MADD_DROME
ID MADD_DROME Reviewed; 2084 AA.
AC Q9VXY2; Q8MSD8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=MAP kinase-activating death domain protein;
DE AltName: Full=Rab3 guanyl-nucleotide exchange factor;
GN Name=Rab3-GEF {ECO:0000312|FlyBase:FBgn0030613};
GN ORFNames=CG5627 {ECO:0000312|FlyBase:FBgn0030613};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000305}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAM50740.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1680-2084, AND RNA EDITING OF
RP POSITIONS 2031 AND 2063.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM50740.1};
RC TISSUE=Head {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=11563850; DOI=10.1006/bbrc.2001.5652;
RA Levivier E., Goud B., Souchet M., Calmels T.P.G., Mornon J.-P.,
RA Callebaut I.;
RT "uDENN, DENN, and dDENN: indissociable domains in Rab and MAP kinases
RT signaling pathways.";
RL Biochem. Biophys. Res. Commun. 287:688-695(2001).
RN [5] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=10798391; DOI=10.1016/s0896-6273(00)81136-8;
RA Lloyd T.E., Verstreken P., Ostrin E.J., Phillippi A., Lichtarge O.,
RA Bellen H.J.;
RT "A genome-wide search for synaptic vesicle cycle proteins in Drosophila.";
RL Neuron 26:45-50(2000).
RN [6] {ECO:0000305}
RP RNA EDITING OF POSITIONS 2031 AND 2063.
RX PubMed=17018572; DOI=10.1261/rna.254306;
RA Stapleton M., Carlson J.W., Celniker S.E.;
RT "RNA editing in Drosophila melanogaster: new targets and functional
RT consequences.";
RL RNA 12:1922-1932(2006).
CC -!- FUNCTION: Guanyl-nucleotide exchange factor that regulates small
CC GTPases (By similarity). Converts GDP-bound inactive form of Rab3 to
CC the GTP-bound active forms (By similarity).
CC {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q8WXG6}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8WXG6}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q8WXG6}.
CC -!- RNA EDITING: Modified_positions=2031 {ECO:0000269|PubMed:12537569,
CC ECO:0000269|PubMed:17018572}, 2063 {ECO:0000269|PubMed:12537569,
CC ECO:0000269|PubMed:17018572}; Note=Partially edited. Target of Adar.
CC {ECO:0000269|PubMed:17018572};
CC -!- SIMILARITY: Belongs to the MADD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM50740.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF48424.2; -; Genomic_DNA.
DR EMBL; AY118880; AAM50740.1; ALT_INIT; mRNA.
DR RefSeq; NP_573001.2; NM_132773.3.
DR AlphaFoldDB; Q9VXY2; -.
DR BioGRID; 58797; 2.
DR IntAct; Q9VXY2; 2.
DR STRING; 7227.FBpp0298037; -.
DR PaxDb; Q9VXY2; -.
DR EnsemblMetazoa; FBtr0307207; FBpp0298036; FBgn0030613.
DR GeneID; 32442; -.
DR KEGG; dme:Dmel_CG5627; -.
DR UCSC; CG5627-RA; d. melanogaster.
DR CTD; 32442; -.
DR FlyBase; FBgn0030613; Rab3-GEF.
DR VEuPathDB; VectorBase:FBgn0030613; -.
DR eggNOG; KOG3570; Eukaryota.
DR GeneTree; ENSGT00940000156718; -.
DR InParanoid; Q9VXY2; -.
DR Reactome; R-DME-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 32442; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 32442; -.
DR PRO; PR:Q9VXY2; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030613; Expressed in brain and 11 other tissues.
DR ExpressionAtlas; Q9VXY2; baseline and differential.
DR Genevisible; Q9VXY2; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0098527; C:neuromuscular junction of somatic muscle; IDA:FlyBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008021; C:synaptic vesicle; NAS:FlyBase.
DR GO; GO:0043195; C:terminal bouton; IDA:FlyBase.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048789; P:cytoskeletal matrix organization at active zone; IMP:FlyBase.
DR GO; GO:0007269; P:neurotransmitter secretion; NAS:FlyBase.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:1902041; P:regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; ISS:FlyBase.
DR GO; GO:0016192; P:vesicle-mediated transport; NAS:FlyBase.
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; 2.
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 2: Evidence at transcript level;
KW Apoptosis; Cell membrane; Cytoplasm; Guanine-nucleotide releasing factor;
KW Membrane; Reference proteome; RNA editing.
FT CHAIN 1..2084
FT /note="MAP kinase-activating death domain protein"
FT /id="PRO_0000278141"
FT DOMAIN 25..352
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 373..514
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 516..678
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 1490..1565
FT /note="Death"
FT REGION 117..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 557..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 730..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 811..863
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 891..963
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1058..1092
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1115..1188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1305..1382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1794..1865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1896..2084
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..170
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 171..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..207
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..825
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 826..844
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 891..905
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 940..963
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1072..1092
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1115..1137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1162..1188
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1305..1357
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1366..1382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1896..1920
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1921..1937
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1938..1955
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1967..1981
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2002..2038
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2055..2077
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 2031
FT /note="Q -> R (in RNA edited version)"
FT VARIANT 2063
FT /note="S -> G (in RNA edited version)"
SQ SEQUENCE 2084 AA; 226055 MW; F5F745B221A54F70 CRC64;
MSDQQKASLC PRLVDYMAIV GAHTTPPMPK GLQGLKAPPV QVPDLLRRYP PSDHADFPLP
LDMVYFCQPE GCTSVGPRRT GSAIRDMTSF VFALTDKDSG KTRYGICVNF YRPIERPSSA
AGSAGAGNDR PGNGGPGGHG GGAGGGAGGG GRGGRRSSAF RRESWRKSME RSSDSAFSSD
YRSNVAPSDS DRELTSRRDS DQQRLHSHHS HHQPHHPSAS PAVPKLGLMA PSADSESGGS
HSPSPRASRK RTKLRNQSLT SLCIISHHPF FTTFRECLFI LKKLIDACNE SSSPKRVGAS
QKINRDNVWT VLTGHVSDAT PSIVLHDVRE IETWILRLLS TPVPVPGSTR VEVEVLSPTV
HEPLLFALPD HTRFSLVDFP LHLPLELLGV ETCLKVWTLI MQENKVLFQS RDYNALSMSV
MAFVTMLYPL EYMFPVIPLL PTCLSCAEQL LLAPTPFVIG VPASFLVYKK NFRLPDDIWV
VDLDSTKLTP PTGGYEEIPP LPEPEGTILK NHLKQALTSM TATNTAVSSQ QLLPSVRDSL
QEPPLLGVSQ VRLPLQTPPH SAQASQRNSM SAQGTISSRQ PSPMNSPALN PFVYGTDVDS
VDVATRVAMV RFFNAQNTLA NFAEHTRTLR LYPRPVVAFQ INSFLRSRPR ASQFLNQFAR
TQAVEFLAEW SLTPTNVAFL RVQTGVMDPM QVGDKPKWFA HALTPIRFSV WDDGSSLNGA
LRSLKQLECQ PTDESGSDSE GADSSSSSYS SLSDFVSEMA SSDLSPSLHD VFGSYNRPHV
VPQTLSSNLD PALVYHPPSK LQYPEGIADA VASKEEEDEE RADSPVSSSS SRSDLSSPSF
NRDSEFDFQP KGGQTLGSTT VGSGAAAPSF ELATPLAMRL EATIKMASIE QESDTVSTAT
GKTIAAGSKL QRHPSDSESR PEKKIPPPLT PPVKQPGVSN ILARTGSSGS SSSSPGRQSS
QSSLFENFAS HAKELVRETT RQSSQEGLLA HVDKFTLHAK KAAGEASKQA LEVSKQAAGV
SKNTLEDLTY VGKSTLGDLT KTAKEAATKK GIIKIEEHSA GGAGPPPKSP GSQLATHKQV
QQSGGQGGGN NFFSAIGTDF NGLASSTSTM FSGMFGKKSQ QKQVPVQQKQ PNVSAGKAKS
GINFDPFPGR KGLVERTPLI KHSGPRQTQE ELTRQQNQER SHSNAENQTF LKDVTNQVLA
GEGVGWLKLN RFKKLMEDES YRTLVLSKLN KTLDKKIAPD DHIDDVCVTK PVWKGMLKCI
QAIAGGLDVT FANFGLGGMA SVFQLMEVAH THYWSKEINE GSDMSSSLLS SHAASPMGSR
ENLRSPSSPN GSHSALGSEW ASPQESRKSS TQLAHGGPGG SHSGAPINRR LSSADSQDGQ
STTEMFKDML SQKRSALKNM LTSFDSDTTT SKDSKKSSGN LWSGKSTLSA GFRYTGGHLI
NTSSSPSPDS PRVYLFEGLL GKDRLNLWNQ MQFWEDAFLD AVSQERDMIG MDQGPIEMME
RYKSLSESER KRLEHDEDRL LSTMLYNLTA ILVMLNVAKD EIRRKIRRLL GKSHIGLVYS
QEVHNVVDQI NNLNGNDIDL KPLGSRLLHR QSFTVHQGTD VNGPLRFMEV RDDGLVLRSV
DGTIVERWWY ERLVNMTYSP KTKLLCLWRR NGGQTQLHKY YTRKCKELYN CIKEAMERGG
TPTNVPELGG EFPVQDMNTG EGGLLQVCLE GVGLLFSNSK FFVRLDHIRK CFTQKGGIFV
LEEYNPKTRN LIQRKYQSSM SDQICYSVLC VFSYVAAGQD QKKNPVVITP QIQDIHAQQK
QKHQQQQQHQ QPQQQQQPHQ TTTQQNQPTA VASAVPTTTA PAGQVNPNRM TAKSQAGSIS
IRHTVPMQKP TITMSTVQPQ ARMPAQVATA SVPVTVPVPP TPAPPTSNPA KLPQLPPRVP
SQPSTESLAS ISSPPPKLRT PMSAPPGPPP AIPPRTGAIS RSGSVPAARS FVRQASANST
PPQYTPQPPP PFVIPKRHSG LARASTLSSS TSPSMSSSSA SNHPGHSQSQ QRASHGSVAA
VLQSMPEAEP GYGSGSGSIS GSSSGSGSAS GSIASASPQA HRKH
