PIDD1_HUMAN
ID PIDD1_HUMAN Reviewed; 910 AA.
AC Q9HB75; Q59FD1; Q59H10; Q59HC7; Q7Z4P8; Q8NC89; Q8NDL2; Q96C25; Q9NRE6;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=p53-induced death domain-containing protein 1 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000269|PubMed:17159900};
DE AltName: Full=Leucine-rich repeat and death domain-containing protein;
DE Contains:
DE RecName: Full=PIDD-N {ECO:0000303|PubMed:17159900};
DE Contains:
DE RecName: Full=PIDD-C {ECO:0000303|PubMed:17159900};
DE Contains:
DE RecName: Full=PIDD-CC {ECO:0000303|PubMed:17159900};
GN Name=PIDD1 {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:16491};
GN Synonyms=LRDD {ECO:0000303|PubMed:10825539},
GN PIDD {ECO:0000303|PubMed:10973264};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, INTERACTION
RP WITH FADD AND MADD, AND VARIANT ARG-331.
RX PubMed=10825539; DOI=10.1016/s0167-4838(00)00029-7;
RA Telliez J.-B., Bean K.M., Lin L.-L.;
RT "LRDD, a novel leucine rich repeat and death domain containing protein.";
RL Biochim. Biophys. Acta 1478:280-288(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INDUCTION, AND VARIANT
RP ARG-331.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT ARG-331.
RC TISSUE=Brain;
RA Zan Q., Guo J.H., Yu L.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7), AND VARIANT ARG-331.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4; 5 AND 6), AND VARIANT
RP ARG-331.
RC TISSUE=Brain, and Spleen;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT ARG-331.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ARG-331.
RC TISSUE=Uterus;
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 [8]
RP PROTEIN SEQUENCE OF 2-37; 69-93; 103-111; 183-316; 343-357; 415-435;
RP 454-497; 552-581; 598-605; 613-623; 626-637; 651-740; 743-759; 768-798 AND
RP 826-870, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2,
RP PHOSPHORYLATION AT SER-299 AND SER-305, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP FUNCTION, AND IDENTIFICATION IN PIDDOSOME COMPLEX.
RX PubMed=15073321; DOI=10.1126/science.1095432;
RA Tinel A., Tschopp J.;
RT "The PIDDosome, a protein complex implicated in activation of caspase-2 in
RT response to genotoxic stress.";
RL Science 304:843-846(2004).
RN [10]
RP FUNCTION, INTERACTION WITH IKBKG AND RIPK1, AND SUBCELLULAR LOCATION.
RX PubMed=16360037; DOI=10.1016/j.cell.2005.09.036;
RA Janssens S., Tinel A., Lippens S., Tschopp J.;
RT "PIDD mediates NF-kappaB activation in response to DNA damage.";
RL Cell 123:1079-1092(2005).
RN [11]
RP IDENTIFICATION IN PIDDOSOME COMPLEX.
RX PubMed=16652156; DOI=10.1038/sj.onc.1209569;
RA Vakifahmetoglu H., Olsson M., Orrenius S., Zhivotovsky B.;
RT "Functional connection between p53 and caspase-2 is essential for apoptosis
RT induced by DNA damage.";
RL Oncogene 25:5683-5692(2006).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CRADD, SUBCELLULAR LOCATION,
RP INDUCTION, DOMAIN, AUTOPROTEOLYTIC PROCESSING, ACTIVE SITE, CLEAVAGE SITE,
RP AND MUTAGENESIS OF HIS-444; PHE-445; SER-446; PHE-582; PHE-587 AND SER-588.
RX PubMed=17159900; DOI=10.1038/sj.emboj.7601473;
RA Tinel A., Janssens S., Lippens S., Cuenin S., Logette E., Jaccard B.,
RA Quadroni M., Tschopp J.;
RT "Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2
RT and pro-survival NF-kappaB pathway.";
RL EMBO J. 26:197-208(2007).
RN [13] {ECO:0007744|PDB:2OF5}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 778-883 IN COMPLEX WITH CRADD,
RP DOMAIN, AND MUTAGENESIS OF LEU-801; TYR-814; ARG-815; ARG-825; ASP-826;
RP LEU-828; GLU-830; PHE-837; ARG-862 AND GLN-863.
RX PubMed=17289572; DOI=10.1016/j.cell.2007.01.019;
RA Park H.H., Logette E., Raunser S., Cuenin S., Walz T., Tschopp J., Wu H.;
RT "Death domain assembly mechanism revealed by crystal structure of the
RT oligomeric PIDDosome core complex.";
RL Cell 128:533-546(2007).
RN [14]
RP VARIANT 863-GLN--ALA-910 DEL.
RX PubMed=28397838; DOI=10.1038/mp.2017.60;
RA Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
RA Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
RA Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
RA Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
RA Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
RA Vincent J.B.;
RT "Mapping autosomal recessive intellectual disability: combined microarray
RT and exome sequencing identifies 26 novel candidate genes in 192
RT consanguineous families.";
RL Mol. Psychiatry 23:973-984(2018).
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, PubMed:15073321, PubMed:16360037,
CC PubMed:17159900). Associated with CRADD and the CASP2 caspase, it forms
CC the PIDDosome a complex that activates CASP2 and triggers apoptosis
CC (PubMed:15073321, PubMed:17159900). Associated with IKBKG and RIPK1, it
CC enhances sumoylation and ubiquitination of IKBKG which is important for
CC activation of the transcription factor NF-kappa-B (PubMed:16360037,
CC PubMed:17159900). {ECO:0000269|PubMed:10973264,
CC ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:16360037,
CC ECO:0000269|PubMed:17159900}.
CC -!- SUBUNIT: Forms a complex named the PIDDosome with CASP2 and CRADD
CC (PubMed:15073321, PubMed:16652156, PubMed:17159900, PubMed:17289572).
CC Forms a complex with IKBKG and RIPK1 (PubMed:16360037). Interacts with
CC FADD and MADD (PubMed:10825539). {ECO:0000269|PubMed:10825539,
CC ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:16360037,
CC ECO:0000269|PubMed:16652156, ECO:0000269|PubMed:17159900,
CC ECO:0000269|PubMed:17289572}.
CC -!- INTERACTION:
CC Q9HB75; P78560: CRADD; NbExp=7; IntAct=EBI-520427, EBI-520375;
CC Q9HB75; Q99750: MDFI; NbExp=3; IntAct=EBI-520427, EBI-724076;
CC Q9HB75-2; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-12326369, EBI-742664;
CC Q9HB75-2; Q7Z7F0-4: KHDC4; NbExp=3; IntAct=EBI-12326369, EBI-9089060;
CC Q9HB75-2; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-12326369, EBI-1389308;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16360037,
CC ECO:0000269|PubMed:17159900}. Nucleus {ECO:0000269|PubMed:16360037,
CC ECO:0000269|PubMed:17159900}. Note=Enriched in the nucleus upon DNA
CC damage. {ECO:0000269|PubMed:17159900}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q9HB75-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HB75-2; Sequence=VSP_019671;
CC Name=3;
CC IsoId=Q9HB75-3; Sequence=VSP_019666, VSP_019667;
CC Name=4;
CC IsoId=Q9HB75-4; Sequence=VSP_019665;
CC Name=5;
CC IsoId=Q9HB75-5; Sequence=VSP_019665, VSP_019669, VSP_019672,
CC VSP_019673;
CC Name=6;
CC IsoId=Q9HB75-6; Sequence=VSP_019664, VSP_019669, VSP_019671,
CC VSP_019672, VSP_019673;
CC Name=7;
CC IsoId=Q9HB75-7; Sequence=VSP_019665, VSP_019668, VSP_019670;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10825539}.
CC -!- INDUCTION: Up-regulated in response to DNA damage.
CC {ECO:0000269|PubMed:10973264, ECO:0000269|PubMed:17159900}.
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:0000269|PubMed:17289572}.
CC -!- DOMAIN: The LRR repeat-containing domain has a regulatory activity,
CC being autoinhibitory for the activation of NF-kappa-B.
CC {ECO:0000269|PubMed:17159900}.
CC -!- PTM: Undergoes autoproteolytic processing whose extent either directs
CC cells towards survival or apoptotic pathways (PubMed:17159900).
CC Autoproteolytically cleaved into two main fragments PIDD-N and PIDD-C
CC (PubMed:17159900). PIDD-C can be further processed into PIDD-CC, a
CC processing which is enhanced by DNA damage (PubMed:17159900). The
CC cleavage producing PIDD-C is required for translocation of PIDD1 to the
CC nucleus upon DNA damage and activation of NF-kappa-B (PubMed:17159900).
CC PIDD-CC mediates the interaction with CRADD and the cleavage producing
CC PIDD-CC is required for the activation of CASP2 (PubMed:17159900).
CC PIDD-N remains associated with PIDD-C and PIDD-CC after cleavage
CC (PubMed:17159900). {ECO:0000269|PubMed:17159900}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92069.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD92186.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD92766.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD38708.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF229178; AAF69491.1; -; mRNA.
DR EMBL; AF274972; AAG13461.1; -; mRNA.
DR EMBL; AF465246; AAP97716.1; -; mRNA.
DR EMBL; AK074893; BAC11272.1; -; mRNA.
DR EMBL; AB208832; BAD92069.1; ALT_INIT; mRNA.
DR EMBL; AB208949; BAD92186.1; ALT_INIT; mRNA.
DR EMBL; AB209529; BAD92766.1; ALT_INIT; mRNA.
DR EMBL; AL833849; CAD38708.1; ALT_INIT; mRNA.
DR EMBL; BC014904; AAH14904.1; -; mRNA.
DR CCDS; CCDS44508.1; -. [Q9HB75-2]
DR CCDS; CCDS7716.1; -. [Q9HB75-1]
DR RefSeq; NP_665893.2; NM_145886.3. [Q9HB75-1]
DR RefSeq; NP_665894.2; NM_145887.3. [Q9HB75-2]
DR RefSeq; XP_011518512.1; XM_011520210.2. [Q9HB75-1]
DR RefSeq; XP_011518513.1; XM_011520211.2. [Q9HB75-2]
DR RefSeq; XP_016873482.1; XM_017017993.1. [Q9HB75-4]
DR PDB; 2OF5; X-ray; 3.20 A; H/I/J/K/L=778-883.
DR PDBsum; 2OF5; -.
DR AlphaFoldDB; Q9HB75; -.
DR SMR; Q9HB75; -.
DR BioGRID; 120645; 45.
DR ComplexPortal; CPX-3905; Caspase-2 PIDDosome.
DR CORUM; Q9HB75; -.
DR IntAct; Q9HB75; 17.
DR MINT; Q9HB75; -.
DR STRING; 9606.ENSP00000337797; -.
DR MEROPS; S68.001; -.
DR MEROPS; S68.002; -.
DR iPTMnet; Q9HB75; -.
DR PhosphoSitePlus; Q9HB75; -.
DR BioMuta; PIDD1; -.
DR DMDM; 116242715; -.
DR jPOST; Q9HB75; -.
DR MassIVE; Q9HB75; -.
DR PaxDb; Q9HB75; -.
DR PeptideAtlas; Q9HB75; -.
DR PRIDE; Q9HB75; -.
DR ProteomicsDB; 81501; -. [Q9HB75-1]
DR ProteomicsDB; 81502; -. [Q9HB75-2]
DR ProteomicsDB; 81503; -. [Q9HB75-3]
DR ProteomicsDB; 81504; -. [Q9HB75-4]
DR Antibodypedia; 22664; 169 antibodies from 25 providers.
DR DNASU; 55367; -.
DR Ensembl; ENST00000347755.10; ENSP00000337797.5; ENSG00000177595.19. [Q9HB75-1]
DR Ensembl; ENST00000411829.6; ENSP00000416801.2; ENSG00000177595.19. [Q9HB75-2]
DR GeneID; 55367; -.
DR KEGG; hsa:55367; -.
DR MANE-Select; ENST00000347755.10; ENSP00000337797.5; NM_145886.4; NP_665893.2.
DR UCSC; uc001lro.3; human. [Q9HB75-1]
DR CTD; 55367; -.
DR DisGeNET; 55367; -.
DR GeneCards; PIDD1; -.
DR HGNC; HGNC:16491; PIDD1.
DR HPA; ENSG00000177595; Low tissue specificity.
DR MalaCards; PIDD1; -.
DR MIM; 605247; gene.
DR neXtProt; NX_Q9HB75; -.
DR OpenTargets; ENSG00000177595; -.
DR PharmGKB; PA30445; -.
DR VEuPathDB; HostDB:ENSG00000177595; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG4177; Eukaryota.
DR GeneTree; ENSGT00940000161780; -.
DR HOGENOM; CLU_017883_0_0_1; -.
DR InParanoid; Q9HB75; -.
DR OMA; HRDNLGA; -.
DR OrthoDB; 176487at2759; -.
DR PhylomeDB; Q9HB75; -.
DR TreeFam; TF331183; -.
DR PathwayCommons; Q9HB75; -.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR SignaLink; Q9HB75; -.
DR SIGNOR; Q9HB75; -.
DR BioGRID-ORCS; 55367; 12 hits in 1075 CRISPR screens.
DR ChiTaRS; PIDD1; human.
DR EvolutionaryTrace; Q9HB75; -.
DR GeneWiki; LRDD; -.
DR GenomeRNAi; 55367; -.
DR Pharos; Q9HB75; Tbio.
DR PRO; PR:Q9HB75; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9HB75; protein.
DR Bgee; ENSG00000177595; Expressed in apex of heart and 116 other tissues.
DR ExpressionAtlas; Q9HB75; baseline and differential.
DR Genevisible; Q9HB75; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:1905369; C:endopeptidase complex; IPI:ComplexPortal.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IC:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005123; F:death receptor binding; TAS:ProtInc.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
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 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cytoplasm;
KW Direct protein sequencing; Disease variant; Hydrolase;
KW Intellectual disability; Leucine-rich repeat; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8"
FT CHAIN 2..910
FT /note="p53-induced death domain-containing protein 1"
FT /id="PRO_0000245243"
FT CHAIN 2..445
FT /note="PIDD-N"
FT /evidence="ECO:0000269|PubMed:17159900"
FT /id="PRO_0000445715"
FT CHAIN 446..910
FT /note="PIDD-C"
FT /evidence="ECO:0000269|PubMed:17159900"
FT /id="PRO_0000445716"
FT CHAIN 589..910
FT /note="PIDD-CC"
FT /evidence="ECO:0000269|PubMed:17159900"
FT /id="PRO_0000445717"
FT REPEAT 126..147
FT /note="LRR 1"
FT REPEAT 149..171
FT /note="LRR 2"
FT REPEAT 172..194
FT /note="LRR 3"
FT REPEAT 195..216
FT /note="LRR 4"
FT REPEAT 218..240
FT /note="LRR 5"
FT REPEAT 241..263
FT /note="LRR 6"
FT REPEAT 264..285
FT /note="LRR 7"
FT DOMAIN 322..454
FT /note="ZU5 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 455..596
FT /note="ZU5 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 788..873
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..452
FT /note="Peptidase S68"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT REGION 566..594
FT /note="Peptidase S68"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT REGION 580..716
FT /note="UPA domain"
FT /evidence="ECO:0000250"
FT REGION 884..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 444
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485,
FT ECO:0000269|PubMed:17159900"
FT ACT_SITE 446
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485,
FT ECO:0000269|PubMed:17159900"
FT ACT_SITE 586
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485,
FT ECO:0000269|PubMed:17159900"
FT ACT_SITE 588
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485,
FT ECO:0000269|PubMed:17159900"
FT SITE 445..446
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17159900"
FT SITE 587..588
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17159900"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|Ref.8"
FT VAR_SEQ 1..492
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_019664"
FT VAR_SEQ 1..313
FT /note="Missing (in isoform 4, isoform 5 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.5"
FT /id="VSP_019665"
FT VAR_SEQ 1..146
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10825539"
FT /id="VSP_019666"
FT VAR_SEQ 579..589
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10825539"
FT /id="VSP_019667"
FT VAR_SEQ 585..621
FT /note="THFSWYWLWYTTKNCVGGLARKAWERLRLHRVNLIAL -> LALVHHQELCG
FT RPGSEGLGAAAAAPCEPHRSAAAPGP (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019668"
FT VAR_SEQ 589
FT /note="W -> WSVPPSFLSPPPPVCTALLTPSSPR (in isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.5"
FT /id="VSP_019669"
FT VAR_SEQ 622..910
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019670"
FT VAR_SEQ 704..720
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5"
FT /id="VSP_019671"
FT VAR_SEQ 759..815
FT /note="RLRGSEGPRRGAGLSLAPLNLGDAETGFLTQSNLLSVAGRLGLDWPAVALHL
FT GVSYR -> VGLRDSRGAGQDRGPGVTRVTWWSWGWSPGLNALFPSNRDFEGPRGHGGG
FT LASPWHP (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.5"
FT /id="VSP_019672"
FT VAR_SEQ 816..910
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.5"
FT /id="VSP_019673"
FT VARIANT 331
FT /note="Q -> R (in dbSNP:rs10902221)"
FT /evidence="ECO:0000269|PubMed:10825539,
FT ECO:0000269|PubMed:10973264, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT /id="VAR_028031"
FT VARIANT 863..910
FT /note="Missing (probable disease-associated variant found
FT in two unrelated families with intellectual disability)"
FT /evidence="ECO:0000269|PubMed:28397838"
FT /id="VAR_080765"
FT MUTAGEN 444
FT /note="H->Q: Loss of the proteolytic cleavage producing
FT PIDD-C."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 445
FT /note="F->H,W: Loss of the proteolytic cleavage producing
FT PIDD-C."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 446
FT /note="S->A: Loss of the proteolytic cleavage producing
FT PIDD-C. Unable to translocate to the nucleus upon DNA
FT damage. No effect on the ability to activate CASP2.
FT Complete loss of proteolytic cleavage; when associated with
FT A-588."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 446
FT /note="S->C: No effect on the proteolytic cleavage
FT producing PIDD-C."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 582
FT /note="F->A: Loss of the proteolytic cleavage producing
FT PIDD-CC."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 587
FT /note="F->H: Loss of the proteolytic cleavage producing
FT PIDD-CC."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 588
FT /note="S->A: Loss of the proteolytic cleavage producing
FT PIDD-CC. Loss of interaction with CRADD and of the ability
FT to activate CASP2. No effect on translocation to the
FT nucleus upon DNA damage. Complete loss of proteolytic
FT cleavage; when associated with A-446."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 588
FT /note="S->C: No effect on the proteolytic cleavage
FT producing PIDD-CC."
FT /evidence="ECO:0000269|PubMed:17159900"
FT MUTAGEN 801
FT /note="L->A: No effect on complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 814
FT /note="Y->A: Loss of complex assembly with CRADD. Loss of
FT PIDDosome assembly. Loss of CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 815
FT /note="R->A: Partial loss of complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 815
FT /note="R->E: Loss of complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 825
FT /note="R->A: Partial loss of complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 825
FT /note="R->E: Partial loss of complex assembly with CRADD.
FT Decreased PIDDosome assembly. Decreased CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 826
FT /note="D->K: Partial loss of complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 828
FT /note="L->E: Loss of complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 830
FT /note="E->K: No effect on complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 837
FT /note="F->D: Loss of complex assembly with CRADD. Loss of
FT PIDDosome assembly. Loss of CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 862
FT /note="R->A: Loss of complex assembly with CRADD. Loss of
FT PIDDosome assembly. Loss of CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 863
FT /note="Q->A: Partial loss of complex assembly with CRADD."
FT /evidence="ECO:0000269|PubMed:17289572"
FT CONFLICT 335
FT /note="V -> A (in Ref. 4; BAC11272)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="W -> L (in Ref. 3; AAP97716)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="S -> F (in Ref. 4; BAC11272)"
FT /evidence="ECO:0000305"
FT CONFLICT 512
FT /note="A -> V (in Ref. 6; CAD38708)"
FT /evidence="ECO:0000305"
FT CONFLICT 601
FT /note="G -> E (in Ref. 6; CAD38708)"
FT /evidence="ECO:0000305"
FT CONFLICT 895
FT /note="A -> V (in Ref. 1; AAF69491)"
FT /evidence="ECO:0000305"
FT TURN 782..784
FT /evidence="ECO:0007829|PDB:2OF5"
FT HELIX 789..797
FT /evidence="ECO:0007829|PDB:2OF5"
FT HELIX 803..809
FT /evidence="ECO:0007829|PDB:2OF5"
FT HELIX 814..823
FT /evidence="ECO:0007829|PDB:2OF5"
FT TURN 824..826
FT /evidence="ECO:0007829|PDB:2OF5"
FT HELIX 828..841
FT /evidence="ECO:0007829|PDB:2OF5"
FT HELIX 849..859
FT /evidence="ECO:0007829|PDB:2OF5"
FT HELIX 863..872
FT /evidence="ECO:0007829|PDB:2OF5"
SQ SEQUENCE 910 AA; 99712 MW; 8C98FC64230B57F8 CRC64;
MAATVEGPEL EAAAAAGDAS EDSDAGSRAL PFLGGNRLSL DLYPGGCQQL LHLCVQQPLQ
LLQVEFLRLS THEDPQLLEA TLAQLPQSLS CLRSLVLKGG QRRDTLGACL RGALTNLPAG
LSGLAHLAHL DLSFNSLETL PACVLQMRGL GALLLSHNCL SELPEALGAL PALTFLTVTH
NRLQTLPPAL GALSTLQRLD LSQNLLDTLP PEIGGLGSLL ELNLASNRLQ SLPASLAGLR
SLRLLVLHSN LLASVPADLA RLPLLTRLDL RDNQLRDLPP ELLDAPFVRL QGNPLGEASP
DAPSSPVAAL IPEMPRLFLT SDLDSFPVTP QGCSVTLACG VRLQFPAGAT ATPITIRYRL
LLPEPGLVPL GPHDALLSHV LELQPHGVAF QQDVGLWLLF TPPQARRCRE VVVRTRNDNS
WGDLETYLEE EAPQRLWAHC QVPHFSWFLV VSRPVSNACL VPPEGTLLCS SGHPGVKVIF
PPGATEEPRR VSMQVVRMAG RELQALLGEP EAAVSPLLCL SQSGPPSFLQ PVTVQLPLPS
GITGLSLDRS RLHLLYWAPP AATWDDITAQ VVLELTHLYA RFQVTHFSWY WLWYTTKNCV
GGLARKAWER LRLHRVNLIA LQRRRDPEQV LLQCLPRNKV DATLRRLLER YRGPEPSDTV
EMFEGEEFFA AFERGIDVDA DRPDCVEGRI CFVFYSHLKN VKEVYVTTTL DREAQAVRGQ
VSFYRGAVPV RVPEEAEAAR QRKGADALWM ATLPIKLPRL RGSEGPRRGA GLSLAPLNLG
DAETGFLTQS NLLSVAGRLG LDWPAVALHL GVSYREVQRI RHEFRDDLDE QIRHMLFSWA
ERQAGQPGAV GLLVQALEQS DRQDVAEEVR AVLELGRRKY QDSIRRMGLA PKDPALPGSS
APQPPEPAQA
