CRADD_HUMAN
ID CRADD_HUMAN Reviewed; 199 AA.
AC P78560; B7Z2Q5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 191.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CASP2
RP AND RIPK1, DOMAIN, AND TISSUE SPECIFICITY.
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] (ISOFORM 1), FUNCTION, INTERACTION WITH CASP2;
RP TNFRSF1A AND TRADD, DOMAIN, TISSUE SPECIFICITY, AND MUTAGENESIS OF LEU-27
RP AND GLY-65.
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] (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
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 [7]
RP FUNCTION, AND 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 [8]
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 interaction
RT in caspase-2 and caspase-9 recruitment.";
RL Cell 94:171-180(1998).
RN [9]
RP FUNCTION, AND INTERACTION WITH PIDD1.
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 [10] {ECO:0007744|PDB:2OF5}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 94-199 IN COMPLEX WITH PIDD1,
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF ASN-121; GLN-125; LEU-136; GLN-142;
RP TYR-146; ARG-147; LYS-149; HIS-154; VAL-156; GLN-169; ARG-170; GLU-188 AND
RP VAL-189.
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 [11]
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., Lawrence J.J.,
RA Mahoney M.H., Miller C.J., Nair D.T., Politi K.A., Worcester K.N.,
RA Setton R.A., Dipiazza R., Sherman E.A., Eastman J.T., Francklyn C.,
RA Robey-Bond S., Rider N.L., Gabriel S., Morton D.H., Strauss K.A.;
RT "Genetic mapping and exome sequencing identify variants associated with
RT five novel diseases.";
RL PLoS ONE 7:E28936-E28936(2012).
CC -!- FUNCTION: Adapter protein that associates with PIDD1 and the caspase
CC CASP2 to form the PIDDosome, a complex that activates CASP2 and
CC triggers apoptosis (PubMed:9044836, PubMed:15073321, PubMed:16652156,
CC PubMed:17159900, PubMed:17289572). Also recruits CASP2 to the TNFR-1
CC signaling complex through its interaction with RIPK1 and TRADD and may
CC play a role in the tumor necrosis factor-mediated signaling pathway
CC (PubMed:8985253). {ECO:0000269|PubMed:15073321,
CC ECO:0000269|PubMed:16652156, ECO:0000269|PubMed:17159900,
CC ECO:0000269|PubMed:17289572, ECO:0000269|PubMed:8985253,
CC ECO:0000269|PubMed:9044836}.
CC -!- SUBUNIT: Forms a complex named the PIDDosome with PIDD1 and CASP2
CC (PubMed:9044836, PubMed:8985253, PubMed:15073321, PubMed:16652156,
CC PubMed:17159900, PubMed:17289572). Interacts (via Death domain) with
CC RIPK1 (via Death domain); the interaction is direct (PubMed:9044836).
CC Interacts with TRADD (PubMed:8985253). Interacts with TNFRSF1A
CC (PubMed:8985253). {ECO:0000269|PubMed:15073321,
CC ECO:0000269|PubMed:16652156, ECO:0000269|PubMed:17159900,
CC ECO:0000269|PubMed:17289572, ECO:0000269|PubMed:8985253,
CC ECO:0000269|PubMed:9044836}.
CC -!- INTERACTION:
CC P78560; P35609: ACTN2; NbExp=3; IntAct=EBI-520375, EBI-77797;
CC P78560; Q8NEU8: APPL2; NbExp=4; IntAct=EBI-520375, EBI-741261;
CC P78560; Q8N3I7: BBS5; NbExp=3; IntAct=EBI-520375, EBI-2892592;
CC P78560; P42575: CASP2; NbExp=23; IntAct=EBI-520375, EBI-520342;
CC P78560; Q7L273: KCTD9; NbExp=3; IntAct=EBI-520375, EBI-4397613;
CC P78560; Q9HB75: PIDD1; NbExp=7; IntAct=EBI-520375, EBI-520427;
CC P78560; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-520375, EBI-2130429;
CC P78560; P14079: tax; Xeno; NbExp=3; IntAct=EBI-520375, EBI-9675698;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O88843}. Nucleus
CC {ECO:0000250|UniProtKB:O88843}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P78560-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78560-2; Sequence=VSP_056892;
CC -!- TISSUE SPECIFICITY: Constitutively expressed in most tissues, with
CC particularly high expression in adult heart, testis, liver, skeletal
CC muscle, fetal liver and kidney. {ECO:0000269|PubMed:8985253,
CC ECO:0000269|PubMed:9044836}.
CC -!- DOMAIN: The Death domain mediates the interaction with PIDD1 and the
CC formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which
CC in turn probably recruit 7 CASP2 to form the PIDDosome
CC (PubMed:17289572). The Death domain mediates a direct interaction with
CC the Death domain of RIPK1 (PubMed:9044836).
CC {ECO:0000269|PubMed:17289572, ECO:0000269|PubMed:9044836}.
CC -!- DOMAIN: The CARD domain mediates a direct interaction with CASP2.
CC {ECO:0000269|PubMed:8985253, ECO:0000269|PubMed:9044836}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 34,
CC with variant lissencephaly (MRT34) [MIM:614499]: A disorder
CC characterized by mild to moderate intellectual disability,
CC megalencephaly or enlarged head circumference, and a mild variant of
CC lissencephaly with anterior-predominant pachygyria with shallow and
CC unusually wide sulci and mildly thickened cortex. Some patients may
CC have seizures. {ECO:0000269|PubMed:22279524}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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DR EMBL; U84388; AAC50952.1; -; mRNA.
DR EMBL; U79115; AAB42217.1; -; mRNA.
DR EMBL; AK294986; BAH11941.1; -; mRNA.
DR EMBL; AC012085; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012464; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017042; AAH17042.1; -; mRNA.
DR CCDS; CCDS9048.1; -. [P78560-1]
DR RefSeq; NP_001307028.1; NM_001320099.1. [P78560-1]
DR RefSeq; NP_001307029.1; NM_001320100.1.
DR RefSeq; NP_001307030.1; NM_001320101.1.
DR RefSeq; NP_003796.1; NM_003805.4. [P78560-1]
DR RefSeq; XP_016875633.1; XM_017020144.1. [P78560-2]
DR PDB; 2O71; X-ray; 2.00 A; A=94-199.
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 AlphaFoldDB; P78560; -.
DR SMR; P78560; -.
DR BioGRID; 114275; 26.
DR ComplexPortal; CPX-3905; Caspase-2 PIDDosome.
DR CORUM; P78560; -.
DR IntAct; P78560; 21.
DR MINT; P78560; -.
DR STRING; 9606.ENSP00000439068; -.
DR iPTMnet; P78560; -.
DR MetOSite; P78560; -.
DR PhosphoSitePlus; P78560; -.
DR BioMuta; CRADD; -.
DR DMDM; 2498833; -.
DR EPD; P78560; -.
DR jPOST; P78560; -.
DR MassIVE; P78560; -.
DR MaxQB; P78560; -.
DR PaxDb; P78560; -.
DR PeptideAtlas; P78560; -.
DR PRIDE; P78560; -.
DR ProteomicsDB; 57654; -. [P78560-1]
DR ProteomicsDB; 6451; -.
DR Antibodypedia; 3943; 544 antibodies from 38 providers.
DR DNASU; 8738; -.
DR Ensembl; ENST00000332896.8; ENSP00000327647.3; ENSG00000169372.13. [P78560-1]
DR Ensembl; ENST00000542893.2; ENSP00000439068.2; ENSG00000169372.13. [P78560-1]
DR Ensembl; ENST00000551065.5; ENSP00000448425.1; ENSG00000169372.13. [P78560-2]
DR GeneID; 8738; -.
DR KEGG; hsa:8738; -.
DR MANE-Select; ENST00000332896.8; ENSP00000327647.3; NM_003805.5; NP_003796.1.
DR UCSC; uc058rts.1; human. [P78560-1]
DR CTD; 8738; -.
DR DisGeNET; 8738; -.
DR GeneCards; CRADD; -.
DR HGNC; HGNC:2340; CRADD.
DR HPA; ENSG00000169372; Low tissue specificity.
DR MalaCards; CRADD; -.
DR MIM; 603454; gene.
DR MIM; 614499; phenotype.
DR neXtProt; NX_P78560; -.
DR OpenTargets; ENSG00000169372; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA26860; -.
DR VEuPathDB; HostDB:ENSG00000169372; -.
DR eggNOG; ENOG502R26C; Eukaryota.
DR GeneTree; ENSGT00390000014448; -.
DR HOGENOM; CLU_118159_0_0_1; -.
DR InParanoid; P78560; -.
DR OMA; NHPHNLQ; -.
DR PhylomeDB; P78560; -.
DR TreeFam; TF333055; -.
DR PathwayCommons; P78560; -.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR SignaLink; P78560; -.
DR SIGNOR; P78560; -.
DR BioGRID-ORCS; 8738; 9 hits in 1084 CRISPR screens.
DR ChiTaRS; CRADD; human.
DR EvolutionaryTrace; P78560; -.
DR GeneWiki; CRADD; -.
DR GenomeRNAi; 8738; -.
DR Pharos; P78560; Tbio.
DR PRO; PR:P78560; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P78560; protein.
DR Bgee; ENSG00000169372; Expressed in heart left ventricle and 179 other tissues.
DR ExpressionAtlas; P78560; baseline and differential.
DR Genevisible; P78560; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1905369; C:endopeptidase complex; IPI:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0070513; F:death domain binding; IPI:BHF-UCL.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097190; P:apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IC:ComplexPortal.
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:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IBA:GO_Central.
DR CDD; cd08327; CARD_RAIDD; 1.
DR CDD; cd08319; Death_RAIDD; 1.
DR DisProt; DP01771; -.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR042148; CARD_RAIDD.
DR InterPro; IPR037939; CRADD.
DR InterPro; IPR037926; CRADD_Death.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR PANTHER; PTHR15034; PTHR15034; 1.
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; Alternative splicing; Apoptosis; Cytoplasm; Disease variant;
KW Intellectual disability; Lissencephaly; Nucleus; Reference proteome.
FT CHAIN 1..199
FT /note="Death domain-containing protein CRADD"
FT /id="PRO_0000079326"
FT DOMAIN 1..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 116..188
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT VAR_SEQ 101..199
FT /note="DRLTGIPSHILNSSPSDRQINQLAQRLGPEWEPMVLSLGLSQTDIYRCKANH
FT PHNVQSQVVEAFIRWRQRFGKQATFQSLHNGLRAVEVDPSLLLHMLE -> CWP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056892"
FT VARIANT 128
FT /note="G -> R (in MRT34; dbSNP:rs387906861)"
FT /evidence="ECO:0000269|PubMed:22279524"
FT /id="VAR_067536"
FT MUTAGEN 27
FT /note="L->F: Loss of interaction with CASP2."
FT /evidence="ECO:0000269|PubMed:8985253"
FT MUTAGEN 65
FT /note="G->A: Loss of interaction with CASP2."
FT /evidence="ECO:0000269|PubMed:8985253"
FT MUTAGEN 121
FT /note="N->D: Loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 125
FT /note="Q->A: Loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 136
FT /note="L->E: Partial loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 142
FT /note="Q->E: Partial loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 146
FT /note="Y->A: Loss of interaction with PIDD1. Decreased
FT PIDDosome assembly. Decreased CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 147
FT /note="R->A: Loss of interaction with PIDD1. Decreased
FT PIDDosome assembly. Decreased CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 147
FT /note="R->E: Loss of interaction with PIDD1. Loss of
FT PIDDosome assembly. Loss of CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 149
FT /note="K->E: Loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 154
FT /note="H->A: Partial loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 156
FT /note="V->D: Loss of interaction with PIDD1. Loss of
FT PIDDosome assembly. Loss of CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 169
FT /note="Q->A: Partial loss of interaction with PIDD1.
FT Decreased PIDDosome assembly. Decreased CASP2 activation."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 169
FT /note="Q->E: Loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 170
FT /note="R->A: Partial loss of interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 188
FT /note="E->K: No effect on interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT MUTAGEN 189
FT /note="V->W,D: No effect on interaction with PIDD1."
FT /evidence="ECO:0000269|PubMed:17289572"
FT HELIX 5..18
FT /evidence="ECO:0007829|PDB:3CRD"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:3CRD"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:3CRD"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:3CRD"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:3CRD"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:3CRD"
FT HELIX 69..75
FT /evidence="ECO:0007829|PDB:3CRD"
FT HELIX 79..92
FT /evidence="ECO:0007829|PDB:3CRD"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 131..137
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 142..151
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 156..171
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 177..186
FT /evidence="ECO:0007829|PDB:2O71"
FT HELIX 192..197
FT /evidence="ECO:0007829|PDB:2O71"
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
