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Protein

Tumor protein p73

Gene

Tp73

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi186ZincBy similarity1
Metal bindingi189ZincBy similarity1
Metal bindingi250ZincBy similarity1
Metal bindingi254ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cell cycle arrest Source: MGI
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to UV Source: GO_Central
  • cerebrospinal fluid secretion Source: MGI
  • digestive tract morphogenesis Source: MGI
  • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: GO_Central
  • forebrain development Source: MGI
  • hippocampus development Source: MGI
  • inflammatory response Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
  • mitotic G1 DNA damage checkpoint Source: GO_Central
  • negative regulation of cardiac muscle cell proliferation Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: GO_Central
  • neuron development Source: MGI
  • positive regulation of apoptotic signaling pathway Source: MGI
  • positive regulation of cell cycle arrest Source: MGI
  • positive regulation of cell size Source: MGI
  • positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • post-embryonic development Source: MGI
  • protein tetramerization Source: InterPro
  • regulation of gene expression Source: MGI
  • regulation of mitotic cell cycle Source: MGI
  • regulation of neuron apoptotic process Source: MGI
  • response to gamma radiation Source: GO_Central
  • response to X-ray Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Cell cycle, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-6804759. Regulation of TP53 Activity through Association with Co-factors.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor protein p73By similarity
Alternative name(s):
p53-like transcription factorBy similarity
p53-related proteinBy similarity
Gene namesi
Name:Tp73
Synonyms:P73Imported, Trp73Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1336991. Trp73.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice lacking Tp73 display a runting phenotype and high rates of mortality due to massive gastrointestinal hemorrhages or intracranial bleeding. The gastrointestinal tract suffers loss of enterocytes and excessive mucosecretions in the duodenum, ileum and cecum. Survivors exhibit hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways.1 Publication

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003702111 – 631Tumor protein p73Add BLAST631

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24Phosphothreonine; by PLK1By similarity1
Modified residuei25Phosphotyrosine; by SRC and HCKBy similarity1
Modified residuei91Phosphotyrosine; by ABL1By similarity1
Cross-linki622Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Sumoylated on Lys-622, which potentiates proteasomal degradation but does not affect transcriptional activity.By similarity
Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function (By similarity). Higher levels of phosphorylation seen in striatal neurons of. mutant huntingtin (htt) transgenic mice.By similarity1 Publication
Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9JJP2.
PRIDEiQ9JJP2.

PTM databases

iPTMnetiQ9JJP2.
PhosphoSitePlusiQ9JJP2.

Expressioni

Tissue specificityi

Found in striatal neurons of mutant huntingtin (htt) transgenic mice (at protein level). Isoform 1 is expressed in the nasal epithelium, the vomeronasal organ, the hippocampus and the hypothalamus.2 Publications

Gene expression databases

BgeeiENSMUSG00000029026.
ExpressionAtlasiQ9JJP2. baseline and differential.
GenevisibleiQ9JJP2. MM.

Interactioni

Subunit structurei

Found in a complex with p53/TP53 and CABLES1. The C-terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2, HIPK2, RANBP9 and WWOX (By similarity). Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain) (By similarity). Interacts with YAP1 (phosphorylated form) (By similarity). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Yap1P469382EBI-1770138,EBI-1211949

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204326. 5 interactors.
DIPiDIP-41942N.
IntActiQ9JJP2. 2 interactors.
MINTiMINT-3388880.
STRINGi10090.ENSMUSP00000101269.

Structurei

3D structure databases

ProteinModelPortaliQ9JJP2.
SMRiQ9JJP2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini479 – 545SAMSequence analysisAdd BLAST67

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 43TransactivationBy similarityAdd BLAST43
Regioni123 – 302DNA-bindingBy similarityAdd BLAST180
Regioni337 – 378OligomerizationSequence analysisAdd BLAST42
Regioni337 – 372Interaction with HIPK2By similarityAdd BLAST36

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi477 – 481WW-bindingBy similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi5 – 10Poly-SerSequence analysis6
Compositional biasi383 – 388Poly-GlnSequence analysis6

Domaini

Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain.By similarity
The WW-binding motif mediates interaction with WWOX.By similarity

Sequence similaritiesi

Belongs to the p53 family.By similarity
Contains 1 SAM (sterile alpha motif) domain.Sequence analysis

Phylogenomic databases

eggNOGiENOG410IGE4. Eukaryota.
ENOG410XV9W. LUCA.
GeneTreeiENSGT00390000015092.
InParanoidiQ9JJP2.
KOiK10148.
PhylomeDBiQ9JJP2.
TreeFamiTF106101.

Family and domain databases

CDDicd08367. P53. 1 hit.
Gene3Di1.10.150.50. 1 hit.
2.60.40.720. 1 hit.
4.10.170.10. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR012346. p53/RUNT-type_TF_DNA-bd.
IPR011615. p53_DNA-bd.
IPR010991. p53_tetrameristn.
IPR002117. p53_tumour_suppressor.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR032646. Tp73.
[Graphical view]
PANTHERiPTHR11447. PTHR11447. 2 hits.
PTHR11447:SF21. PTHR11447:SF21. 2 hits.
PfamiPF00870. P53. 1 hit.
PF07710. P53_tetramer. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
PRINTSiPR00386. P53SUPPRESSR.
SMARTiSM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47719. SSF47719. 1 hit.
SSF47769. SSF47769. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEiPS00348. P53. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9JJP2-1) [UniParc]FASTAAdd to basket
Also known as: AlphaBy similarity

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAQTSSSSSS TFEHLWSSLE PDSTYFDLPQ PSQGTSEASG SEESNMDVFH
60 70 80 90 100
LQGMAQFNLL SSAMDQMGSR AAPASPYTPE HAASAPTHSP YAQPSSTFDT
110 120 130 140 150
MSPAPVIPSN TDYPGPHHFE VTFQQSSTAK SATWTYSPLL KKLYCQIAKT
160 170 180 190 200
CPIQIKVSTP PPPGTAIRAM PVYKKAEHVT DIVKRCPNHE LGRDFNEGQS
210 220 230 240 250
APASHLIRVE GNNLAQYVDD PVTGRQSVVV PYEPPQVGTE FTTILYNFMC
260 270 280 290 300
NSSCVGGMNR RPILVIITLE TRDGQVLGRR SFEGRICACP GRDRKADEDH
310 320 330 340 350
YREQQALNES TTKNGAASKR AFKQSPPAIP ALGTNVKKRR HGDEDMFYMH
360 370 380 390 400
VRGRENFEIL MKVKESLELM ELVPQPLVDS YRQQQQQQLL QRPSHLQPPS
410 420 430 440 450
YGPVLSPMNK VHGGVNKLPS VNQLVGQPPP HSSAAGPNLG PMGSGMLNSH
460 470 480 490 500
GHSMPANGEM NGGHSSQTMV SGSHCTPPPP YHADPSLVSF LTGLGCPNCI
510 520 530 540 550
ECFTSQGLQS IYHLQNLTIE DLGALKVPDQ YRMTIWRGLQ DLKQSHDCGQ
560 570 580 590 600
QLLRSSSNAA TISIGGSGEL QRQRVMEAVH FRVRHTITIP NRGGAGAVTG
610 620 630
PDEWADFGFD LPDCKSRKQP IKEEFTETES H
Length:631
Mass (Da):69,096
Last modified:October 1, 2000 - v1
Checksum:iE364D566A90CBF1D
GO
Isoform 22 Publications (identifier: Q9JJP2-2) [UniParc]FASTAAdd to basket
Also known as: dN-AlphaBy similarity

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MAQTSSSSSSTFEHLWSSLEPDSTYFDLPQPSQGTSEASGSEESNMDVFHLQGM → MLYVGDPMRHLAT

Note: Produced by alternative promoter usage.Curated1 Publication
Show »
Length:590
Mass (Da):64,725
Checksum:i8580C7EFA21B5797
GO
Isoform 3 (identifier: Q9JJP2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MAQTSSSSSSTFEHLWSSLEPDSTYFDLPQPSQGTSEASGSEESNMDVFHLQGM → MLYVGDPMRHLAT
     489-493: SFLTG → RTLGL
     494-631: Missing.

Note: Produced by alternative splicing of isoform 2. No experimental confirmation available.Curated1 Publication
Show »
Length:452
Mass (Da):49,392
Checksum:i13C8757F5A4A5FFC
GO
Isoform 41 Publication (identifier: Q9JJP2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MAQTSSSSSSTFEHLWSSLEPDSTYFDLPQPSQGTSEASGSEESNMDVFHLQGM → MLYVGDPMRHLAT
     394-489: Missing.

Note: Produced by alternative splicing of isoform 2. No experimental confirmation available.Curated1 Publication
Show »
Length:494
Mass (Da):55,025
Checksum:iFA7D89986822E491
GO

Sequence cautioni

The sequence CAM18775 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118H → D in BAB30732 (PubMed:16141072).Curated1
Sequence conflicti127S → G in BAE24089 (PubMed:16141072).Curated1
Sequence conflicti254C → S in AAD32213 (PubMed:15489334).Curated1
Sequence conflicti352 – 353RG → SAS in AAD32213 (PubMed:15489334).Curated2
Sequence conflicti376P → H in AAD32213 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0530811 – 54MAQTS…HLQGM → MLYVGDPMRHLAT in isoform 2, isoform 3 and isoform 4. 3 PublicationsAdd BLAST54
Alternative sequenceiVSP_053082394 – 489Missing in isoform 4. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_053083489 – 493SFLTG → RTLGL in isoform 3. Curated5
Alternative sequenceiVSP_053084494 – 631Missing in isoform 3. CuratedAdd BLAST138

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y19234 mRNA. Translation: CAB81953.1.
Y19235 mRNA. Translation: CAB81954.1.
AK017412 mRNA. Translation: BAB30732.1.
AK139633 mRNA. Translation: BAE24089.1.
AL806525 Genomic DNA. Translation: CAM18773.1.
AL806525 Genomic DNA. Translation: CAM18774.1.
AL806525 Genomic DNA. Translation: CAM18775.1. Different initiation.
CH466594 Genomic DNA. Translation: EDL14957.1.
BC066045 mRNA. Translation: AAH66045.1.
AF138873 Genomic DNA. Translation: AAD32213.1.
CCDSiCCDS51396.1. [Q9JJP2-4]
CCDS51397.1. [Q9JJP2-2]
RefSeqiNP_001119802.1. NM_001126330.1. [Q9JJP2-2]
NP_001119803.1. NM_001126331.1. [Q9JJP2-4]
NP_035772.2. NM_011642.3.
UniGeneiMm.78015.

Genome annotation databases

EnsembliENSMUST00000097762; ENSMUSP00000095368; ENSMUSG00000029026. [Q9JJP2-4]
ENSMUST00000105643; ENSMUSP00000101268; ENSMUSG00000029026. [Q9JJP2-3]
ENSMUST00000133533; ENSMUSP00000114418; ENSMUSG00000029026. [Q9JJP2-2]
GeneIDi22062.
KEGGimmu:22062.
UCSCiuc008wbg.2. mouse. [Q9JJP2-2]
uc012dqi.1. mouse. [Q9JJP2-4]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y19234 mRNA. Translation: CAB81953.1.
Y19235 mRNA. Translation: CAB81954.1.
AK017412 mRNA. Translation: BAB30732.1.
AK139633 mRNA. Translation: BAE24089.1.
AL806525 Genomic DNA. Translation: CAM18773.1.
AL806525 Genomic DNA. Translation: CAM18774.1.
AL806525 Genomic DNA. Translation: CAM18775.1. Different initiation.
CH466594 Genomic DNA. Translation: EDL14957.1.
BC066045 mRNA. Translation: AAH66045.1.
AF138873 Genomic DNA. Translation: AAD32213.1.
CCDSiCCDS51396.1. [Q9JJP2-4]
CCDS51397.1. [Q9JJP2-2]
RefSeqiNP_001119802.1. NM_001126330.1. [Q9JJP2-2]
NP_001119803.1. NM_001126331.1. [Q9JJP2-4]
NP_035772.2. NM_011642.3.
UniGeneiMm.78015.

3D structure databases

ProteinModelPortaliQ9JJP2.
SMRiQ9JJP2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204326. 5 interactors.
DIPiDIP-41942N.
IntActiQ9JJP2. 2 interactors.
MINTiMINT-3388880.
STRINGi10090.ENSMUSP00000101269.

PTM databases

iPTMnetiQ9JJP2.
PhosphoSitePlusiQ9JJP2.

Proteomic databases

PaxDbiQ9JJP2.
PRIDEiQ9JJP2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000097762; ENSMUSP00000095368; ENSMUSG00000029026. [Q9JJP2-4]
ENSMUST00000105643; ENSMUSP00000101268; ENSMUSG00000029026. [Q9JJP2-3]
ENSMUST00000133533; ENSMUSP00000114418; ENSMUSG00000029026. [Q9JJP2-2]
GeneIDi22062.
KEGGimmu:22062.
UCSCiuc008wbg.2. mouse. [Q9JJP2-2]
uc012dqi.1. mouse. [Q9JJP2-4]

Organism-specific databases

CTDi22062.
MGIiMGI:1336991. Trp73.

Phylogenomic databases

eggNOGiENOG410IGE4. Eukaryota.
ENOG410XV9W. LUCA.
GeneTreeiENSGT00390000015092.
InParanoidiQ9JJP2.
KOiK10148.
PhylomeDBiQ9JJP2.
TreeFamiTF106101.

Enzyme and pathway databases

ReactomeiR-MMU-6804759. Regulation of TP53 Activity through Association with Co-factors.

Miscellaneous databases

PROiQ9JJP2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029026.
ExpressionAtlasiQ9JJP2. baseline and differential.
GenevisibleiQ9JJP2. MM.

Family and domain databases

CDDicd08367. P53. 1 hit.
Gene3Di1.10.150.50. 1 hit.
2.60.40.720. 1 hit.
4.10.170.10. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR012346. p53/RUNT-type_TF_DNA-bd.
IPR011615. p53_DNA-bd.
IPR010991. p53_tetrameristn.
IPR002117. p53_tumour_suppressor.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR032646. Tp73.
[Graphical view]
PANTHERiPTHR11447. PTHR11447. 2 hits.
PTHR11447:SF21. PTHR11447:SF21. 2 hits.
PfamiPF00870. P53. 1 hit.
PF07710. P53_tetramer. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
PRINTSiPR00386. P53SUPPRESSR.
SMARTiSM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47719. SSF47719. 1 hit.
SSF47769. SSF47769. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEiPS00348. P53. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP73_MOUSE
AccessioniPrimary (citable) accession number: Q9JJP2
Secondary accession number(s): B1AX89
, B1AX90, Q3UT91, Q9CU77, Q9JJP1, Q9WUJ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Activated and stabilized by interaction with RANBP9.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.