Full text data of CRADD
CRADD
(RAIDD)
[Confidence: low (only semi-automatic identification from reviews)]
Death domain-containing protein CRADD (Caspase and RIP adapter with death domain; RIP-associated protein with a death domain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Death domain-containing protein CRADD (Caspase and RIP adapter with death domain; RIP-associated protein with a death domain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P78560
ID CRADD_HUMAN Reviewed; 199 AA.
AC P78560;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1997, sequence version 1.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Death domain-containing protein CRADD;
DE AltName: Full=Caspase and RIP adapter with death domain;
DE AltName: Full=RIP-associated protein with a death domain;
GN Name=CRADD; Synonyms=RAIDD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9044836;
RA Ahmad M., Srinivasula S.M., Wang L., Talanian R.V., Litwack G.,
RA Fernandes-Alnemri T., Alnemri E.S.;
RT "CRADD, a novel human apoptotic adaptor molecule for caspase-2, and
RT FasL/tumor necrosis factor receptor-interacting protein RIP.";
RL Cancer Res. 57:615-619(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8985253; DOI=10.1038/385086a0;
RA Duan H., Dixit V.M.;
RT "RAIDD is a new 'death' adaptor molecule.";
RL Nature 385:86-89(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH PIDD.
RX PubMed=15073321; DOI=10.1126/science.1095432;
RA Tinel A., Tschopp J.;
RT "The PIDDosome, a protein complex implicated in activation of caspase-
RT 2 in response to genotoxic stress.";
RL Science 304:843-846(2004).
RN [5]
RP INTERACTION WITH PIDD.
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
RT apoptosis induced by DNA damage.";
RL Oncogene 25:5683-5692(2006).
RN [6]
RP STRUCTURE BY NMR OF 1-100.
RX PubMed=9695946; DOI=10.1016/S0092-8674(00)81417-8;
RA Chou J.J., Matsuo H., Duan H., Wagner G.;
RT "Solution structure of the RAIDD CARD and model for CARD/CARD
RT interaction in caspase-2 and caspase-9 recruitment.";
RL Cell 94:171-180(1998).
RN [7]
RP VARIANT MRT34 ARG-128.
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.,
RA Lawrence J.J., Mahoney M.H., Miller C.J., Nair D.T., Politi K.A.,
RA Worcester K.N., Setton R.A., Dipiazza R., Sherman E.A., Eastman J.T.,
RA Francklyn C., Robey-Bond S., Rider N.L., Gabriel S., Morton D.H.,
RA Strauss K.A.;
RT "Genetic mapping and exome sequencing identify variants associated
RT with five novel diseases.";
RL PLoS ONE 7:E28936-E28936(2012).
CC -!- FUNCTION: Apoptotic adaptor molecule specific for caspase-2 and
CC FASL/TNF receptor-interacting protein RIP. In the presence of RIP
CC and TRADD, CRADD recruits caspase-2 to the TNFR-1 signalling
CC complex.
CC -!- SUBUNIT: Interacts with PIDD.
CC -!- INTERACTION:
CC P42575:CASP2; NbExp=9; IntAct=EBI-520375, EBI-520342;
CC Q9HB75:PIDD; NbExp=8; IntAct=EBI-520375, EBI-520427;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- TISSUE SPECIFICITY: Constitutively expressed in most tissues, with
CC particularly high expression in adult heart, testis, liver,
CC skeletal muscle, fetal liver and kidney.
CC -!- DOMAIN: Contains a death domain involved in the binding of RIP
CC protein.
CC -!- DOMAIN: The CARD domain mediates the interaction with caspase-2.
CC -!- DISEASE: Mental retardation, autosomal recessive 34 (MRT34)
CC [MIM:614499]: A disorder characterized by significantly below
CC average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. MRT34 is a non-syndromic form. Affected
CC individuals have mildly delayed development and significantly
CC impaired cognitive function, precluding independent living and
CC self-care. Speech is rudimentary, but articulate; autism is not
CC present. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Contains 1 CARD domain.
CC -!- SIMILARITY: Contains 1 death domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U84388; AAC50952.1; -; mRNA.
DR EMBL; U79115; AAB42217.1; -; mRNA.
DR EMBL; BC017042; AAH17042.1; -; mRNA.
DR RefSeq; NP_003796.1; NM_003805.3.
DR UniGene; Hs.38533; -.
DR UniGene; Hs.591016; -.
DR PDB; 2O71; X-ray; 2.00 A; A=95-199.
DR PDB; 2OF5; X-ray; 3.20 A; A/B/C/D/E/F/G=94-199.
DR PDB; 3CRD; NMR; -; A=1-100.
DR PDBsum; 2O71; -.
DR PDBsum; 2OF5; -.
DR PDBsum; 3CRD; -.
DR ProteinModelPortal; P78560; -.
DR SMR; P78560; 1-100, 109-199.
DR IntAct; P78560; 11.
DR MINT; MINT-1520976; -.
DR STRING; 9606.ENSP00000327647; -.
DR DMDM; 2498833; -.
DR PaxDb; P78560; -.
DR PRIDE; P78560; -.
DR DNASU; 8738; -.
DR Ensembl; ENST00000332896; ENSP00000327647; ENSG00000169372.
DR Ensembl; ENST00000542893; ENSP00000439068; ENSG00000169372.
DR GeneID; 8738; -.
DR KEGG; hsa:8738; -.
DR UCSC; uc001tda.3; human.
DR CTD; 8738; -.
DR GeneCards; GC12P094004; -.
DR HGNC; HGNC:2340; CRADD.
DR HPA; CAB005337; -.
DR MIM; 603454; gene.
DR MIM; 614499; phenotype.
DR neXtProt; NX_P78560; -.
DR Orphanet; 88616; Autosomal recessive nonsyndromic intellectual deficit.
DR PharmGKB; PA26860; -.
DR eggNOG; NOG41343; -.
DR HOGENOM; HOG000111965; -.
DR HOVERGEN; HBG051112; -.
DR InParanoid; P78560; -.
DR KO; K02832; -.
DR OMA; VRWRQRY; -.
DR SignaLink; P78560; -.
DR EvolutionaryTrace; P78560; -.
DR GeneWiki; CRADD; -.
DR GenomeRNAi; 8738; -.
DR NextBio; 32779; -.
DR PRO; PR:P78560; -.
DR ArrayExpress; P78560; -.
DR Bgee; P78560; -.
DR CleanEx; HS_CRADD; -.
DR Genevestigator; P78560; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP: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; IC:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom.
DR InterPro; IPR000488; Death_domain.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF00531; Death; 1.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00005; DEATH; 1.
DR SUPFAM; SSF47986; SSF47986; 2.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Complete proteome; Cytoplasm;
KW Disease mutation; Mental retardation; Nucleus; Reference proteome.
FT CHAIN 1 199 Death domain-containing protein CRADD.
FT /FTId=PRO_0000079326.
FT DOMAIN 1 91 CARD.
FT DOMAIN 116 188 Death.
FT VARIANT 128 128 G -> R (in MRT34).
FT /FTId=VAR_067536.
FT HELIX 5 18
FT HELIX 27 33
FT HELIX 38 44
FT STRAND 48 50
FT HELIX 51 60
FT TURN 61 63
FT HELIX 69 75
FT HELIX 79 92
FT HELIX 110 112
FT HELIX 117 126
FT HELIX 131 137
FT HELIX 142 151
FT HELIX 156 171
FT HELIX 172 174
FT HELIX 177 186
FT HELIX 192 197
SQ SEQUENCE 199 AA; 22745 MW; 3437CC612C85E402 CRC64;
MEARDKQVLR SLRLELGAEV LVEGLVLQYL YQEGILTENH IQEINAQTTG LRKTMLLLDI
LPSRGPKAFD TFLDSLQEFP WVREKLKKAR EEAMTDLPAG DRLTGIPSHI LNSSPSDRQI
NQLAQRLGPE WEPMVLSLGL SQTDIYRCKA NHPHNVQSQV VEAFIRWRQR FGKQATFQSL
HNGLRAVEVD PSLLLHMLE
//
ID CRADD_HUMAN Reviewed; 199 AA.
AC P78560;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1997, sequence version 1.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Death domain-containing protein CRADD;
DE AltName: Full=Caspase and RIP adapter with death domain;
DE AltName: Full=RIP-associated protein with a death domain;
GN Name=CRADD; Synonyms=RAIDD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9044836;
RA Ahmad M., Srinivasula S.M., Wang L., Talanian R.V., Litwack G.,
RA Fernandes-Alnemri T., Alnemri E.S.;
RT "CRADD, a novel human apoptotic adaptor molecule for caspase-2, and
RT FasL/tumor necrosis factor receptor-interacting protein RIP.";
RL Cancer Res. 57:615-619(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8985253; DOI=10.1038/385086a0;
RA Duan H., Dixit V.M.;
RT "RAIDD is a new 'death' adaptor molecule.";
RL Nature 385:86-89(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH PIDD.
RX PubMed=15073321; DOI=10.1126/science.1095432;
RA Tinel A., Tschopp J.;
RT "The PIDDosome, a protein complex implicated in activation of caspase-
RT 2 in response to genotoxic stress.";
RL Science 304:843-846(2004).
RN [5]
RP INTERACTION WITH PIDD.
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
RT apoptosis induced by DNA damage.";
RL Oncogene 25:5683-5692(2006).
RN [6]
RP STRUCTURE BY NMR OF 1-100.
RX PubMed=9695946; DOI=10.1016/S0092-8674(00)81417-8;
RA Chou J.J., Matsuo H., Duan H., Wagner G.;
RT "Solution structure of the RAIDD CARD and model for CARD/CARD
RT interaction in caspase-2 and caspase-9 recruitment.";
RL Cell 94:171-180(1998).
RN [7]
RP VARIANT MRT34 ARG-128.
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.,
RA Lawrence J.J., Mahoney M.H., Miller C.J., Nair D.T., Politi K.A.,
RA Worcester K.N., Setton R.A., Dipiazza R., Sherman E.A., Eastman J.T.,
RA Francklyn C., Robey-Bond S., Rider N.L., Gabriel S., Morton D.H.,
RA Strauss K.A.;
RT "Genetic mapping and exome sequencing identify variants associated
RT with five novel diseases.";
RL PLoS ONE 7:E28936-E28936(2012).
CC -!- FUNCTION: Apoptotic adaptor molecule specific for caspase-2 and
CC FASL/TNF receptor-interacting protein RIP. In the presence of RIP
CC and TRADD, CRADD recruits caspase-2 to the TNFR-1 signalling
CC complex.
CC -!- SUBUNIT: Interacts with PIDD.
CC -!- INTERACTION:
CC P42575:CASP2; NbExp=9; IntAct=EBI-520375, EBI-520342;
CC Q9HB75:PIDD; NbExp=8; IntAct=EBI-520375, EBI-520427;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- TISSUE SPECIFICITY: Constitutively expressed in most tissues, with
CC particularly high expression in adult heart, testis, liver,
CC skeletal muscle, fetal liver and kidney.
CC -!- DOMAIN: Contains a death domain involved in the binding of RIP
CC protein.
CC -!- DOMAIN: The CARD domain mediates the interaction with caspase-2.
CC -!- DISEASE: Mental retardation, autosomal recessive 34 (MRT34)
CC [MIM:614499]: A disorder characterized by significantly below
CC average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. MRT34 is a non-syndromic form. Affected
CC individuals have mildly delayed development and significantly
CC impaired cognitive function, precluding independent living and
CC self-care. Speech is rudimentary, but articulate; autism is not
CC present. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Contains 1 CARD domain.
CC -!- SIMILARITY: Contains 1 death domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U84388; AAC50952.1; -; mRNA.
DR EMBL; U79115; AAB42217.1; -; mRNA.
DR EMBL; BC017042; AAH17042.1; -; mRNA.
DR RefSeq; NP_003796.1; NM_003805.3.
DR UniGene; Hs.38533; -.
DR UniGene; Hs.591016; -.
DR PDB; 2O71; X-ray; 2.00 A; A=95-199.
DR PDB; 2OF5; X-ray; 3.20 A; A/B/C/D/E/F/G=94-199.
DR PDB; 3CRD; NMR; -; A=1-100.
DR PDBsum; 2O71; -.
DR PDBsum; 2OF5; -.
DR PDBsum; 3CRD; -.
DR ProteinModelPortal; P78560; -.
DR SMR; P78560; 1-100, 109-199.
DR IntAct; P78560; 11.
DR MINT; MINT-1520976; -.
DR STRING; 9606.ENSP00000327647; -.
DR DMDM; 2498833; -.
DR PaxDb; P78560; -.
DR PRIDE; P78560; -.
DR DNASU; 8738; -.
DR Ensembl; ENST00000332896; ENSP00000327647; ENSG00000169372.
DR Ensembl; ENST00000542893; ENSP00000439068; ENSG00000169372.
DR GeneID; 8738; -.
DR KEGG; hsa:8738; -.
DR UCSC; uc001tda.3; human.
DR CTD; 8738; -.
DR GeneCards; GC12P094004; -.
DR HGNC; HGNC:2340; CRADD.
DR HPA; CAB005337; -.
DR MIM; 603454; gene.
DR MIM; 614499; phenotype.
DR neXtProt; NX_P78560; -.
DR Orphanet; 88616; Autosomal recessive nonsyndromic intellectual deficit.
DR PharmGKB; PA26860; -.
DR eggNOG; NOG41343; -.
DR HOGENOM; HOG000111965; -.
DR HOVERGEN; HBG051112; -.
DR InParanoid; P78560; -.
DR KO; K02832; -.
DR OMA; VRWRQRY; -.
DR SignaLink; P78560; -.
DR EvolutionaryTrace; P78560; -.
DR GeneWiki; CRADD; -.
DR GenomeRNAi; 8738; -.
DR NextBio; 32779; -.
DR PRO; PR:P78560; -.
DR ArrayExpress; P78560; -.
DR Bgee; P78560; -.
DR CleanEx; HS_CRADD; -.
DR Genevestigator; P78560; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP: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; IC:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom.
DR InterPro; IPR000488; Death_domain.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF00531; Death; 1.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00005; DEATH; 1.
DR SUPFAM; SSF47986; SSF47986; 2.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Complete proteome; Cytoplasm;
KW Disease mutation; Mental retardation; Nucleus; Reference proteome.
FT CHAIN 1 199 Death domain-containing protein CRADD.
FT /FTId=PRO_0000079326.
FT DOMAIN 1 91 CARD.
FT DOMAIN 116 188 Death.
FT VARIANT 128 128 G -> R (in MRT34).
FT /FTId=VAR_067536.
FT HELIX 5 18
FT HELIX 27 33
FT HELIX 38 44
FT STRAND 48 50
FT HELIX 51 60
FT TURN 61 63
FT HELIX 69 75
FT HELIX 79 92
FT HELIX 110 112
FT HELIX 117 126
FT HELIX 131 137
FT HELIX 142 151
FT HELIX 156 171
FT HELIX 172 174
FT HELIX 177 186
FT HELIX 192 197
SQ SEQUENCE 199 AA; 22745 MW; 3437CC612C85E402 CRC64;
MEARDKQVLR SLRLELGAEV LVEGLVLQYL YQEGILTENH IQEINAQTTG LRKTMLLLDI
LPSRGPKAFD TFLDSLQEFP WVREKLKKAR EEAMTDLPAG DRLTGIPSHI LNSSPSDRQI
NQLAQRLGPE WEPMVLSLGL SQTDIYRCKA NHPHNVQSQV VEAFIRWRQR FGKQATFQSL
HNGLRAVEVD PSLLLHMLE
//
MIM
603454
*RECORD*
*FIELD* NO
603454
*FIELD* TI
*603454 CASP2 AND RIPK1 DOMAIN-CONTAINING ADAPTOR WITH DEATH DOMAIN; CRADD
;;CASPASE AND RIP ADAPTOR WITH DEATH DOMAIN;;
read moreRIP-ASSOCIATED ICH1/CED3-HOMOLOGOUS PROTEIN WITH DEATH DOMAIN; RAIDD
*FIELD* TX
CLONING
Caspases are a family of cysteine proteases related to ICE (147678) and
represent the effector arm of the cell death pathway. In metazoan cells,
caspases exist as inactive polypeptide precursors (zymogens), each of
which is composed of a large and small catalytic subunit and a
prodomain, which is cleaved to activate the protease. Adaptor molecules
containing protein-protein interaction motifs are thought to mediate the
coupling of these death proteases to signaling pathways. Duan and Dixit
(1997) isolated cDNAs encoding such an adaptor molecule, which they
designated RAIDD (RIP-associated ICH1/CED3-homologous protein with a
death domain). The predicted 199-amino acid protein contained an
N-terminal domain (NTD) homologous to the prodomain of ICH1 (CASP2;
600639) and a death domain (DD) similar to that found in RIP (603453).
The NTD mediated the binding of RAIDD to ICH1 in vitro and in vivo.
RAIDD specifically bound RIP, but not the DD-containing receptors FAS
(134637) or TNFR1 (191190), or the DD-containing receptor-associated
proteins FADD (602457) or TRADD (603500). However, coimmunoprecipitation
studies indicated that TNFR1 complexed with RAIDD in the presence of
TRADD and RIP, and through RAIDD, ICH1 was recruited to the signaling
complex. Overexpression of RAIDD in mammalian cells induced apoptosis.
Duan and Dixit (1997) concluded that RAIDD can function as an adaptor
molecule in recruiting the death protease ICH1 to the TNFR1 signaling
complex. Northern blot analysis revealed that RAIDD is expressed
ubiquitously as a 1.35-kb mRNA. Independently, Ahmad et al. (1997)
cloned cDNAs encoding RAIDD, which they called CRADD for 'caspase and
RIP adaptor with death domain.' Using in vitro binding studies, they
found that CRADD interacted specifically with RIP and CASP2.
GENE FUNCTION
Tinel and Tschopp (2004) showed that activation of caspase-2 occurs in a
complex that contains the death domain-containing protein PIDD (605247),
whose expression is induced by p53 (191170), 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, Tinel and Tschopp (2004)
concluded that the complex assembled by PIDD and caspase-2 is likely to
regulate apoptosis induced by genotoxins.
MAPPING
Horvat and Medrano (1998) analyzed clones spanning the region of mouse
chromosome 10 deleted in mutant 'high growth' (hg) mice. They found that
this deletion spans approximately 500 kb and includes the mouse Raidd
gene.
By analysis of a radiation hybrid panel, Horvat and Medrano (1998)
mapped the human RAIDD gene to 12q21.33-q23.1.
MOLECULAR GENETICS
By homozygosity mapping followed by exome sequencing of 5 Mennonite
patients with nonsyndromic autosomal recessive mental retardation-34
(MRT34; 614499), Puffenberger et al. (2012) identified a homozygous
mutation in the CRADD gene (G128R; 603454.0001). Seven heterozygous
carriers of this mutation were found among 203 Mennonite control
samples, yielding a population-specific allele frequency of 1.72%.
(Puffenberger (2012) stated that the correct population-specific allele
frequency data appear in Table 4; corresponding data in the text are
incorrect.)
*FIELD* AV
.0001
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34
CRADD, GLY128ARG
In 5 Mennonite patients with autosomal recessive nonsyndromic mental
retardation-34 (MRT34; 614499), Puffenberger et al. (2012) identified a
homozygous 382G-C transversion in the CRADD gene, resulting in a
gly128-to-arg (G128R) substitution in a highly conserved residue in the
CRADD death domain. The mutation was found by homozygosity mapping
followed by exome sequencing. Seven heterozygous carriers of this
mutation were found among 203 Mennonite control samples, yielding a
population-specific allele frequency of 1.72%. (Puffenberger (2012)
stated that the correct population-specific allele frequency data appear
in Table 4; corresponding data in the text are incorrect.)
Overexpression of mutant murine Cradd with the G128R mutation showed
normal protein localization to the nucleus and cytoplasm. However, when
co-overexpressed with wildtype Pidd (605247), mutant G128R Cradd formed
large cytoplasmic aggregates with a relative loss of Cradd expression in
the nucleus. The findings suggested that the G128R mutation alters 1 of
the interaction surfaces of the CRADD death domain to decrease affinity
for the PIDD death domain.
*FIELD* RF
1. Ahmad, M.; Srinivasula, S. M.; Wang, L.; Talanian, R. V.; Litwack,
G.; Fernandes-Alnemri, T.; Alnemri, E. S.: CRADD, a novel human apoptotic
adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting
protein RIP. Cancer Res. 57: 615-619, 1997.
2. Duan, H.; Dixit, V. M.: RAIDD is a new 'death' adaptor molecule. Nature 385:
86-89, 1997.
3. Horvat, S.; Medrano, J. F.: A 500-kb YAC and BAC contig encompassing
the high-growth deletion in mouse chromosome 10 and identification
of the murine Raidd/Cradd gene in the candidate region. Genomics 54:
159-164, 1998.
4. Puffenberger, E. G.: Personal Communication. Strasburg, Pa.
2/28/2012.
5. Puffenberger, E. G.; Jinks, R. N.; Sougnez, C.; Cibulskis, K.;
Willert, R. A.; Achilly, N. P.; Cassidy, R. P.; Fiorentini, C. J.;
Heiken, K. F.; Lawrence, J. J.; Mahoney, M. H.; Miller, C. J.; and
13 others: Genetic mapping and exome sequencing identify variants
associated with five novel diseases. PLoS One 7: e28936, 2012. Note:
Electronic Article.
6. Tinel, A.; Tschopp, J.: The PIDDosome, a protein complex implicated
in activation of caspase-2 in response to genotoxic stress. Science 304:
843-846, 2004.
*FIELD* CN
Cassandra L. Kniffin - updated: 2/27/2012
Ada Hamosh - updated: 7/29/2004
*FIELD* CD
Rebekah S. Rasooly: 1/22/1999
*FIELD* ED
carol: 03/05/2012
terry: 3/2/2012
ckniffin: 3/1/2012
ckniffin: 2/27/2012
alopez: 7/12/2010
tkritzer: 7/29/2004
terry: 7/29/2004
alopez: 5/11/1999
alopez: 2/8/1999
alopez: 1/22/1999
*RECORD*
*FIELD* NO
603454
*FIELD* TI
*603454 CASP2 AND RIPK1 DOMAIN-CONTAINING ADAPTOR WITH DEATH DOMAIN; CRADD
;;CASPASE AND RIP ADAPTOR WITH DEATH DOMAIN;;
read moreRIP-ASSOCIATED ICH1/CED3-HOMOLOGOUS PROTEIN WITH DEATH DOMAIN; RAIDD
*FIELD* TX
CLONING
Caspases are a family of cysteine proteases related to ICE (147678) and
represent the effector arm of the cell death pathway. In metazoan cells,
caspases exist as inactive polypeptide precursors (zymogens), each of
which is composed of a large and small catalytic subunit and a
prodomain, which is cleaved to activate the protease. Adaptor molecules
containing protein-protein interaction motifs are thought to mediate the
coupling of these death proteases to signaling pathways. Duan and Dixit
(1997) isolated cDNAs encoding such an adaptor molecule, which they
designated RAIDD (RIP-associated ICH1/CED3-homologous protein with a
death domain). The predicted 199-amino acid protein contained an
N-terminal domain (NTD) homologous to the prodomain of ICH1 (CASP2;
600639) and a death domain (DD) similar to that found in RIP (603453).
The NTD mediated the binding of RAIDD to ICH1 in vitro and in vivo.
RAIDD specifically bound RIP, but not the DD-containing receptors FAS
(134637) or TNFR1 (191190), or the DD-containing receptor-associated
proteins FADD (602457) or TRADD (603500). However, coimmunoprecipitation
studies indicated that TNFR1 complexed with RAIDD in the presence of
TRADD and RIP, and through RAIDD, ICH1 was recruited to the signaling
complex. Overexpression of RAIDD in mammalian cells induced apoptosis.
Duan and Dixit (1997) concluded that RAIDD can function as an adaptor
molecule in recruiting the death protease ICH1 to the TNFR1 signaling
complex. Northern blot analysis revealed that RAIDD is expressed
ubiquitously as a 1.35-kb mRNA. Independently, Ahmad et al. (1997)
cloned cDNAs encoding RAIDD, which they called CRADD for 'caspase and
RIP adaptor with death domain.' Using in vitro binding studies, they
found that CRADD interacted specifically with RIP and CASP2.
GENE FUNCTION
Tinel and Tschopp (2004) showed that activation of caspase-2 occurs in a
complex that contains the death domain-containing protein PIDD (605247),
whose expression is induced by p53 (191170), 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, Tinel and Tschopp (2004)
concluded that the complex assembled by PIDD and caspase-2 is likely to
regulate apoptosis induced by genotoxins.
MAPPING
Horvat and Medrano (1998) analyzed clones spanning the region of mouse
chromosome 10 deleted in mutant 'high growth' (hg) mice. They found that
this deletion spans approximately 500 kb and includes the mouse Raidd
gene.
By analysis of a radiation hybrid panel, Horvat and Medrano (1998)
mapped the human RAIDD gene to 12q21.33-q23.1.
MOLECULAR GENETICS
By homozygosity mapping followed by exome sequencing of 5 Mennonite
patients with nonsyndromic autosomal recessive mental retardation-34
(MRT34; 614499), Puffenberger et al. (2012) identified a homozygous
mutation in the CRADD gene (G128R; 603454.0001). Seven heterozygous
carriers of this mutation were found among 203 Mennonite control
samples, yielding a population-specific allele frequency of 1.72%.
(Puffenberger (2012) stated that the correct population-specific allele
frequency data appear in Table 4; corresponding data in the text are
incorrect.)
*FIELD* AV
.0001
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34
CRADD, GLY128ARG
In 5 Mennonite patients with autosomal recessive nonsyndromic mental
retardation-34 (MRT34; 614499), Puffenberger et al. (2012) identified a
homozygous 382G-C transversion in the CRADD gene, resulting in a
gly128-to-arg (G128R) substitution in a highly conserved residue in the
CRADD death domain. The mutation was found by homozygosity mapping
followed by exome sequencing. Seven heterozygous carriers of this
mutation were found among 203 Mennonite control samples, yielding a
population-specific allele frequency of 1.72%. (Puffenberger (2012)
stated that the correct population-specific allele frequency data appear
in Table 4; corresponding data in the text are incorrect.)
Overexpression of mutant murine Cradd with the G128R mutation showed
normal protein localization to the nucleus and cytoplasm. However, when
co-overexpressed with wildtype Pidd (605247), mutant G128R Cradd formed
large cytoplasmic aggregates with a relative loss of Cradd expression in
the nucleus. The findings suggested that the G128R mutation alters 1 of
the interaction surfaces of the CRADD death domain to decrease affinity
for the PIDD death domain.
*FIELD* RF
1. Ahmad, M.; Srinivasula, S. M.; Wang, L.; Talanian, R. V.; Litwack,
G.; Fernandes-Alnemri, T.; Alnemri, E. S.: CRADD, a novel human apoptotic
adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting
protein RIP. Cancer Res. 57: 615-619, 1997.
2. Duan, H.; Dixit, V. M.: RAIDD is a new 'death' adaptor molecule. Nature 385:
86-89, 1997.
3. Horvat, S.; Medrano, J. F.: A 500-kb YAC and BAC contig encompassing
the high-growth deletion in mouse chromosome 10 and identification
of the murine Raidd/Cradd gene in the candidate region. Genomics 54:
159-164, 1998.
4. Puffenberger, E. G.: Personal Communication. Strasburg, Pa.
2/28/2012.
5. Puffenberger, E. G.; Jinks, R. N.; Sougnez, C.; Cibulskis, K.;
Willert, R. A.; Achilly, N. P.; Cassidy, R. P.; Fiorentini, C. J.;
Heiken, K. F.; Lawrence, J. J.; Mahoney, M. H.; Miller, C. J.; and
13 others: Genetic mapping and exome sequencing identify variants
associated with five novel diseases. PLoS One 7: e28936, 2012. Note:
Electronic Article.
6. Tinel, A.; Tschopp, J.: The PIDDosome, a protein complex implicated
in activation of caspase-2 in response to genotoxic stress. Science 304:
843-846, 2004.
*FIELD* CN
Cassandra L. Kniffin - updated: 2/27/2012
Ada Hamosh - updated: 7/29/2004
*FIELD* CD
Rebekah S. Rasooly: 1/22/1999
*FIELD* ED
carol: 03/05/2012
terry: 3/2/2012
ckniffin: 3/1/2012
ckniffin: 2/27/2012
alopez: 7/12/2010
tkritzer: 7/29/2004
terry: 7/29/2004
alopez: 5/11/1999
alopez: 2/8/1999
alopez: 1/22/1999
MIM
614499
*RECORD*
*FIELD* NO
614499
*FIELD* TI
#614499 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34; MRT34
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read moremental retardation-34 (MRT34) is caused by homozygous mutation in the
CRADD gene (603454) on chromosome 12q.
CLINICAL FEATURES
Puffenberger et al. (2012) reported 5 Mennonite patients with
nonsyndromic mental retardation. Affected individuals had mildly delayed
development and significantly impaired cognitive function, precluding
independent living and self-care. Speech was rudimentary, but
articulate; autism was not present.
INHERITANCE
The transmission pattern in the families reported by Puffenberger et al.
(2012) was consistent with autosomal recessive inheritance.
MOLECULAR GENETICS
By homozygosity mapping followed by exome sequencing of 5 Mennonite
patients with nonsyndromic mental retardation, Puffenberger et al.
(2012) identified a homozygous mutation in the CRADD gene (G128R;
603454.0001). Seven heterozygous carriers of this mutation were found
among 203 Mennonite control samples, yielding a population-specific
allele frequency of 1.72%. (Puffenberger (2012) stated that the correct
population-specific allele frequency data appear in Table 4;
corresponding data in the text are incorrect.)
*FIELD* RF
1. Puffenberger, E. G.: Personal Communication. Strasburg, Pa.
2/28/2012.
2. Puffenberger, E. G.; Jinks, R. N.; Sougnez, C.; Cibulskis, K.;
Willert, R. A.; Achilly, N. P.; Cassidy, R. P.; Fiorentini, C. J.;
Heiken, K. F.; Lawrence, J. J.; Mahoney, M. H.; Miller, C. J.; and
13 others: Genetic mapping and exome sequencing identify variants
associated with five novel diseases. PLoS One 7: e28936, 2012. Note:
Electronic Article.
*FIELD* CD
Cassandra L. Kniffin: 2/27/2012
*FIELD* ED
carol: 03/05/2012
terry: 3/2/2012
ckniffin: 3/1/2012
ckniffin: 2/27/2012
*RECORD*
*FIELD* NO
614499
*FIELD* TI
#614499 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34; MRT34
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read moremental retardation-34 (MRT34) is caused by homozygous mutation in the
CRADD gene (603454) on chromosome 12q.
CLINICAL FEATURES
Puffenberger et al. (2012) reported 5 Mennonite patients with
nonsyndromic mental retardation. Affected individuals had mildly delayed
development and significantly impaired cognitive function, precluding
independent living and self-care. Speech was rudimentary, but
articulate; autism was not present.
INHERITANCE
The transmission pattern in the families reported by Puffenberger et al.
(2012) was consistent with autosomal recessive inheritance.
MOLECULAR GENETICS
By homozygosity mapping followed by exome sequencing of 5 Mennonite
patients with nonsyndromic mental retardation, Puffenberger et al.
(2012) identified a homozygous mutation in the CRADD gene (G128R;
603454.0001). Seven heterozygous carriers of this mutation were found
among 203 Mennonite control samples, yielding a population-specific
allele frequency of 1.72%. (Puffenberger (2012) stated that the correct
population-specific allele frequency data appear in Table 4;
corresponding data in the text are incorrect.)
*FIELD* RF
1. Puffenberger, E. G.: Personal Communication. Strasburg, Pa.
2/28/2012.
2. Puffenberger, E. G.; Jinks, R. N.; Sougnez, C.; Cibulskis, K.;
Willert, R. A.; Achilly, N. P.; Cassidy, R. P.; Fiorentini, C. J.;
Heiken, K. F.; Lawrence, J. J.; Mahoney, M. H.; Miller, C. J.; and
13 others: Genetic mapping and exome sequencing identify variants
associated with five novel diseases. PLoS One 7: e28936, 2012. Note:
Electronic Article.
*FIELD* CD
Cassandra L. Kniffin: 2/27/2012
*FIELD* ED
carol: 03/05/2012
terry: 3/2/2012
ckniffin: 3/1/2012
ckniffin: 2/27/2012