CED2_CAEEL
ID CED2_CAEEL Reviewed; 279 AA.
AC Q9NHC3;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Cell death abnormality protein 2 {ECO:0000303|PubMed:6857247};
DE AltName: Full=Cell-corpse engulfment protein CED-2 {ECO:0000312|EMBL:AAF33845.1};
GN Name=ced-2 {ECO:0000312|WormBase:Y41D4B.13a};
GN ORFNames=Y41D4B.13 {ECO:0000312|WormBase:Y41D4B.13a};
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, ECO:0000312|EMBL:AAF33845.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CED-5, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=10707082; DOI=10.1038/35004000;
RA Reddien P.W., Horvitz H.R.;
RT "CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in
RT Caenorhabditis elegans.";
RL Nat. Cell Biol. 2:131-136(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=6857247; DOI=10.1126/science.6857247;
RA Hedgecock E.M., Sulston J.E., Thomson J.N.;
RT "Mutations affecting programmed cell deaths in the nematode Caenorhabditis
RT elegans.";
RL Science 220:1277-1279(1983).
RN [4] {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 [5] {ECO:0000305}
RP IDENTIFICATION IN A TERNARY COMPLEX WITH CED-5 AND CED-12.
RX PubMed=11703940; DOI=10.1016/s1534-5807(01)00056-9;
RA Wu Y.-C., Tsai M.-C., Cheng L.-C., Chou C.-J., Weng N.-Y.;
RT "C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to
RT control cell migration and cell corpse engulfment.";
RL Dev. Cell 1:491-502(2001).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11449278; DOI=10.1038/35084096;
RA Reddien P.W., Cameron S., Horvitz H.R.;
RT "Phagocytosis promotes programmed cell death in C. elegans.";
RL Nature 412:198-202(2001).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15744306; DOI=10.1038/nature03263;
RA Kinchen J.M., Cabello J., Klingele D., Wong K., Feichtinger R.,
RA Schnabel H., Schnabel R., Hengartner M.O.;
RT "Two pathways converge at CED-10 to mediate actin rearrangement and corpse
RT removal in C. elegans.";
RL Nature 434:93-99(2005).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19402756; DOI=10.1371/journal.pbio.1000099;
RA Hurwitz M.E., Vanderzalm P.J., Bloom L., Goldman J., Garriga G.,
RA Horvitz H.R.;
RT "Abl kinase inhibits the engulfment of apopotic cells in Caenorhabditis
RT elegans.";
RL PLoS Biol. 7:E99-E99(2009).
RN [9]
RP FUNCTION, AND INTERACTION WITH SRC-1.
RX PubMed=20226672; DOI=10.1016/j.cub.2010.01.062;
RA Hsu T.Y., Wu Y.C.;
RT "Engulfment of apoptotic cells in C. elegans is mediated by integrin
RT alpha/SRC signaling.";
RL Curr. Biol. 20:477-486(2010).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF 153-TRP--GLU-279.
RX PubMed=29346382; DOI=10.1371/journal.pgen.1007125;
RA Offenburger S.L., Ho X.Y., Tachie-Menson T., Coakley S., Hilliard M.A.,
RA Gartner A.;
RT "6-OHDA-induced dopaminergic neurodegeneration in Caenorhabditis elegans is
RT promoted by the engulfment pathway and inhibited by the transthyretin-
RT related protein TTR-33.";
RL PLoS Genet. 14:E1007125-E1007125(2018).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS), AND INTERACTION WITH CED-5.
RX PubMed=21616056; DOI=10.1016/j.bbrc.2011.05.051;
RA Kang Y., Xu J., Liu Y., Sun J., Sun D., Hu Y., Liu Y.;
RT "Crystal structure of the cell corpse engulfment protein CED-2 in
RT Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 410:189-194(2011).
CC -!- FUNCTION: Required for cell migration and engulfment of cell corpses
CC but not for programmed cell death/apoptosis (PubMed:10707082,
CC PubMed:6857247, PubMed:1936965, PubMed:11449278, PubMed:15744306,
CC PubMed:19402756, PubMed:20226672). Has a role in the migration of the 2
CC gonadal distal tip cells (DTCs) (PubMed:10707082). Plays a role in
CC protecting dopaminergic neurons from oxidative stress-induced
CC degeneration (PubMed:29346382). {ECO:0000269|PubMed:10707082,
CC ECO:0000269|PubMed:11449278, ECO:0000269|PubMed:15744306,
CC ECO:0000269|PubMed:1936965, ECO:0000269|PubMed:19402756,
CC ECO:0000269|PubMed:20226672, ECO:0000269|PubMed:29346382,
CC ECO:0000269|PubMed:6857247}.
CC -!- SUBUNIT: Interacts with ced-5 (via C-terminus which contains a
CC candidate SH3-binding, proline-rich region) (PubMed:10707082,
CC PubMed:11703940, PubMed:21616056). Forms a ternary complex with ced-5
CC and ced-12 (PubMed:11703940). Interacts (via SH2 domain) with src-1
CC (when activated and phosphorylated at 'Tyr-416') (PubMed:20226672).
CC {ECO:0000269|PubMed:10707082, ECO:0000269|PubMed:11703940,
CC ECO:0000269|PubMed:20226672, ECO:0000269|PubMed:21616056}.
CC -!- DISRUPTION PHENOTYPE: Dead cells/corpses fail to be engulfed. Defective
CC in the migration of distal tip cells and gonad development. Actin halos
CC are absent. {ECO:0000269|PubMed:10707082, ECO:0000269|PubMed:11449278,
CC ECO:0000269|PubMed:15744306, ECO:0000269|PubMed:1936965,
CC ECO:0000269|PubMed:19402756, ECO:0000269|PubMed:6857247}.
CC -!- SIMILARITY: Belongs to the CRK family. {ECO:0000255}.
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DR EMBL; AF226866; AAF33845.1; -; mRNA.
DR EMBL; BX284604; CCD66714.1; -; Genomic_DNA.
DR RefSeq; NP_500105.1; NM_067704.4.
DR PDB; 3QWX; X-ray; 2.01 A; X=1-174.
DR PDB; 3QWY; X-ray; 2.52 A; A/B=1-279.
DR PDBsum; 3QWX; -.
DR PDBsum; 3QWY; -.
DR AlphaFoldDB; Q9NHC3; -.
DR SMR; Q9NHC3; -.
DR BioGRID; 42124; 13.
DR DIP; DIP-25408N; -.
DR IntAct; Q9NHC3; 6.
DR STRING; 6239.Y41D4B.13a; -.
DR EPD; Q9NHC3; -.
DR PaxDb; Q9NHC3; -.
DR PeptideAtlas; Q9NHC3; -.
DR EnsemblMetazoa; Y41D4B.13a.1; Y41D4B.13a.1; WBGene00000416.
DR GeneID; 176968; -.
DR KEGG; cel:CELE_Y41D4B.13; -.
DR UCSC; Y41D4B.13; c. elegans.
DR CTD; 176968; -.
DR WormBase; Y41D4B.13a; CE28360; WBGene00000416; ced-2.
DR eggNOG; KOG4792; Eukaryota.
DR HOGENOM; CLU_060542_0_0_1; -.
DR InParanoid; Q9NHC3; -.
DR OMA; WWNAEDG; -.
DR OrthoDB; 1414461at2759; -.
DR PhylomeDB; Q9NHC3; -.
DR Reactome; R-CEL-170968; Frs2-mediated activation.
DR Reactome; R-CEL-170984; ARMS-mediated activation.
DR Reactome; R-CEL-186763; Downstream signal transduction.
DR Reactome; R-CEL-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-CEL-8875555; MET activates RAP1 and RAC1.
DR Reactome; R-CEL-8875656; MET receptor recycling.
DR Reactome; R-CEL-912631; Regulation of signaling by CBL.
DR SignaLink; Q9NHC3; -.
DR EvolutionaryTrace; Q9NHC3; -.
DR PRO; PR:Q9NHC3; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00000416; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q9NHC3; baseline and differential.
DR GO; GO:0005886; C:plasma membrane; NAS:WormBase.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IMP:UniProtKB.
DR GO; GO:1903356; P:positive regulation of distal tip cell migration; IMP:UniProtKB.
DR GO; GO:1901076; P:positive regulation of engulfment of apoptotic cell; IMP:UniProtKB.
DR GO; GO:0012501; P:programmed cell death; IMP:WormBase.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR DisProt; DP00868; -.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Phagocytosis; Reference proteome; Repeat; SH2 domain;
KW SH3 domain.
FT CHAIN 1..279
FT /note="Cell death abnormality protein 2"
FT /id="PRO_0000379934"
FT DOMAIN 14..115
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 116..176
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 214..277
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 181..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 153..279
FT /note="Missing: In e1752; dopaminergic neurodegeneration in
FT 60% of animals in response to oxidative stress induced by
FT the neurotoxin 6-hydroxydopamine (6-OHDA)."
FT /evidence="ECO:0000269|PubMed:29346382"
FT HELIX 8..14
FT /evidence="ECO:0007829|PDB:3QWX"
FT HELIX 21..29
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 87..91
FT /evidence="ECO:0007829|PDB:3QWX"
FT HELIX 92..98
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 118..125
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 142..147
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:3QWX"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:3QWX"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:3QWX"
SQ SEQUENCE 279 AA; 30879 MW; 5CE7DA478948970B CRC64;
MTTNGFDPFE WRSFYFPGMS REEAHKLLGE PQVSIGTFLM RDSSRPGEYS LTVREADEGN
AVCHYLIERG EPKEDGTAAA GVKIANQSFP DIPALLNHFK MRVLTEASLL AAYKKPIIEV
VVGTFKFTGE RETDLPFEQG ERLEILSKTN QDWWEARNAL GTTGLVPANY VQIQMEFHND
RTSKGASQSS IGSSGGGAER FSSASTSSDN IELQPRLPAK AKVTFDRVPN AYDPTQLRVK
KGQTVLVTQK MSNGMYKAEL DGQIGSVPHT YLRFTAVSE
