Reviewed,
UniProtKB/Swiss-Prot P12270 (TPR_HUMAN)
Last modified
November 25, 2008.
Version 87.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Nucleoprotein TPR | ||
| Gene names |
| ||
| 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
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
| ||||||||||||||||||
References
| « Hide '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. 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. 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. |
Cross-references
Sequence databases | |
|---|---|
| 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 |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |

Clusters with