CED12_CAEEL
ID CED12_CAEEL Reviewed; 731 AA.
AC Q8STE5;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Cell death abnormality protein 12 {ECO:0000303|PubMed:11703939};
GN Name=ced-12 {ECO:0000312|EMBL:AAL38510.1}; ORFNames=Y106G6E.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, ECO:0000312|EMBL:AAL38510.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=11703939; DOI=10.1016/s1534-5807(01)00058-2;
RA Zhou Z., Caron E., Hartwieg E., Hall A., Horvitz H.R.;
RT "The C. elegans PH domain protein CED-12 regulates cytoskeletal
RT reorganization via a Rho/Rac GTPase signaling pathway.";
RL Dev. Cell 1:477-489(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL49495.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TERNARY COMPLEX WITH CED-2 AND CED-5,
RP AND DISRUPTION PHENOTYPE.
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 [3] {ECO:0000312|EMBL:CAD12890.1}
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 [4] {ECO:0000305}
RP FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=11146658; DOI=10.1038/35046585;
RA Chung S., Gumienny T.L., Hengartner M.O., Driscoll M.;
RT "A common set of engulfment genes mediates removal of both apoptotic and
RT necrotic cell corpses in C. elegans.";
RL Nat. Cell Biol. 2:931-937(2000).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=11595183; DOI=10.1016/s0092-8674(01)00520-7;
RA Gumienny T.L., Brugnera E., Tosello-Trampont A.-C., Kinchen J.M.,
RA Haney L.B., Nishiwaki K., Walk S.F., Nemergut M.E., Macara I.G.,
RA Francis R., Schedl T., Qin Y., Van Aelst L., Hengartner M.O.,
RA Ravichandran K.S.;
RT "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required
RT for phagocytosis and cell migration.";
RL Cell 107:27-41(2001).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=12297102; DOI=10.1006/dbio.2002.0785;
RA Wu Y.C., Cheng T.W., Lee M.C., Weng N.Y.;
RT "Distinct rac activation pathways control Caenorhabditis elegans cell
RT migration and axon outgrowth.";
RL Dev. Biol. 250:145-155(2002).
RN [7] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH PSR-1.
RX PubMed=14645848; DOI=10.1126/science.1087641;
RA Wang X., Wu Y.-C., Fadok V.A., Lee M.-C., Gengyo-Ando K., Cheng L.-C.,
RA Ledwich D., Hsu P.-K., Chen J.-Y., Chou B.-K., Henson P., Mitani S.,
RA Xue D.;
RT "Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor
RT through CED-5 and CED-12.";
RL Science 302:1563-1566(2003).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15620647; DOI=10.1016/j.cub.2004.12.029;
RA deBakker C.D., Haney L.B., Kinchen J.M., Grimsley C., Lu M., Klingele D.,
RA Hsu P.K., Chou B.K., Cheng L.C., Blangy A., Sondek J., Hengartner M.O.,
RA Wu Y.C., Ravichandran K.S.;
RT "Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG
RT signaling module and armadillo repeats of CED-12/ELMO.";
RL Curr. Biol. 14:2208-2216(2004).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15247908; DOI=10.1038/nsmb800;
RA Lu M., Kinchen J.M., Rossman K.L., Grimsley C., deBakker C., Brugnera E.,
RA Tosello-Trampont A.-C., Haney L.B., Klingele D., Sondek J.,
RA Hengartner M.O., Ravichandran K.S.;
RT "PH domain of ELMO functions in trans to regulate Rac activation via
RT Dock180.";
RL Nat. Struct. Mol. Biol. 11:756-762(2004).
RN [10] {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 [11]
RP FUNCTION, AND DOMAIN.
RX PubMed=21490059; DOI=10.1242/dev.060012;
RA Neukomm L.J., Nicot A.S., Kinchen J.M., Almendinger J., Pinto S.M.,
RA Zeng S., Doukoumetzidis K., Tronchere H., Payrastre B., Laporte J.F.,
RA Hengartner M.O.;
RT "The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse
RT clearance through CED-5-CED-12 in C. elegans.";
RL Development 138:2003-2014(2011).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26292279; DOI=10.1371/journal.pgen.1005446;
RA Levy-Strumpf N., Krizus M., Zheng H., Brown L., Culotti J.G.;
RT "The Wnt frizzled receptor MOM-5 regulates the UNC-5 Netrin receptor
RT through small GTPase-dependent signaling to determine the polarity of
RT migrating cells.";
RL PLoS Genet. 11:E1005446-E1005446(2015).
CC -!- FUNCTION: Involved in programmed apoptosis and necrosis. Required for
CC the cell corpse engulfment process. Has roles in the formation of actin
CC halos and distal tip cell migration (PubMed:11703939, PubMed:11703940,
CC PubMed:11146658, PubMed:11595183, PubMed:14645848, PubMed:15620647,
CC PubMed:15247908, PubMed:15744306, PubMed:21490059). Negatively
CC regulates the unc-6/Netrin receptor unc-5 to control distal tip cell
CC migration along the anterior-posterior axis of the body
CC (PubMed:26292279). Plays no role in amphid axon outgrowth
CC (PubMed:12297102). {ECO:0000269|PubMed:11146658,
CC ECO:0000269|PubMed:11595183, ECO:0000269|PubMed:11703939,
CC ECO:0000269|PubMed:11703940, ECO:0000269|PubMed:12297102,
CC ECO:0000269|PubMed:14645848, ECO:0000269|PubMed:15247908,
CC ECO:0000269|PubMed:15620647, ECO:0000269|PubMed:15744306,
CC ECO:0000269|PubMed:21490059, ECO:0000269|PubMed:26292279}.
CC -!- SUBUNIT: Interacts with psr-1. Forms a ternary complex with ced-2 and
CC ced-5. {ECO:0000269|PubMed:14645848}.
CC -!- INTERACTION:
CC Q8STE5; G5EEN3: ced-5; NbExp=4; IntAct=EBI-6390460, EBI-6390483;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11703939}.
CC Note=Punctate localization. {ECO:0000269|PubMed:11703939}.
CC -!- DEVELOPMENTAL STAGE: Expressed in developing embryos.
CC {ECO:0000269|PubMed:11703939}.
CC -!- DOMAIN: The PH domain binds phosphatidylinositol 3,5-biphosphate,
CC phosphatidylinositol 4-phosphate and phosphatidylinositol 3,4,5-
CC trisphosphate in vitro (PubMed:21490059). Required for punctate
CC localization in the cytoplasm and cell corpse engulfment
CC (PubMed:11703939). Required for distal cell tip migration
CC (PubMed:15247908). {ECO:0000269|PubMed:11703939,
CC ECO:0000269|PubMed:15247908, ECO:0000269|PubMed:21490059}.
CC -!- DISRUPTION PHENOTYPE: Deformity in the gonadal arm (PubMed:11703940).
CC Defective distal tip cell migration (PubMed:11703939, PubMed:11703940,
CC PubMed:15247908, PubMed:26292279). Defective cell corpse engulfment
CC with an increased number of cell corpses (PubMed:11703939,
CC PubMed:11703940, PubMed:11146658, PubMed:15620647). Absent actin
CC 'halos' around early apoptotic corpses, which is likely indicative of
CC defective actin reorganization around the apoptotic cell
CC (PubMed:15744306). Double knockout in an unc-5 or unc-40 mutant
CC background suppresses the distal tip cell migratory defect in the
CC respective single mutants (PubMed:26292279).
CC {ECO:0000269|PubMed:11146658, ECO:0000269|PubMed:11703939,
CC ECO:0000269|PubMed:11703940, ECO:0000269|PubMed:15247908,
CC ECO:0000269|PubMed:15620647, ECO:0000269|PubMed:15744306,
CC ECO:0000269|PubMed:26292279}.
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DR EMBL; AF416781; AAL38510.1; -; mRNA.
DR EMBL; AF324505; AAL49495.1; -; mRNA.
DR EMBL; AL032656; CAD12890.1; -; Genomic_DNA.
DR RefSeq; NP_492693.1; NM_060292.6.
DR AlphaFoldDB; Q8STE5; -.
DR SMR; Q8STE5; -.
DR BioGRID; 38308; 5.
DR IntAct; Q8STE5; 4.
DR MINT; Q8STE5; -.
DR STRING; 6239.Y106G6E.5.1; -.
DR EPD; Q8STE5; -.
DR PaxDb; Q8STE5; -.
DR PeptideAtlas; Q8STE5; -.
DR PRIDE; Q8STE5; -.
DR EnsemblMetazoa; Y106G6E.5a.1; Y106G6E.5a.1; WBGene00000426.
DR GeneID; 172890; -.
DR UCSC; Y106G6E.5.1; c. elegans.
DR CTD; 34633; -.
DR WormBase; Y106G6E.5a; CE27228; WBGene00000426; ced-12.
DR eggNOG; KOG2999; Eukaryota.
DR HOGENOM; CLU_339579_0_0_1; -.
DR InParanoid; Q8STE5; -.
DR PhylomeDB; Q8STE5; -.
DR Reactome; R-CEL-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR SignaLink; Q8STE5; -.
DR PRO; PR:Q8STE5; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000426; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q8STE5; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:WormBase.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:WormBase.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:WormBase.
DR GO; GO:0070064; F:proline-rich region binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; TAS:WormBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:WormBase.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IDA:WormBase.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0060097; P:cytoskeletal rearrangement involved in phagocytosis, engulfment; IMP:UniProtKB.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IMP:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IGI:UniProtKB.
DR GO; GO:0035262; P:gonad morphogenesis; IMP:UniProtKB.
DR GO; GO:0070986; P:left/right axis specification; IGI:UniProtKB.
DR GO; GO:0006911; P:phagocytosis, engulfment; IMP:UniProtKB.
DR GO; GO:1903356; P:positive regulation of distal tip cell migration; IGI:UniProtKB.
DR GO; GO:1901076; P:positive regulation of engulfment of apoptotic cell; IGI:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:GOC.
DR GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR024574; ELMO_ARM.
DR InterPro; IPR006816; ELMO_dom.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF11841; DUF3361; 1.
DR Pfam; PF16457; PH_12; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51335; ELMO; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Lipid-binding; Phagocytosis; Reference proteome;
KW SH3-binding.
FT CHAIN 1..731
FT /note="Cell death abnormality protein 12"
FT /id="PRO_0000379436"
FT DOMAIN 339..485
FT /note="ELMO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00664"
FT DOMAIN 544..679
FT /note="PH"
FT /evidence="ECO:0000255"
FT MOTIF 715..718
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
SQ SEQUENCE 731 AA; 83148 MW; 5243F167AE0C868B CRC64;
MAFHMPLKEL QPVDTSLPEH VVKGAVVIDK EFTIWNHRAV IPSNALHTVF ITINLLEQKL
TDVVKMAARS MNLSEDDSYG LMADKPKRFI TDDNLNSLGS GFILTLCASP DHYVKRITEI
LTEGNNISQM ENAVKTLDEF SLDPALIEAF YRCSSLELLF SLIRDDRVCM SSTLLSTCLR
ALSSMLELAV GDFTWKSVPN DVVVSMASLV TGKAKREEAN TLLAALQMLE QLVIGDDTTR
DWILEEVPIE TLIRHVEKSD ERIALCALSL MNSMIRRCPD DEKRFELIKS LEVVPFRNAV
HSSLLRGGGG VRNLNAIEQL VEVQRSLISA YETSPPTDAE VQKILDIESS EDVSEEIREM
WKSQIGEHRC GRLAAISMVQ FAEKSPQDLR MLISENTMRI EGGKWQLIPM WMRCCDIAAE
LFRVIPGRDE LDRLIVVLFS TETPFPAVFA CIVHLFHRTW REMQAKGGEM EKVACVVLEQ
LRHVLKRREI QDVEELSADL ETFSYRAMQE IWREEQLGKE NIQLHSEAVI QLKSKLRPKM
EELVRINHLN YLKLGAVFRK PQKSKSLAKL AFWHWKLDAS EKMLTITGCD GENYVEGVQR
DDIRQVWIKD IADVTNNDEI DRKASSSRFT SSPSTQMLRG IRVQLKTTND MKEGEVLMAL
TSDETQSVIW LEGLAELIGS KAVKSETDAM VERMLKMELR VRLLNVKLTN PEEKPEIPPI
PDDIKSFISK F
