CRADD (Homo sapiens)
Description [+]
- Synonyms: CRADD, RAIDD
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Death domain-containing protein CRADD (Caspase and RIP adapter with death domain)(RIP-associated protein with a death domain) [Source:UniProtKB/Swiss-Prot;Acc:P78560]
- Family: Death Domain-containing protein : DD adapter protein
- Process: apoptosis,
- Pathways:
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Cradd
- WIKI: CRADD-H_sapiens
References [+]
- RAIDD is a new 'death' adaptor molecule.
- Duan H, Dixit VM
- The effector arm of the cell-death pathway is composed of cysteine proteases belonging to the ICE/CED-3 family. In metazoan cells these exist as inactive polypeptide precursors (zymogens), each composed of a prodomain, which is cleaved to activate the protease, and a large and small catalytic subunit. The coupling of these 'death' proteases to signalling pathways is probably mediated by adaptor molecules that contain protein-protein interaction motifs such as the death domain. Here we describe such an adaptor molecule, RAIDD, which has an unusual bipartite architecture comprising a carboxy-terminal death domain that binds to the homologous domain in RIP, a serine/threonine kinase component of the death pathway. The amino-terminal domain is surprisingly homologous with the sequence of the prodomain of two ICE/CED-3 family members, human ICH-1 (ref. 5) and Caenorhabditis elegans CED-3 (ref. 6). This similar region mediates the binding of RAIDD to ICH-1 and CED-3, serving as a direct link to the death proteases, indicating that the prodomain may, through homophilic interactions, determine the specificity of binding of ICE/CED-3 zymogens to regulatory adaptor molecules. Finally, alternations in the sequence of the N-terminal domain that are equivalent to inactivating mutations in the C. elegans ced-3 gene prevent homophilic binding, highlighting the potentially primordial nature of this interaction. Nature. 1997 Jan 2;385(6611):86-9.
- 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.
- RAIDD is required for apoptosis of PC12 cells and sympathetic neurons induced by trophic factor withdrawal.
- Wang Q, Maniati M, Jabado O, Pavlaki M, Troy CM, Greene LA, Stefanis L
- Caspase 2 has been implicated in trophic deprivation-induced neuronal death. We have shown that overexpression of the caspase 2-binding protein RAIDD induces neuronal apoptosis, acting synergistically with trophic deprivation. Currently, we examine the role of endogenous RAIDD in apoptosis of PC12 cells and sympathetic neurons. Expression of a truncated caspase recruitment domain-only form of caspase 2, which presumably disrupts the RAIDD interaction with endogenous caspase 2, attenuated trophic deprivation-induced apoptosis. Furthermore, downregulation of RAIDD by small interfering RNA led to inhibition of trophic deprivation-induced death, whereas death induced by DNA damage, which is not caspase 2-mediated, was not inhibited. Therefore, RAIDD, likely through interaction with caspase 2, is involved in trophic deprivation-induced neuronal apoptosis. This is the first demonstration of the involvement of RAIDD in apoptosis, and provides further support for the idea that apoptotic pathways in the same system may differ depending on the initiating stimulus. Cell Death Differ. 2006 Jan;13(1):75-83.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | CARD | 6 | 89 |
| PFAM A | Death | 117 | 198 |
Protein sequence [+]
CRADD | Homo sapiens | 9606 | length:199
MEARDKQVLRSLRLELGAEVLVEGLVLQYLYQEGILTENHIQEINAQTTGLRKTMLLLDI
LPSRGPKAFDTFLDSLQEFPWVREKLKKAREEAMTDLPAGDRLTGIPSHILNSSPSDRQI
NQLAQRLGPEWEPMVLSLGLSQTDIYRCKANHPHNVQSQVVEAFIRWRQRFGKQATFQSL
HNGLRAVEVDPSLLLHMLE
LPSRGPKAFDTFLDSLQEFPWVREKLKKAREEAMTDLPAGDRLTGIPSHILNSSPSDRQI
NQLAQRLGPEWEPMVLSLGLSQTDIYRCKANHPHNVQSQVVEAFIRWRQRFGKQATFQSL
HNGLRAVEVDPSLLLHMLE
Structure links:
- Smartdomain prediction information: SM00114
- Smartdomain prediction information: SM00005
- Prosite motif and domain information: PS00290
- Profile motif and domain profile information: PS50209
- Profile motif and domain profile information: PS50017
- Interpro domain information: P78560
- PFAM domain and domain family information: P78560
- Protein 3D structures from PDB: 2O71 2OF5
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_001025919.1 | orthology | Chicken |
| CRADD | orthology | Chimpanzee |
| NP_001077242.1 | orthology | Cow |
| CRADD | orthology | Dog |
| CRADD | orthology | Fugu |
| CRADD | orthology | Gasterosteus |
| CRADD | orthology | Horse |
| CRADD | orthology | Lyzard |
| CRADD | orthology | Macaca |
| CRADD | orthology | Medaka |
| CRADD | orthology | Monodelphis |
| Cradd | orthology | Mouse |
| CRADD_PONPY | orthology | Orangutan |
| CRADD | orthology | Ornithorhynchus |
| CRADD | orthology | Rabbit |
| Cradd | orthology | Rat |
| CRADD | orthology | Tetraodon |
| X_tropicalis_ENSXETP00000033446 | orthology | Xenopus |
| cradd | orthology | Xenopus |
| CRADD | orthology | Zebra finch |
| zgc:101717 | orthology | Zebrafish |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| CASP2 | paralogy | Fugu |
| CASP2 | paralogy | Gasterosteus |
| CASP2 | paralogy | Lyzard |
| CASP2 | paralogy | Medaka |
| FADD | paralogy | Monodelphis |
| CASP2 | paralogy | Tetraodon |
| casp2 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006917 | induction of apoptosis | biological_proccess | IDA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0007165 | signal transduction | biological_proccess | IEA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0008625 | induction of apoptosis via death domain receptors | biological_proccess | TAS |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0070513 | death domain binding | mollecular_function | IPI |
| GO:0002020 | protease binding | mollecular_function | IPI |
| GO:0030674 | protein binding, bridging | mollecular_function | IPI |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from HGNC [?] :2340
- Gene related info from GeneCards [?] : CRADD
- Ensembl genome browser [?] : ENSG00000169372
- Expression info from Arrayexpress [?] : ENSG00000169372
- Protein expression from Protein Atlas: [?] ENSG00000169372
- Community gene edition from Wikigenes: [?] 8738
- OMIM gene information: 603454
- OMIM disease information:
Click on [?] for more information.
