LRDD (Homo sapiens)

Description [+]

Synonyms: LRDD, PIDD, MGC16925, DKFZP434D229
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Leucine-rich repeat and death domain-containing protein (p53-induced protein with a death domain) [Source:UniProtKB/Swiss-Prot;Acc:Q9HB75]
Family: Death Domain-containing protein : DD adapter protein
Process:
Pathways:
Criteria: manually curated
Curator comment:
Mouse ortholog(s): Lrdd
WIKI: LRDD-H_sapiens

References [+]

Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis.
Lin Y, Ma W, Benchimol S
The p53 tumour suppressor promotes cell-cycle arrest or apoptosis in response to cellular stress, such as DNA damage and oncogenesis. This role of p53 is important for its tumour-suppression function and depends, at least in part, on its ability to bind to specific DNA sequences and activate the transcription of target genes. The pathway through which p53 promotes apoptosis is not fully understood. Here we describe a new gene regulated by p53 that encodes a predicted protein of 915 amino acids in mice (910 amino acids in humans), which we have named Pidd. The mouse Pidd cDNA contains a p53 consensus DNA binding sequence upstream of the Pidd-coding region. This sequence element bound to p53 and conferred p53-dependent inducibility on a heterologous reporter gene. Moreover, Pidd RNA was induced by ionizing radiation in a p53-dependent manner and the basal level of Pidd RNA was dependent on Trp53 status. Overexpression of Pidd inhibited cell growth in a p53-like manner by inducing apoptosis. Antisense inhibition of Pidd expression attenuated p53-mediated apoptosis. Our data suggest that Pidd is an effector of p53-dependent apoptosis. Nat Genet. 2000 Sep;26(1):122-7.

The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress.
Tinel A, Tschopp J
Apoptosis is triggered by activation of initiator caspases upon complex-mediated clustering of the inactive zymogen, as occurs in the caspase-9-activating apoptosome complex. Likewise, caspase-2, which is involved in stress-induced apoptosis, is recruited into a large protein complex, the molecular composition of which remains elusive. We show that activation of caspase-2 occurs in a complex that contains the death domain-containing protein PIDD, whose expression is induced by p53, and the adaptor protein RAIDD. Increased PIDD expression resulted in spontaneous activation of caspase-2 and sensitization to apoptosis by genotoxic stimuli. Because PIDD functions in p53-mediated apoptosis, the complex assembled by PIDD and caspase-2 is likely to regulate apoptosis induced by genotoxins. Science. 2004 May 7;304(5672):843-6. Epub 2004 Apr 8.

References from Mouse ortholog(s):

Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis.
Lin Y, Ma W, Benchimol S
The p53 tumour suppressor promotes cell-cycle arrest or apoptosis in response to cellular stress, such as DNA damage and oncogenesis. This role of p53 is important for its tumour-suppression function and depends, at least in part, on its ability to bind to specific DNA sequences and activate the transcription of target genes. The pathway through which p53 promotes apoptosis is not fully understood. Here we describe a new gene regulated by p53 that encodes a predicted protein of 915 amino acids in mice (910 amino acids in humans), which we have named Pidd. The mouse Pidd cDNA contains a p53 consensus DNA binding sequence upstream of the Pidd-coding region. This sequence element bound to p53 and conferred p53-dependent inducibility on a heterologous reporter gene. Moreover, Pidd RNA was induced by ionizing radiation in a p53-dependent manner and the basal level of Pidd RNA was dependent on Trp53 status. Overexpression of Pidd inhibited cell growth in a p53-like manner by inducing apoptosis. Antisense inhibition of Pidd expression attenuated p53-mediated apoptosis. Our data suggest that Pidd is an effector of p53-dependent apoptosis. Nat Genet. 2000 Sep;26(1):122-7.

Caspase-2 activation in the absence of PIDDosome formation.
Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A
PIDD (p53-induced protein with a death domain [DD]), together with the bipartite adapter protein RAIDD (receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a DD), is implicated in the activation of pro-caspase-2 in a high molecular weight complex called the PIDDosome during apoptosis induction after DNA damage. To investigate the role of PIDD in cell death initiation, we generated PIDD-deficient mice. Processing of caspase-2 is readily detected in the absence of PIDDosome formation in primary lymphocytes. Although caspase-2 processing is delayed in simian virus 40-immortalized pidd(-/-) mouse embryonic fibroblasts, it still depends on loss of mitochondrial integrity and effector caspase activation. Consistently, apoptosis occurs normally in all cell types analyzed, suggesting alternative biological roles for caspase-2 after DNA damage. Because loss of either PIDD or its adapter molecule RAIDD did not affect subcellular localization, nuclear translocation, or caspase-2 activation in high molecular weight complexes, we suggest that at least one alternative PIDDosome-independent mechanism of caspase-2 activation exists in mammals in response to DNA damage. J Cell Biol. 2009 Apr 20;185(2):291-303. Epub 2009 Apr 13.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	Peptidase_S68	421	454
PFAM A	Death	787	873

Protein sequence [+]

Structure links:

Smartdomain prediction information: SM00369
Smartdomain prediction information: SM00364
Smartdomain prediction information: SM00218
Smartdomain prediction information: SM00005
Profile motif and domain profile information: PS50319
Profile motif and domain profile information: PS50017
Profile motif and domain profile information: PS51145
Interpro domain information: Q9HB75
PFAM domain and domain family information: Q9HB75
Protein 3D structures from PDB: 2OF5

Evolution [+]

View protein alignment and tree with Jalview:

Explore tree at phylomeDB: Click here.

Homologs list [+]

Name	Relationship	Species
LRDD	orthology	Chicken
LRDD	orthology	Chimpanzee
XR_042560.1	orthology	Cow
LRDD	orthology	Dog
LRDD	orthology	Fugu
LRDD	orthology	Gasterosteus
LRDD	orthology	Gorilla
LRDD	orthology	Lyzard
LRDD	orthology	Macaca
LRDD	orthology	Medaka
LRDD	orthology	Monodelphis
Lrdd	orthology	Mouse
LRDD	orthology	Orangutan
Lrdd	orthology	Rat
LRDD	orthology	Tetraodon
LRDD	orthology	Zebra finch
A_aegypti_AAEL013466-PA	paralogy	Aedes
A_gambiae_AGAP009937-PA	paralogy	Anopheles
Ank	paralogy	Fly
ANK1	paralogy	Gorilla
ANK3	paralogy	Horse
ANK3	paralogy	Lyzard
ANK1	paralogy	Macaca
ANK1 (1 of 2)	paralogy	Medaka
ANK1	paralogy	Orangutan
ANK3	paralogy	Ornithorhynchus
ANK1	paralogy	Zebra finch
ANK1	paralogy	Zebrafish

Download tree (Newick format): Click here.

Display HTML alignment Click here.

Download alignment (Fasta format): Click here.

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Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0007165	signal transduction	biological_proccess	IEA
GO:0007165	signal transduction	biological_proccess	TAS
GO:0006915	apoptosis	biological_proccess	IEA
GO:0005515	protein binding	mollecular_function	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0005123	death receptor binding	mollecular_function	TAS
GO:0005634	nucleus	cell_component	IEA
GO:0005737	cytoplasm	cell_component	IEA

KEGG Pathways [+]

Curated Isoforms [+]

Transcript	Translation
OTTHUMT00000257103 *	OTTHUMP00000164429 *

Information from other databases [+]

Gene related links:

Gene info from HGNC [?] :16491
Gene related info from GeneCards [?] : LRDD
Ensembl genome browser [?] : ENSG00000177595
Expression info from Arrayexpress [?] : ENSG00000177595
Protein expression from Protein Atlas: [?] ENSG00000177595
Community gene edition from Wikigenes: [?] 55367

Protein related links:

Uniprot protein info: Q9HB75
PIR protein info: Q9HB75
Protein interactions from IntAct: Q9HB75

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 605247
OMIM disease information:

Other links

entrezgene: 55367
refseq_dna: NM_018494
refseq_dna: NM_145886
refseq_dna: NM_145887
refseq_peptide: NP_060964
refseq_peptide: NP_665894
refseq_peptide: NP_665893

Click on [?] for more information.