MADD_HUMAN
ID MADD_HUMAN Reviewed; 1647 AA.
AC Q8WXG6; A8K8S7; B5MEE5; D3DQR4; O15065; O15293; Q15732; Q15741; Q8IWD7;
AC Q8WXG3; Q8WXG4; Q8WXG5; Q8WZ63;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=MAP kinase-activating death domain protein;
DE AltName: Full=Differentially expressed in normal and neoplastic cells;
DE AltName: Full=Insulinoma glucagonoma clone 20;
DE AltName: Full=Rab3 GDP/GTP exchange factor;
DE Short=RabGEF {ECO:0000305};
DE AltName: Full=Rab3 GDP/GTP exchange protein {ECO:0000305};
DE Short=Rab3GEP {ECO:0000305};
GN Name=MADD {ECO:0000312|EMBL:AAB57735.1, ECO:0000312|HGNC:HGNC:6766};
GN Synonyms=DENN {ECO:0000312|EMBL:AAD12154.1},
GN IG20 {ECO:0000312|EMBL:AAL40265.1}, KIAA0358 {ECO:0000312|EMBL:BAA20814.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD12154.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Fetal liver {ECO:0000312|EMBL:AAD12154.1};
RX PubMed=8988362; DOI=10.3109/10425179609020873;
RA Chow V.T.K., Lee S.S.;
RT "DENN, a novel human gene differentially expressed in normal and neoplastic
RT cells.";
RL DNA Seq. 6:263-273(1996).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAB57735.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, INTERACTION WITH
RP TNFRSF1A, VARIANT MET-751, AND TISSUE SPECIFICITY.
RX PubMed=9115275; DOI=10.1074/jbc.272.18.12069;
RA Schievella A.R., Chen J.H., Graham J.R., Lin L.-L.;
RT "MADD, a novel death domain protein that interacts with the type 1 tumor
RT necrosis factor receptor and activates mitogen-activated protein kinase.";
RL J. Biol. Chem. 272:12069-12075(1997).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAD12154.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), AND TISSUE SPECIFICITY.
RC TISSUE=Liver {ECO:0000312|EMBL:AAD12154.1};
RX PubMed=9796103; DOI=10.1139/g98-050;
RA Chow V.T.K., Lim K.M., Lim D.;
RT "The human DENN gene: genomic organization, alternative splicing, and
RT localization to chromosome 11p11.21-p11.22.";
RL Genome 41:543-552(1998).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAL40265.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 4; 5 AND 6), FUNCTION, AND
RP INTERACTION WITH TNFRSF1A.
RC TISSUE=Insulinoma {ECO:0000269|PubMed:11577081};
RX PubMed=11577081; DOI=10.1074/jbc.m104835200;
RA Al-Zoubi A.M., Efimova E.V., Kaithamana S., Martinez O.,
RA El-Azami El-Idrissi M., Dogan R.E., Prabhakar B.S.;
RT "Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on
RT tumor necrosis factor alpha-induced apoptosis and activation of caspase-8
RT and -3.";
RL J. Biol. Chem. 276:47202-47211(2001).
RN [5] {ECO:0000305, ECO:0000312|EMBL:BAA20814.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Brain {ECO:0000312|EMBL:BAA20814.2};
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9] {ECO:0000305, ECO:0000312|EMBL:AAH40484.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANTS THR-696;
RP GLY-968 AND PHE-1040.
RC TISSUE=Testis {ECO:0000312|EMBL:AAH40484.1};
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 [10]
RP INTERACTION WITH PIDD1.
RX PubMed=10825539; DOI=10.1016/s0167-4838(00)00029-7;
RA Telliez J.-B., Bean K.M., Lin L.-L.;
RT "LRDD, a novel leucine rich repeat and death domain containing protein.";
RL Biochim. Biophys. Acta 1478:280-288(2000).
RN [11] {ECO:0000305}
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=14716293; DOI=10.1038/sj.onc.1207210;
RA Efimova E.V., Al-Zoubi A.M., Martinez O., Kaithamana S., Lu S., Arima T.,
RA Prabhakar B.S.;
RT "IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell
RT survival, and enhances their susceptibility to apoptosis and cancer
RT drugs.";
RL Oncogene 23:1076-1087(2004).
RN [12]
RP INTERACTION WITH YWHAZ.
RX PubMed=16959763; DOI=10.1074/mcp.m600147-mcp200;
RA Angrand P.O., Segura I., Voelkel P., Ghidelli S., Terry R., Brajenovic M.,
RA Vintersten K., Klein R., Superti-Furga G., Drewes G., Kuster B.,
RA Bouwmeester T., Acker-Palmer A.;
RT "Transgenic mouse proteomics identifies new 14-3-3-associated proteins
RT involved in cytoskeletal rearrangements and cell signaling.";
RL Mol. Cell. Proteomics 5:2211-2227(2006).
RN [13]
RP FUNCTION.
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-818; SER-820 AND SER-921, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP FUNCTION AS GUANYL-NUCLEOTIDE EXCHANGE FACTOR.
RX PubMed=20937701; DOI=10.1083/jcb.201008051;
RA Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A.;
RT "Family-wide characterization of the DENN domain Rab GDP-GTP exchange
RT factors.";
RL J. Cell Biol. 191:367-381(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-692; SER-858;
RP SER-862; SER-916; SER-921; SER-1059; THR-1237; SER-1239 AND SER-1270, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP INVOLVEMENT IN NEDDISH, VARIANTS NEDDISH HIS-198 AND ARG-327--1647-SER DEL,
RP AND VARIANT ARG-1040.
RX PubMed=28940097; DOI=10.1007/s00439-017-1843-2;
RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A.,
RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M.,
RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A.,
RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S.,
RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T.,
RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C.,
RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M.,
RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.;
RT "Expanding the genetic heterogeneity of intellectual disability.";
RL Hum. Genet. 136:1419-1429(2017).
RN [23]
RP ERRATUM OF PUBMED:28940097.
RX PubMed=29288388; DOI=10.1007/s00439-017-1859-7;
RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A.,
RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M.,
RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A.,
RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S.,
RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T.,
RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C.,
RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M.,
RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.;
RT "Correction to: Expanding the genetic heterogeneity of intellectual
RT disability.";
RL Hum. Genet. 137:105-109(2018).
RN [24]
RP INVOLVEMENT IN DEEAH, VARIANTS DEEAH ARG-216--1647-SER DEL; PHE-257;
RP VAL-305; ARG-327--1647-SER DEL; LEU-372; ARG-1040 AND TRP-1431--1647-SER
RP DEL, VARIANTS NEDDISH PRO-346; LEU-354; PRO-945; SER-1213--1647-SER DEL;
RP SER-1283; ARG-1318 AND ARG-1532--1647-SER DEL, CHARACTERIZATION OF VARIANTS
RP DEEAH VAL-305; ARG-1040, AND FUNCTION.
RX PubMed=32761064; DOI=10.1093/brain/awaa204;
RG Undiagnosed Diseases Network;
RA Schneeberger P.E., Kortuem F., Korenke G.C., Alawi M., Santer R., Woidy M.,
RA Buhas D., Fox S., Juusola J., Alfadhel M., Webb B.D., Coci E.G.,
RA Abou Jamra R., Siekmeyer M., Biskup S., Heller C., Maier E.M.,
RA Javaher-Haghighi P., Bedeschi M.F., Ajmone P.F., Iascone M., Peeters H.,
RA Ballon K., Jaeken J., Rodriguez Alonso A., Palomares-Bralo M.,
RA Santos-Simarro F., Meuwissen M.E.C., Beysen D., Kooy R.F., Houlden H.,
RA Murphy D., Doosti M., Karimiani E.G., Mojarrad M., Maroofian R.,
RA Noskova L., Kmoch S., Honzik T., Cope H., Sanchez-Valle A., Gelb B.D.,
RA Kurth I., Hempel M., Kutsche K.;
RT "Biallelic MADD variants cause a phenotypic spectrum ranging from
RT developmental delay to a multisystem disorder.";
RL Brain 143:2437-2453(2020).
CC -!- FUNCTION: Guanyl-nucleotide exchange factor that regulates small
CC GTPases of the Rab family (PubMed:20937701, PubMed:18559336). Converts
CC GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active
CC forms (PubMed:20937701, PubMed:18559336). Converts GDP-bound inactive
CC form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases
CC involved in synaptic vesicle exocytosis and vesicle secretion (By
CC similarity). Plays a role in synaptic vesicle formation and in vesicle
CC trafficking at the neuromuscular junction (By similarity). Involved in
CC up-regulating a post-docking step of synaptic exocytosis in central
CC synapses (By similarity). Probably by binding to the motor proteins
CC KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-
CC positive vesicles to the presynaptic nerve terminals (By similarity).
CC Plays a role in TNFA-mediated activation of the MAPK pathway, including
CC ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation
CC (PubMed:9115275). May be involved in the regulation of TNFA-induced
CC apoptosis (PubMed:11577081, PubMed:32761064).
CC {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q80U28,
CC ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:18559336,
CC ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:32761064,
CC ECO:0000269|PubMed:9115275}.
CC -!- SUBUNIT: Interacts (via death domain) with TNFRSF1A (via death domain)
CC (PubMed:9115275, PubMed:11577081). Interacts with PIDD1
CC (PubMed:10825539). Interacts with YWHAZ (PubMed:16959763). Interacts
CC (via death domain) with KIF1B (By similarity). Interacts with KIF1A (By
CC similarity). Interacts (via uDENN domain) with RAB3A, RAB3B, RAB3C and
CC RAB3D; the GTP-bound form of the Rab proteins is preferred for
CC interaction (By similarity). {ECO:0000250|UniProtKB:Q80U28,
CC ECO:0000269|PubMed:10825539, ECO:0000269|PubMed:11577081,
CC ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:9115275}.
CC -!- INTERACTION:
CC Q8WXG6; Q9NUX5: POT1; NbExp=2; IntAct=EBI-310528, EBI-752420;
CC Q8WXG6; Q16849: PTPRN; NbExp=4; IntAct=EBI-310528, EBI-728153;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8988362}.
CC Cytoplasm {ECO:0000269|PubMed:8988362}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q80U28}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1 {ECO:0000269|PubMed:11577081}; Synonyms=IG20
CC {ECO:0000269|PubMed:11577081}, IG20-FL {ECO:0000269|PubMed:14716293};
CC IsoId=Q8WXG6-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:11577081}; Synonyms=IG20
CC {ECO:0000269|PubMed:14716293}, IG20-PA {ECO:0000269|PubMed:11577081},
CC IG20-PASV {ECO:0000269|PubMed:11577081};
CC IsoId=Q8WXG6-2; Sequence=VSP_052295, VSP_052296;
CC Name=3 {ECO:0000269|PubMed:8988362, ECO:0000269|PubMed:9115275,
CC ECO:0000269|PubMed:9796103}; Synonyms=DENN {ECO:0000269|PubMed:8988362,
CC ECO:0000269|PubMed:9796103}, IG20-SV1 {ECO:0000269|PubMed:14716293},
CC MADD {ECO:0000269|PubMed:9115275};
CC IsoId=Q8WXG6-3; Sequence=VSP_052294, VSP_052295, VSP_055676,
CC VSP_052296;
CC Name=4 {ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:8988362,
CC ECO:0000269|PubMed:9796103}; Synonyms=IG20-SV2
CC {ECO:0000269|PubMed:11577081};
CC IsoId=Q8WXG6-4; Sequence=VSP_052293, VSP_052295, VSP_052296;
CC Name=5 {ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:15489334};
CC Synonyms=DENN-SV {ECO:0000269|PubMed:15489334}, IG20-SV3
CC {ECO:0000269|PubMed:11577081};
CC IsoId=Q8WXG6-5; Sequence=VSP_052293, VSP_052294, VSP_052295,
CC VSP_052296;
CC Name=6 {ECO:0000269|PubMed:11577081}; Synonyms=IG20-SV4
CC {ECO:0000269|PubMed:11577081};
CC IsoId=Q8WXG6-6; Sequence=VSP_052293, VSP_052294, VSP_052295,
CC VSP_052296, VSP_052297, VSP_052298;
CC Name=7 {ECO:0000269|PubMed:9205841}; Synonyms=KIAA0358
CC {ECO:0000303|PubMed:32761064};
CC IsoId=Q8WXG6-7; Sequence=VSP_052297, VSP_052298;
CC Name=8;
CC IsoId=Q8WXG6-8; Sequence=VSP_052293, VSP_052294, VSP_052295,
CC VSP_044848, VSP_052296;
CC -!- TISSUE SPECIFICITY: Expressed in testis, ovary, brain and heart
CC (PubMed:8988362). Expressed in spleen, thymus, prostate, testis, ovary,
CC small instestine and colon (PubMed:9115275). Expressed in liver
CC (PubMed:9796103). {ECO:0000269|PubMed:8988362,
CC ECO:0000269|PubMed:9115275, ECO:0000269|PubMed:9796103}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Not detected in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Expressed in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- TISSUE SPECIFICITY: [Isoform 6]: Not detected in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- TISSUE SPECIFICITY: [Isoform 7]: Not detected in the brain, breast,
CC kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
CC {ECO:0000269|PubMed:14716293}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain and kidney.
CC {ECO:0000269|PubMed:8988362}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 7]: Expressed in fetal liver.
CC {ECO:0000269|PubMed:8988362}.
CC -!- DISEASE: DEEAH syndrome (DEEAH) [MIM:619004]: An autosomal recessive
CC disorder characterized by moderate to severe global developmental
CC delay, impaired intellectual development, poor or absent speech, and
CC endocrine, pancreatic exocrine and autonomic dysfunction, as well as
CC hematologic abnormalities. Additional features include facial
CC dysmorphism, seizures, undescended testes, and distal skeletal
CC anomalies. Death in early childhood may occur.
CC {ECO:0000269|PubMed:32761064}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neurodevelopmental disorder with dysmorphic facies, impaired
CC speech, and hypotonia (NEDDISH) [MIM:619005]: An autosomal recessive
CC disorder characterized by global developmental delay, mildly to
CC severely impaired intellectual development, poor speech and language
CC acquisition. Some patients may have early normal development with onset
CC of the disorder in the first years of life. More variable neurologic
CC abnormalities include hypotonia, seizures, apnea, mild signs of
CC autonomic or peripheral neuropathy, and autism.
CC {ECO:0000269|PubMed:28940097, ECO:0000269|PubMed:32761064}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Overexpression of MADD activates the mitogen-activated
CC protein (MAP) kinase extracellular signal-regulated kinase (ERK).
CC Expression of the MADD death domain stimulates both the ERK and c-JUN
CC N-terminal kinase MAP kinases and induces the phosphorylation of
CC cytosolic phospholipase A2. {ECO:0000269|PubMed:9115275}.
CC -!- SIMILARITY: Belongs to the MADD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20814.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; U44953; AAD12154.1; -; mRNA.
DR EMBL; U77352; AAB57735.1; -; mRNA.
DR EMBL; AF440100; AAL40265.1; -; mRNA.
DR EMBL; AF440101; AAL40266.1; -; mRNA.
DR EMBL; AF440102; AAL40267.1; -; mRNA.
DR EMBL; AF440103; AAL40268.1; -; mRNA.
DR EMBL; AF440434; AAL35261.1; -; mRNA.
DR EMBL; AB002356; BAA20814.2; ALT_INIT; mRNA.
DR EMBL; AK292442; BAF85131.1; -; mRNA.
DR EMBL; AC018410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW67931.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW67932.1; -; Genomic_DNA.
DR EMBL; BC040484; AAH40484.1; -; mRNA.
DR CCDS; CCDS41642.1; -. [Q8WXG6-7]
DR CCDS; CCDS44586.1; -. [Q8WXG6-3]
DR CCDS; CCDS44587.1; -. [Q8WXG6-4]
DR CCDS; CCDS44588.1; -. [Q8WXG6-5]
DR CCDS; CCDS44589.1; -. [Q8WXG6-8]
DR CCDS; CCDS44590.1; -. [Q8WXG6-6]
DR CCDS; CCDS7930.1; -. [Q8WXG6-1]
DR CCDS; CCDS7932.1; -. [Q8WXG6-2]
DR RefSeq; NP_001129415.1; NM_001135943.1.
DR RefSeq; NP_001129416.1; NM_001135944.1. [Q8WXG6-8]
DR RefSeq; NP_003673.3; NM_003682.3. [Q8WXG6-1]
DR RefSeq; NP_569826.2; NM_130470.2.
DR RefSeq; NP_569827.2; NM_130471.2. [Q8WXG6-4]
DR RefSeq; NP_569828.2; NM_130472.2. [Q8WXG6-5]
DR RefSeq; NP_569829.2; NM_130473.2. [Q8WXG6-2]
DR RefSeq; NP_569830.2; NM_130474.2. [Q8WXG6-6]
DR RefSeq; NP_569831.1; NM_130475.2. [Q8WXG6-7]
DR RefSeq; NP_569832.2; NM_130476.2. [Q8WXG6-3]
DR RefSeq; XP_005253246.1; XM_005253189.2. [Q8WXG6-1]
DR RefSeq; XP_005253253.1; XM_005253196.2. [Q8WXG6-2]
DR RefSeq; XP_005253256.1; XM_005253199.2.
DR RefSeq; XP_005253258.1; XM_005253201.2. [Q8WXG6-4]
DR RefSeq; XP_005253260.1; XM_005253203.2.
DR RefSeq; XP_005253261.1; XM_005253204.2.
DR RefSeq; XP_005253262.1; XM_005253205.1. [Q8WXG6-6]
DR AlphaFoldDB; Q8WXG6; -.
DR BioGRID; 114136; 107.
DR ELM; Q8WXG6; -.
DR IntAct; Q8WXG6; 26.
DR MINT; Q8WXG6; -.
DR STRING; 9606.ENSP00000310933; -.
DR GlyGen; Q8WXG6; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q8WXG6; -.
DR MetOSite; Q8WXG6; -.
DR PhosphoSitePlus; Q8WXG6; -.
DR BioMuta; MADD; -.
DR DMDM; 126215742; -.
DR EPD; Q8WXG6; -.
DR jPOST; Q8WXG6; -.
DR MassIVE; Q8WXG6; -.
DR MaxQB; Q8WXG6; -.
DR PaxDb; Q8WXG6; -.
DR PeptideAtlas; Q8WXG6; -.
DR PRIDE; Q8WXG6; -.
DR ProteomicsDB; 6231; -.
DR ProteomicsDB; 75032; -. [Q8WXG6-1]
DR ProteomicsDB; 75033; -. [Q8WXG6-2]
DR ProteomicsDB; 75034; -. [Q8WXG6-3]
DR ProteomicsDB; 75035; -. [Q8WXG6-4]
DR ProteomicsDB; 75036; -. [Q8WXG6-5]
DR ProteomicsDB; 75037; -. [Q8WXG6-6]
DR ProteomicsDB; 75038; -. [Q8WXG6-7]
DR Antibodypedia; 13636; 180 antibodies from 35 providers.
DR DNASU; 8567; -.
DR Ensembl; ENST00000311027.9; ENSP00000310933.4; ENSG00000110514.19. [Q8WXG6-1]
DR Ensembl; ENST00000349238.7; ENSP00000304505.6; ENSG00000110514.19. [Q8WXG6-2]
DR Ensembl; ENST00000395336.7; ENSP00000378745.3; ENSG00000110514.19. [Q8WXG6-7]
DR Ensembl; ENST00000395344.7; ENSP00000378753.3; ENSG00000110514.19. [Q8WXG6-8]
DR Ensembl; ENST00000402192.6; ENSP00000384287.2; ENSG00000110514.19. [Q8WXG6-3]
DR Ensembl; ENST00000402799.5; ENSP00000385585.1; ENSG00000110514.19. [Q8WXG6-5]
DR Ensembl; ENST00000406482.5; ENSP00000384435.1; ENSG00000110514.19. [Q8WXG6-6]
DR Ensembl; ENST00000407859.7; ENSP00000384204.3; ENSG00000110514.19. [Q8WXG6-4]
DR GeneID; 8567; -.
DR KEGG; hsa:8567; -.
DR UCSC; uc001ner.2; human. [Q8WXG6-1]
DR CTD; 8567; -.
DR DisGeNET; 8567; -.
DR GeneCards; MADD; -.
DR HGNC; HGNC:6766; MADD.
DR HPA; ENSG00000110514; Tissue enhanced (retina).
DR MalaCards; MADD; -.
DR MIM; 603584; gene+phenotype.
DR MIM; 619004; phenotype.
DR MIM; 619005; phenotype.
DR neXtProt; NX_Q8WXG6; -.
DR OpenTargets; ENSG00000110514; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA30523; -.
DR VEuPathDB; HostDB:ENSG00000110514; -.
DR eggNOG; KOG3570; Eukaryota.
DR GeneTree; ENSGT00940000156718; -.
DR HOGENOM; CLU_001270_1_0_1; -.
DR InParanoid; Q8WXG6; -.
DR OMA; TFEDLTY; -.
DR PhylomeDB; Q8WXG6; -.
DR TreeFam; TF318583; -.
DR PathwayCommons; Q8WXG6; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. [Q8WXG6-3]
DR SignaLink; Q8WXG6; -.
DR SIGNOR; Q8WXG6; -.
DR BioGRID-ORCS; 8567; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; MADD; human.
DR GeneWiki; MADD_(gene); -.
DR GenomeRNAi; 8567; -.
DR Pharos; Q8WXG6; Tbio.
DR PRO; PR:Q8WXG6; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8WXG6; protein.
DR Bgee; ENSG00000110514; Expressed in right hemisphere of cerebellum and 190 other tissues.
DR ExpressionAtlas; Q8WXG6; baseline and differential.
DR Genevisible; Q8WXG6; HS.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005123; F:death receptor binding; TAS:ProtInc.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; TAS:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:1902041; P:regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; IDA: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; 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; Intellectual disability; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1647
FT /note="MAP kinase-activating death domain protein"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT /id="PRO_0000278138"
FT DOMAIN 14..268
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 289..429
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 431..565
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 1340..1415
FT /note="Death"
FT /evidence="ECO:0000255"
FT REGION 108..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 604..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..842
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 913..941
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1051..1110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1146..1243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..156
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 689..719
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 793..808
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 817..842
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1159..1215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 689
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 692
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 813
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 818
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 858
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 862
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 916
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 930
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 1059
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1061
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O08873"
FT MOD_RES 1066
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80U28"
FT MOD_RES 1110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80U28"
FT MOD_RES 1237
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 762..804
FT /note="Missing (in isoform 4, isoform 5, isoform 6 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:11577081,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8988362, ECO:0000303|PubMed:9796103"
FT /id="VSP_052293"
FT VAR_SEQ 885..904
FT /note="Missing (in isoform 3, isoform 5, isoform 6 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:11577081,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8988362, ECO:0000303|PubMed:9115275,
FT ECO:0000303|PubMed:9796103"
FT /id="VSP_052294"
FT VAR_SEQ 1121..1139
FT /note="ELWNKHQEVKKQKALEKQR -> G (in isoform 2, isoform 3,
FT isoform 4, isoform 5, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11577081,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8988362, ECO:0000303|PubMed:9115275,
FT ECO:0000303|PubMed:9796103"
FT /id="VSP_052295"
FT VAR_SEQ 1197..1200
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044848"
FT VAR_SEQ 1201
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8988362,
FT ECO:0000303|PubMed:9115275, ECO:0000303|PubMed:9796103"
FT /id="VSP_055676"
FT VAR_SEQ 1291..1311
FT /note="Missing (in isoform 2, isoform 3, isoform 4, isoform
FT 5, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11577081,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8988362, ECO:0000303|PubMed:9115275,
FT ECO:0000303|PubMed:9796103"
FT /id="VSP_052296"
FT VAR_SEQ 1575..1582
FT /note="VFIELNHI -> FLKLKKW (in isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:11577081,
FT ECO:0000303|PubMed:9205841"
FT /id="VSP_052297"
FT VAR_SEQ 1583..1647
FT /note="Missing (in isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:11577081,
FT ECO:0000303|PubMed:9205841"
FT /id="VSP_052298"
FT VARIANT 198
FT /note="R -> H (in NEDDISH; unknown pathological
FT significance; dbSNP:rs149316791)"
FT /evidence="ECO:0000269|PubMed:28940097"
FT /id="VAR_084659"
FT VARIANT 216..1647
FT /note="Missing (in DEEAH; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084660"
FT VARIANT 257
FT /note="S -> F (in DEEAH; impaired TNFA-induced activation
FT of the MAP kinases ERK1/2; enhanced susceptibility to TNFA-
FT induced apoptosis; decreased EGF internalization)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084661"
FT VARIANT 305
FT /note="G -> V (in DEEAH; impaired TNFA-induced activation
FT of the MAP kinases ERK1/2; enhanced susceptibility to TNFA-
FT induced apoptosis; decreased EGF internalization)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084662"
FT VARIANT 327..1647
FT /note="Missing (in DEEAH and NEDDISH; unknown pathological
FT significance; dbSNP:rs147179561)"
FT /evidence="ECO:0000269|PubMed:28940097,
FT ECO:0000269|PubMed:32761064"
FT /id="VAR_084663"
FT VARIANT 346
FT /note="L -> P (in NEDDISH; unknown pathological
FT significance; dbSNP:rs1591767154)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084664"
FT VARIANT 354
FT /note="P -> L (in NEDDISH; impaired TNFA-induced activation
FT of the MAP kinases ERK1/2; enhanced susceptibility to TNFA-
FT induced apoptosis; decreased EGF internalization;
FT dbSNP:rs370382902)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084665"
FT VARIANT 372
FT /note="P -> L (in DEEAH; unknown pathological significance;
FT dbSNP:rs147713337)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084666"
FT VARIANT 696
FT /note="P -> T (in dbSNP:rs17854007)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030666"
FT VARIANT 751
FT /note="V -> M (in dbSNP:rs1051006)"
FT /evidence="ECO:0000269|PubMed:9115275"
FT /id="VAR_030667"
FT VARIANT 765
FT /note="R -> Q (in dbSNP:rs3736101)"
FT /id="VAR_051148"
FT VARIANT 945
FT /note="L -> P (in NEDDISH; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084667"
FT VARIANT 968
FT /note="R -> G (in dbSNP:rs17854008)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030668"
FT VARIANT 1040
FT /note="L -> F (in dbSNP:rs17854009)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030669"
FT VARIANT 1040
FT /note="L -> R (in DEEAH; impaired TNFA-induced activation
FT of the MAP kinases ERK1/2; enhanced susceptibility to TNFA-
FT induced apoptosis; decreased EGF internalization)"
FT /evidence="ECO:0000269|PubMed:28940097,
FT ECO:0000269|PubMed:32761064"
FT /id="VAR_084668"
FT VARIANT 1213..1647
FT /note="Missing (in NEDDISH; impaired TNFA-induced
FT activation of the MAP kinases ERK1/2; enhanced
FT susceptibility to TNFA-induced apoptosis; decreased EGF
FT internalization)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084669"
FT VARIANT 1283
FT /note="Y -> S (in NEDDISH; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084670"
FT VARIANT 1318
FT /note="W -> R (in NEDDISH; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084671"
FT VARIANT 1431..1647
FT /note="Missing (in DEEAH; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084672"
FT VARIANT 1518
FT /note="L -> P (in dbSNP:rs34534575)"
FT /id="VAR_051149"
FT VARIANT 1532..1647
FT /note="Missing (in NEDDISH; unknown pathological
FT significance; dbSNP:rs971864929)"
FT /evidence="ECO:0000269|PubMed:32761064"
FT /id="VAR_084673"
FT CONFLICT 108
FT /note="E -> G (in Ref. 4; AAL40265/AAL40266/AAL40267/
FT AAL40268/AAL35261)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="L -> F (in Ref. 4; AAL40265/AAL40266/AAL40267/
FT AAL40268/AAL35261)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="E -> G (in Ref. 6; BAF85131)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="V -> L (in Ref. 4; AAL40265/AAL40266/AAL40267/
FT AAL40268/AAL35261)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="V -> A (in Ref. 4; AAL40265/AAL40266/AAL40267/
FT AAL40268/AAL35261)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="A -> V (in Ref. 6; BAF85131)"
FT /evidence="ECO:0000305"
FT CONFLICT 1262
FT /note="S -> C (in Ref. 4; AAL40265/AAL40266/AAL40267/
FT AAL40268/AAL35261)"
FT /evidence="ECO:0000305"
FT CONFLICT 1592
FT /note="F -> S (in Ref. 6; BAF85131)"
FT /evidence="ECO:0000305"
FT CONFLICT 1639
FT /note="R -> G (in Ref. 6; BAF85131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1647 AA; 183303 MW; 2CA9A3519269757E CRC64;
MVQKKKFCPR LLDYLVIVGA RHPSSDSVAQ TPELLRRYPL EDHTEFPLPP DVVFFCQPEG
CLSVRQRRMS LRDDTSFVFT LTDKDTGVTR YGICVNFYRS FQKRISKEKG EGGAGSRGKE
GTHATCASEE GGTESSESGS SLQPLSADST PDVNQSPRGK RRAKAGSRSR NSTLTSLCVL
SHYPFFSTFR ECLYTLKRLV DCCSERLLGK KLGIPRGVQR DTMWRIFTGS LLVEEKSSAL
LHDLREIEAW IYRLLRSPVP VSGQKRVDIE VLPQELQPAL TFALPDPSRF TLVDFPLHLP
LELLGVDACL QVLTCILLEH KVVLQSRDYN ALSMSVMAFV AMIYPLEYMF PVIPLLPTCM
ASAEQLLLAP TPYIIGVPAS FFLYKLDFKM PDDVWLVDLD SNRVIAPTNA EVLPILPEPE
SLELKKHLKQ ALASMSLNTQ PILNLEKFHE GQEIPLLLGR PSNDLQSTPS TEFNPLIYGN
DVDSVDVATR VAMVRFFNSA NVLQGFQMHT RTLRLFPRPV VAFQAGSFLA SRPRQTPFAE
KLARTQAVEY FGEWILNPTN YAFQRIHNNM FDPALIGDKP KWYAHQLQPI HYRVYDSNSQ
LAEALSVPPE RDSDSEPTDD SGSDSMDYDD SSSSYSSLGD FVSEMMKCDI NGDTPNVDPL
THAALGDASE VEIDELQNQK EAEEPGPDSE NSQENPPLRS SSSTTASSSP STVIHGANSE
PADSTEMDDK AAVGVSKPLP SVPPSIGKSN VDRRQAEIGE GSVRRRIYDN PYFEPQYGFP
PEEDEDEQGE SYTPRFSQHV SGNRAQKLLR PNSLRLASDS DAESDSRASS PNSTVSNTST
EGFGGIMSFA SSLYRNHSTS FSLSNLTLPT KGAREKATPF PSLKVFGLNT LMEIVTEAGP
GSGEGNRRAL VDQKSSVIKH SPTVKREPPS PQGRSSNSSE NQQFLKEVVH SVLDGQGVGW
LNMKKVRRLL ESEQLRVFVL SKLNRMVQSE DDARQDIIPD VEISRKVYKG MLDLLKCTVL
SLEQSYAHAG LGGMASIFGL LEIAQTHYYS KEPDKRKRSP TESVNTPVGK DPGLAGRGDP
KAMAQLRVPQ LGPRAPSATG KGPKELDTRS LKEENFIASI ELWNKHQEVK KQKALEKQRP
EVIKPVFDLG ETEEKKSQIS ADSGVSLTSS SQRTDQDSVI GVSPAVMIRS SSQDSEVSTV
VSNSSGETLG ADSDLSSNAG DGPGGEGSVH LASSRGTLSD SEIETNSATS TIFGKAHSLK
PSIKEKLAGS PIRTSEDVSQ RVYLYEGLLG RDKGSMWDQL EDAAMETFSI SKERSTLWDQ
MQFWEDAFLD AVMLEREGMG MDQGPQEMID RYLSLGEHDR KRLEDDEDRL LATLLHNLIS
YMLLMKVNKN DIRKKVRRLM GKSHIGLVYS QQINEVLDQL ANLNGRDLSI WSSGSRHMKK
QTFVVHAGTD TNGDIFFMEV CDDCVVLRSN IGTVYERWWY EKLINMTYCP KTKVLCLWRR
NGSETQLNKF YTKKCRELYY CVKDSMERAA ARQQSIKPGP ELGGEFPVQD LKTGEGGLLQ
VTLEGINLKF MHNQVFIELN HIKKCNTVRG VFVLEEFVPE IKEVVSHKYK TPMAHEICYS
VLCLFSYVAA VHSSEEDLRT PPRPVSS
