PIDD1_MOUSE
ID PIDD1_MOUSE Reviewed; 915 AA.
AC Q9ERV7; A6H6F4;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=p53-induced death domain-containing protein 1 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000250|UniProtKB:Q9HB75};
DE AltName: Full=Leucine-rich repeat and death domain-containing protein;
DE Contains:
DE RecName: Full=PIDD-N {ECO:0000250|UniProtKB:Q9HB75};
DE Contains:
DE RecName: Full=PIDD-C {ECO:0000250|UniProtKB:Q9HB75};
DE Contains:
DE RecName: Full=PIDD-CC {ECO:0000250|UniProtKB:Q9HB75};
GN Name=Pidd1 {ECO:0000312|MGI:MGI:1889507};
GN Synonyms=Lrdd, Pidd {ECO:0000303|PubMed:10973264};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, AND FUNCTION.
RX PubMed=10973264; DOI=10.1038/79102;
RA Lin Y., Ma W., Benchimol S.;
RT "Pidd, a new death-domain-containing protein, is induced by p53 and
RT promotes apoptosis.";
RL Nat. Genet. 26:122-127(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH CRADD.
RX PubMed=22279524; DOI=10.1371/journal.pone.0028936;
RA Puffenberger E.G., Jinks R.N., Sougnez C., Cibulskis K., Willert R.A.,
RA Achilly N.P., Cassidy R.P., Fiorentini C.J., Heiken K.F., Lawrence J.J.,
RA Mahoney M.H., Miller C.J., Nair D.T., Politi K.A., Worcester K.N.,
RA Setton R.A., Dipiazza R., Sherman E.A., Eastman J.T., Francklyn C.,
RA Robey-Bond S., Rider N.L., Gabriel S., Morton D.H., Strauss K.A.;
RT "Genetic mapping and exome sequencing identify variants associated with
RT five novel diseases.";
RL PLoS ONE 7:E28936-E28936(2012).
CC -!- FUNCTION: Component of the DNA damage/stress response pathway that
CC functions downstream of p53/TP53 and can either promote cell survival
CC or apoptosis (PubMed:10973264). Associated with CRADD and the CASP2
CC caspase, it forms the PIDDosome a complex that activates CASP2 and
CC triggers apoptosis. Associated with IKBKG and RIPK1, it enhances
CC sumoylation and ubiquitination of IKBKG which is important for
CC activation of the transcription factor NF-kappa-B (By similarity).
CC {ECO:0000250|UniProtKB:Q9HB75, ECO:0000269|PubMed:10973264}.
CC -!- SUBUNIT: Forms a complex named the PIDDosome with CASP2 and CRADD
CC (PubMed:22279524). Forms a complex with IKBKG and RIPK1. Interacts with
CC FADD and MADD (By similarity). {ECO:0000250|UniProtKB:Q9HB75,
CC ECO:0000269|PubMed:22279524}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9HB75}. Nucleus
CC {ECO:0000250|UniProtKB:Q9HB75}. Note=Enriched in the nucleus upon DNA
CC damage. {ECO:0000250|UniProtKB:Q9HB75}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10973264}.
CC -!- INDUCTION: Induced by TP53/tumor suppressor p53 AND gamma-irradiation.
CC {ECO:0000269|PubMed:10973264}.
CC -!- DOMAIN: The Death domain mediates the interaction with CRADD and the
CC formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which
CC in turn recruit 7 CASP2 to form the PIDDosome.
CC {ECO:0000250|UniProtKB:Q9HB75}.
CC -!- DOMAIN: The LRR repeat-containing domain has a regulatory activity,
CC being autoinhibitory for the activation of NF-kappa-B.
CC {ECO:0000250|UniProtKB:Q9HB75}.
CC -!- PTM: Undergoes autoproteolytic processing whose extent either directs
CC cells towards survival or apoptotic pathways. Autoproteolytically
CC cleaved into two main fragments PIDD-N and PIDD-C. PIDD-C can be
CC further processed into PIDD-CC, a processing which is enhanced by DNA
CC damage. The cleavage producing PIDD-C is required for translocation of
CC PIDD1 to the nucleus upon DNA damage and activation of NF-kappa-B.
CC PIDD-CC mediates the interaction with CRADD and the cleavage producing
CC PIDD-CC is required for the activation of CASP2. PIDD-N remains
CC associated with PIDD-C and PIDD-CC after cleavage.
CC {ECO:0000250|UniProtKB:Q9HB75}.
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DR EMBL; AF274973; AAG13462.1; -; mRNA.
DR EMBL; BC145857; AAI45858.1; -; mRNA.
DR CCDS; CCDS22014.1; -.
DR RefSeq; NP_073145.1; NM_022654.1.
DR RefSeq; XP_006536281.1; XM_006536218.3.
DR AlphaFoldDB; Q9ERV7; -.
DR SMR; Q9ERV7; -.
DR BioGRID; 208363; 3.
DR ComplexPortal; CPX-3963; Caspase-2 PIDDosome.
DR STRING; 10090.ENSMUSP00000026580; -.
DR iPTMnet; Q9ERV7; -.
DR PhosphoSitePlus; Q9ERV7; -.
DR EPD; Q9ERV7; -.
DR MaxQB; Q9ERV7; -.
DR PaxDb; Q9ERV7; -.
DR PRIDE; Q9ERV7; -.
DR ProteomicsDB; 289421; -.
DR Antibodypedia; 22664; 169 antibodies from 25 providers.
DR DNASU; 57913; -.
DR Ensembl; ENSMUST00000026580; ENSMUSP00000026580; ENSMUSG00000025507.
DR Ensembl; ENSMUST00000106005; ENSMUSP00000101627; ENSMUSG00000025507.
DR GeneID; 57913; -.
DR KEGG; mmu:57913; -.
DR UCSC; uc009klc.1; mouse.
DR CTD; 55367; -.
DR MGI; MGI:1889507; Pidd1.
DR VEuPathDB; HostDB:ENSMUSG00000025507; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG4177; Eukaryota.
DR GeneTree; ENSGT00940000161780; -.
DR HOGENOM; CLU_017883_0_0_1; -.
DR InParanoid; Q9ERV7; -.
DR OMA; HRDNLGA; -.
DR OrthoDB; 176487at2759; -.
DR PhylomeDB; Q9ERV7; -.
DR TreeFam; TF331183; -.
DR Reactome; R-MMU-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR BioGRID-ORCS; 57913; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Pidd1; mouse.
DR PRO; PR:Q9ERV7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9ERV7; protein.
DR Bgee; ENSMUSG00000025507; Expressed in nasal cavity respiratory epithelium and 105 other tissues.
DR ExpressionAtlas; Q9ERV7; baseline and differential.
DR Genevisible; Q9ERV7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:1905369; C:endopeptidase complex; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IGI:MGI.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; ISO:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0016540; P:protein autoprocessing; ISO:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR019502; Peptidase_S68_pidd.
DR InterPro; IPR000906; ZU5_dom.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF13855; LRR_8; 2.
DR Pfam; PF10461; Peptidase_S68; 1.
DR Pfam; PF00791; ZU5; 2.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS51450; LRR; 7.
DR PROSITE; PS51145; ZU5; 2.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cytoplasm; Hydrolase; Leucine-rich repeat; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT CHAIN 2..915
FT /note="p53-induced death domain-containing protein 1"
FT /id="PRO_0000245244"
FT CHAIN 2..450
FT /note="PIDD-N"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT /id="PRO_0000445718"
FT CHAIN 451..915
FT /note="PIDD-C"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT /id="PRO_0000445719"
FT CHAIN 594..915
FT /note="PIDD-CC"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT /id="PRO_0000445720"
FT REPEAT 131..152
FT /note="LRR 1"
FT REPEAT 154..176
FT /note="LRR 2"
FT REPEAT 177..199
FT /note="LRR 3"
FT REPEAT 200..221
FT /note="LRR 4"
FT REPEAT 223..245
FT /note="LRR 5"
FT REPEAT 246..268
FT /note="LRR 6"
FT REPEAT 269..290
FT /note="LRR 7"
FT DOMAIN 327..459
FT /note="ZU5 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 460..601
FT /note="ZU5 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 793..878
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 428..457
FT /note="Peptidase S68"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT REGION 571..599
FT /note="Peptidase S68"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT REGION 585..721
FT /note="UPA domain"
FT /evidence="ECO:0000250"
FT REGION 888..915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 898..915
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 449
FT /evidence="ECO:0000250|UniProtKB:Q9HB75,
FT ECO:0000255|PROSITE-ProRule:PRU00485"
FT ACT_SITE 451
FT /evidence="ECO:0000250|UniProtKB:Q9HB75,
FT ECO:0000255|PROSITE-ProRule:PRU00485"
FT ACT_SITE 591
FT /evidence="ECO:0000250|UniProtKB:Q9HB75,
FT ECO:0000255|PROSITE-ProRule:PRU00485"
FT ACT_SITE 593
FT /evidence="ECO:0000250|UniProtKB:Q9HB75,
FT ECO:0000255|PROSITE-ProRule:PRU00485"
FT SITE 450..451
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT SITE 592..593
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HB75"
SQ SEQUENCE 915 AA; 101141 MW; 49FAA7B91D08E135 CRC64;
MAAVLEGQEP EETAAAAEDA ATSTLEAVDA GPGAPFLPAG NQLNLDLRPG GCHRLQYLCS
QQPPQLLQVE FLRLSTHEDP QLLDDTLAKV PWSLLRLRSL VLKGGQSRGA LGACLHGTLT
TLPAGLSDLA CLAHLDLSFN RLETLPTCVP ELHGLDALLL SHNHLSELPE ALGALPALTF
LTVTHNRLER LPLTLGSLST LQRLDLSENL LDTIPSEIGN LRSLSELNLA SNRLQSLPAS
LAGLRSLRLL VLHSNLLTSV PTGLVHLPLI TRLDLRDNRL RDLPAELLDA PFVRLQGNPL
GEASPAPPSP PDISQVPEMP RLLLTSDLDS FLVTPHGCSV TLACGVRLQF PAGATTTPVT
IHYRLWLPEP GLVSLGPHDF LLSSVLELQP HGVAFQQDVS LWLLFVPPRV RRCREVVVRT
RSNNTWNDLE TQLEEEAPKR LWARCQVPHF SWFLVVLRPV SNTCLLPPEG ALLCSSGHPG
VRVTFPPGVT EEPRQVSMQV VHMAGLELRT LLEESEASVS PLLCLSQSGP PSFLQPVTVQ
LPLPPGVTGF SLDRSHLHLL YRTPLTTTWD DITTQVALEF THLYARFQVT HFSWYWLWYT
TKTCVGGLAR KAWERLRLHR VNLIALQRRR DPEQVLLQCL PRNKVDATLS RLLVRYRGPE
PSETVEMFEG EKFFAAFERG IDVDADRPDC VDGRICFVFY SHLKNVKEVY ITTALDREAQ
DVRGQVSFYR GSLPVEVPAE AEAARQRKGT DALWMATLPI KLPRLRGAQG SGQGTDFSLM
PLNLGDAETG FLTQSNLLSV ASRLGPDWPA VALHLGMPYH KLQRIRHEFR DDLDGQVRHM
LFSWAERQTG QPGAVGHLVQ ALEQSDRRDV AEEVRAILEL GRHKYQDSIR RTGLAPEDST
LPGTSASQTP ESAQA
