Reviewed, UniProtKB/Swiss-Prot P12270 (TPR_HUMAN)

Names and origin

Protein names

Recommended name:
    Nucleoprotein TPR

Gene names

Name:

TPR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 cytoplasmic fibrils of the nuclear pore complex implicated in nuclear protein import. Its N-terminus is involved in activation of oncogenic kinases.
Subcellular location	Nucleus › nuclear pore complex. Nucleus membrane; Peripheral membrane protein; Cytoplasmic side. Note= The assembly of the NPC is a stepwise process in which Trp-containing peripheral structures assemble after other components, including p62.
Tissue specificity	Highest in testis, lung, thymus, spleen and brain, lower levels in heart, liver and kidney.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Chromosomal aberrations involving TPR are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. 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.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport mRNA transport
Cellular component	Membrane Nuclear pore complex Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	intracellular protein transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW protein import into nucleus Ref.2 Traceable author statement. Source: ProtInc seryl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Ref.2 Traceable author statement. Source: ProtInc nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear pore Ref.2 Traceable author statement. Source: ProtInc nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro serine-tRNA ligase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 2363	2362	Nucleoprotein TPR		PRO_0000204920
Regions
	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
	Modified residue	646	1	Phosphoserine
	Modified residue	920	1	Phosphoserine
	Modified residue	1185	1	Phosphoserine
	Modified residue	2034	1	Phosphoserine
	Modified residue	2037	1	Phosphoserine
	Modified residue	2050	1	Phosphoserine
	Modified residue	2073	1	Phosphoserine
	Modified residue	2155	1	Phosphoserine
Natural variations
	Natural variant	960	1	S → N: dbSNP rs3753565.		VAR_020429
	Natural variant	1428	1	V → G: dbSNP rs35550453.		VAR_047289
	Natural variant	1707	1	T → A: dbSNP rs35766045.		VAR_047290
Experimental info
	Sequence conflict	32	1	Q → R in CAA44719. Ref.5
	Sequence conflict	32	1	Q → R in CAA68681. Ref.6
	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)
	P12270-1 [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

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 1437155] [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: 7798308] [Abstract] Cited for: SEQUENCE REVISION, CHARACTERIZATION.
[3]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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: 1532241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-191, CHROMOSOMAL REARRANGEMENT WITH NTRK1.
[6]	"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: 3387099] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-142.
[7]	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.
[8]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2037, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2073 AND SER-2155, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"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: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1185, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"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: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2155, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-646; SER-1185 AND SER-2155, MASS SPECTROMETRY.
[13]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-920; SER-2034 AND SER-2050, MASS SPECTROMETRY.
[14]	"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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2155, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	X66397 mRNA. Translation: CAA47021.1. 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.
PIR	S23741.
RefSeq	NP_003283.2.
UniGene	Hs.279640
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P12270.
PTM databases
PhosphoSite	P12270.
Genome annotation databases
Ensembl	ENSG00000047410. Homo sapiens. [Contig view]
GeneID	7175.
KEGG	hsa:7175. son:SO_2140.
Organism-specific databases
H-InvDB	HIX0001427.
HGNC	HGNC:12017. TPR.
MIM	188550. phenotype. 189940. gene.
Orphanet	146. Thyroid carcinoma, papillary or follicular.
PharmGKB	PA36696.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P12270.
Enzyme and pathway databases
Reactome	REACT_6185. HIV Infection.
Gene expression databases
ArrayExpress	P12270.
CleanEx	HS_TPR.
GermOnline	ENSG00000047410. Homo sapiens.
Family and domain databases
InterPro	IPR015866. Ser-tRNA-synth_IIa_N. IPR012929. TPR_MLP1_2. [Graphical view]
Gene3D	G3DSA:1.10.287.40. Ser-tRNA-synth_IIa_N. 1 hit.
Pfam	PF07926. TPR_MLP1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	28128.
SOURCE	Search...

Entry information

Entry name

TPR_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 25, 2008
Last modified:	November 25, 2008
This is version 87 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)