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Description:
Tumor protein p73 (p53-like transcription factor) (p53-relatedprotein).
Molecular weight: 69623
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
mismatch repair( GO:0006298 )
Important dates:
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-JAN-1998, sequence version 1.
07-FEB-2006, entry version 64.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein P73_HUMAN:
Keywords:
3D-structure; Activator; Alternative splicing; Anti-oncogene; Apoptosis; Cell cycle; DNA-binding; Metal-binding; Nuclear protein; Phosphorylation; Transcription; Transcription regulation; Ubl conjugation; Zinc.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RC TISSUE=Colon;
RX MEDLINE=97433090; PubMed=9288759; DOI=10.1016/S0092-8674(00)80540-1;
RA Kaghad M., Bonnet H., Yang A., Creancier L., Biscan J.-C., Valent A.,
RA Minty A., Chalon P., Lelias J.-M., Dumont X., Ferrara P., McKeon F.,
RA Caput D.;
RT "Monoallelically expressed gene related to p53 at 1p36, a region
RT frequently deleted in neuroblastoma and other human cancers.";
RL Cell 90:809-819(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
RX MEDLINE=98389621; PubMed=9721206; DOI=10.1006/geno.1998.5387;
RA Mai M., Huang H., Reed C., Qian C., Smith J.S., Alderete B.,
RA Jenkins R., Smith D.I., Liu W.;
RT "Genomic organization and mutation analysis of p73 in
RT oligodendrogliomas with chromosome 1 p-arm deletions.";
RL Genomics 51:359-363(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GAMMA AND DELTA).
RC TISSUE=Neuroblastoma;
RX MEDLINE=99021697; PubMed=9802988; DOI=10.1084/jem.188.9.1763;
RA De Laurenzi V., Costanzo A., Barcaroli D., Terrinoni A., Falco M.,
RA Annicchiarico-Petruzzelli M., Levrero M., Melino G.;
RT "Two new p73 splice variants, gamma and delta, with different
RT transcriptional activity.";
RL J. Exp. Med. 188:1763-1768(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS EPSILON AND ZETA).
RC TISSUE=Hepatoma, Lymphocyte, Mammary cancer, and Skin;
RX MEDLINE=99310938; PubMed=10381648; DOI=10.1038/sj.cdd.4400521;
RA De Laurenzi V., Catani M.V., Terrinoni A., Corazzari M., Melino G.,
RA Costanzo A., Levrero M., Knight R.A.;
RT "Additional complexity in p73: induction by mitogens in lymphoid cells
RT and identification of two new splicing variants epsilon and zeta.";
RL Cell Death Differ. 6:389-390(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
RX MEDLINE=99289209; PubMed=10362363; DOI=10.1038/sj.onc.1202677;
RA Yoshikawa H., Nagashima M., Khan M.A., McMenamin M.G., Hagiwara K.,
RA Harris C.C.;
RT "Mutational analysis of p73 and p53 in human cancer cell lines.";
RL Oncogene 18:3415-3421(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DN-ALPHA; DN-BETA AND DN-GAMMA).
RX MEDLINE=21621977; PubMed=11753569; DOI=10.1038/sj/cdd/4400962;
RA Grob T.J., Novak U., Maisse C., Barcaroli D., Luthi A.U., Pirnia F.,
RA Hugli B., Graber H.U., De Laurenzi V., Fey M.F., Melino G., Tobler A.;
RT "Human DeltaNp73 regulates a dominant negative feedback loop for TAp73
RT and p53.";
RL Cell Death Differ. 8:1213-1223(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DN-ALPHA AND DN-BETA).
RA Nakagawa T., Takahashi M., Ozaki T., Watanabe K., Nakagawara A.;
RT "Identification of the p73-specific target sequence present in the
RT deltaNp73 proper promoter.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PHOSPHORYLATION (ISOFORMS ALPHA AND BETA).
RX MEDLINE=99318135; PubMed=10391251; DOI=10.1038/21704;
RA Yuan Z.-M., Shioya H., Ishiko T., Sun X., Gu J., Huang Y., Lu H.,
RA Kharbanda S., Weichselbaum R., Kufe D.;
RT "p73 is regulated by tyrosine kinase c-Abl in the apoptotic response
RT to DNA damage.";
RL Nature 399:814-817(1999).
RN [10]
RP ERRATUM.
RA Yuan Z.-M., Shioya H., Ishiko T., Sun X., Gu J., Huang Y., Lu H.,
RA Kharbanda S., Weichselbaum R., Kufe D.;
RL Nature 400:792-792(1999).
RN [11]
RP FUNCTION.
RX MEDLINE=99217940; PubMed=10203277; DOI=10.1093/jnci/91.7.594;
RA Kaelin W.G. Jr.;
RT "The emerging p53 gene family.";
RL J. Natl. Cancer Inst. 91:594-598(1999).
RN [12]
RP SUMOYLATION SITE LYS-627, AND MUTAGENESIS OF LYS-627.
RX MEDLINE=20549653; PubMed=10961991; DOI=10.1074/jbc.M004293200;
RA Minty A., Dumont X., Kaghad M., Caput D.;
RT "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening
RT with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1
RT interaction motif.";
RL J. Biol. Chem. 275:36316-36323(2000).
RN [13]
RP INTERACTION WITH HIPK2.
RX MEDLINE=22191252; PubMed=11925430; DOI=10.1074/jbc.M200153200;
RA Kim E.-J., Park J.-S., Um S.-J.;
RT "Identification and characterization of HIPK2 interacting with p73 and
RT modulating functions of the p53 family in vivo.";
RL J. Biol. Chem. 277:32020-32028(2002).
RN [14]
RP INTERACTION WITH WWOX, DOMAIN, AND MUTAGENESIS OF TYR-487.
RX PubMed=15070730; DOI=10.1073/pnas.0400805101;
RA Aqeilan R.I., Pekarsky Y., Herrero J.J., Palamarchuk A., Letofsky J.,
RA Druck T., Trapasso F., Han S.-Y., Melino G., Huebner K., Croce C.M.;
RT "Functional association between Wwox tumor suppressor protein and p73,
RT a p53 homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4401-4406(2004).
RN [15]
RP INTERACTION WITH RANBP9, AND SUBCELLULAR LOCATION.
RX PubMed=15558019; DOI=10.1038/sj.onc.1208257;
RA Kramer S., Ozaki T., Miyazaki K., Kato C., Hanamoto T., Nakagawara A.;
RT "Protein stability and function of p73 are modulated by a physical
RT interaction with RanBPM in mammalian cultured cells.";
RL Oncogene 24:938-944(2005).
RN [16]
RP IDENTIFICATION IN A COMPLEX WITH CABLES1 AND TP53.
RX MEDLINE=21659718; PubMed=11706030; DOI=10.1074/jbc.M108535200;
RA Tsuji K., Mizumoto K., Yamochi T., Nishimoto I., Matsuoka M.;
RT "Differential effect of ik3-1/cables on p53- and p73-induced cell
RT death.";
RL J. Biol. Chem. 277:2951-2957(2002).
RN [17]
RP STRUCTURE BY NMR OF 487-554.
RX MEDLINE=99380160; PubMed=10449409; DOI=10.1093/emboj/18.16.4438;
RA Chi S.W., Ayed A., Arrowsmith C.H.;
RT "Solution structure of a conserved C-terminal domain of p73 with
RT structural homology to the SAM domain.";
RL EMBO J. 18:4438-4445(1999).
Feature:
CHAIN 1 636 Tumor protein p73.
/FTId=PRO_0000185728.
REGION 1 46 Transactivation (By similarity).
REGION 131 310 DNA-binding (Potential).
REGION 345 380 Interaction with HIPK2.
REGION 346 435 Mediates oligomerization (Potential).
MOTIF 287 304 Nuclear localization signal (Potential).
MOTIF 483 487 WW-binding.
COMPBIAS 1 55 Asp/Glu-rich (acidic).
COMPBIAS 168 171 Poly-Pro.
COMPBIAS 391 394 Poly-Gln.
COMPBIAS 483 486 Poly-Pro.
METAL 194 194 Zinc (By similarity).
METAL 197 197 Zinc (By similarity).
METAL 258 258 Zinc (By similarity).
METAL 262 262 Zinc (By similarity).
MOD_RES 99 99 Phosphotyrosine (by ABL) (in isoform
Beta).
CROSSLNK 627 627 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO) (in
isoform Alpha).
VARSPLIC 1 62 MAQSTATSPDGGTTFEHLWSSLEPDSTYFDLPQSSRGNNEV
VGGTDSSMDVFHLEGMTTSVM -> MLYVGDPARHLAT
(in isoform dN-Alpha, isoform dN-Beta and
isoform dN-Gamma).
/FTId=VSP_014368.
VARSPLIC 400 495 Missing (in isoform Zeta).
/FTId=VSP_006546.
VARSPLIC 400 476 SHLQPPSYGPVLSPMNKVHGGMNKLPSVNQLVGQPPPHSSA
ATPNLGPVGPGMLNNHGHAVPANGEMSSSHSAQSMV -> P
RDAQQPWPRSASQQRRDEQQPQRPVHGLGVPLHSATPLPRR
PQPRQFFNRIGVSKLHRVFHLPRVTEHLPPAEPDH (in
isoform Gamma and isoform dN-Gamma).
/FTId=VSP_006540.
VARSPLIC 400 445 SHLQPPSYGPVLSPMNKVHGGMNKLPSVNQLVGQPPPHSSA
ATPNL -> PRDAQQPWPRSASQQRRDEQQPQRPVHGLGVP
LHSATPLPRRPQPR (in isoform Epsilon).
/FTId=VSP_006544.
VARSPLIC 400 403 SHLQ -> TWGP (in isoform Delta).
/FTId=VSP_006542.
VARSPLIC 404 636 Missing (in isoform Delta).
/FTId=VSP_006543.
VARSPLIC 446 526 Missing (in isoform Epsilon).
/FTId=VSP_006545.
VARSPLIC 477 636 Missing (in isoform Gamma and isoform dN-
Gamma).
/FTId=VSP_006541.
VARSPLIC 495 636 SFLTGLGCPNCIEYFTSQGLQSIYHLQNLTIEDLGALKIPE
QYRMTIWRGLQDLKQGHDYSTAQQLLRSSNAATISIGGSGE
LQRQRVMEAVHFRVRHTITIPNRGGPGGGPDEWADFGFDLP
DCKARKQPIKEEFTEAEIH -> RTWGP (in isoform
Beta and isoform dN-Beta).
/FTId=VSP_006539.
MUTAGEN 487 487 Y->A: Loss of interaction with WWOX.
MUTAGEN 627 627 K->R: Strongly diminishes sumoylation but
does not affect transcriptional activity.
HELIX 493 499
TURN 500 501
TURN 503 504
STRAND 505 505
HELIX 506 510
TURN 511 513
HELIX 517 521
TURN 522 522
HELIX 525 530
TURN 531 532
TURN 535 537
HELIX 538 547
Comments:
-!- FUNCTION: Participates in the apoptotic response to DNA damage.
When overproduced, activates transcription from p53-responsive
promoters and induces apoptosis. May be a tumor suppressor
protein.
-!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
-!- SUBUNIT: The C-terminal oligomerization domain binds to the ABL1
tyrosine kinase SH3 domain. Isoform Beta interacts homotypically
and with p53/TP53, whereas isoform Alpha does not. Isoform Gamma
interacts homotypically and with all p73 isoforms. Isoform Delta
interacts with isoform Gamma, isoform Alpha, and homotypically.
Isoforms Alpha and Beta interact with HIPK2. Isoform Alpha
interacts with RANBP9. Found in a complex with p53/TP53 and
CABLES1. Isoform Beta interacts with WWOX.
-!- INTERACTION:
Q9ESJ1:Cables1 (xeno); NbExp=1; IntAct=EBI-389606, EBI-604411;
P09429:HMGB1; NbExp=1; IntAct=EBI-389606, EBI-389432;
-!- SUBCELLULAR LOCATION: Nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=9;
Name=Alpha;
IsoId=O15350-1; Sequence=Displayed;
Name=Beta;
IsoId=O15350-2; Sequence=VSP_006539;
Name=Gamma;
IsoId=O15350-3; Sequence=VSP_006540, VSP_006541;
Note=The splicing of exon 11 results in a frameshift from the
original reading frame;
Name=Delta;
IsoId=O15350-4; Sequence=VSP_006542, VSP_006543;
Name=Epsilon;
IsoId=O15350-5; Sequence=VSP_006544, VSP_006545;
Note=The splicing of exon 11 results in a frameshift from the
original reading frame. The splicing of exon 13 reverts the
reading frame to the sequence of isoform Alpha;
Name=Zeta;
IsoId=O15350-6; Sequence=VSP_006546;
Name=dN-Alpha;
IsoId=O15350-8; Sequence=VSP_014368;
Name=dN-Beta;
IsoId=O15350-9; Sequence=VSP_014368, VSP_006539;
Name=dN-Gamma;
IsoId=O15350-10; Sequence=VSP_014368, VSP_006540, VSP_006541;
-!- TISSUE SPECIFICITY: Brain, kidney, placenta, colon, heart, liver,
spleen, skeletal muscle, prostate, thymus and pancreas.
-!- INDUCTION: Not induced by DNA damage.
-!- DOMAIN: Possesses an acidic transactivation domain, a central DNA
binding domain and a C-terminal oligomerization domain that binds
to the ABL tyrosine kinase SH3 domain.
-!- DOMAIN: The WW-binding motif mediates interaction with WWOX.
-!- PTM: Isoform alpha (but not isoform beta) is sumoylated on Lys-
627, which potentiates proteasomal degradation but does not affect
transcriptional activity.
-!- DISEASE: Maps to a chromosome region frequently mutated in diverse
cell lines of human cancer. Appears not to be frequently mutated
in human cancers, in contrast to p53. Hemizygosity is observed in
neuroblastoma and oligodendroglioma.
-!- MISCELLANEOUS: Activated and stabilized by interaction with
RANBP9.
-!- SIMILARITY: Belongs to the p53 family.
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Sequence length: 636
MAQSTATSPD GGTTFEHLWS SLEPDSTYFD LPQSSRGNNE VVGGTDSSMD VFHLEGMTTS
VMAQFNLLSS TMDQMSSRAA SASPYTPEHA ASVPTHSPYA QPSSTFDTMS PAPVIPSNTD
YPGPHHFEVT FQQSSTAKSA TWTYSPLLKK LYCQIAKTCP IQIKVSTPPP PGTAIRAMPV
YKKAEHVTDV VKRCPNHELG RDFNEGQSAP ASHLIRVEGN NLSQYVDDPV TGRQSVVVPY
EPPQVGTEFT TILYNFMCNS SCVGGMNRRP ILIIITLEMR DGQVLGRRSF EGRICACPGR
DRKADEDHYR EQQALNESSA KNGAASKRAF KQSPPAVPAL GAGVKKRRHG DEDTYYLQVR
GRENFEILMK LKESLELMEL VPQPLVDSYR QQQQLLQRPS HLQPPSYGPV LSPMNKVHGG
MNKLPSVNQL VGQPPPHSSA ATPNLGPVGP GMLNNHGHAV PANGEMSSSH SAQSMVSGSH
CTPPPPYHAD PSLVSFLTGL GCPNCIEYFT SQGLQSIYHL QNLTIEDLGA LKIPEQYRMT
IWRGLQDLKQ GHDYSTAQQL LRSSNAATIS IGGSGELQRQ RVMEAVHFRV RHTITIPNRG
GPGGGPDEWA DFGFDLPDCK ARKQPIKEEF TEAEIH