P12270 (TPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nucleoprotein TPR

Alternative name(s):
Megator
NPC-associated intranuclear protein
Translocated promoter region protein

Gene names

Name:

TPR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2363 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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 (Ref.37 and Ref.13). 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. Ref.10 Ref.13 Ref.15 Ref.17 Ref.20 Ref.23 Ref.25 Ref.28 Ref.31 Ref.32 Ref.35 Ref.37
Subunit structure	Interacts with IFI204 (via C-terminus region). Interacts with IFI203 By similarity. Homodimer. Part of the nuclear pore complex (NPC). Associates with the XPO1/CRM1-mediated nuclear export complex, the Importin alpha/Importin beta receptor and the dynein 1 complex. Interacts (via C-terminus domain) with the KPNB1; the interaction occurs in a RanGTP-dependent manner. Interacts (via C-terminus region and phosphorylated form) with MAPK1/ERK2 (via phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation. Interacts with MAPK3/ERK1; the interaction increases following EGF stimulation. Interacts (via coiled coil region) with NUP153; the interaction is direct. Interacts with HSF1; the interaction increases in a stress-responsive manner and stimulates export of stress-induced HSP70 mRNA. Interacts with huntingtin/HTT; the interaction is inhibited by aggregated huntingtin/HTT forms with expanded polyglutamine stretch. Interacts with MAD1L1 (via N-terminus region), MAD2L1, and TTK; the interactions occurs in a microtubule-independent manner. Interacts (via middle region) with DYNLL1. Interacts with DCTN1, dynein, NUP153 and tubulin. Ref.11 Ref.15 Ref.16 Ref.17 Ref.20 Ref.23 Ref.25 Ref.27 Ref.28 Ref.32 Ref.37
Subcellular location	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 (Ref.2). 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 (Ref.23). Colocalizes with MAD2L1 in the spindle matrix but not at kinetochore (Ref.28). Colocalizes with dynein, dynactin, tubulin at kinetochore during the metaphase-anaphase transition. Colocalizes with DYNLL1 at the mitotic spindle. Ref.3 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.23 Ref.25 Ref.28 Ref.31 Ref.32 Ref.37
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. Ref.3 Ref.12
Domain	The N-terminus domain mediates intranuclear attachment to the nuclear pore complex. The C-terminus domain mediates its nuclear import. Ref.9 Ref.10
Post-translational modification	Phosphorylated. Phosphorylation occurs on serine and threonine residues (comprised in the C-terminus region) by MAPK1/ERK2 and stabilizes the interaction between these two proteins. Ref.25 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.
Involvement in disease	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. Involved in tumorigenic rearrangements with the MET or RAF genes.
Sequence similarities	Belongs to the TPR family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Protein transport Translocation Transport mRNA transport
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Membrane Nuclear pore complex Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MAPK import into nucleus Inferred from mutant phenotype Ref.25. Source: UniProtKB RNA import into nucleus Inferred from direct assay Ref.10. Source: UniProtKB carbohydrate metabolic process Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW cellular response to interferon-alpha Inferred from sequence or structural similarity. Source: UniProtKB cytokine-mediated signaling pathway Traceable author statement. Source: Reactome glucose transport Traceable author statement. Source: Reactome mRNA export from nucleus in response to heat stress Inferred from direct assay Ref.20. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle assembly checkpoint Inferred from mutant phenotype Ref.23Ref.32. Source: UniProtKB negative regulation of RNA export from nucleus Inferred from direct assay Ref.37. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.35. Source: UniProtKB negative regulation of translational initiation Inferred from mutant phenotype Ref.35. Source: UniProtKB nuclear pore organization Inferred from mutant phenotype Ref.16. Source: UniProtKB positive regulation of heterochromatin assembly Inferred from mutant phenotype Ref.31. Source: UniProtKB positive regulation of mitotic cell cycle spindle assembly checkpoint Inferred from mutant phenotype Ref.28. Source: UniProtKB positive regulation of protein export from nucleus Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein import into nucleus Inferred from mutant phenotype Ref.25. Source: UniProtKB regulation of glucose transport Traceable author statement. Source: Reactome regulation of mitotic sister chromatid separation Inferred from mutant phenotype Ref.32. Source: UniProtKB regulation of spindle assembly involved in mitosis Inferred from mutant phenotype Ref.28. Source: UniProtKB response to epidermal growth factor stimulus Inferred from direct assay Ref.25. Source: UniProtKB seryl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome viral reproductive process Traceable author statement. Source: Reactome
Cellular_component	cytoplasmic dynein complex Inferred from direct assay Ref.32. Source: UniProtKB extrinsic to membrane Inferred from direct assay Ref.15. Source: UniProtKB kinetochore Inferred from direct assay Ref.32. Source: UniProtKB mitotic spindle Inferred from direct assay Ref.32. Source: UniProtKB nuclear inclusion body Inferred from direct assay Ref.11Ref.14. Source: UniProtKB nuclear membrane Inferred from direct assay Ref.11Ref.14Ref.13Ref.15Ref.16Ref.25Ref.31Ref.37Ref.3Ref.9Ref.10. Source: UniProtKB nuclear periphery Inferred from direct assay Ref.11Ref.14Ref.13Ref.16PubMed 22401879Ref.3. Source: UniProtKB nuclear pore nuclear basket Inferred from direct assay Ref.14Ref.16Ref.3. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro chromatin binding Inferred from direct assay Ref.20. Source: UniProtKB dynein complex binding Inferred from direct assay Ref.32. Source: UniProtKB heat shock protein binding Inferred from direct assay Ref.20. Source: UniProtKB mRNA binding Inferred from direct assay Ref.20. Source: UniProtKB mitogen-activated protein kinase binding Inferred from direct assay Ref.25. Source: UniProtKB nucleocytoplasmic transporter activity Inferred from direct assay Ref.37. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.11Ref.15. Source: UniProtKB serine-tRNA ligase activity Inferred from electronic annotation. Source: InterPro tubulin binding Inferred from direct assay Ref.32. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 2363	2362	Nucleoprotein TPR		PRO_0000204920
Regions
	Region	3 – 13	11	Sufficient for interaction with TPR
	Region	14 – 117	104	Necessary for interaction with HSF1
	Region	437 – 513	77	Necessary for association to the NPC
	Region	1218 – 1320	103	Necessary for interaction with HSF1
	Region	1812 – 1867	56	Sufficient and essential for mediating its nuclear import
	Coiled coil	29 – 370	342	Potential
	Coiled coil	423 – 602	180	Potential
	Coiled coil	661 – 1173	513	Potential
	Coiled coil	1215 – 1630	416	Potential
	Compositional bias	527 – 530	4	Poly-Ser
	Compositional bias	1833 – 1836	4	Poly-Glu
	Compositional bias	1971 – 1978	8	Poly-Asp
	Compositional bias	2309 – 2312	4	Poly-Ser
Sites
	Site	191	1	Breakpoint for translocation to form TRK-T1
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.8
	Modified residue	252	1	N6-acetyllysine Ref.30
	Modified residue	312	1	N6-acetyllysine Ref.30
	Modified residue	345	1	N6-acetyllysine Ref.30
	Modified residue	379	1	Phosphoserine Ref.26 Ref.33
	Modified residue	428	1	N6-acetyllysine Ref.30
	Modified residue	457	1	N6-acetyllysine Ref.30
	Modified residue	713	1	N6-acetyllysine Ref.30
	Modified residue	723	1	N6-acetyllysine Ref.30
	Modified residue	748	1	N6-acetyllysine Ref.30
	Modified residue	755	1	N6-acetyllysine Ref.30
	Modified residue	1185	1	Phosphoserine Ref.19 Ref.26 Ref.29 Ref.33 Ref.36
	Modified residue	1692	1	Phosphothreonine Ref.33
	Modified residue	2048	1	Phosphoserine Ref.26
	Modified residue	2050	1	Phosphoserine Ref.22 Ref.29
	Modified residue	2073	1	Phosphoserine Ref.18 Ref.33 Ref.36
	Modified residue	2155	1	Phosphoserine Ref.21 Ref.24 Ref.26 Ref.29 Ref.33
Natural variations
	Natural variant	960	1	S → N. Corresponds to variant rs3753565 [ dbSNP | Ensembl ].		VAR_020429
	Natural variant	1428	1	V → G. Corresponds to variant rs35550453 [ dbSNP | Ensembl ].		VAR_047289
	Natural variant	1707	1	T → A. Corresponds to variant rs35766045 [ dbSNP | Ensembl ].		VAR_047290
Experimental info
	Mutagenesis	458	1	L → P: Diminishes association to NPC but not homodimerization. Inhibits association to NPC, interaction with NUP153 and nuclear membrane localization but not homodimerization; when associated with P-489. Ref.11 Ref.15
	Mutagenesis	489	1	M → P: Diminishes association to NPC but not homodimerization. Inhibits association to NPC, interaction with NUP153 and nuclear membrane localization but not homodimerization; when associated with P-458. Ref.11 Ref.15
	Sequence conflict	32	1	Q → R in CAA44719. Ref.5
	Sequence conflict	32	1	Q → R in CAA68681. Ref.6
	Sequence conflict	779	1	V → I in AAB48030. Ref.3
	Sequence conflict	906	1	Q → R in AAB48030. Ref.3
	Sequence conflict	1239	1	Q → E in CAA47021. Ref.2
	Sequence conflict	1952 – 1965	14	Missing in CAA47021. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P12270 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 01E669CBDC496772	FASTA	2,363	267,293
	10 20 30 40 50 60 MAAVLQQVLE RTELNKLPKS VQNKLEKFLA DQQSEIDGLK GRHEKFKVES EQQYFEIEKR 70 80 90 100 110 120 LSHSQERLVN ETRECQSLRL ELEKLNNQLK ALTEKNKELE IAQDRNIAIQ SQFTRTKEEL 130 140 150 160 170 180 EAEKRDLIRT NERLSQELEY LTEDVKRLNE KLKESNTTKG ELQLKLDELQ ASDVSVKYRE 190 200 210 220 230 240 KRLEQEKELL HSQNTWLNTE LKTKTDELLA LGREKGNEIL ELKCNLENKK EEVSRLEEQM 250 260 270 280 290 300 NGLKTSNEHL QKHVEDLLTK LKEAKEQQAS MEEKFHNELN AHIKLSNLYK SAADDSEAKS 310 320 330 340 350 360 NELTRAVEEL HKLLKEAGEA NKAIQDHLLE VEQSKDQMEK EMLEKIGRLE KELENANDLL 370 380 390 400 410 420 SATKRKGAIL SEEELAAMSP TAAAVAKIVK PGMKLTELYN AYVETQDQLL LEKLENKRIN 430 440 450 460 470 480 KYLDEIVKEV EAKAPILKRQ REEYERAQKA VASLSVKLEQ AMKEIQRLQE DTDKANKQSS 490 500 510 520 530 540 VLERDNRRME IQVKDLSQQI RVLLMELEEA RGNHVIRDEE VSSADISSSS EVISQHLVSY 550 560 570 580 590 600 RNIEELQQQN QRLLVALREL GETREREEQE TTSSKITELQ LKLESALTEL EQLRKSRQHQ 610 620 630 640 650 660 MQLVDSIVRQ RDMYRILLSQ TTGVAIPLHA SSLDDVSLAS TPKRPSTSQT VSTPAPVPVI 670 680 690 700 710 720 ESTEAIEAKA ALKQLQEIFE NYKKEKAENE KIQNEQLEKL QEQVTDLRSQ NTKISTQLDF 730 740 750 760 770 780 ASKRYEMLQD NVEGYRREIT SLHERNQKLT ATTQKQEQII NTMTQDLRGA NEKLAVAEVR 790 800 810 820 830 840 AENLKKEKEM LKLSEVRLSQ QRESLLAEQR GQNLLLTNLQ TIQGILERSE TETKQRLSSQ 850 860 870 880 890 900 IEKLEHEISH LKKKLENEVE QRHTLTRNLD VQLLDTKRQL DTETNLHLNT KELLKNAQKE 910 920 930 940 950 960 IATLKQHLSN MEVQVASQSS QRTGKGQPSN KEDVDDLVSQ LRQTEEQVND LKERLKTSTS 970 980 990 1000 1010 1020 NVEQYQAMVT SLEESLNKEK QVTEEVRKNI EVRLKESAEF QTQLEKKLME VEKEKQELQD 1030 1040 1050 1060 1070 1080 DKRRAIESME QQLSELKKTL SSVQNEVQEA LQRASTALSN EQQARRDCQE QAKIAVEAQN 1090 1100 1110 1120 1130 1140 KYERELMLHA ADVEALQAAK EQVSKMASVR QHLEETTQKA ESQLLECKAS WEERERMLKD 1150 1160 1170 1180 1190 1200 EVSKCVCRCE DLEKQNRLLH DQIEKLSDKV VASVKEGVQG PLNVSLSEEG KSQEQILEIL 1210 1220 1230 1240 1250 1260 RFIRREKEIA ETRFEVAQVE SLRYRQRVEL LERELQELQD SLNAEREKVQ VTAKTMAQHE 1270 1280 1290 1300 1310 1320 ELMKKTETMN VVMETNKMLR EEKERLEQDL QQMQAKVRKL ELDILPLQEA NAELSEKSGM 1330 1340 1350 1360 1370 1380 LQAEKKLLEE DVKRWKARNQ HLVSQQKDPD TEEYRKLLSE KEVHTKRIQQ LTEEIGRLKA 1390 1400 1410 1420 1430 1440 EIARSNASLT NNQNLIQSLK EDLNKVRTEK ETIQKDLDAK IIDIQEKVKT ITQVKKIGRR 1450 1460 1470 1480 1490 1500 YKTQYEELKA QQDKVMETSA QSSGDHQEQH VSVQEMQELK ETLNQAETKS KSLESQVENL 1510 1520 1530 1540 1550 1560 QKTLSEKETE ARNLQEQTVQ LQSELSRLRQ DLQDRTTQEE QLRQQITEKE EKTRKAIVAA 1570 1580 1590 1600 1610 1620 KSKIAHLAGV KDQLTKENEE LKQRNGALDQ QKDELDVRIT ALKSQYEGRI SRLERELREH 1630 1640 1650 1660 1670 1680 QERHLEQRDE PQEPSNKVPE QQRQITLKTT PASGERGIAS TSDPPTANIK PTPVVSTPSK 1690 1700 1710 1720 1730 1740 VTAAAMAGNK STPRASIRPM VTPATVTNPT TTPTATVMPT TQVESQEAMQ SEGPVEHVPV 1750 1760 1770 1780 1790 1800 FGSTSGSVRS TSPNVQPSIS QPILTVQQQT QATAFVQPTQ QSHPQIEPAN QELSSNIVEV 1810 1820 1830 1840 1850 1860 VQSSPVERPS TSTAVFGTVS ATPSSSLPKR TREEEEDSTI EASDQVSDDT VEMPLPKKLK 1870 1880 1890 1900 1910 1920 SVTPVGTEEE VMAEESTDGE VETQVYNQDS QDSIGEGVTQ GDYTPMEDSE ETSQSLQIDL 1930 1940 1950 1960 1970 1980 GPLQSDQQTT TSSQDGQGKG DDVIVIDSDD EEEDDDENDG EHEDYEEDEE DDDDDEDDTG 1990 2000 2010 2020 2030 2040 MGDEGEDSNE GTGSADGNDG YEADDAEGGD GTDPGTETEE SMGGGEGNHR AADSQNSGEG 2050 2060 2070 2080 2090 2100 NTGAAESSFS QEVSREQQPS SASERQAPRA PQSPRRPPHP LPPRLTIHAP PQELGPPVQR 2110 2120 2130 2140 2150 2160 IQMTRRQSVG RGLQLTPGIG GMQQHFFDDE DRTVPSTPTL VVPHRTDGFA EAIHSPQVAG 2170 2180 2190 2200 2210 2220 VPRFRFGPPE DMPQTSSSHS DLGQLASQGG LGMYETPLFL AHEEESGGRS VPTTPLQVAA 2230 2240 2250 2260 2270 2280 PVTVFTESTT SDASEHASQS VPMVTTSTGT LSTTNETATG DDGDEVFVEA ESEGISSEAG 2290 2300 2310 2320 2330 2340 LEIDSQQEEE PVQASDESDL PSTSQDPPSS SSVDTSSSQP KPFRRVRLQT TLRQGVRGRQ 2350 2360 FNRQRGVSHA MGGRGGINRG NIN

References

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[1]	"The human tpr gene encodes a protein of 2094 amino acids that has extensive coiled-coil regions and an acidic C-terminal domain." Mitchell P.J., Cooper C.S. Oncogene 7:2329-2333(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Tpr, a large coiled coil protein whose amino terminus is involved in activation of oncogenic kinases, is localized to the cytoplasmic surface of the nuclear pore complex." Byrd D.A., Sweet D.J., Pante N., Konstantinov K.N., Guan T., Saphire A.C.S., Mitchell P.J., Cooper C.S., Aebi U., Gerace L. J. Cell Biol. 127:1515-1526(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION, CHARACTERIZATION.
[3]	"Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments." Cordes V.C., Reidenbach S., Rackwitz H.R., Franke W.W. J. Cell Biol. 136:515-529(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Embryonic brain.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in human papillary thyroid carcinomas." Greco A., Pierotti M.A., Bongarzone I., Pagliardini S., Lanzi C., Della Porta G. Oncogene 7:237-242(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-191, CHROMOSOMAL REARRANGEMENT WITH NTRK1.
[7]	"tpr homologues activate met and raf." King H.W.S., Tempest P.R., Merrifield K.R., Rance A.J. Oncogene 2:617-619(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-142.
[8]	Bienvenut W.V., Glen H., Brunton V.G., Frame M.C., Boldt K., von Kriegsheim A.F., Kolch W. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11; 502-511; 1192-1201 AND 1421-1427, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Hepatoma and Osteosarcoma.
[9]	"Molecular segments of protein Tpr that confer nuclear targeting and association with the nuclear pore complex." Cordes V.C., Hase M.E., Muller L. Exp. Cell Res. 245:43-56(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, NPC-BINDING DOMAIN AND NUCLEAR IMPORT DOMAIN.
[10]	"Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export." Bangs P., Burke B., Powers C., Craig R., Purohit A., Doxsey S. J. Cell Biol. 143:1801-1812(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, NPC-BINDING DOMAIN AND NUCLEAR IMPORT DOMAIN, SUBCELLULAR LOCATION.
[11]	"Amino acid substitutions of coiled-coil protein Tpr abrogate anchorage to the nuclear pore complex but not parallel, in-register homodimerization." Hase M.E., Kuznetsov N.V., Cordes V.C. Mol. Biol. Cell 12:2433-2452(2001) [PubMed] [Europe PMC] [Abstract] Cited for: HOMODIMERIZATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-458 AND MET-489.
[12]	"The evolutionarily conserved single-copy gene for murine Tpr encodes one prevalent isoform in somatic cells and lacks paralogs in higher eukaryotes." Kuznetsov N.V., Sandblad L., Hase M.E., Hunziker A., Hergt M., Cordes V.C. Chromosoma 111:236-255(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[13]	"Nucleocytoplasmic transport of proteins and poly(A)+ RNA in reconstituted Tpr-less nuclei in living mammalian cells." Shibata S., Matsuoka Y., Yoneda Y. Genes Cells 7:421-434(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]	"Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export." Frosst P., Guan T., Subauste C., Hahn K., Gerace L. J. Cell Biol. 156:617-630(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[15]	"Direct interaction with nup153 mediates binding of Tpr to the periphery of the nuclear pore complex." Hase M.E., Cordes V.C. Mol. Biol. Cell 14:1923-1940(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ABSENCE OF FUNCTION IN ANCHORING NUCLEOPORINS, INTERACTION WITH NUP153, HOMODIMERIZATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-458 AND MET-489.
[16]	"Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket." Krull S., Thyberg J., Bjorkroth B., Rackwitz H.R., Cordes V.C. Mol. Biol. Cell 15:4261-4277(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN THE NUCLEAR PORE COMPLEX.
[17]	"Polyglutamine expansion of huntingtin impairs its nuclear export." Cornett J., Cao F., Wang C.E., Ross C.A., Bates G.P., Li S.H., Li X.J. Nat. Genet. 37:198-204(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NUCLEAR PROTEIN EXPORT, INTERACTION WITH HTT.
[18]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2073, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA." Skaggs H.S., Xing H., Wilkerson D.C., Murphy L.A., Hong Y., Mayhew C.N., Sarge K.D. J. Biol. Chem. 282:33902-33907(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN STRESS-INDUCED NUCLEAR MRNA EXPORT, INTERACTION WITH HSF1.
[21]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2155, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2050, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[23]	"Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint." Lee S.H., Sterling H., Burlingame A., McCormick F. Genes Dev. 22:2926-2931(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAD2L1 AND MAD1L1, FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[24]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2155, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction." Vomastek T., Iwanicki M.P., Burack W.R., Tiwari D., Kumar D., Parsons J.T., Weber M.J., Nandicoori V.K. Mol. Cell. Biol. 28:6954-6966(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PROTEIN IMPORT, INTERACTION WITH MAPK1, PHOSPHORYLATION BY MAPK1, SUBCELLULAR LOCATION.
[26]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-1185; SER-2048 AND SER-2155, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Karyopherin binding interactions and nuclear import mechanism of nuclear pore complex protein Tpr." Ben-Efraim I., Frosst P.D., Gerace L. BMC Cell Biol. 10:74-74(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH XPO1/CRM1 AND IMPORTIN ALPHA/IMPORTIN BETA RECEPTOR, INTERACTION WITH KPNB1.
[28]	"Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator." Lince-Faria M., Maffini S., Orr B., Ding Y., Florindo C., Sunkel C.E., Tavares A., Johansen J., Johansen K.M., Maiato H. J. Cell Biol. 184:647-657(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAD1L1; MAD2L1 AND TTK, SUBCELLULAR LOCATION.
[29]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185; SER-2050 AND SER-2155, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[30]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-252; LYS-312; LYS-345; LYS-428; LYS-457; LYS-713; LYS-723; LYS-748 AND LYS-755, MASS SPECTROMETRY.
[31]	"Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion." Krull S., Dorries J., Boysen B., Reidenbach S., Magnius L., Norder H., Thyberg J., Cordes V.C. EMBO J. 29:1659-1673(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ORGANIZATION OF PERINUCLEAR CHROMATIN, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[32]	"Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis." Nakano H., Funasaka T., Hashizume C., Wong R.W. J. Biol. Chem. 285:10841-10849(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DCTN1; DYNEIN; DYNLL1; MAD2L1; NUP153 AND TUBULIN, SUBCELLULAR LOCATION.
[33]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-1185; THR-1692; SER-2073 AND SER-2155, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[34]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]	"The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway." Coyle J.H., Bor Y.C., Rekosh D., Hammarskjold M.L. RNA 17:1344-1356(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UNSPLICED RNA EXPORT.
[36]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185 AND SER-2073, MASS SPECTROMETRY.
[37]	"Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA." Rajanala K., Nandicoori V.K. PLoS ONE 7:E29921-E29921(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UNSPLICED RNA EXPORT, INTERACTION WITH MAPK1, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	X66397 mRNA. Translation: CAA47021.1. U69668 mRNA. Translation: AAB48030.1. AL596220, AL133553 Genomic DNA. Translation: CAI13119.1. AL133553, AL596220 Genomic DNA. Translation: CAI17859.1. CH471067 Genomic DNA. Translation: EAW91205.1. X62947 mRNA. Translation: CAA44719.1. Different termination. Y00672 mRNA. Translation: CAA68681.1.
IPI	IPI00742682.
PIR	S23741.
RefSeq	NP_003283.2. NM_003292.2.
UniGene	Hs.279640.
3D structure databases
ProteinModelPortal	P12270.
ModBase	Search...
Protein-protein interaction databases
IntAct	P12270. 8 interactions.
MINT	MINT-4993169.
STRING	9606.ENSP00000356448.
PTM databases
PhosphoSite	P12270.
Polymorphism databases
DMDM	215274208.
Proteomic databases
PaxDb	P12270.
PRIDE	P12270.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367478; ENSP00000356448; ENSG00000047410.
GeneID	7175.
KEGG	hsa:7175.
UCSC	uc001grv.3. human.
Organism-specific databases
CTD	7175.
GeneCards	GC01M186281.
HGNC	HGNC:12017. TPR.
HPA	HPA019661. HPA019663. HPA024336.
MIM	188550. phenotype. 189940. gene.
neXtProt	NX_P12270.
Orphanet	146. Papillary or follicular thyroid carcinoma.
PharmGKB	PA36696.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG12793.
HOGENOM	HOG000139431.
HOVERGEN	HBG009158.
InParanoid	P12270.
KO	K09291.
OMA	RFIRREK.
OrthoDB	EOG42RD6D.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_116125. Disease. REACT_15518. Transmembrane transport of small molecules. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P12270.
Bgee	P12270.
CleanEx	HS_TPR.
Genevestigator	P12270.
GermOnline	ENSG00000047410. Homo sapiens.
Family and domain databases
Gene3D	1.10.287.40. 1 hit.
InterPro	IPR009053. Prefoldin. IPR015866. Ser-tRNA-synth_1_N. IPR012929. TPR_MLP1_2. [Graphical view]
Pfam	PF07926. TPR_MLP1_2. 1 hit. [Graphical view]
SUPFAM	SSF46579. Prefoldin. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	7175.
NextBio	18907.
PMAP-CutDB	P12270.
SOURCE	Search...

Entry information

Entry name

TPR_HUMAN

Accession

Primary (citable) accession number: P12270
Secondary accession number(s): Q15655, Q5SWY0, Q99968

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 25, 2008
Last modified:	May 29, 2013
This is version 135 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.