Tumor protein p73

Details

Name
Tumor protein p73
Kind
protein
Synonyms
  • p53-like transcription factor
  • p53-related protein
  • P73
Gene Name
TP73
UniProtKB Entry
O15350Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0049702|Tumor protein p73
MAQSTATSPDGGTTFEHLWSSLEPDSTYFDLPQSSRGNNEVVGGTDSSMDVFHLEGMTTS
VMAQFNLLSSTMDQMSSRAASASPYTPEHAASVPTHSPYAQPSSTFDTMSPAPVIPSNTD
YPGPHHFEVTFQQSSTAKSATWTYSPLLKKLYCQIAKTCPIQIKVSTPPPPGTAIRAMPV
YKKAEHVTDVVKRCPNHELGRDFNEGQSAPASHLIRVEGNNLSQYVDDPVTGRQSVVVPY
EPPQVGTEFTTILYNFMCNSSCVGGMNRRPILIIITLEMRDGQVLGRRSFEGRICACPGR
DRKADEDHYREQQALNESSAKNGAASKRAFKQSPPAVPALGAGVKKRRHGDEDTYYLQVR
GRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQRPSHLQPPSYGPVLSPMNKVHGG
MNKLPSVNQLVGQPPPHSSAATPNLGPVGPGMLNNHGHAVPANGEMSSSHSAQSMVSGSH
CTPPPPYHADPSLVSFLTGLGCPNCIEYFTSQGLQSIYHLQNLTIEDLGALKIPEQYRMT
IWRGLQDLKQGHDYSTAQQLLRSSNAATISIGGSGELQRQRVMEAVHFRVRHTITIPNRG
GPGGGPDEWADFGFDLPDCKARKQPIKEEFTEAEIH
Number of residues
636
Molecular Weight
69622.865
Theoretical pI
Not Available
GO Classification
Functions
DNA-binding transcription activator activity, RNA polymerase II-specific / DNA-binding transcription factor activity / DNA-binding transcription factor activity, RNA polymerase II-specific / DNA-binding transcription factor binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / transcription cis-regulatory region binding / transcription corepressor binding
Processes
DNA damage response / negative regulation of cell population proliferation / positive regulation of apoptotic process / positive regulation of DNA-templated transcription / positive regulation of lung ciliated cell differentiation / positive regulation of MAPK cascade / positive regulation of transcription by RNA polymerase II / regulation of cell cycle / regulation of transcription by RNA polymerase II / response to xenobiotic stimulus
General Function
Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression (By similarity). It is an essential factor for the positive regulation of lung ciliated cell differentiation (PubMed:34077761)
Specific Function
Dna-binding transcription activator activity, rna polymerase ii-specific
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0049703|Tumor protein p73 (TP73)
ATGGCCCAGTCCACCGCCACCTCCCCTGATGGGGGCACCACGTTTGAGCACCTCTGGAGC
TCTCTGGAACCAGACAGCACCTACTTCGACCTTCCCCAGTCAAGCCGGGGGAATAATGAG
GTGGTGGGCGGAACGGATTCCAGCATGGACGTCTTCCACCTGGAGGGCATGACTACATCT
GTCATGGCCCAGTTCAATCTGCTGAGCAGCACCATGGACCAGATGAGCAGCCGCGCGGCC
TCGGCCAGCCCCTACACCCCAGAGCACGCCGCCAGCGTGCCCACCCACTCGCCCTACGCA
CAACCCAGCTCCACCTTCGACACCATGTCGCCGGCGCCTGTCATCCCCTCCAACACCGAC
TACCCCGGACCCCACCACTTTGAGGTCACTTTCCAGCAGTCCAGCACGGCCAAGTCAGCC
ACCTGGACGTACTCCCCGCTCTTGAAGAAACTCTACTGCCAGATCGCCAAGACATGCCCC
ATCCAGATCAAGGTGTCCACCCCGCCACCCCCAGGCACCGCCATCCGGGCCATGCCTGTT
TACAAGAAAGCGGAGCACGTGACCGACGTCGTGAAACGCTGCCCCAACCACGAGCTCGGG
AGGGACTTCAACGAAGGACAGTCTGCTCCAGCCAGCCACCTCATCCGCGTGGAAGGCAAT
AATCTCTCGCAGTATGTGGATGACCCTGTCACCGGCAGGCAGAGCGTCGTGGTGCCCTAT
GAGCCACCACAGGTGGGGACGGAATTCACCACCATCCTGTACAACTTCATGTGTAACAGC
AGCTGTGTAGGGGGCATGAACCGGCGGCCCATCCTCATCATCATCACCCTGGAGATGCGG
GATGGGCAGGTGCTGGGCCGCCGGTCCTTTGAGGGCCGCATCTGCGCCTGTCCTGGCCGC
GACCGAAAAGCTGATGAGGACCACTACCGGGAGCAGCAGGCCCTGAACGAGAGCTCCGCC
AAGAACGGGGCCGCCAGCAAGCGTGCCTTCAAGCAGAGCCCCCCTGCCGTCCCCGCCCTT
GGTGCCGGTGTGAAGAAGCGGCGGCATGGAGACGAGGACACGTACTACCTTCAGGTGCGA
GGCCGGGAGAACTTTGAGATCCTGATGAAGCTGAAAGAGAGCCTGGAGCTGATGGAGTTG
GTGCCGCAGCCACTGGTGGACTCCTATCGGCAGCAGCAGCAGCTCCTACAGAGGCCGAGT
CACCTACAGCCCCCGTCCTACGGGCCGGTCCTCTCGCCCATGAACAAGGTGCACGGGGGC
ATGAACAAGCTGCCCTCCGTCAACCAGCTGGTGGGCCAGCCTCCCCCGCACAGTTCGGCA
GCTACACCCAACCTGGGGCCCGTGGGCCCCGGGATGCTCAACAACCATGGCCACGCAGTG
CCAGCCAACGGCGAGATGAGCAGCAGCCACAGCGCCCAGTCCATGGTCTCGGGGTCCCAC
TGCACTCCGCCACCCCCCTACCACGCCGACCCCAGCCTCGTCAGTTTTTTAACAGGATTG
GGGTGTCCAAACTGCATCGAGTATTTCACCTCCCAAGGGTTACAGAGCATTTACCACCTG
CAGAACCTGACCATTGAGGACCTGGGGGCCCTGAAGATCCCCGAGCAGTACCGCATGACC
ATCTGGCGGGGCCTGCAGGACCTGAAGCAGGGCCACGACTACAGCACCGCGCAGCAGCTG
CTCCGCTCTAGCAACGCGGCCACCATCTCCATCGGCGGCTCAGGGGAACTGCAGCGCCAG
CGGGTCATGGAGGCCGTGCACTTCCGCGTGCGCCACACCATCACCATCCCCAACCGCGGC
GGCCCAGGCGGCGGCCCTGACGAGTGGGCGGACTTCGGCTTCGACCTGCCCGACTGCAAG
GCCCGCAAGCAGCCCATCAAGGAGGAGTTCACGGAGGCCGAGATCCACTGA
Chromosome Location
1
Locus
1p36.32
External Identifiers
ResourceLink
UniProtKB IDO15350
UniProtKB Entry NameP73_HUMAN
GeneCard IDTP73
HGNC IDHGNC:12003
PDB ID(s)1COK, 1DXS, 2KBY, 2MPS, 2NB1, 2WQI, 2WQJ, 2WTT, 2XWC, 3VD0, 3VD1, 3VD2, 4A63, 4G82, 4G83, 4GUO, 4GUQ, 5HOB, 5HOC, 5KBD, 6FGS, 6IJQ, 7EZJ, 8P9C, 8P9D, 8P9E
KEGG IDhsa:7161
NCBI Gene ID7161
General References
  1. Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D: Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997 Aug 22;90(4):809-19. [Article]
  2. Mai M, Huang H, Reed C, Qian C, Smith JS, Alderete B, Jenkins R, Smith DI, Liu W: Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. Genomics. 1998 Aug 1;51(3):359-63. [Article]
  3. De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M, Levrero M, Melino G: Two new p73 splice variants, gamma and delta, with different transcriptional activity. J Exp Med. 1998 Nov 2;188(9):1763-8. [Article]
  4. De Laurenzi VD, Catani MV, Terrinoni A, Corazzari M, Melino G, Costanzo A, Levrero M, Knight RA: Additional complexity in p73: induction by mitogens in lymphoid cells and identification of two new splicing variants epsilon and zeta. Cell Death Differ. 1999 May;6(5):389-90. [Article]
  5. Yoshikawa H, Nagashima M, Khan MA, McMenamin MG, Hagiwara K, Harris CC: Mutational analysis of p73 and p53 in human cancer cell lines. Oncogene. 1999 Jun 3;18(22):3415-21. [Article]
  6. Grob TJ, Novak U, Maisse C, Barcaroli D, Luthi AU, Pirnia F, Hugli B, Graber HU, De Laurenzi V, Fey MF, Melino G, Tobler A: Human delta Np73 regulates a dominant negative feedback loop for TAp73 and p53. Cell Death Differ. 2001 Dec;8(12):1213-23. [Article]
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  10. Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, Lu H, Kharbanda S, Weichselbaum R, Kufe D: p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage. Nature. 1999 Jun 24;399(6738):814-7. [Article]
  11. Kaelin WG Jr: The emerging p53 gene family. J Natl Cancer Inst. 1999 Apr 7;91(7):594-8. [Article]
  12. Minty A, Dumont X, Kaghad M, Caput D: Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif. J Biol Chem. 2000 Nov 17;275(46):36316-23. [Article]
  13. Tsuji K, Mizumoto K, Yamochi T, Nishimoto I, Matsuoka M: Differential effect of ik3-1/cables on p53- and p73-induced cell death. J Biol Chem. 2002 Jan 25;277(4):2951-7. Epub 2001 Nov 12. [Article]
  14. Kim EJ, Park JS, Um SJ: Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo. J Biol Chem. 2002 Aug 30;277(35):32020-8. Epub 2002 Mar 29. [Article]
  15. Miyazaki K, Ozaki T, Kato C, Hanamoto T, Fujita T, Irino S, Watanabe K, Nakagawa T, Nakagawara A: A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity. Biochem Biophys Res Commun. 2003 Aug 15;308(1):106-13. [Article]
  16. Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, Trapasso F, Han SY, Melino G, Huebner K, Croce CM: Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4401-6. [Article]
  17. Kramer S, Ozaki T, Miyazaki K, Kato C, Hanamoto T, Nakagawara A: Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells. Oncogene. 2005 Jan 27;24(5):938-44. [Article]
  18. Hoshino M, Qi ML, Yoshimura N, Miyashita T, Tagawa K, Wada Y, Enokido Y, Marubuchi S, Harjes P, Arai N, Oyanagi K, Blandino G, Sudol M, Rich T, Kanazawa I, Wanker EE, Saitoe M, Okazawa H: Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73. J Cell Biol. 2006 Feb 13;172(4):589-604. Epub 2006 Feb 6. [Article]
  19. Soond SM, Barry SP, Melino G, Knight RA, Latchman DS, Stephanou A: p73-mediated transcriptional activity is negatively regulated by polo-like kinase 1. Cell Cycle. 2008 May 1;7(9):1214-23. Epub 2008 Feb 15. [Article]
  20. Koida N, Ozaki T, Yamamoto H, Ono S, Koda T, Ando K, Okoshi R, Kamijo T, Omura K, Nakagawara A: Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis through physical interaction and phosphorylation. J Biol Chem. 2008 Mar 28;283(13):8555-63. doi: 10.1074/jbc.M710608200. Epub 2008 Jan 3. [Article]
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  23. Sang M, Ando K, Okoshi R, Koida N, Li Y, Zhu Y, Shimozato O, Geng C, Shan B, Nakagawara A, Ozaki T: Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation. Genes Cells. 2009 Jul;14(7):775-88. doi: 10.1111/j.1365-2443.2009.01309.x. Epub 2009 May 28. [Article]
  24. Peschiaroli A, Scialpi F, Bernassola F, Pagano M, Melino G: The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73. Oncogene. 2009 Sep 3;28(35):3157-66. doi: 10.1038/onc.2009.177. Epub 2009 Jul 6. [Article]
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  26. Sahu SK, Mohanty S, Kumar A, Kundu CN, Verma SC, Choudhuri T: Epstein-Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor. Virology. 2014 Jan 5;448:333-43. doi: 10.1016/j.virol.2013.10.023. Epub 2013 Nov 12. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Zincapproved, investigationalunknowntargetcofactorDetails
Zinc acetateapproved, investigationalunknowntargetDetails
Zinc chlorideapproved, investigationalunknowntargetchaperoneDetails
Zinc sulfate, unspecified formapproved, experimentalunknowntargetchaperoneDetails