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   12-SEP-2018, entry version 102.
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}.
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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; Expressed in 5 organ(s), highest expression level in multi-cellular organism.
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
//