MADD_MOUSE
ID MADD_MOUSE Reviewed; 1577 AA.
AC Q80U28; Q3TQK3; Q6P4I6; Q80W52; Q80WL3; Q80WL4; Q80WL5; Q80WL6; Q80WL7;
AC Q80WL8; Q80WL9; Q80WM0; Q80WM1; Q80WM2; Q8CBC1;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 25-MAY-2022, entry version 119.
DE RecName: Full=MAP kinase-activating death domain protein;
DE AltName: Full=Rab3 GDP/GTP exchange factor;
DE Short=RabGEF {ECO:0000305};
DE AltName: Full=Rab3 GDP/GTP exchange protein {ECO:0000303|PubMed:11359932};
DE Short=Rab3GEP {ECO:0000303|PubMed:11359932};
GN Name=Madd {ECO:0000312|MGI:MGI:2444672};
GN Synonyms=Kiaa0358 {ECO:0000312|EMBL:BAC65539.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP22159.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4; 5; 6; 7; 8; 9; 10; 11 AND 12).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAP22159.1};
RA Al-Zoubi A.M., Efimova E.V., Lu S., Prabhakar B.P.;
RT "Genomic organization and alternative splicing of IG20 isoforms in mouse
RT tissues.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAC65539.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAC65539.1};
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAC29392.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 13), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1011-1577 (ISOFORM 15).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC29392.1};
RC TISSUE=Cerebellum {ECO:0000312|EMBL:BAC29392.1}, and
RC Corpora quadrigemina {ECO:0000312|EMBL:BAE37379.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH63386.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 643-1577 (ISOFORM 14).
RC TISSUE=Eye {ECO:0000312|EMBL:AAH63386.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11359932; DOI=10.1091/mbc.12.5.1421;
RA Tanaka M., Miyoshi J., Ishizaki H., Togawa A., Ohnishi K., Endo K.,
RA Matsubara K., Mizoguchi A., Nagano T., Sato M., Sasaki T., Takai Y.;
RT "Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at
RT the mouse neuromuscular junction.";
RL Mol. Biol. Cell 12:1421-1430(2001).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12388783; DOI=10.1073/pnas.212511399;
RA Yamaguchi K., Tanaka M., Mizoguchi A., Hirata Y., Ishizaki H., Kaneko K.,
RA Miyoshi J., Takai Y.;
RT "A GDP/GTP exchange protein for the Rab3 small G protein family up-
RT regulates a postdocking step of synaptic exocytosis in central synapses.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14536-14541(2002).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18559336; DOI=10.1074/jbc.m804134200;
RA Figueiredo A.C., Wasmeier C., Tarafder A.K., Ramalho J.S., Baron R.A.,
RA Seabra M.C.;
RT "Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a
RT in melanocytes.";
RL J. Biol. Chem. 283:23209-23216(2008).
RN [11]
RP FUNCTION, INTERACTION WITH KIF1B; KIF1A; RAB3A; RAB3B; RAB3C AND RAB3D,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18849981; DOI=10.1038/ncb1785;
RA Niwa S., Tanaka Y., Hirokawa N.;
RT "KIF1Bbeta- and KIF1A-mediated axonal transport of presynaptic regulator
RT Rab3 occurs in a GTP-dependent manner through DENN/MADD.";
RL Nat. Cell Biol. 10:1269-1279(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-817; SER-819; SER-1058;
RP THR-1065; SER-1109; THR-1235 AND SER-1237, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Guanyl-nucleotide exchange factor that regulates small
CC GTPases of the Rab family (PubMed:18559336, PubMed:11359932). Converts
CC GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active
CC forms (PubMed:18559336). Converts GDP-bound inactive form of RAB3A,
CC RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in
CC synaptic vesicle exocytosis and vesicle secretion (By similarity).
CC Plays a role in synaptic vesicle formation and in vesicle trafficking
CC at the neuromuscular junction (PubMed:11359932, PubMed:12388783,
CC PubMed:18849981). Involved in up-regulating a post-docking step of
CC synaptic exocytosis in central synapses (PubMed:12388783). Probably by
CC binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent
CC transport of GTP-RAB3A-positive vesicles to the presynaptic nerve
CC terminals (PubMed:18849981). Plays a role in TNFA-mediated activation
CC of the MAPK pathway, including ERK1/2 (By similarity). May link
CC TNFRSF1A with MAP kinase activation (By similarity). May be involved in
CC the regulation of TNFA-induced apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q8WXG6,
CC ECO:0000269|PubMed:11359932, ECO:0000269|PubMed:12388783,
CC ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:18849981}.
CC -!- SUBUNIT: Interacts (via death domain) with TNFRSF1A (via death domain)
CC (By similarity). Interacts with PIDD1 (By similarity). Interacts with
CC YWHAZ (By similarity). Interacts (via death domain) with KIF1B
CC (PubMed:18849981). Interacts with KIF1A (PubMed:18849981). Interacts
CC (via uDENN domain) with RAB3A, RAB3B, RAB3C and RAB3D; the GTP-bound
CC form of the Rab proteins is preferred for interaction
CC (PubMed:18849981). {ECO:0000250|UniProtKB:Q8WXG6,
CC ECO:0000269|PubMed:18849981}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8WXG6}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q8WXG6}. Cell projection, axon
CC {ECO:0000269|PubMed:18849981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=15;
CC Name=1 {ECO:0000269|PubMed:12693553};
CC IsoId=Q80U28-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|Ref.1}; Synonyms=IG20 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-2; Sequence=VSP_052309, VSP_052312, VSP_052313;
CC Name=3 {ECO:0000269|PubMed:15489334};
CC IsoId=Q80U28-3; Sequence=VSP_052301, VSP_052309;
CC Name=4 {ECO:0000269|Ref.1}; Synonyms=IG20-PASV {ECO:0000269|Ref.1};
CC IsoId=Q80U28-4; Sequence=VSP_052302, VSP_052309, VSP_052311,
CC VSP_052312, VSP_052313;
CC Name=5 {ECO:0000269|Ref.1}; Synonyms=IG20-SV4 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-5; Sequence=VSP_052300, VSP_052301, VSP_052302,
CC VSP_052309, VSP_052311, VSP_052312,
CC VSP_052314;
CC Name=6 {ECO:0000269|Ref.1}; Synonyms=IG20-SV5 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-6; Sequence=VSP_052300, VSP_052301, VSP_052302,
CC VSP_052308, VSP_052311, VSP_052312,
CC VSP_052314;
CC Name=7 {ECO:0000269|Ref.1}; Synonyms=IG20-SV2 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-7; Sequence=VSP_052299, VSP_052302, VSP_052309,
CC VSP_052311, VSP_052312, VSP_052313;
CC Name=8 {ECO:0000269|Ref.1}; Synonyms=IG20-SV1 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-8; Sequence=VSP_052301, VSP_052302, VSP_052309,
CC VSP_052311, VSP_052312, VSP_052313;
CC Name=9 {ECO:0000269|Ref.1}; Synonyms=IG20-SV6 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-9; Sequence=VSP_052300, VSP_052301, VSP_052302,
CC VSP_052306, VSP_052311, VSP_052312,
CC VSP_052314;
CC Name=10 {ECO:0000269|Ref.1}; Synonyms=IG20-SV7 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-10; Sequence=VSP_052300, VSP_052301, VSP_052302,
CC VSP_052305, VSP_052311, VSP_052312,
CC VSP_052314;
CC Name=11 {ECO:0000269|Ref.1}; Synonyms=IG20-SV3 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-11; Sequence=VSP_052299, VSP_052301, VSP_052302,
CC VSP_052309, VSP_052311, VSP_052312,
CC VSP_052313;
CC Name=12 {ECO:0000269|Ref.1}; Synonyms=IG20-SV8 {ECO:0000269|Ref.1};
CC IsoId=Q80U28-12; Sequence=VSP_052300, VSP_052301, VSP_052302,
CC VSP_052305, VSP_052310;
CC Name=13 {ECO:0000269|PubMed:16141072};
CC IsoId=Q80U28-13; Sequence=VSP_052301, VSP_052303, VSP_052304;
CC Name=14 {ECO:0000269|PubMed:15489334};
CC IsoId=Q80U28-14; Sequence=VSP_052301, VSP_052309, VSP_052315;
CC Name=15 {ECO:0000269|PubMed:16141072};
CC IsoId=Q80U28-15; Sequence=VSP_052307;
CC -!- TISSUE SPECIFICITY: Expressed in the brain.
CC {ECO:0000269|PubMed:18849981}.
CC -!- DISRUPTION PHENOTYPE: Apparently normal in utero development but
CC immediate death after birth, probably due acute respiratory failure
CC (PubMed:11359932). Absent GDP/GTP exchange activity of Rab3A
CC (PubMed:11359932). Apparently normal development of the central nervous
CC system during embryonic stages (PubMed:11359932). At 18.5 dpc, no
CC evoked action potentials of the diaphragm and gastrocnemius muscles in
CC response to electrical stimulation of the phrenic and sciatic nerves,
CC respectively. In contrast, axonal conduction of the spinal cord and the
CC phrenic nerve are not impaired. Reduced total numbers of synaptic
CC vesicles at the neuromuscular junction, especially those docked at the
CC presynaptic plasma membrane, whereas postsynaptic structures and
CC functions appear normal (PubMed:11359932). Reduction of excitatory
CC postsynaptic current amplitude in neurons (PubMed:12388783). Synaptic
CC vesicles locate remote from the presynaptic membrane in the central
CC region instead of at the active zones of the presynaptic terminal
CC (PubMed:12388783). RNAi-mediated knockdown results in reduced levels of
CC Rab27a in the activated GTP-bound form (PubMed:18559336). In
CC melanocytes, results in aggregation and perinuclear clustering of
CC melanosomes (PubMed:18559336). RNAi-mediated knockdown in hippocampal
CC neurons leads reduced interaction between Kif1b and Rab3 and to reduced
CC axonal transport of Rab3 (PubMed:18849981).
CC {ECO:0000269|PubMed:11359932, ECO:0000269|PubMed:12388783,
CC ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:18849981}.
CC -!- SIMILARITY: Belongs to the MADD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65539.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY263980; AAP22159.1; -; mRNA.
DR EMBL; AY263981; AAP22160.1; -; mRNA.
DR EMBL; AY263982; AAP22161.1; -; mRNA.
DR EMBL; AY263983; AAP22162.1; -; mRNA.
DR EMBL; AY263984; AAP22163.1; -; mRNA.
DR EMBL; AY263985; AAP22164.1; -; mRNA.
DR EMBL; AY263986; AAP22165.1; -; mRNA.
DR EMBL; AY263987; AAP22166.1; -; mRNA.
DR EMBL; AY263988; AAP22167.1; -; mRNA.
DR EMBL; AY263989; AAP22168.1; -; mRNA.
DR EMBL; AK122257; BAC65539.1; ALT_INIT; mRNA.
DR EMBL; AK036347; BAC29392.1; -; mRNA.
DR EMBL; AK163518; BAE37379.1; -; mRNA.
DR EMBL; AL691450; CAM17578.1; -; Genomic_DNA.
DR EMBL; BC042212; AAH42212.1; -; mRNA.
DR EMBL; BC063386; AAH63386.1; -; mRNA.
DR CCDS; CCDS38178.1; -. [Q80U28-3]
DR CCDS; CCDS50635.1; -. [Q80U28-14]
DR CCDS; CCDS50638.1; -. [Q80U28-1]
DR RefSeq; NP_001171190.1; NM_001177719.1.
DR RefSeq; NP_001171191.1; NM_001177720.1.
DR RefSeq; NP_663502.3; NM_145527.4.
DR RefSeq; XP_017173117.1; XM_017317628.1.
DR AlphaFoldDB; Q80U28; -.
DR BioGRID; 230724; 8.
DR IntAct; Q80U28; 4.
DR MINT; Q80U28; -.
DR STRING; 10090.ENSMUSP00000077094; -.
DR iPTMnet; Q80U28; -.
DR PhosphoSitePlus; Q80U28; -.
DR EPD; Q80U28; -.
DR jPOST; Q80U28; -.
DR MaxQB; Q80U28; -.
DR PaxDb; Q80U28; -.
DR PeptideAtlas; Q80U28; -.
DR PRIDE; Q80U28; -.
DR ProteomicsDB; 295761; -. [Q80U28-1]
DR ProteomicsDB; 295762; -. [Q80U28-2]
DR ProteomicsDB; 295763; -. [Q80U28-3]
DR ProteomicsDB; 295764; -. [Q80U28-4]
DR ProteomicsDB; 295765; -. [Q80U28-5]
DR ProteomicsDB; 295766; -. [Q80U28-6]
DR ProteomicsDB; 295767; -. [Q80U28-7]
DR ProteomicsDB; 295768; -. [Q80U28-8]
DR ProteomicsDB; 295769; -. [Q80U28-9]
DR ProteomicsDB; 295770; -. [Q80U28-10]
DR ProteomicsDB; 295771; -. [Q80U28-11]
DR ProteomicsDB; 295772; -. [Q80U28-12]
DR ProteomicsDB; 295773; -. [Q80U28-13]
DR ProteomicsDB; 295774; -. [Q80U28-14]
DR ProteomicsDB; 295775; -. [Q80U28-15]
DR DNASU; 228355; -.
DR GeneID; 228355; -.
DR KEGG; mmu:228355; -.
DR CTD; 8567; -.
DR MGI; MGI:2444672; Madd.
DR eggNOG; KOG3570; Eukaryota.
DR InParanoid; Q80U28; -.
DR OrthoDB; 162625at2759; -.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 228355; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Madd; mouse.
DR PRO; PR:Q80U28; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q80U28; protein.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0048490; P:anterograde synaptic vesicle transport; IDA:SynGO.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0060125; P:negative regulation of growth hormone secretion; ISO:MGI.
DR GO; GO:1902277; P:negative regulation of pancreatic amylase secretion; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:1902041; P:regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; ISO:MGI.
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; Cell projection; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1577
FT /note="MAP kinase-activating death domain protein"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT /id="PRO_0000278139"
FT DOMAIN 13..267
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 288..428
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 430..564
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 1336..1411
FT /note="Death"
FT /evidence="ECO:0000255"
FT REGION 106..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 604..635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 676..840
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 912..940
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1050..1109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1127..1272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..155
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 688..718
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..764
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 792..807
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 816..840
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 915..940
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1127..1157
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1158..1213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1230..1251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 819
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 857
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT MOD_RES 929
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 1058
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1060
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 1065
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1109
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1235
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1237
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG6"
FT VAR_SEQ 719..744
FT /note="EAADSTEMGDKATAGISKPLPPVPPS -> VREHLAG (in isoform 7
FT and isoform 11)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052299"
FT VAR_SEQ 719..743
FT /note="Missing (in isoform 5, isoform 6, isoform 9, isoform
FT 10 and isoform 12)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052300"
FT VAR_SEQ 884..903
FT /note="Missing (in isoform 3, isoform 5, isoform 6, isoform
FT 8, isoform 9, isoform 10, isoform 11, isoform 12, isoform
FT 13 and isoform 14)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|Ref.1"
FT /id="VSP_052301"
FT VAR_SEQ 1120..1138
FT /note="ELWNKHQEVKKQKALEKQR -> G (in isoform 4, isoform 5,
FT isoform 6, isoform 7, isoform 8, isoform 9, isoform 10,
FT isoform 11 and isoform 12)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052302"
FT VAR_SEQ 1120..1135
FT /note="ELWNKHQEVKKQKALE -> DLTENLLMFGVSLFTL (in isoform
FT 13)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052303"
FT VAR_SEQ 1136..1577
FT /note="Missing (in isoform 13)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052304"
FT VAR_SEQ 1172..1198
FT /note="Missing (in isoform 10 and isoform 12)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052305"
FT VAR_SEQ 1183..1200
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052306"
FT VAR_SEQ 1196..1198
FT /note="Missing (in isoform 15)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052307"
FT VAR_SEQ 1198..1200
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052308"
FT VAR_SEQ 1199
FT /note="V -> VV (in isoform 2, isoform 3, isoform 4, isoform
FT 5, isoform 7, isoform 8, isoform 11 and isoform 14)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_052309"
FT VAR_SEQ 1219..1577
FT /note="Missing (in isoform 12)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052310"
FT VAR_SEQ 1287..1307
FT /note="Missing (in isoform 4, isoform 5, isoform 6, isoform
FT 7, isoform 8, isoform 9, isoform 10 and isoform 11)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052311"
FT VAR_SEQ 1511..1534
FT /note="CRELYYCVKDSMERAAARQQSIKP -> VLRVCVWAGDWI (in isoform
FT 2, isoform 4, isoform 5, isoform 6, isoform 7, isoform 8,
FT isoform 9, isoform 10 and isoform 11)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052312"
FT VAR_SEQ 1559..1577
FT /note="LEGINLKFMHNQFLKLKKW -> PGRDQSQVHAQPGFHRAESH (in
FT isoform 2, isoform 4, isoform 7, isoform 8 and isoform 11)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052313"
FT VAR_SEQ 1559..1577
FT /note="LEGINLKFMHNQFLKLKKW -> PGRDQSQVHAQPVPEIKEVVSHKYKTPMA
FT HEICYSVLCLFSYVAAVRSSEEDLRTPPRPVSS (in isoform 5, isoform 6,
FT isoform 9 and isoform 10)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052314"
FT VAR_SEQ 1571..1577
FT /note="FLKLKKW -> ERKVFIELNHIKKCNTVRGVFVLEEFVPEIKEVVSHKYKTP
FT MAHEICYSVLCLFSYVAAVRSSEEDLRTPPRPVSS (in isoform 14)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052315"
FT CONFLICT 132
FT /note="T -> A (in Ref. 3; BAC29392, 4; CAM17578 and 5;
FT AAH63386)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="I -> V (in Ref. 3; BAC29392, 4; CAM17578 and 5;
FT AAH63386)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="W -> R (in Ref. 1; AAP22159/AAP22160/AAP22161/
FT AAP22162/AAP22163/AAP22164/AAP22165/AAP22166/AAP22167/
FT AAP22168, 3; BAC29392, 4; CAM17578 and 5; AAH63386)"
FT /evidence="ECO:0000305"
FT CONFLICT 1159
FT /note="S -> R (in Ref. 3; BAE37379)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1577 AA; 175180 MW; 5D604F8DDD1EF481 CRC64;
MVQKKFCPRL LDYLVIVGAR HPSSDSVAQT PELLRRYPLE DHPEFPLPPD VVFFCQPEGC
LSVRQRRMSL RDDTSFVFTL TDKDTGVTRY GICVNFYRSF QKRMPKEKVE GGAGPRGKEG
AHTSGASEEA ATGSSESGST LQPPSADSTP DINQSPWGKR RAKAGSRSRN STLTSLCVLS
HYPFFSTFRE CLYTLKRLVD CCSERLLGKK LGIPRGVQRD TMWRIFTGSL LVEEKSSALL
QDLREIEAWI YRLLRSPVPV SGQKRVDIEV LPQELQQALT FALPDPSRFT LVDFPLHLPL
ELLGVDACLQ VLTCILLEHK VVLQSRDYNA LSMSVMAFVA MIYPLEYMFP VIPLLPTCMA
SAEQLLLAPT PYIIGVPASF FLYKLDFKMP DDVWLVDLDS NRVIAPTNAE VLPILPEPES
LELKKHLKQA LASMSLNTQP ILNLEKFHEG QEIPLLLGRP SNDLQSTPST EFNPLIYGND
VDSVDVATRV AMVRFFNSAN VLQGFQMHTR TLRLFPRPVV AFQAGSFLAS RPRQTPFAEK
LARTQAVEYF GEWILNPSNY AFQRIHNNTF DPALIGDKPK WYAHQLQPIH YRVYDGNSQL
AEALSVPPER DSDSDPTEDS GSDSQDYDDS SSSYSSLGDF VSEMMKCDIN GDTPNVDPLT
HAALGDASEV EIDELQPQKE GEEPGPDSEN SQENPPLRSS SSTTASSSPS TVVHSAHSEA
ADSTEMGDKA TAGISKPLPP VPPSICKSTV DRRQTETGEG SVCQRTYDNP YFEPQYGFPP
EEDEEEQGES YTPRFSQHVS GSRAQKLLRP NSLKLASDSD AESDSRASSP NSTVSNNSTE
GFGGIMSFAS SLYRNHSTSF SLSNLTLPTK GAREKTTPFP SLKVFGLNTL MEIVTEAGPG
SGEGNRRALV DQKSSVIKHS PTVKREPSSP QGRSSNSSEN QQFLKEVVHS VLDGQGVGWL
NMKKVRRLLE SEQLRVFVLS KLNRAVQSED DARQDVIQDV EISRKVYKGM LDLLKCTVLS
LEQSYAHAGL GGMASIFGLL EIAQTHYYSK EPDKRKRSPT ENVNTPVGKD PGLAGRGDPK
AMAQLRVPQL GPRAPSATGK GPKELDTRSL KEENFVASVE LWNKHQEVKK QKALEKQRPE
GIKPVFDLGE TEEKKSQMSA DSGVSLTSAS QRTDQDSVIG VSPAVMIRSS SQDSEVSTVS
NSSGETLGAD SDLSSNAGDG PGGEGSAHLA SSRATLSDSE IETNSATSAI FGKAHSLKPK
EKPAGSPIRS SEDVSQRVYL YEGLLGRDKG SMWDQLEDAA METFSLSKER STLWDQMQFW
EDAFLDAVML EREGMGMDQG PQEMIDRYLS LGEHDRKRLE DDEDRLLATL LHNLISYMLL
MKVNKNDIRK KVRRLMGKSH IGLVYSQQVN EVLDQLNSLN GRDLSIRSSG SRHMKKQTFV
VHAGTDTNGD IFFMEVCDDC VVLRSNIGTV YERWWYEKLI NMTYCPKTKV LCLWRRNGSE
TQLNKFYTKK CRELYYCVKD SMERAAARQQ SIKPGPELGG EFPVQDMKTG EGGLLQVTLE
GINLKFMHNQ FLKLKKW
