
8 HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA. J Biol Chem. 2007 Nov 23;282(47):33902-7.
9 Polyglutamine expansion of huntingtin impairs its nuclear export. Nat Genet. 2005 Feb;37(2):198-204.
10 Nucleocytoplasmic transport of proteins and poly(A)+ RNA in reconstituted Tpr-less nuclei in living mammalian cells. Genes Cells. 2002 Apr;7(4):421-34.
11 Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export. J Cell Biol. 1998 Dec 28;143(7):1801-12.
12 Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
13 RNA-Protein Interaction Analysis of SARS-CoV-2 5 and 3 Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection. mSystems. 2021 Aug 31;6(4):e0064321.
14 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
15 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.