ID TPR_HUMAN Reviewed; 2363 AA. AC P12270; Q15624; Q15655; Q5SWY0; Q99968; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 27-MAR-2024, entry version 224. DE RecName: Full=Nucleoprotein TPR; DE AltName: Full=Megator; DE AltName: Full=NPC-associated intranuclear protein; DE AltName: Full=Translocated promoter region protein; GN Name=TPR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=1549355; RA Mitchell P.J., Cooper C.S.; RT "Nucleotide sequence analysis of human tpr cDNA clones."; RL Oncogene 7:383-388(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1437155; RA Mitchell P.J., Cooper C.S.; RT "The human tpr gene encodes a protein of 2094 amino acids that has RT extensive coiled-coil regions and an acidic C-terminal domain."; RL Oncogene 7:2329-2333(1992). RN [3] RP SEQUENCE REVISION, CHARACTERIZATION, AND SUBCELLULAR LOCATION. RX PubMed=7798308; DOI=10.1083/jcb.127.6.1515; RA Byrd D.A., Sweet D.J., Pante N., Konstantinov K.N., Guan T., RA Saphire A.C.S., Mitchell P.J., Cooper C.S., Aebi U., Gerace L.; RT "Tpr, a large coiled coil protein whose amino terminus is involved in RT activation of oncogenic kinases, is localized to the cytoplasmic surface of RT the nuclear pore complex."; RL J. Cell Biol. 127:1515-1526(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Embryonic brain; RX PubMed=9024684; DOI=10.1083/jcb.136.3.515; RA Cordes V.C., Reidenbach S., Rackwitz H.R., Franke W.W.; RT "Identification of protein p270/Tpr as a constitutive component of the RT nuclear pore complex-attached intranuclear filaments."; RL J. Cell Biol. 136:515-529(1997). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-191 (ISOFORM 1/2), AND CHROMOSOMAL RP REARRANGEMENT WITH NTRK1. RX PubMed=1532241; RA Greco A., Pierotti M.A., Bongarzone I., Pagliardini S., Lanzi C., RA Della Porta G.; RT "TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in RT human papillary thyroid carcinomas."; RL Oncogene 7:237-242(1992). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-142 (ISOFORM 1/2). RX PubMed=3387099; RA King H.W.S., Tempest P.R., Merrifield K.R., Rance A.J.; RT "tpr homologues activate met and raf."; RL Oncogene 2:617-619(1988). RN [9] RP PROTEIN SEQUENCE OF 2-11; 502-511; 1192-1201 AND 1421-1427, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Hepatoma, and Osteosarcoma; RA Bienvenut W.V., Glen H., Brunton V.G., Frame M.C., Boldt K., RA von Kriegsheim A.F., Kolch W.; RL Submitted (JUL-2007) to UniProtKB. RN [10] RP CHROMOSOMAL REARRANGEMENT WITH MET. RX PubMed=2300559; DOI=10.1073/pnas.87.2.738; RA Soman N.R., Wogan G.N., Rhim J.S.; RT "TPR-MET oncogenic rearrangement: detection by polymerase chain reaction RT amplification of the transcript and expression in human tumor cell lines."; RL Proc. Natl. Acad. Sci. U.S.A. 87:738-742(1990). RN [11] RP SUBCELLULAR LOCATION, AND NPC-BINDING DOMAIN AND NUCLEAR IMPORT DOMAIN. RX PubMed=9828100; DOI=10.1006/excr.1998.4246; RA Cordes V.C., Hase M.E., Muller L.; RT "Molecular segments of protein Tpr that confer nuclear targeting and RT association with the nuclear pore complex."; RL Exp. Cell Res. 245:43-56(1998). RN [12] RP FUNCTION, NPC-BINDING DOMAIN AND NUCLEAR IMPORT DOMAIN, AND SUBCELLULAR RP LOCATION. RX PubMed=9864356; DOI=10.1083/jcb.143.7.1801; RA Bangs P., Burke B., Powers C., Craig R., Purohit A., Doxsey S.; RT "Functional analysis of Tpr: identification of nuclear pore complex RT association and nuclear localization domains and a role in mRNA export."; RL J. Cell Biol. 143:1801-1812(1998). RN [13] RP HOMODIMERIZATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-458 AND RP MET-489. RX PubMed=11514627; DOI=10.1091/mbc.12.8.2433; RA Hase M.E., Kuznetsov N.V., Cordes V.C.; RT "Amino acid substitutions of coiled-coil protein Tpr abrogate anchorage to RT the nuclear pore complex but not parallel, in-register homodimerization."; RL Mol. Biol. Cell 12:2433-2452(2001). RN [14] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12424524; DOI=10.1007/s00412-002-0208-2; RA Kuznetsov N.V., Sandblad L., Hase M.E., Hunziker A., Hergt M., Cordes V.C.; RT "The evolutionarily conserved single-copy gene for murine Tpr encodes one RT prevalent isoform in somatic cells and lacks paralogs in higher RT eukaryotes."; RL Chromosoma 111:236-255(2002). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11952838; DOI=10.1046/j.1365-2443.2002.00525.x; RA Shibata S., Matsuoka Y., Yoneda Y.; RT "Nucleocytoplasmic transport of proteins and poly(A)+ RNA in reconstituted RT Tpr-less nuclei in living mammalian cells."; RL Genes Cells 7:421-434(2002). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=11839768; DOI=10.1083/jcb.200106046; RA Frosst P., Guan T., Subauste C., Hahn K., Gerace L.; RT "Tpr is localized within the nuclear basket of the pore complex and has a RT role in nuclear protein export."; RL J. Cell Biol. 156:617-630(2002). RN [17] RP ABSENCE OF FUNCTION IN ANCHORING NUCLEOPORINS, INTERACTION WITH NUP153, RP HOMODIMERIZATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-458 AND RP MET-489. RX PubMed=12802065; DOI=10.1091/mbc.e02-09-0620; RA Hase M.E., Cordes V.C.; RT "Direct interaction with nup153 mediates binding of Tpr to the periphery of RT the nuclear pore complex."; RL Mol. Biol. Cell 14:1923-1940(2003). RN [18] RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE NUCLEAR PORE COMPLEX. RX PubMed=15229283; DOI=10.1091/mbc.e04-03-0165; RA Krull S., Thyberg J., Bjorkroth B., Rackwitz H.R., Cordes V.C.; RT "Nucleoporins as components of the nuclear pore complex core structure and RT Tpr as the architectural element of the nuclear basket."; RL Mol. Biol. Cell 15:4261-4277(2004). RN [19] RP FUNCTION IN NUCLEAR PROTEIN EXPORT, AND INTERACTION WITH HTT. RX PubMed=15654337; DOI=10.1038/ng1503; RA Cornett J., Cao F., Wang C.E., Ross C.A., Bates G.P., Li S.H., Li X.J.; RT "Polyglutamine expansion of huntingtin impairs its nuclear export."; RL Nat. Genet. 37:198-204(2005). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2073, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [22] RP FUNCTION IN STRESS-INDUCED NUCLEAR MRNA EXPORT, AND INTERACTION WITH HSF1. RX PubMed=17897941; DOI=10.1074/jbc.m704054200; RA Skaggs H.S., Xing H., Wilkerson D.C., Murphy L.A., Hong Y., Mayhew C.N., RA Sarge K.D.; RT "HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA."; RL J. Biol. Chem. 282:33902-33907(2007). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2155, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells RT and high confident phosphopeptide identification by cross-validation of RT MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2050, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [25] RP INTERACTION WITH MAD2L1 AND MAD1L1, FUNCTION, IDENTIFICATION BY MASS RP SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=18981471; DOI=10.1101/gad.1677208; RA Lee S.H., Sterling H., Burlingame A., McCormick F.; RT "Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2- RT mediated mitotic spindle checkpoint."; RL Genes Dev. 22:2926-2931(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2155, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [27] RP FUNCTION IN PROTEIN IMPORT, INTERACTION WITH MAPK1, PHOSPHORYLATION BY RP MAPK1, AND SUBCELLULAR LOCATION. RX PubMed=18794356; DOI=10.1128/mcb.00925-08; RA Vomastek T., Iwanicki M.P., Burack W.R., Tiwari D., Kumar D., Parsons J.T., RA Weber M.J., Nandicoori V.K.; RT "Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and RT docking domain on the nuclear pore complex protein Tpr cooperatively RT regulate ERK2-Tpr interaction."; RL Mol. Cell. Biol. 28:6954-6966(2008). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-1185; SER-2048 AND RP SER-2155, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [30] RP ASSOCIATION WITH XPO1/CRM1 AND IMPORTIN ALPHA/IMPORTIN BETA RECEPTOR, AND RP INTERACTION WITH KPNB1. RX PubMed=19835572; DOI=10.1186/1471-2121-10-74; RA Ben-Efraim I., Frosst P.D., Gerace L.; RT "Karyopherin binding interactions and nuclear import mechanism of nuclear RT pore complex protein Tpr."; RL BMC Cell Biol. 10:74-74(2009). RN [31] RP FUNCTION, INTERACTION WITH MAD1L1; MAD2L1 AND TTK, AND SUBCELLULAR RP LOCATION. RX PubMed=19273613; DOI=10.1083/jcb.200811012; RA Lince-Faria M., Maffini S., Orr B., Ding Y., Florindo C., Sunkel C.E., RA Tavares A., Johansen J., Johansen K.M., Maiato H.; RT "Spatiotemporal control of mitosis by the conserved spindle matrix protein RT Megator."; RL J. Cell Biol. 184:647-657(2009). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185; SER-2050 AND SER-2155, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [33] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-252; LYS-312; LYS-345; LYS-428; RP LYS-457; LYS-713; LYS-723; LYS-748 AND LYS-755, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [34] RP FUNCTION, ORGANIZATION OF PERINUCLEAR CHROMATIN, SUBCELLULAR LOCATION, AND RP PROTEOLYTIC PROCESSING. RX PubMed=20407419; DOI=10.1038/emboj.2010.54; RA Krull S., Dorries J., Boysen B., Reidenbach S., Magnius L., Norder H., RA Thyberg J., Cordes V.C.; RT "Protein Tpr is required for establishing nuclear pore-associated zones of RT heterochromatin exclusion."; RL EMBO J. 29:1659-1673(2010). RN [35] RP FUNCTION, INTERACTION WITH DCTN1; DYNEIN; DYNLL1; MAD2L1; NUP153 AND RP TUBULIN, AND SUBCELLULAR LOCATION. RX PubMed=20133940; DOI=10.1074/jbc.m110.105890; RA Nakano H., Funasaka T., Hashizume C., Wong R.W.; RT "Nucleoporin translocated promoter region (Tpr) associates with dynein RT complex, preventing chromosome lagging formation during mitosis."; RL J. Biol. Chem. 285:10841-10849(2010). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-1185; THR-1692 AND RP SER-2155, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [38] RP FUNCTION IN UNSPLICED RNA EXPORT. RX PubMed=21613532; DOI=10.1261/rna.2616111; RA Coyle J.H., Bor Y.C., Rekosh D., Hammarskjold M.L.; RT "The Tpr protein regulates export of mRNAs with retained introns that RT traffic through the Nxf1 pathway."; RL RNA 17:1344-1356(2011). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185 AND SER-2073, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [40] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [41] RP FUNCTION IN UNSPLICED RNA EXPORT, INTERACTION WITH MAPK1, AND SUBCELLULAR RP LOCATION. RX PubMed=22253824; DOI=10.1371/journal.pone.0029921; RA Rajanala K., Nandicoori V.K.; RT "Localization of nucleoporin Tpr to the nuclear pore complex is essential RT for Tpr mediated regulation of the export of unspliced RNA."; RL PLoS ONE 7:E29921-E29921(2012). RN [42] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-1185; THR-1692; RP SER-2034; SER-2037; SER-2048; SER-2050; THR-2137 AND SER-2155, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-522; SER-523; RP SER-632; SER-1893 AND SER-2155, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [45] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-2111, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [46] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MTA1. RX PubMed=24970816; DOI=10.18632/oncotarget.2095; RA Liu J., Xu D., Wang H., Zhang Y., Chang Y., Zhang J., Wang J., Li C., RA Liu H., Zhao M., Lin C., Zhan Q., Huang C., Qian H.; RT "The subcellular distribution and function of MTA1 in cancer RT differentiation."; RL Oncotarget 5:5153-5164(2014). RN [47] RP INVOLVEMENT IN MRT79, AND VARIANT MRT79 2209-ARG--ASN-2363 DEL. RX PubMed=34494102; DOI=10.1093/hmg/ddab248; RG MCRI Rare Diseases Flagship; RA Van Bergen N.J., Bell K.M., Carey K., Gear R., Massey S., Murrell E.K., RA Gallacher L., Pope K., Lockhart P.J., Kornberg A., Pais L., Walkiewicz M., RA Simons C., Wickramasinghe V.O., White S.M., Christodoulou J.; RT "Pathogenic variants in nucleoporin TPR (translocated promoter region, RT nuclear basket protein) cause severe intellectual disability in humans."; RL Hum. Mol. Genet. 31:362-375(2022). CC -!- FUNCTION: Component of the nuclear pore complex (NPC), a complex CC required for the trafficking across the nuclear envelope. Functions as CC a scaffolding element in the nuclear phase of the NPC essential for CC normal nucleocytoplasmic transport of proteins and mRNAs, plays a role CC in the establishment of nuclear-peripheral chromatin CC compartmentalization in interphase, and in the mitotic spindle CC checkpoint signaling during mitosis. Involved in the quality control CC and retention of unspliced mRNAs in the nucleus; in association with CC NUP153, regulates the nuclear export of unspliced mRNA species bearing CC constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent CC manner. Negatively regulates both the association of CTE-containing CC mRNA with large polyribosomes and translation initiation. Does not play CC any role in Rev response element (RRE)-mediated export of unspliced CC mRNAs. Implicated in nuclear export of mRNAs transcribed from heat CC shock gene promoters; associates both with chromatin in the HSP70 CC promoter and with mRNAs transcribed from this promoter under stress- CC induced conditions. Modulates the nucleocytoplasmic transport of CC activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site CC for the XPO1/CRM1-mediated nuclear export complex. According to some CC authors, plays a limited role in the regulation of nuclear protein CC export (PubMed:22253824, PubMed:11952838). Also plays a role as a CC structural and functional element of the perinuclear chromatin CC distribution; involved in the formation and/or maintenance of NPC- CC associated perinuclear heterochromatin exclusion zones (HEZs). Finally, CC acts as a spatial regulator of the spindle-assembly checkpoint (SAC) CC response ensuring a timely and effective recruitment of spindle CC checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore CC during the metaphase-anaphase transition before chromosome congression. CC Its N-terminus is involved in activation of oncogenic kinases. CC {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, CC ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, CC ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, CC ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, CC ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, CC ECO:0000269|PubMed:9864356}. CC -!- SUBUNIT: Interacts with IFI204 (via C-terminal region). Interacts with CC IFI203 (By similarity). Homodimer. Part of the nuclear pore complex CC (NPC). Associates with the XPO1/CRM1-mediated nuclear export complex, CC the Importin alpha/Importin beta receptor and the dynein 1 complex. CC Interacts (via C-terminal domain) with the KPNB1; the interaction CC occurs in a RanGTP-dependent manner. Interacts (via C-terminal CC regionand phosphorylated form) with MAPK1/ERK2 (via phosphorylated CC form); the interaction requires dimerization of MAPK1/ERK2 and CC increases following EGF stimulation. Interacts with MAPK3/ERK1; the CC interaction increases following EGF stimulation. Interacts (via coiled CC coil region) with NUP153; the interaction is direct. Interacts with CC HSF1; the interaction increases in a stress-responsive manner and CC stimulates export of stress-induced HSP70 mRNA. Interacts with CC huntingtin/HTT; the interaction is inhibited by aggregated CC huntingtin/HTT forms with expanded polyglutamine stretch. Interacts CC with MAD1L1 (via N-terminal region), MAD2L1, and TTK; the interactions CC occurs in a microtubule-independent manner. Interacts (via middle CC region) with DYNLL1. Interacts with DCTN1, dynein, NUP153 and tubulin. CC Interacts with MTA1. {ECO:0000250, ECO:0000269|PubMed:12802065, CC ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:15654337, CC ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, CC ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, CC ECO:0000269|PubMed:19835572, ECO:0000269|PubMed:20133940, CC ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:24970816}. CC -!- INTERACTION: CC P12270; Q9Y6D9: MAD1L1; NbExp=2; IntAct=EBI-1048528, EBI-742610; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12802065}. Nucleus CC membrane {ECO:0000269|PubMed:11514627, ECO:0000269|PubMed:11952838, CC ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:9024684, CC ECO:0000269|PubMed:9828100, ECO:0000269|PubMed:9864356}; Peripheral CC membrane protein {ECO:0000269|PubMed:11514627, CC ECO:0000269|PubMed:9024684, ECO:0000269|PubMed:9828100, CC ECO:0000269|PubMed:9864356}; Nucleoplasmic side CC {ECO:0000269|PubMed:11514627, ECO:0000269|PubMed:9024684, CC ECO:0000269|PubMed:9828100, ECO:0000269|PubMed:9864356}. Nucleus CC envelope {ECO:0000269|PubMed:12424524, ECO:0000269|PubMed:7798308}. CC Nucleus, nuclear pore complex {ECO:0000269|PubMed:11514627, CC ECO:0000269|PubMed:11839768, ECO:0000269|PubMed:12802065, CC ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:18981471, CC ECO:0000269|PubMed:7798308, ECO:0000269|PubMed:9024684, CC ECO:0000269|PubMed:9828100, ECO:0000269|PubMed:9864356}. Cytoplasm CC {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:12802065}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000269|PubMed:19273613}. Chromosome, CC centromere, kinetochore {ECO:0000269|PubMed:18981471}. Nucleus membrane CC {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, CC ECO:0000269|PubMed:7798308}; Peripheral membrane protein CC {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, CC ECO:0000269|PubMed:7798308}; Cytoplasmic side CC {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, CC ECO:0000269|PubMed:7798308}. Note=Detected as discrete intranuclear CC foci with IFI204 (By similarity). In interphase, localizes to the CC nucleoplasmic side of the nuclear pore complex (NPC) core structure, CC forming a fibrous structure called the nuclear basket. Detected CC exclusively to the cytoplasmic margin of NPC (PubMed:7798308). Docking CC to the inner nucleoplasmic side of the NPC is mediated through binding CC to nucleoporins. Anchored by NUP153 to the NPC. The assembly of the NPC CC is a stepwise process in which Trp-containing peripheral structures CC assemble after other components, including p62. Detected as filaments CC that emanate from the nuclear basket of the NPC and extend to the CC nucleolus to delineate a chromatin-free network extending from the CC nuclear envelope to the perinucleolar region. Detected in diffuse and CC discrete spheroidal intranuclear foci. Nucleocytoplasmic shuttling CC protein imported into the nucleus in a XPO1/CRM1- and Importin CC alpha/Importin beta receptor-dependent manner. Remains localized to the CC nuclear membrane after poliovirus (PV) infection. During mitosis, CC remains associated with the nuclear envelope until prometaphase. CC Associated with the mitotic spindle from late prometaphase until CC anaphase. Reorganized during mitosis in a viscous and dynamic nuclear- CC derived spindle matrix that embeds the microtubule spindle apparatus CC from pole to pole in a microtubule-independent manner. Recruited to the CC reforming nuclear envelope during telophase and cytokinesis. Detected CC at kinetochores during prometaphase (PubMed:18981471). Colocalizes with CC MAD2L1 in the spindle matrix but not at kinetochore (PubMed:19273613). CC Colocalizes with dynein, dynactin, tubulin at kinetochore during the CC metaphase-anaphase transition. Colocalizes with DYNLL1 at the mitotic CC spindle. {ECO:0000250, ECO:0000269|PubMed:18981471, CC ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:7798308}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P12270-1; Sequence=Displayed; CC Name=2; CC IsoId=P12270-2; Sequence=VSP_057406, VSP_057407; CC -!- TISSUE SPECIFICITY: Expressed in esophagus, ovary, liver, skin, smooth CC muscles, cerebrum and fetal cerebellum (at protein level). Highest in CC testis, lung, thymus, spleen and brain, lower levels in heart, liver CC and kidney. {ECO:0000269|PubMed:12424524, ECO:0000269|PubMed:9024684}. CC -!- DOMAIN: The N-terminal domain mediates intranuclear attachment to the CC nuclear pore complex. The C-terminal domain mediates its nuclear CC import. CC -!- PTM: Phosphorylated. Phosphorylation occurs on serine and threonine CC residues (comprised in the C-terminal region) by MAPK1/ERK2 and CC stabilizes the interaction between these two proteins. CC {ECO:0000269|PubMed:18794356}. CC -!- PTM: Proteolytically degraded after poliovirus (PV) infection; CC degradation is restricted to its unfolded C-terminal tail domain CC whereas its coiled-coil domain containing NCP- and NUP153-binding CC domains withstand degradation. CC -!- DISEASE: Note=A chromosomal aberration involving TPR has been found in CC papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement CC that links the 5'-end of the TPR gene to the protein kinase domain of CC NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein CC reacting with antibodies against the carboxy terminus of the NTRK1 CC protein. {ECO:0000269|PubMed:1532241}. CC -!- DISEASE: Note=Involved in tumorigenic rearrangements with the MET. CC {ECO:0000269|PubMed:2300559}. CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 79 CC (MRT79) [MIM:620393]: An autosomal recessive neurodevelopmental CC disorder apparent from infancy and characterized by global CC developmental delay, severe intellectual disability, poor or absent CC speech, ataxia, and postnatal microcephaly. CC {ECO:0000269|PubMed:34494102}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the TPR family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/282/TPR"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X63105; CAA44819.1; -; mRNA. DR EMBL; X66397; CAA47021.1; -; mRNA. DR EMBL; U69668; AAB48030.1; -; mRNA. DR EMBL; AL596220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133553; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91205.1; -; Genomic_DNA. DR EMBL; X62947; CAA44719.1; ALT_TERM; mRNA. DR EMBL; Y00672; CAA68681.1; -; mRNA. DR CCDS; CCDS41446.1; -. [P12270-1] DR PIR; S23741; S23741. DR RefSeq; NP_003283.2; NM_003292.2. [P12270-1] DR PDB; 5TO5; X-ray; 2.50 A; A/B=2-142. DR PDB; 5TO6; X-ray; 2.70 A; A/B/C/D=2-142. DR PDB; 5TO7; X-ray; 2.60 A; A/B/C/D=2-142. DR PDB; 5TVB; X-ray; 2.75 A; A/B=2-142. DR PDBsum; 5TO5; -. DR PDBsum; 5TO6; -. DR PDBsum; 5TO7; -. DR PDBsum; 5TVB; -. DR AlphaFoldDB; P12270; -. DR SMR; P12270; -. DR BioGRID; 113028; 249. DR ComplexPortal; CPX-873; Nuclear pore complex. DR DIP; DIP-50405N; -. DR IntAct; P12270; 63. DR MINT; P12270; -. DR STRING; 9606.ENSP00000356448; -. DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family. DR GlyConnect; 2850; 1 O-GlcNAc glycan (1 site). DR GlyCosmos; P12270; 8 sites, 2 glycans. DR GlyGen; P12270; 24 sites, 2 O-linked glycans (24 sites). DR iPTMnet; P12270; -. DR MetOSite; P12270; -. DR PhosphoSitePlus; P12270; -. DR SwissPalm; P12270; -. DR BioMuta; TPR; -. DR DMDM; 215274208; -. DR EPD; P12270; -. DR jPOST; P12270; -. DR MassIVE; P12270; -. DR MaxQB; P12270; -. DR PaxDb; 9606-ENSP00000356448; -. DR PeptideAtlas; P12270; -. DR ProteomicsDB; 52840; -. [P12270-1] DR Pumba; P12270; -. DR Antibodypedia; 11198; 258 antibodies from 30 providers. DR DNASU; 7175; -. DR Ensembl; ENST00000367478.9; ENSP00000356448.3; ENSG00000047410.14. [P12270-1] DR Ensembl; ENST00000613151.1; ENSP00000483425.1; ENSG00000047410.14. [P12270-2] DR GeneID; 7175; -. DR KEGG; hsa:7175; -. DR MANE-Select; ENST00000367478.9; ENSP00000356448.3; NM_003292.3; NP_003283.2. DR UCSC; uc001grv.4; human. [P12270-1] DR UCSC; uc057nyz.1; human. DR AGR; HGNC:12017; -. DR CTD; 7175; -. DR DisGeNET; 7175; -. DR GeneCards; TPR; -. DR HGNC; HGNC:12017; TPR. DR HPA; ENSG00000047410; Low tissue specificity. DR MalaCards; TPR; -. DR MIM; 189940; gene. DR MIM; 620393; phenotype. DR neXtProt; NX_P12270; -. DR OpenTargets; ENSG00000047410; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR Orphanet; 146; Differentiated thyroid carcinoma. DR PharmGKB; PA36696; -. DR VEuPathDB; HostDB:ENSG00000047410; -. DR eggNOG; KOG4674; Eukaryota. DR GeneTree; ENSGT00730000111014; -. DR HOGENOM; CLU_001059_0_0_1; -. DR InParanoid; P12270; -. DR OMA; HAQQNYE; -. DR OrthoDB; 3135837at2759; -. DR PhylomeDB; P12270; -. DR TreeFam; TF350364; -. DR PathwayCommons; P12270; -. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-159227; Transport of the SLBP independent Mature mRNA. DR Reactome; R-HSA-159230; Transport of the SLBP Dependant Mature mRNA. DR Reactome; R-HSA-159231; Transport of Mature mRNA Derived from an Intronless Transcript. DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript. DR Reactome; R-HSA-165054; Rev-mediated nuclear export of HIV RNA. DR Reactome; R-HSA-168271; Transport of Ribonucleoproteins into the Host Nucleus. DR Reactome; R-HSA-168276; NS1 Mediated Effects on Host Pathways. DR Reactome; R-HSA-168325; Viral Messenger RNA Synthesis. DR Reactome; R-HSA-168333; NEP/NS2 Interacts with the Cellular Export Machinery. DR Reactome; R-HSA-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein. DR Reactome; R-HSA-180746; Nuclear import of Rev protein. DR Reactome; R-HSA-180910; Vpr-mediated nuclear import of PICs. DR Reactome; R-HSA-191859; snRNP Assembly. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins. DR Reactome; R-HSA-3301854; Nuclear Pore Complex (NPC) Disassembly. DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-HSA-4085377; SUMOylation of SUMOylation proteins. DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins. DR Reactome; R-HSA-4570464; SUMOylation of RNA binding proteins. DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins. DR Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs. DR Reactome; R-HSA-5619107; Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC). DR Reactome; R-HSA-6784531; tRNA processing in the nucleus. DR Reactome; R-HSA-9609690; HCMV Early Events. DR Reactome; R-HSA-9610379; HCMV Late Events. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; P12270; -. DR SIGNOR; P12270; -. DR BioGRID-ORCS; 7175; 727 hits in 1166 CRISPR screens. DR ChiTaRS; TPR; human. DR GenomeRNAi; 7175; -. DR Pharos; P12270; Tbio. DR PRO; PR:P12270; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P12270; Protein. DR Bgee; ENSG00000047410; Expressed in tendon of biceps brachii and 213 other cell types or tissues. DR ExpressionAtlas; P12270; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005868; C:cytoplasmic dynein complex; IDA:UniProtKB. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0042405; C:nuclear inclusion body; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0034399; C:nuclear periphery; IDA:UniProtKB. DR GO; GO:0005643; C:nuclear pore; IDA:UniProtKB. DR GO; GO:0044615; C:nuclear pore nuclear basket; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0070840; F:dynein complex binding; IDA:UniProtKB. DR GO; GO:0031072; F:heat shock protein binding; IDA:UniProtKB. DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IDA:UniProtKB. DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0017056; F:structural constituent of nuclear pore; IDA:UniProtKB. DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB. DR GO; GO:0035457; P:cellular response to interferon-alpha; ISS:UniProtKB. DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB. DR GO; GO:0006406; P:mRNA export from nucleus; IBA:GO_Central. DR GO; GO:0031990; P:mRNA export from nucleus in response to heat stress; IDA:UniProtKB. DR GO; GO:0046832; P:negative regulation of RNA export from nucleus; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0045947; P:negative regulation of translational initiation; IMP:UniProtKB. DR GO; GO:0006999; P:nuclear pore organization; IMP:UniProtKB. DR GO; GO:0006913; P:nucleocytoplasmic transport; NAS:ComplexPortal. DR GO; GO:0031453; P:positive regulation of heterochromatin formation; IMP:UniProtKB. DR GO; GO:0090316; P:positive regulation of intracellular protein transport; IMP:UniProtKB. DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISS:UniProtKB. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; IMP:UniProtKB. DR GO; GO:0010965; P:regulation of mitotic sister chromatid separation; IMP:UniProtKB. DR GO; GO:1901673; P:regulation of mitotic spindle assembly; IMP:UniProtKB. DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB. DR GO; GO:0070849; P:response to epidermal growth factor; IDA:UniProtKB. DR GO; GO:0006405; P:RNA export from nucleus; IMP:UniProtKB. DR GO; GO:0006404; P:RNA import into nucleus; IDA:UniProtKB. DR Gene3D; 1.10.287.1490; -; 2. DR InterPro; IPR012929; TPR/MLP1. DR PANTHER; PTHR18898:SF2; NUCLEOPROTEIN TPR; 1. DR PANTHER; PTHR18898; NUCLEOPROTEIN TPR-RELATED; 1. DR Pfam; PF07926; TPR_MLP1_2; 1. DR Genevisible; P12270; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division; KW Centromere; Chromosomal rearrangement; Chromosome; Coiled coil; Cytoplasm; KW Cytoskeleton; Direct protein sequencing; Disease variant; KW Intellectual disability; Kinetochore; Membrane; Methylation; Mitosis; KW mRNA transport; Nuclear pore complex; Nucleus; Phosphoprotein; KW Protein transport; Proto-oncogene; Reference proteome; Translocation; KW Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..2363 FT /note="Nucleoprotein TPR" FT /id="PRO_0000204920" FT REGION 3..13 FT /note="Sufficient for interaction with TPR" FT REGION 14..117 FT /note="Necessary for interaction with HSF1" FT /evidence="ECO:0000269|PubMed:17897941" FT REGION 437..513 FT /note="Necessary for association to the NPC" FT REGION 912..935 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1218..1320 FT /note="Necessary for interaction with HSF1" FT /evidence="ECO:0000269|PubMed:17897941" FT REGION 1454..1474 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1619..1674 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1803..2134 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1812..1867 FT /note="Sufficient and essential for mediating its nuclear FT import" FT REGION 2227..2363 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 29..370 FT /evidence="ECO:0000255" FT COILED 423..602 FT /evidence="ECO:0000255" FT COILED 661..1173 FT /evidence="ECO:0000255" FT COILED 1215..1630 FT /evidence="ECO:0000255" FT COMPBIAS 912..927 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1619..1636 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1637..1674 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1803..1827 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1880..1898 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1905..1938 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1945..1985 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2000..2014 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2030..2068 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2071..2090 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2227..2260 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2296..2325 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 191 FT /note="Breakpoint for translocation to form TRK-T1" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 252 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 312 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 345 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 379 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 428 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 457 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 477 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 522 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 523 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 632 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 713 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 723 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 748 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 755 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1185 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1690 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 1692 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1893 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 2034 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2037 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2048 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2050 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 2073 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:21406692" FT MOD_RES 2106 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 2111 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 2116 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 2137 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2155 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17924679, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 2163 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 2343 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 2345 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT MOD_RES 2354 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:F6ZDS4" FT VAR_SEQ 726 FT /note="E -> L (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1549355" FT /id="VSP_057406" FT VAR_SEQ 727..2363 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1549355" FT /id="VSP_057407" FT VARIANT 960 FT /note="S -> N (in dbSNP:rs3753565)" FT /id="VAR_020429" FT VARIANT 1428 FT /note="V -> G (in dbSNP:rs35550453)" FT /id="VAR_047289" FT VARIANT 1707 FT /note="T -> A (in dbSNP:rs35766045)" FT /id="VAR_047290" FT VARIANT 2209..2363 FT /note="Missing (in MRT79; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:34494102" FT /id="VAR_088605" FT MUTAGEN 458 FT /note="L->P: Diminishes association to NPC but not FT homodimerization. Inhibits association to NPC, interaction FT with NUP153 and nuclear membrane localization but not FT homodimerization; when associated with P-489." FT /evidence="ECO:0000269|PubMed:11514627, FT ECO:0000269|PubMed:12802065" FT MUTAGEN 489 FT /note="M->P: Diminishes association to NPC but not FT homodimerization. Inhibits association to NPC, interaction FT with NUP153 and nuclear membrane localization but not FT homodimerization; when associated with P-458." FT /evidence="ECO:0000269|PubMed:11514627, FT ECO:0000269|PubMed:12802065" FT CONFLICT 32 FT /note="Q -> R (in Ref. 5; CAA44719 and 6; CAA68681)" FT /evidence="ECO:0000305" FT CONFLICT 779 FT /note="V -> I (in Ref. 4; AAB48030)" FT /evidence="ECO:0000305" FT CONFLICT 906 FT /note="Q -> R (in Ref. 4; AAB48030)" FT /evidence="ECO:0000305" FT CONFLICT 1239 FT /note="Q -> E (in Ref. 3; CAA47021)" FT /evidence="ECO:0000305" FT CONFLICT 1952..1965 FT /note="Missing (in Ref. 3; CAA47021)" FT /evidence="ECO:0000305" FT HELIX 5..8 FT /evidence="ECO:0007829|PDB:5TO5" FT HELIX 11..14 FT /evidence="ECO:0007829|PDB:5TO5" FT HELIX 19..140 FT /evidence="ECO:0007829|PDB:5TO5" SQ SEQUENCE 2363 AA; 267293 MW; 01E669CBDC496772 CRC64; MAAVLQQVLE RTELNKLPKS VQNKLEKFLA DQQSEIDGLK GRHEKFKVES EQQYFEIEKR LSHSQERLVN ETRECQSLRL ELEKLNNQLK ALTEKNKELE IAQDRNIAIQ SQFTRTKEEL EAEKRDLIRT NERLSQELEY LTEDVKRLNE KLKESNTTKG ELQLKLDELQ ASDVSVKYRE KRLEQEKELL HSQNTWLNTE LKTKTDELLA LGREKGNEIL ELKCNLENKK EEVSRLEEQM NGLKTSNEHL QKHVEDLLTK LKEAKEQQAS MEEKFHNELN AHIKLSNLYK SAADDSEAKS NELTRAVEEL HKLLKEAGEA NKAIQDHLLE VEQSKDQMEK EMLEKIGRLE KELENANDLL SATKRKGAIL SEEELAAMSP TAAAVAKIVK PGMKLTELYN AYVETQDQLL LEKLENKRIN KYLDEIVKEV EAKAPILKRQ REEYERAQKA VASLSVKLEQ AMKEIQRLQE DTDKANKQSS VLERDNRRME IQVKDLSQQI RVLLMELEEA RGNHVIRDEE VSSADISSSS EVISQHLVSY RNIEELQQQN QRLLVALREL GETREREEQE TTSSKITELQ LKLESALTEL EQLRKSRQHQ MQLVDSIVRQ RDMYRILLSQ TTGVAIPLHA SSLDDVSLAS TPKRPSTSQT VSTPAPVPVI ESTEAIEAKA ALKQLQEIFE NYKKEKAENE KIQNEQLEKL QEQVTDLRSQ NTKISTQLDF ASKRYEMLQD NVEGYRREIT SLHERNQKLT ATTQKQEQII NTMTQDLRGA NEKLAVAEVR AENLKKEKEM LKLSEVRLSQ QRESLLAEQR GQNLLLTNLQ TIQGILERSE TETKQRLSSQ IEKLEHEISH LKKKLENEVE QRHTLTRNLD VQLLDTKRQL DTETNLHLNT KELLKNAQKE IATLKQHLSN MEVQVASQSS QRTGKGQPSN KEDVDDLVSQ LRQTEEQVND LKERLKTSTS NVEQYQAMVT SLEESLNKEK QVTEEVRKNI EVRLKESAEF QTQLEKKLME VEKEKQELQD DKRRAIESME QQLSELKKTL SSVQNEVQEA LQRASTALSN EQQARRDCQE QAKIAVEAQN KYERELMLHA ADVEALQAAK EQVSKMASVR QHLEETTQKA ESQLLECKAS WEERERMLKD EVSKCVCRCE DLEKQNRLLH DQIEKLSDKV VASVKEGVQG PLNVSLSEEG KSQEQILEIL RFIRREKEIA ETRFEVAQVE SLRYRQRVEL LERELQELQD SLNAEREKVQ VTAKTMAQHE ELMKKTETMN VVMETNKMLR EEKERLEQDL QQMQAKVRKL ELDILPLQEA NAELSEKSGM LQAEKKLLEE DVKRWKARNQ HLVSQQKDPD TEEYRKLLSE KEVHTKRIQQ LTEEIGRLKA EIARSNASLT NNQNLIQSLK EDLNKVRTEK ETIQKDLDAK IIDIQEKVKT ITQVKKIGRR YKTQYEELKA QQDKVMETSA QSSGDHQEQH VSVQEMQELK ETLNQAETKS KSLESQVENL QKTLSEKETE ARNLQEQTVQ LQSELSRLRQ DLQDRTTQEE QLRQQITEKE EKTRKAIVAA KSKIAHLAGV KDQLTKENEE LKQRNGALDQ QKDELDVRIT ALKSQYEGRI SRLERELREH QERHLEQRDE PQEPSNKVPE QQRQITLKTT PASGERGIAS TSDPPTANIK PTPVVSTPSK VTAAAMAGNK STPRASIRPM VTPATVTNPT TTPTATVMPT TQVESQEAMQ SEGPVEHVPV FGSTSGSVRS TSPNVQPSIS QPILTVQQQT QATAFVQPTQ QSHPQIEPAN QELSSNIVEV VQSSPVERPS TSTAVFGTVS ATPSSSLPKR TREEEEDSTI EASDQVSDDT VEMPLPKKLK SVTPVGTEEE VMAEESTDGE VETQVYNQDS QDSIGEGVTQ GDYTPMEDSE ETSQSLQIDL GPLQSDQQTT TSSQDGQGKG DDVIVIDSDD EEEDDDENDG EHEDYEEDEE DDDDDEDDTG MGDEGEDSNE GTGSADGNDG YEADDAEGGD GTDPGTETEE SMGGGEGNHR AADSQNSGEG NTGAAESSFS QEVSREQQPS SASERQAPRA PQSPRRPPHP LPPRLTIHAP PQELGPPVQR IQMTRRQSVG RGLQLTPGIG GMQQHFFDDE DRTVPSTPTL VVPHRTDGFA EAIHSPQVAG VPRFRFGPPE DMPQTSSSHS DLGQLASQGG LGMYETPLFL AHEEESGGRS VPTTPLQVAA PVTVFTESTT SDASEHASQS VPMVTTSTGT LSTTNETATG DDGDEVFVEA ESEGISSEAG LEIDSQQEEE PVQASDESDL PSTSQDPPSS SSVDTSSSQP KPFRRVRLQT TLRQGVRGRQ FNRQRGVSHA MGGRGGINRG NIN //