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 29-SEP-2021, entry version 115. DE RecName: Full=Cell death abnormality protein 8 {ECO:0000305}; GN Name=ced-8 {ECO:0000303|PubMed:10882128, ECO:0000312|WormBase:F08F1.5}; GN ORFNames=F08F1.5 {ECO:0000312|WormBase:F08F1.5}; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC 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 investigating RT 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 cell RT 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 elegans RT hermaphrodite germline."; RL Development 126:1011-1022(1999). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF RP 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, AND CATALYTIC ACTIVITY. 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: Phospholipid scramblase that acts downstream of ced-9 and CC caspase ced-3 to promote phosphatidylserine exposure on apoptotic cell CC surface (PubMed:24225442, PubMed:23845944). Phosphatidylserine is a CC specific marker only present at the surface of apoptotic cells and acts CC as a specific signal for engulfment (PubMed:24225442, PubMed:23845944). CC Regulates apoptosis kinetics during embryonic development CC (PubMed:10882128, PubMed:1936965, PubMed:24225442, PubMed:23845944). CC Not required for engulfment of germ cell corpses (PubMed:9927601). CC {ECO:0000269|PubMed:10882128, ECO:0000269|PubMed:1936965, CC ECO:0000269|PubMed:23845944, ECO:0000269|PubMed:24225442, CC ECO:0000269|PubMed:9927601}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl- CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663, CC ChEBI:CHEBI:57262; Evidence={ECO:0000305|PubMed:23845944}; 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:0000305}. 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 BioGRID; 48989; 1. 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; F08F1.5.1; F08F1.5.1; 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 GeneTree; ENSGT00940000170176; -. DR HOGENOM; CLU_028534_5_0_1; -. DR InParanoid; O17386; -. DR OMA; PAHMTKS; -. DR OrthoDB; 1230316at2759; -. DR PhylomeDB; O17386; -. DR PRO; PR:O17386; -. DR Proteomes; UP000001940; Chromosome X. DR Bgee; WBGene00000422; Expressed in multi-cellular organism and 5 other tissues. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB. 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; Membrane; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1..458 FT /note="Cell death abnormality protein 8" FT /id="PRO_0000379936" FT TOPO_DOM 1..45 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 46..66 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 67..77 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 78..98 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 99..123 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 124..144 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 145..219 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 220..240 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 241..274 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 275..295 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 296..316 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 317 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 318..338 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 339..353 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 354..374 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 375..378 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 379..399 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 400..458 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT SITE 21..22 FT /note="Cleavage; by ced-3" FT /evidence="ECO:0000269|PubMed:24225442" FT MUTAGEN 1..22 FT /note="Missing: Causes constitutive phosphatidylserine cell FT surface exposure." FT /evidence="ECO:0000269|PubMed:24225442" FT MUTAGEN 21 FT /note="D->A: Loss of ced-3-mediated cleavage." FT /evidence="ECO:0000269|PubMed:24225442" FT MUTAGEN 21 FT /note="D->E: Loss of ced-3-mediated cleavage. Reduced FT phosphatidylserine cell surface exposure in apoptotic FT cells. Reduced number of cell corpses at the comma stage FT followed by an increase at the 4-fold stage." FT /evidence="ECO:0000269|PubMed:24225442" FT MUTAGEN 163 FT /note="D->A: No defect in apoptosis during embryogenesis." FT /evidence="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 //