ID CED4_CAEEL Reviewed; 571 AA. AC P30429; Q5BHI5; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 29-MAR-2005, sequence version 2. DT 16-JUN-2009, entry version 74. DE RecName: Full=Cell death protein 4; GN Name=ced-4; ORFNames=C35D10.9; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Nematoda; Chromadorea; Rhabditida; Rhabditoidea; OC Rhabditidae; Peloderinae; Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, DEVELOPMENTAL RP STAGE, AND DISRUPTION PHENOTYPE. RX MEDLINE=93161939; PubMed=1286611; RA Yuan J., Horvitz H.R.; RT "The Caenorhabditis elegans cell death gene ced-4 encodes a novel RT protein and is expressed during the period of extensive programmed RT cell death."; RL Development 116:309-320(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX MEDLINE=99069613; 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] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=8706125; DOI=10.1016/S0092-8674(00)80092-6; RA Shaham S., Horvitz H.R.; RT "An alternatively spliced C. elegans ced-4 RNA encodes a novel cell RT death inhibitor."; RL Cell 86:201-208(1996). RN [4] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CED-9. RX PubMed=9027313; DOI=10.1126/science.275.5303.1126; RA Wu D., Wallen H.D., Nunez G.; RT "Interaction and regulation of subcellular localization of CED-4 by RT CED-9."; RL Science 275:1126-1129(1997). RN [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX MEDLINE=20156769; PubMed=10688797; DOI=10.1126/science.287.5457.1485; RA Chen F., Hersh B.M., Conradt B., Zhou Z., Riemer D., Gruenbaum Y., RA Horvitz H.R.; RT "Translocation of C. elegans CED-4 to nuclear membranes during RT programmed cell death."; RL Science 287:1485-1489(2000). RN [6] RP FUNCTION, AND INTERACTION WITH CED-9. RX PubMed=15383288; DOI=10.1016/j.molcel.2004.08.022; RA Yan N., Gu L., Kokel D., Chai J., Li W., Han A., Chen L., Xue D., RA Shi Y.; RT "Structural, biochemical, and functional analyses of CED-9 recognition RT by the proapoptotic proteins EGL-1 and CED-4."; RL Mol. Cell 15:999-1006(2004). CC -!- FUNCTION: Isoform a plays a major role in programmed cell death CC (PCD, apoptosis). Egl-1 binds to and directly inhibits the CC activity of ced-9, releasing the cell death activator ced-4 from a CC ced-9/ced-4 containing protein complex and allowing ced-4 to CC activate the cell-killing caspase ced-3. Isoform b prevents PCD. CC -!- SUBUNIT: Interacts with ced-9. CC -!- INTERACTION: CC Q07817:BCL2L1 (xeno); NbExp=2; IntAct=EBI-494118, EBI-78035; CC Q14790:CASP8 (xeno); NbExp=1; IntAct=EBI-494118, EBI-78060; CC P42573:ced-3; NbExp=3; IntAct=EBI-536271, EBI-494247; CC P42573:ced-3; NbExp=3; IntAct=EBI-494118, EBI-494247; CC P41958:ced-9; NbExp=7; IntAct=EBI-494118, EBI-494110; CC -!- SUBCELLULAR LOCATION: Mitochondrion. Note=In non cell death CC induced cells. Ced-9 is required for mitochondrial localization. CC Perinuclear in cell death induced cells. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=b; Synonyms=Long; CC IsoId=P30429-1; Sequence=Displayed; CC Note=Minor transcript; CC Name=a; Synonyms=Short; CC IsoId=P30429-2; Sequence=VSP_013199; CC Note=Major transcript; CC -!- DEVELOPMENTAL STAGE: Most abundant during embryogenesis and is CC also detected at later stages during periods of extensive CC programmed cell death. CC -!- DISRUPTION PHENOTYPE: Mutants exhibit a block in almost all CC programmed cell deaths that normally occur during development. CC -!- SIMILARITY: Contains 1 CARD domain. CC -!- SIMILARITY: Contains 1 NB-ARC domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X69016; CAA48781.1; -; Genomic_DNA. DR EMBL; U21324; AAA62564.1; -; Genomic_DNA. DR EMBL; U21324; AAX22294.1; -; Genomic_DNA. DR PIR; S72566; S72566. DR RefSeq; NP_001021203.1; -. DR UniGene; Cel.10679; -. DR PDB; 2A5Y; X-ray; 2.60 A; B/C=1-571. DR PDBsum; 2A5Y; -. DR DIP; DIP:1016N; -. DR IntAct; P30429; 6. DR Ensembl; C35D10.9; Caenorhabditis elegans. DR GeneID; 175643; -. DR WormBase; WBGene00000418; ced-4. DR WormPep; C35D10.9a; CE01203. DR WormPep; C35D10.9b; CE38154. DR OMA; P30429; TRDVEIS. DR NextBio; 889028; -. DR ArrayExpress; P30429; -. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0006915; P:apoptosis; IMP:UniProtKB. DR GO; GO:0042981; P:regulation of apoptosis; IEA:InterPro. DR InterPro; IPR016854; Apop_reg_Ced-4. DR InterPro; IPR001315; CARD. DR InterPro; IPR002182; NB-ARC. DR Pfam; PF00619; CARD; 1. DR Pfam; PF00931; NB-ARC; 1. DR PIRSF; PIRSF027202; Apop_reg_Ced-4; 1. DR SMART; SM00114; CARD; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; KW Complete proteome; Mitochondrion; Nucleotide-binding. FT CHAIN 1 571 Cell death protein 4. FT /FTId=PRO_0000089470. FT DOMAIN 1 91 CARD. FT DOMAIN 116 440 NB-ARC. FT NP_BIND 159 166 ATP (Potential). FT VAR_SEQ 212 234 ARVVSDTDDSHSITDFINRVLSR -> K (in isoform FT a). FT /FTId=VSP_013199. FT HELIX 4 20 FT HELIX 23 26 FT HELIX 27 32 FT HELIX 38 45 FT STRAND 47 49 FT HELIX 50 64 FT STRAND 66 68 FT HELIX 69 77 FT HELIX 81 96 FT HELIX 101 104 FT TURN 105 108 FT HELIX 112 121 FT HELIX 134 147 FT STRAND 150 158 FT HELIX 165 175 FT TURN 181 183 FT STRAND 184 191 FT HELIX 199 211 FT TURN 234 236 FT HELIX 250 261 FT STRAND 267 274 FT HELIX 277 285 FT STRAND 289 296 FT HELIX 297 302 FT STRAND 307 311 FT HELIX 317 326 FT HELIX 336 348 FT HELIX 352 359 FT STRAND 364 366 FT HELIX 367 380 FT STRAND 389 395 FT HELIX 396 405 FT HELIX 409 414 FT HELIX 417 419 FT HELIX 429 435 FT HELIX 450 458 FT TURN 459 461 FT STRAND 462 464 FT STRAND 466 469 FT STRAND 471 473 FT STRAND 475 477 FT HELIX 480 487 FT HELIX 493 499 FT TURN 503 505 FT HELIX 559 562 SQ SEQUENCE 571 AA; 65336 MW; 6BE9893946B79E6C CRC64; MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI YRRQASELGP LIDFFNYNNQ SHLADFLEDY IDFAINEPDL LRPVVIAPQF SRQMLDRKLL LGNVPKQMTC YIREYHVDRV IKKLDEMCDL DSFFLFLHGR AGSGKSVIAS QALSKSDQLI GINYDSIVWL KDSGTAPKST FDLFTDILLM LARVVSDTDD SHSITDFINR VLSRSEDDLL NFPSVEHVTS VVLKRMICNA LIDRPNTLFV FDDVVQEETI RWAQELRLRC LVTTRDVEIS NAASQTCEFI EVTSLEIDEC YDFLEAYGMP MPVGEKEEDV LNKTIELSSG NPATLMMFFK SCEPKTFEKM AQLNNKLESR GLVGVECITP YSYKSLAMAL QRCVEVLSDE DRSALAFAVV MPPGVDIPVK LWSCVIPVDI CSNEEEQLDD EVADRLKRLS KRGALLSGKR MPVLTFKIDH IIHMFLKHVV DAQTIANGIS ILEQRLLEIG NNNVSVPERH IPSHFQKFRR SSASEMYPKT TEETVIRPED FPKFMQLHQK FYDSLKNFAC C //