AC T04931
XX
ID T04931
XX
DT 27.11.2001 (created); rge.
DT 10.06.2015 (updated); asv.
CO Copyright (C), QIAGEN.
XX
FA p73alpha
XX
SY p53-like transcription factor; p53-related protein; p73; TAp73alpha; tp73; tumor protein p73 isoform a.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G005523 TP73; HGNC: tp73.
XX
CL C0057; P53; 6.3.1.0.3.1.
XX
SZ 636 AA; 69.6 kDa (cDNA) (calc.).
XX
SQ MAQSTATSPDGGTTFEHLWSSLEPDSTYFDLPQSSRGNNEVVGGTDSSMDVFHLEGMTTS
SQ VMAQFNLLSSTMDQMSSRAASASPYTPEHAASVPTHSPYAQPSSTFDTMSPAPVIPSNTD
SQ YPGPHHFEVTFQQSSTAKSATWTYSPLLKKLYCQIAKTCPIQIKVSTPPPPGTAIRAMPV
SQ YKKAEHVTDVVKRCPNHELGRDFNEGQSAPASHLIRVEGNNLSQYVDDPVTGRQSVVVPY
SQ EPPQVGTEFTTILYNFMCNSSCVGGMNRRPILIIITLEMRDGQVLGRRSFEGRICACPGR
SQ DRKADEDHYREQQALNESSAKNGAASKRAFKQSPPAVPALGAGVKKRRHGDEDTYYLQVR
SQ GRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQRPSHLQPPSYGPVLSPMNKVHGG
SQ MNKLPSVNQLVGQPPPHSSAATPNLGPVGPGMLNNHGHAVPANGEMSSSHSAQSMVSGSH
SQ CTPPPPYHADPSLVSFLTGLGCPNCIEYFTSQGLQSIYHLQNLTIEDLGALKIPEQYRMT
SQ IWRGLQDLKQGHDYSTAQQLLRSSNAATISIGGSGELQRQRVMEAVHFRVRHTITIPNRG
SQ GPGGGPDEWADFGFDLPDCKARKQPIKEEFTEAEIH
XX
SC Swiss-Prot#O15350-1
XX
FT 24 583 
PF00478; IMP dehydrogenase / GMP reductase domain.
FT 62 130 
PRD, proline-rich domain [20].
FT 113 309 
PF00870; P53 DNA-binding domain.
FT 228 312 
interaction with c-Myc [24].
FT 228 312 
interaction with CTF2 [29].
FT 312 381 
essential for interaction with HMGB1 [25].
FT 316 636 
suppresses transcriptional activity of p73beta [17].
FT 327 348 
NLS, nuclear localization signal [26].
FT 345 386 
PF07710; P53 tetramerisation motif.
FT 352 382 
OD, oligomerization domain [7].
FT 367 378 NES, nuclear export signal [26].
FT 382 426 enhances binding to HMGB1 [25].
FT 383 512 putative TAD2 [17].
FT 485 551 PF07647; SAM domain (Sterile alpha motif).
FT 485 551 SM00454; SAM.
FT 487 598 SAM (sterile alpha motif) homology domain [6].
XX
SF several alternative products are known, p73alpha T04931, p73beta T06137, p73gamma T06142, p73delta T06143, p73epsilon T06144, p73zeta T06145, p73kappa T06139, p73eta T06179, DeltaN p73alpha T06002, DeltaN p73beta T06003, DeltaNp73gamma T06013;
SF this isoform has very low tendency to form homooligomers, in contrast to p53 and p73beta [1];
SF C-terminal structure represses transcriptional activity of p73alpha [17] [21];
SF SAM homology domain is a globular alpha-helical domain [6];
SF SAM domain is necessary for direct interactions with NF-YB and NF-YC [23];
SF C-terminal SAM homology domain is highly conserved between human p73 alpha and human p63alpha T06132 [6];
SF DBD is required for c-Myc binding [24];
SF NLS is a bipartite structure with KR on one end and KKRR on the other end [26];
SF both TAD and OD are required for interactions with co-activator PCAF T06148 [28];
SF TA domain is necessary for induction of apoptosis [22];
XX
FF tumor suppressor [1];
FF is able to induce p21waf gene and suppress cell growth [1] [12];
FF weak to intermediate transcriptional activator in comparison with p53 [11] [12] [18];
FF weak transcriptional activator in comparison with p73beta [27];
FF activates mdm2 and bax genes [14];
FF diminishes transactivation ability and DNA binding by p53 [11] [18];
FF represses promoter of PDGF beta-receptor by direct interactions with NF-Y activator [23];
FF mRNA expression is activated by E2F-1 (high level), by E2F-2 and E2F-4 (intermediate level) [13] [15] [19];
FF mRNA expression is activated by c-Myc and E1A [19];
FF enhances binding of c-Myc:Max heterodimers to E-boxes [24];
FF enhances binding of CTF2 T00177 to DNA [29];
FF activates DeltaN p73 promoter forming a negative regulatory feedback loop [14];
FF activity is significantly diminished by DeltaN p73 isoforms [14] [16];
FF in response to DNA damage is phosphorylated by c-Abl [5] [10];
FF is required for apoptosis in response to DNA damage [22];
FF recruits co-activator p300/CBP [8];
FF recruits co-activator PCAF [28];
FF ASPP1 and ASPP2 stimulate transcriptional activity of p73alpha on promoters of Bax, PIG3, and PUMA but not of mdm2 and p21 [30];
FF if the DNA-binding domain of p53 is denatured caused by mutation or heat stress, p53 is able to inhibit p73alpha [1];
XX
IN T01077 Abl; human, Homo sapiens.
IN T06367 ASPP1; human, Homo sapiens.
IN T06368 ASPP2; human, Homo sapiens.
IN T00140 c-Myc-isoform1; human, Homo sapiens.
IN T00177 CTF-2; human, Homo sapiens.
IN T02944 Daxx; human, Homo sapiens.
IN T06243 HMGB1; human, Homo sapiens.
IN T18835 Mi2-alpha; human, Homo sapiens.
IN T00616 NF-YB; mouse, Mus musculus.
IN T02478 NF-YC-isoform3; human, Homo sapiens.
IN T06148 p/CAF; human, Homo sapiens.
IN T01427 p300; human, Homo sapiens.
IN T06377 PML; human, Homo sapiens.
IN T01003 SSRP1; human, Homo sapiens.
XX
MX M00761 V$P53DECAMER_Q2.
MX M03558 V$P73_Q6.
XX
BS R15699.
BS R15700.
BS R15701.
BS R68168.
BS R11272.
BS R16694.
BS R15624.
XX
DR TRANSPATH: MO000042276.
DR EMBL: AF077617; AF077617.
DR EMBL: AF077618; AF077618.
DR EMBL: AF077619; AF077619.
DR EMBL: AF077620; AF077620.
DR EMBL: AF077621; AF077621.
DR EMBL: AF077624; AF077624.
DR EMBL: AF077625; AF077625.
DR EMBL: AF077626; AF077626.
DR EMBL: AF077627; AF077627.
DR EMBL: AF077628; AF077628.
DR EMBL: AF079082; AF079082.
DR EMBL: AF079083; AF079083.
DR EMBL: AF079084; AF079084.
DR EMBL: AF079085; AF079085.
DR EMBL: AF079086; AF079086.
DR EMBL: AF079087; AF079087.
DR EMBL: AF079088; AF079088.
DR EMBL: AF079089; AF079089.
DR EMBL: AF079090; AF079090.
DR EMBL: AF079091; AF079091.
DR EMBL: AF079092; AF079092.
DR EMBL: AF079093; AF079093.
DR EMBL: AF079094; AF079094.
DR EMBL: AL136528; AL136528.
DR EMBL: Y11416;
DR UniProtKB: O15350-1;
XX
RN [1]; RE0017266.
RX PUBMED: 9288759.
RA Kaghad M., Bonnet H., Yang A., Creancier L., Biscan J. C., Valent A., Minty A., Chalon P., Lelias J. M., Dumont X., Ferrara P., McKeon F., Caput D.
RT Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers
RL Cell 90:809-819 (1997).
RN [2]; RE0017267.
RX PUBMED: 10362363.
RA Yoshikawa H., Nagashima M., Khan M. A., McMenamin M. G., Hagiwara K., Harris C. C.
RT Mutational analysis of p73 and p53 in human cancer cell lines
RL Oncogene 18:3415-3421 (1999).
RN [3]; RE0017268.
RX PUBMED: 9721206.
RA Mai M., Huang H., Reed C., Qian C., Smith J. S., Alderete B., Jenkins R., Smith D. I., Liu W.
RT Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions
RL Genomics 51:359-363 (1998).
RN [4]; RE0017269.
RX PUBMED: 9802988.
RA De Laurenzi V., Costanzo A., Barcaroli D., Terrinoni A., Falco M., Annicchiarico-Petruzzelli M., Levrero M., Melino G.
RT Two new p73 splice variants, gamma and delta, with different transcriptional activity
RL J. Exp. Med. 188:1763-1768 (1998).
RN [5]; RE0017271.
RX PUBMED: 10391251.
RA Yuan Z. M., Shioya H., Ishiko T., Sun X., Gu J., Huang Y. Y., Lu H., Kharbanda S., Weichselbaum R., Kufe D.
RT p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage
RL Nature 399:814-817 (1999).
RN [6]; RE0017273.
RX PUBMED: 10449409.
RA Chi S. W., Ayed A., Arrowsmith C. H.
RT Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain
RL EMBO J. 18:4438-4445 (1999).
RN [7]; RE0024342.
RX PUBMED: 10373484.
RA Davison T. S., Vagner C., Kaghad M., Ayed A., Caput D., Arrowsmith C. H.
RT p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53.
RL J. Biol. Chem. 274:18709-18714 (1999).
RN [8]; RE0024351.
RX PUBMED: 10648616.
RA Zeng X., Li X., Miller A., Yuan Z., Yuan W., Kwok R. P., Goodman R., Lu H.
RT The N-terminal domain of p73 interacts with the CH1 domain of p300/CREB binding protein and mediates transcriptional activation and apoptosis.
RL Mol. Cell. Biol. 20:1299-1310 (2000).
RN [9]; RE0024353.
RX PUBMED: 12954612.
RA Barrera F. N., Poveda J. A., Gonzalez-Ros J. M., Neira J. L.
RT Binding of the C-terminal sterile alpha motif (SAM) domain of human p73 to lipid membranes.
RL J. Biol. Chem. 278:46878-46885 (2003).
RN [10]; RE0024376.
RX PUBMED: 10391250.
RA Agami R., Blandino G., Oren M., Shaul Y.
RT Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis.
RL Nature 399:809-813 (1999).
RN [11]; RE0024734.
RX PUBMED: 10606650.
RA Vikhanskaya F., D Incalci M., Broggini M.
RT p73 competes with p53 and attenuates its response in a human ovarian cancer cell line.
RL Nucleic Acids Res. 28:513-519 (2000).
RN [12]; RE0024735.
RX PUBMED: 10809758.
RA De Laurenzi V., Raschella G., Barcaroli D., Annicchiarico-Petruzzelli M., Ranalli M., Catani M. V., Tanno B., Costanzo A., Levrero M., Melino G.
RT Induction of neuronal differentiation by p73 in a neuroblastoma cell line.
RL J. Biol. Chem. 275:15226-15231 (2000).
RN [13]; RE0024738.
RX PUBMED: 11034215.
RA Irwin M., Marin M. C., Phillips A. C., Seelan R. S., Smith D. I., Liu W., Flores E. R., Tsai K. Y., Jacks T., Vousden K. H., Kaelin WG J. r.
RT Role for the p53 homologue p73 in E2F-1-induced apoptosis.
RL Nature 407:645-648 (2000).
RN [14]; RE0024741.
RX PUBMED: 11909952.
RA Nakagawa T., Takahashi M., Ozaki T., Watanabe Ki K., Todo S., Mizuguchi H., Hayakawa T., Nakagawara A.
RT Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter.
RL Mol. Cell. Biol. 22:2575-2585 (2002).
RN [15]; RE0024742.
RX PUBMED: 11988839.
RA Seelan R. S., Irwin M., van der Stoop P., Qian C., Kaelin W.G., Liu W.
RT The human p73 promoter: characterization and identification of functional E2F binding sites.
RL Neoplasia 4:195-203 (2002).
RN [16]; RE0024754.
RX PUBMED: 11313982.
RA Fillippovich I., Sorokina N., Gatei M., haupt Y., Hobson K., Moallem E., Spring K., Mould M., McGuckin M. A., Lavin M. F., Khanna K. K.
RT Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53.
RL Oncogene 20:514-522 (2001).
RN [17]; RE0024768.
RX PUBMED: 11389695.
RA Ueda Y., Hijikata M., Takagi S., Chiba T., Shimotohno K.
RT Transcriptional activities of p73 splicing variants are regulated by inter-variant association.
RL Biochem. J. 356:859-866 (2001).
RN [18]; RE0024769.
RX PUBMED: 10490834.
RA Ueda Y., Hijikata M., Takagi S., Chiba T., Shimotohno K.
RT New p73 variants with altered C-terminal structures have varied transcriptional activities.
RL Oncogene 18:4993-4998 (1999).
RN [19]; RE0024772.
RX PUBMED: 11115495.
RA Zaika A., Irwin M., Sansome C., Moll U. M.
RT Oncogenes induce and activate endogenous p73 protein.
RL J. Biol. Chem. 276:11310-11316 (2001).
RN [20]; RE0024793.
RX PUBMED: 15081420.
RA Tanaka Y., Kameoka M., Itaya A., Ota K., Yoshihara K.
RT Regulation of HSF1-responsive gene expression by N-terminal truncated form of p73alpha.
RL Biochem. Biophys. Res. Commun. 317:865-872 (2004).
RN [21]; RE0024803.
RX PUBMED: 10606232.
RA Ozaki T., Naka M., Takada N., Tada M., Sakiyama S., Nakagawara A.
RT Deletion of the COOH-terminal region of p73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells.
RL Cancer Res. 59:5902-5907 (1999).
RN [22]; RE0024849.
RX PUBMED: 11932750.
RA Flores E. R., Tsai K. Y., Crowley D., Sengupta S., Yang A., McKeon F., Jacks T.
RT p63 and p73 are required for p53-dependent apoptosis in response to DNA damage.
RL Nature 416:560-564 (2002).
RN [23]; RE0024850.
RX PUBMED: 12167641.
RA Hackzell A., Uramoto H., Izumi H., Kohno K., Funa K.
RT p73 independent of c-Myc represses transcription of platelet-derived growth factor beta-receptor through interaction with NF-Y.
RL J. Biol. Chem. 277:39769-39776 (2002).
RN [24]; RE0024863.
RX PUBMED: 12080043.
RA Uramoto H., Izumi H., Ise T., Tada M., Uchiumi T., Kuwano M., Yasumoto K., Funa K., Kohno K.
RT p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression.
RL J. Biol. Chem. 277:31694-31702 (2002).
RN [25]; RE0024867.
RX PUBMED: 11748232.
RA Stros M., Ozaki T., Bacikova A., Kageyama H., Nakagawara A.
RT HMGB1 and HMGB2 cell-specifically down-regulate the p53- and p73-dependent sequence-specific transactivation from the human Bax gene promoter.
RL J. Biol. Chem. 277:7157-7164 (2002).
RN [26]; RE0024875.
RX PUBMED: 11847229.
RA Inoue T., Stuart J., Leno R., Maki C. G.
RT Nuclear import and export signals in control of the p53-related protein p73.
RL J. Biol. Chem. 277:15053-15060 (2002).
RN [27]; RE0024883.
RX PUBMED: 14647469.
RA Tullo A., Mastropasqua G., Bourdon J. C., Centonze P., Gostissa M., Costanzo A., Levrero M., Del Sal G., Saccone C., Sbisa E.
RT Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target.
RL Oncogene 22:8738-8748 (2003).
RN [28]; RE0024884.
RX PUBMED: 14614455.
RA Zhao L. Y., Liu Y., Bertos N. R., Yang X. J., Liao D.
RT PCAF is a coactivator for p73-mediated transactivation.
RL Oncogene 22:8316-8329 (2003).
RN [29]; RE0024885.
RX PUBMED: 12534345.
RA Uramoto H., Izumi H., Nagatani G., Ohmori H., Nagasue N., Ise T., Yoshida T., Yasumoto K., Kohno K.
RT Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression.
RL Biochem. J. 371:301-310 (2003).
RN [30]; RE0025178.
RX PUBMED: 14729977.
RA Bergamaschi D., Samuels Y., Jin B., Duraisingham S., Crook T., Lu X.
RT ASPP1 and ASPP2: common activators of p53 family members.
RL Mol. Cell. Biol. 24:1341-1350 (2004).
RN [31]; RE0025207.
RX PUBMED: 12519788.
RA Bensaad K., Le Bras M., Unsal K., Strano S., Blandino G., Tominaga O., Rouillard D., Soussi T.
RT Change of conformation of the DNA-binding domain of p53 is the only key element for binding of and interference with p73.
RL J. Biol. Chem. 278:10546-10555 (2003).
RN [32]; RE0047826.
RX PUBMED: 15678106.
RA Rossi M., De Laurenzi V., Munarriz E., Green D. R., Liu Y. C., Vousden K. H., Cesareni G., Melino G.
RT The ubiquitin-protein ligase Itch regulates p73 stability.
RL EMBO J. 24:836-848 (2005).
RN [33]; RE0049678.
RX PUBMED: 15572666.
RA Munarriz E., Barcaroli D., Stephanou A., Townsend P. A., Maisse C., Terrinoni A., Neale M. H., Martin S. J., Latchman D. S., Knight R. A., Melino G., De Laurenzi V.
RT PIAS-1 is a checkpoint regulator which affects exit from G1 and G2 by sumoylation of p73.
RL Mol. Cell. Biol. 24:10593-10610 (2004).
RN [34]; RE0049870.
RX PUBMED: 12730672.
RA Alisi A., Giambartolomei S., Cupelli F., Merlo P., Fontemaggi G., Spaziani A., Balsano C.
RT Physical and functional interaction between HCV core protein and the different p73 isoforms.
RL Oncogene 22:2573-2580 (2003).
RN [35]; RE0050052.
RX PUBMED: 17452332.
RA Furuya K., Ozaki T., Hanamoto T., Hosoda M., Hayashi S., Barker P. A., Takano K., Matsumoto M., Nakagawara A.
RT Stabilization of p73 by nuclear IKK-alpha mediates cisplatin-induced apoptosis.
RL J. Biol. Chem. 282:18365-18378 (2007).
RN [36]; RE0050074.
RX PUBMED: 15723830.
RA Hanamoto T., Ozaki T., Furuya K., Hosoda M., Hayashi S., Nakanishi M., Yamamoto H., Kikuchi H., Todo S., Nakagawara A.
RT Identification of protein kinase A catalytic subunit beta as a novel binding partner of p73 and regulation of p73 function.
RL J. Biol. Chem. 280:16665-16675 (2005).
RN [37]; RE0050157.
RX PUBMED: 17535448.
RA Paliwal P., Radha V., Swarup G.
RT Regulation of p73 by Hck through kinase-dependent and independent mechanisms.
RL BMC Mol. Biol. 8:45 (2007).
RN [38]; RE0063151.
RX PUBMED: 17304243.
RA Crighton D., O'Prey J., Bell H. S., Ryan K. M.
RT p73 regulates DRAM-independent autophagy that does not contribute to programmed cell death.
RL Cell Death Differ. 14:1071-1079 (2007).
RN [39]; RE0067465.
RX PUBMED: 20471636.
RA Zhang C., Yuan X., Yue L., Fu J., Luo L., Yin Z.
RT PIASy interacts with p73alpha and regulates cell cycle in HEK293 cells.
RL Cell Immunol. 263:235-240 (2010).
RN [40]; RE0024338.
RX PUBMED: 14585975.
RA Gonzalez S., Prives C., Cordon-Cardo C.
RT p73alpha regulation by Chk1 in response to DNA damage.
RL Mol. Cell. Biol. 23:8161-8171 (2003).
XX
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