MADD_CAEEL
ID MADD_CAEEL Reviewed; 1409 AA.
AC O02626; Q27467; Q8MQF4;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=MAP kinase-activating death domain protein;
DE AltName: Full=Aboc, expulsion defective protein 3;
DE AltName: Full=Regulator of presynaptic activity aex-3;
GN Name=aex-3; ORFNames=C02H7.3;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2;
RX PubMed=9136770; DOI=10.1016/s0896-6273(00)80302-5;
RA Iwasaki K., Staunton J., Saifee O., Nonet M., Thomas J.H.;
RT "aex-3 encodes a novel regulator of presynaptic activity in C. elegans.";
RL Neuron 18:613-622(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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]
RP FUNCTION, AND INTERACTION WITH CAB-1.
RX PubMed=10970871; DOI=10.1093/emboj/19.17.4806;
RA Iwasaki K., Toyonaga R.;
RT "The rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in
RT synaptic transmission.";
RL EMBO J. 19:4806-4816(2000).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18852466; DOI=10.1073/pnas.0803617105;
RA Mahoney T.R., Luo S., Round E.K., Brauner M., Gottschalk A., Thomas J.H.,
RA Nonet M.L.;
RT "Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in
RT Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16350-16355(2008).
RN [5]
RP FUNCTION.
RX PubMed=21029864; DOI=10.1016/j.cell.2010.09.024;
RA Bai J., Hu Z., Dittman J.S., Pym E.C., Kaplan J.M.;
RT "Endophilin functions as a membrane-bending molecule and is delivered to
RT endocytic zones by exocytosis.";
RL Cell 143:430-441(2010).
RN [6]
RP FUNCTION.
RX PubMed=25849533; DOI=10.1371/journal.pone.0124515;
RA Sheng M., Hosseinzadeh A., Muralidharan S.V., Gaur R., Selstam E., Tuck S.;
RT "Aberrant fat metabolism in Caenorhabditis elegans mutants with defects in
RT the defecation motor program.";
RL PLoS ONE 10:E0124515-E0124515(2015).
RN [7]
RP FUNCTION.
RX PubMed=27116976; DOI=10.1534/genetics.115.186064;
RA Bhat J.M., Hutter H.;
RT "Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide
RT Exchange Factor for RAB-3 in Caenorhabditis elegans.";
RL Genetics 203:1235-1247(2016).
CC -!- FUNCTION: Guanyl-nucleotide exchange factor that regulates small
CC GTPases (By similarity). Converts GDP-bound inactive form of rab-3 and
CC cab-1 to the GTP-bound active forms. Regulator of presynaptic activity
CC that interacts with rab-3 to regulate synaptic vesicle release
CC (PubMed:9136770, PubMed:10970871). Is also a regulator of the cab-1
CC synaptic transmission pathway (PubMed:10970871). Probably by converting
CC rab-3 to its GTP-bound active form, plays a role in the recruitment of
CC endophilin unc-57 to synaptic vesicles (PubMed:21029864). Probably by
CC activating rab-3 and thus regulating the trafficking of dense-core
CC vesicles, plays a role in AVG neuron-mediated formation of the right
CC axon tract of the ventral nerve cord (PubMed:27116976). Regulates
CC anterior body muscle contractions (aBOC) and the expulsion steps during
CC the defecation motor program (DMP) (PubMed:18852466). Probably by
CC regulating DMP, required for fatty acid uptake by intestinal cells
CC (PubMed:25849533). {ECO:0000250|UniProtKB:Q8WXG6,
CC ECO:0000269|PubMed:10970871, ECO:0000269|PubMed:18852466,
CC ECO:0000269|PubMed:21029864, ECO:0000269|PubMed:25849533,
CC ECO:0000269|PubMed:27116976, ECO:0000269|PubMed:9136770}.
CC -!- SUBUNIT: Interacts with cab-1. {ECO:0000269|PubMed:10970871}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8WXG6}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q8WXG6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=O02626-1; Sequence=Displayed;
CC Name=b;
CC IsoId=O02626-2; Sequence=VSP_015555;
CC -!- TISSUE SPECIFICITY: Expressed in nearly all neurons.
CC {ECO:0000269|PubMed:9136770}.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit pleiotropic behavioral defects that
CC are suggestive of reduced synaptic transmission (PubMed:9136770). RNAi-
CC mediated knockdown in the intestine causes a mild defect in the
CC expulsion step of the defecation cycle (PubMed:18852466).
CC {ECO:0000269|PubMed:18852466, ECO:0000269|PubMed:9136770}.
CC -!- SIMILARITY: Belongs to the MADD family. {ECO:0000305}.
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DR EMBL; U93842; AAB52421.1; -; mRNA.
DR EMBL; FO080298; CCD62710.1; -; Genomic_DNA.
DR EMBL; FO080298; CCD62711.1; -; Genomic_DNA.
DR PIR; T37188; T37188.
DR RefSeq; NP_001024342.1; NM_001029171.3. [O02626-2]
DR RefSeq; NP_741710.1; NM_171618.3. [O02626-1]
DR AlphaFoldDB; O02626; -.
DR BioGRID; 45373; 1.
DR STRING; 6239.C02H7.3a; -.
DR EPD; O02626; -.
DR PaxDb; O02626; -.
DR PeptideAtlas; O02626; -.
DR PRIDE; O02626; -.
DR EnsemblMetazoa; C02H7.3a.1; C02H7.3a.1; WBGene00000086. [O02626-1]
DR EnsemblMetazoa; C02H7.3b.1; C02H7.3b.1; WBGene00000086. [O02626-2]
DR GeneID; 180420; -.
DR KEGG; cel:CELE_C02H7.3; -.
DR UCSC; C02H7.3a; c. elegans. [O02626-1]
DR CTD; 180420; -.
DR WormBase; C02H7.3a; CE16806; WBGene00000086; aex-3. [O02626-1]
DR WormBase; C02H7.3b; CE30850; WBGene00000086; aex-3. [O02626-2]
DR eggNOG; KOG3570; Eukaryota.
DR GeneTree; ENSGT00940000156718; -.
DR HOGENOM; CLU_001270_0_0_1; -.
DR InParanoid; O02626; -.
DR OMA; TFEDLTY; -.
DR OrthoDB; 162625at2759; -.
DR PhylomeDB; O02626; -.
DR Reactome; R-CEL-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR PRO; PR:O02626; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000086; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:WormBase.
DR GO; GO:0030421; P:defecation; IMP:WormBase.
DR GO; GO:0010877; P:lipid transport involved in lipid storage; IMP:UniProtKB.
DR GO; GO:0007618; P:mating; IMP:WormBase.
DR GO; GO:0018991; P:oviposition; IMP:WormBase.
DR GO; GO:0014057; P:positive regulation of acetylcholine secretion, neurotransmission; IMP:WormBase.
DR GO; GO:1905488; P:positive regulation of anterior/posterior axon guidance; IMP:UniProtKB.
DR GO; GO:2000294; P:positive regulation of defecation; IMP:UniProtKB.
DR GO; GO:1904731; P:positive regulation of intestinal lipid absorption; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; IBA:GO_Central.
DR GO; GO:0007419; P:ventral cord development; IMP:UniProtKB.
DR Gene3D; 3.40.50.11500; -; 1.
DR InterPro; IPR001194; cDENN_dom.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR043153; DENN_C.
DR InterPro; IPR039980; MADD.
DR InterPro; IPR037516; Tripartite_DENN.
DR InterPro; IPR005113; uDENN_dom.
DR PANTHER; PTHR13008; PTHR13008; 1.
DR Pfam; PF02141; DENN; 1.
DR Pfam; PF03456; uDENN; 1.
DR SMART; SM00801; dDENN; 1.
DR SMART; SM00799; DENN; 1.
DR SMART; SM00800; uDENN; 1.
DR PROSITE; PS50211; DENN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cell membrane; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Reference proteome.
FT CHAIN 1..1409
FT /note="MAP kinase-activating death domain protein"
FT /id="PRO_0000064469"
FT DOMAIN 26..230
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 251..390
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 392..496
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 1109..1184
FT /note="Death"
FT REGION 654..701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 761..784
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 902..1008
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1015..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 654..692
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 902..916
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 936..959
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 962..1005
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1385..1409
FT /note="DQICYAVLCVFSLAAAGHKKEEHSK -> VDIAWAMHRVFSVQFAISCQKDT
FT N (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015555"
SQ SEQUENCE 1409 AA; 157459 MW; 2DDE6395AC963313 CRC64;
MNDKEKEICP RLIDFLVVVG KRNRTRGASQ SSPDATTDTT VTYPEILRRY PTDDHKDFIL
PTDVTVFCQP EGCTTTSARL RKNARNDPQF FVFMLTEKDS AKVRYGICLN FYQSFDRRST
PKDEIKKVPD DAHHKKRDSH VSLTSLCFIS HHPFVSIFHQ VLLLLKRIID SSNHRAAQRT
GLKDVVWAIL TGHYNEPIVP EVMKEIKEIE TWILMLLSSP VPVPGKTKVQ IEVMPMDLSQ
VFEFALPDHT RFTLIDFPLH IPFEILGIDM ALRVLTAAML EFKIVIQSRN YNAVSMCILS
IVALLYPLEY MFPVIPLLPA YMPSAEQLLL APTPFLIGVP SSFFHHRKIR ELPSDVILVD
LDTNCLQVPD DLYIPDLPEP DATHLKERLK NAINKMTTMT VDNETSVTDA DFGIDIDSVD
VACRVAMVQF FNSANVFGNF SEHTRTLRLY PRPVVSLQTD SFLRSRPQCT QLITDLCRTQ
AVEYFAECCL CPKNETFVRV QAGIESAEQV GDKPKWFSES LMPVHFMVYP NNSTLDSAIR
VYNAEIDNDD YEDDSATSTE NSNSIDDLVF DENQVTDAGG EVTKPLAEVN YIYKEPMTLE
LPQSESVVSI DSSLSSGRSS PDSSLSTSAV DSEADFARLA DNLALKSNSQ GAFSFDHGSD
SEYESTPVSQ RRKTIHNPGS DASDTPTSRG SIKSGLRMKG LTTLTDSGEK VLGPSLMNAI
NGYAEKSQSV FSQVINKTAP KAQALKERTM KPLANRIEQS QHIVRSKTQP NPTSQQTANQ
QSKNQQTVKE FCDQALVGQS VGMFSAPKLK RLMEDESLRE LVCSKLNLGL EVKLSEDEYV
KEVQLTKGQF KAYVKILKAC LEGIEVSFNT PGCCGFASVF HVLEIAHTHY WAMGGGEVIT
PSSSAPSTMT TPSEHSNDIL KESRPKLPAS TIDLRTPTKP LGQNVTPTST NNHEIAQSTR
SPALPPPVPP REAPPIPKRN PPPLGAPPKV PEGARAPPPL PPRPKVKTTA VDETPQNLVP
NNQPAQPSSP SFLADADEQT KPLLKPAPPT TLPVGKQEPC KVLPTPNEPV RHYIYQELIL
AVQHQIWQNL QFWENAFVDL VAQEREIVGM DQEPSEMIDR YSALNDSEKK RLELEEDRLL
STLLHNMTAY MIMCGTGQKA LQQKVRRLLG KAHIGLVCSK EINKLLDELP STQGNFIPLK
PLGSRLVQKQ SFTVCPGQSS DGQMMFMEVC DDAVVLRSIT GAATERWWYE RLVNITYSPK
TKILCLWRRH DDKVHMHKFH TKKCRELYQC MKAAMERAAA RGKVNVEGRA LGGEFPVHDT
ETNQGGLLQV RCDGVAVIFA HNQIFIGLSN IKKCNTFGGN VFLLEEFDRK KGEIIQRRYF
SQMADQICYA VLCVFSLAAA GHKKEEHSK
