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 27-MAR-2024, entry version 125.
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; DOI=10.1093/genetics/129.1.79;
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; DOI=10.1242/dev.126.5.1011;
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}.
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DR EMBL; FO081089; CCD69028.1; -; Genomic_DNA.
DR PIR; T32470; T32470.
DR RefSeq; NP_509427.2; NM_077026.6.
DR AlphaFoldDB; O17386; -.
DR SMR; O17386; -.
DR BioGRID; 48989; 1.
DR STRING; 6239.F08F1.5.1; -.
DR TCDB; 2.A.112.1.2; the kx blood-group antigen (kxa) family.
DR EPD; O17386; -.
DR PaxDb; 6239-F08F1-5; -.
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 AGR; WB:WBGene00000422; -.
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; NIWPHEA; -.
DR OrthoDB; 2879793at2759; -.
DR PhylomeDB; O17386; -.
DR PRO; PR:O17386; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000422; Expressed in germ line (C elegans) and 4 other cell types or tissues.
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 PANTHER; PTHR16024:SF6; CELL DEATH ABNORMALITY PROTEIN 8; 1.
DR PANTHER; PTHR16024; XK-RELATED PROTEIN; 1.
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
//
