LRDD

Leucine-rich repeats and death domain containing, also known as LRDD or p53-induced protein with a death domain (PIDD), is a protein which in humans is encoded by the LRDD gene.[5]

PIDD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2OF5
Identifiers
Aliases	PIDD1, LRDD, PIDD, p53-induced death domain protein 1
External IDs	OMIM: 605247 MGI: 1889507 HomoloGene: 11220 GeneCards: PIDD1
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.5 Start 799,179 bp[1] End 809,753 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F5 Start 141,438,113 bp[2] End 141,444,025 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • death receptor binding • GO:0001948 protein binding • volume-sensitive anion channel activity • endopeptidase activity • hydrolase activity Cellular component • Golgi apparatus • cell nucleus • nucleoplasm • cytoplasm • cytosol • ion channel complex Biological process • positive regulation of extrinsic apoptotic signaling pathway via death domain receptors • apoptotic process • positive regulation of extrinsic apoptotic signaling pathway • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest • negative regulation of apoptotic process • positive regulation of apoptotic signaling pathway • activation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of NF-kappaB transcription factor activity • signal transduction • cellular response to DNA damage stimulus • positive regulation of apoptotic process • regulation of apoptotic process • inorganic anion transport • anion transmembrane transport • protein autoprocessing • regulation of I-kappaB kinase/NF-kappaB signaling • extrinsic apoptotic signaling pathway via death domain receptors • apoptotic signaling pathway • extrinsic apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55367	57913
Ensembl	ENSG00000177595	ENSMUSG00000025507
UniProt	Q9HB75	Q9ERV7
RefSeq (mRNA)	NM_018494 NM_145886 NM_145887	NM_022654 NM_001360523 NM_001360524
RefSeq (protein)	NP_665893 NP_665894	NP_073145 NP_001347452 NP_001347453
Location (UCSC)	Chr 11: 0.8 – 0.81 Mb	Chr 7: 141.44 – 141.44 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene contains a leucine-rich repeat and a death domain. This protein has been shown to interact with other death domain proteins, such as Fas (TNFRSF6)-associated via death domain (FADD) and MAP-kinase activating death domain-containing protein (MADD), and thus may function as an adaptor protein in cell death-related signaling processes. The expression of the mouse counterpart of this gene has been found to be positively regulated by the tumor suppressor p53 and to induce cell apoptosis in response to DNA damage, which suggests a role for this gene as an effector of p53-dependent apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been reported.[5] Besides its pro-apoptotic function it may also be involved in DNA repair as part of a protein complex formed together with the catalytic subunit of DNA-PK (DNA-PKcs)and caspase 2.

References

1. GRCh38: Ensembl release 89: ENSG00000177595 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025507 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: LRDD leucine-rich repeats and death domain containing".

Further reading

• Telliez JB, Bean KM, Lin LL (2000). "LRDD, a novel leucine rich repeat and death domain containing protein". Biochim. Biophys. Acta. 1478 (2): 280–8. doi:10.1016/S0167-4838(00)00029-7. PMID 10825539.
• Lin Y, Ma W, Benchimol S (2000). "Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis". Nat. Genet. 26 (1): 122–7. doi:10.1038/79102. PMID 10973264.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Tinel A, Tschopp J (2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress". Science. 304 (5672): 843–6. doi:10.1126/science.1095432. PMID 15073321.
• Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Janssens S, Tinel A, Lippens S, Tschopp J (2006). "PIDD mediates NF-kappaB activation in response to DNA damage". Cell. 123 (6): 1079–92. doi:10.1016/j.cell.2005.09.036. PMID 16360037.
• Vakifahmetoglu H, Olsson M, Orrenius S, Zhivotovsky B (2006). "Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage". Oncogene. 25 (41): 5683–92. doi:10.1038/sj.onc.1209569. PMID 16652156.
• Pick R, Badura S, Bösser S, Zörnig M (2006). "Upon intracellular processing, the C-terminal death domain-containing fragment of the p53-inducible PIDD/LRDD protein translocates to the nucleoli and interacts with nucleolin". Biochem. Biophys. Res. Commun. 349 (4): 1329–38. doi:10.1016/j.bbrc.2006.08.176. PMID 16982033.
• Tinel A, Janssens S, Lippens S, et al. (2007). "Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway". EMBO J. 26 (1): 197–208. doi:10.1038/sj.emboj.7601473. PMC 1782377. PMID 17159900.
• Park HH, Wu H (2007). "Crystallization and preliminary X-ray crystallographic studies of the oligomeric death-domain complex between PIDD and RAIDD". Acta Crystallographica Section F. 63 (Pt 3): 229–32. doi:10.1107/S1744309107007889. PMC 2330181. PMID 17329820.
• Bradley G, Tremblay S, Irish J, et al. (2007). "The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma". Br. J. Cancer. 96 (9): 1425–32. doi:10.1038/sj.bjc.6603745. PMC 2360189. PMID 17437012.