ID CED8_CAEEL Reviewed; 458 AA. AC O17386; DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 2. DT 30-AUG-2017, entry version 101. DE RecName: Full=Cell death abnormality protein 8; GN Name=ced-8; ORFNames=F08F1.5; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis. OX NCBI_TaxID=6239; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10882128; DOI=10.1016/S1097-2765(00)80437-2; RA Stanfield G.M., Horvitz H.R.; RT "The ced-8 gene controls the timing of programmed cell deaths in C. RT elegans."; RL Mol. Cell 5:423-433(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for RT investigating biology."; RL Science 282:2012-2018(1998). RN [3] {ECO:0000305} RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=1936965; RA Ellis R.E., Jacobson D.M., Horvitz H.R.; RT "Genes required for the engulfment of cell corpses during programmed RT cell death in Caenorhabditis elegans."; RL Genetics 129:79-94(1991). RN [4] {ECO:0000305} RP FUNCTION. RX PubMed=9927601; RA Gumienny T.L., Lambie E., Hartwieg E., Horvitz H.R., Hengartner M.O.; RT "Genetic control of programmed cell death in the Caenorhabditis RT elegans hermaphrodite germline."; RL Development 126:1011-1022(1999). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS RP OF 1-MET--ASP-21; ASP-21 AND ASP-163. RX PubMed=24225442; DOI=10.1038/ncomms3726; RA Chen Y.Z., Mapes J., Lee E.S., Skeen-Gaar R.R., Xue D.; RT "Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes RT apoptosis and phosphatidylserine externalization."; RL Nat. Commun. 4:2726-2726(2013). RN [6] RP FUNCTION. RX PubMed=23845944; DOI=10.1126/science.1236758; RA Suzuki J., Denning D.P., Imanishi E., Horvitz H.R., Nagata S.; RT "Xk-Related protein 8 and CED-8 promote phosphatidylserine exposure in RT apoptotic cells."; RL Science 341:403-406(2013). CC -!- FUNCTION: Acts downstream of ced-9 and caspase ced-3 to promote CC phosphatidylserine exposure on apoptotic cell surface, possibly by CC mediating phospholipid scrambling (PubMed:24225442, CC PubMed:23845944). Phosphatidylserine is a specific marker only CC present at the surface of apoptotic cells and acts as a specific CC signal for engulfment (PubMed:24225442, PubMed:23845944). CC Regulates apoptosis kinetics during embryonic development CC (PubMed:10882128, PubMed:1936965, PubMed:24225442, CC PubMed:23845944). Not required for engulfment of germ cell corpses CC (PubMed:9927601). {ECO:0000269|PubMed:10882128, CC ECO:0000269|PubMed:1936965, ECO:0000269|PubMed:23845944, CC ECO:0000269|PubMed:24225442, ECO:0000269|PubMed:9927601}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10882128, CC ECO:0000269|PubMed:24225442}; Multi-pass membrane protein CC {ECO:0000269|PubMed:10882128}. CC -!- PTM: Cleavage by ced-3 activates ced-8 function in promoting CC phosphatidylserine exposure at the surface of apoptotic cells. CC {ECO:0000269|PubMed:24225442}. CC -!- DISRUPTION PHENOTYPE: Delayed cell death process. CC {ECO:0000269|PubMed:1936965}. CC -!- SIMILARITY: Belongs to the XK family. {ECO:0000255}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; FO081089; CCD69028.1; -; Genomic_DNA. DR PIR; T32470; T32470. DR RefSeq; NP_509427.2; NM_077026.6. DR UniGene; Cel.11044; -. DR STRING; 6239.F08F1.5; -. DR TCDB; 2.A.112.1.2; the kx blood-group antigen (kxa) family. DR EPD; O17386; -. DR PaxDb; O17386; -. DR EnsemblMetazoa; F08F1.5; F08F1.5; WBGene00000422. DR GeneID; 184190; -. DR KEGG; cel:CELE_F08F1.5; -. DR UCSC; F08F1.5; c. elegans. DR CTD; 184190; -. DR WormBase; F08F1.5; CE34294; WBGene00000422; ced-8. DR eggNOG; KOG4790; Eukaryota. DR eggNOG; ENOG410YRUD; LUCA. DR GeneTree; ENSGT00530000062854; -. DR HOGENOM; HOG000022315; -. DR InParanoid; O17386; -. DR OMA; IMIQENR; -. DR OrthoDB; EOG091G0C1B; -. DR PhylomeDB; O17386; -. DR PRO; PR:O17386; -. DR Proteomes; UP000001940; Chromosome X. DR Bgee; WBGene00000422; -. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005215; F:transporter activity; TAS:WormBase. DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB. DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB. DR GO; GO:0043652; P:engulfment of apoptotic cell; IMP:UniProtKB. DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB. DR GO; GO:0070782; P:phosphatidylserine exposure on apoptotic cell surface; IMP:UniProtKB. DR GO; GO:0012501; P:programmed cell death; IMP:UniProtKB. DR InterPro; IPR018629; XK-rel. DR Pfam; PF09815; XK-related; 1. PE 1: Evidence at protein level; KW Apoptosis; Cell membrane; Complete proteome; Membrane; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1 458 Cell death abnormality protein 8. FT /FTId=PRO_0000379936. FT TOPO_DOM 1 45 Cytoplasmic. {ECO:0000305}. FT TRANSMEM 46 66 Helical. {ECO:0000255}. FT TOPO_DOM 67 77 Extracellular. {ECO:0000305}. FT TRANSMEM 78 98 Helical. {ECO:0000255}. FT TOPO_DOM 99 123 Cytoplasmic. {ECO:0000305}. FT TRANSMEM 124 144 Helical. {ECO:0000255}. FT TOPO_DOM 145 219 Extracellular. {ECO:0000305}. FT TRANSMEM 220 240 Helical. {ECO:0000255}. FT TOPO_DOM 241 274 Cytoplasmic. {ECO:0000305}. FT TRANSMEM 275 295 Helical. {ECO:0000255}. FT TRANSMEM 296 316 Helical. {ECO:0000255}. FT TOPO_DOM 317 317 Extracellular. {ECO:0000305}. FT TRANSMEM 318 338 Helical. {ECO:0000255}. FT TOPO_DOM 339 353 Cytoplasmic. {ECO:0000305}. FT TRANSMEM 354 374 Helical. {ECO:0000255}. FT TOPO_DOM 375 378 Extracellular. {ECO:0000305}. FT TRANSMEM 379 399 Helical. {ECO:0000255}. FT TOPO_DOM 400 458 Cytoplasmic. {ECO:0000305}. FT SITE 21 22 Cleavage; by ced-3. FT {ECO:0000269|PubMed:24225442}. FT MUTAGEN 1 22 Missing: Causes constitutive FT phosphatidylserine cell surface exposure. FT {ECO:0000269|PubMed:24225442}. FT MUTAGEN 21 21 D->A: Loss of ced-3-mediated cleavage. FT {ECO:0000269|PubMed:24225442}. FT MUTAGEN 21 21 D->E: Loss of ced-3-mediated cleavage. FT Reduced phosphatidylserine cell surface FT exposure in apoptotic cells. Reduced FT number of cell corpses at the comma stage FT followed by an increase at the 4-fold FT stage. {ECO:0000269|PubMed:24225442}. FT MUTAGEN 163 163 D->A: No defect in apoptosis during FT embryogenesis. FT {ECO:0000269|PubMed:24225442}. SQ SEQUENCE 458 AA; 53273 MW; 9E04EEBB0299DB2C CRC64; MFLKKHKSKL LLVPRDEEQE DAGIVAVLTD RIPSVLLVRW FDLFCFGFAM CSYALDFFSD IGIAIFHFWA GRYLSGSLVL AFALLPSVII NIISMVWMLD DEMHWKRRAH PRRTGTFELN QKRFIPLSKM IVLCICQMGP LFWYYKALYY GWMFRKSSNE NTDGEKRKCF SKMVEAERDA TLLRFFEAFL ESAPQLIIQG SIAASYFQNY YQTGTYPYWL YFQAASLLLS IISISWSVVV QNRSLRMIRD DKVNIWPHEA VLQFCWRFLT ILARIITLVA LVLIFGINVV PLISVHLLVT LVHVIFLQAI HIDACTHIEK LLLLINTFIH IFIPFNMVEG NTRWRYLTAY SVEFIEMMLV CWLLPLSLNT FPYIEKVQVG VPISFIAGIA IMMMYYQFFH PNRRQLIVTQ SQEDLSLNVQ KSVETLTPKL ESSLEISGEQ NTSQDLVSEL LLDVEHEN //