NRADD_MOUSE
ID NRADD_MOUSE Reviewed; 228 AA.
AC Q8CJ26; Q3TVC1;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Death domain-containing membrane protein NRADD;
DE AltName: Full=Neurotrophin receptor homolog-2;
DE Short=NRH2;
DE AltName: Full=Neurotrophin receptor-alike death domain protein;
GN Name=Nradd;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RC STRAIN=C57BL/6J;
RX PubMed=12728256; DOI=10.1038/sj.cdd.4401208;
RA Wang X., Shao Z., Zetoune F.S., Zeidler M.G., Gowrishankar K., Vincenz C.;
RT "NRADD, a novel membrane protein with a death domain involved in mediating
RT apoptosis in response to ER stress.";
RL Cell Death Differ. 10:580-591(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [5]
RP FUNCTION, GLYCOSYLATION, PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=12843241; DOI=10.1523/jneurosci.23-13-05425.2003;
RA Kanning K.C., Hudson M., Amieux P.S., Wiley J.C., Bothwell M.,
RA Schecterson L.C.;
RT "Proteolytic processing of the p75 neurotrophin receptor and two homologs
RT generates C-terminal fragments with signaling capability.";
RL J. Neurosci. 23:5425-5436(2003).
RN [6]
RP INTERACTION WITH NTRK1.
RX PubMed=18624909; DOI=10.1111/j.1471-4159.2008.05539.x;
RA Wong A.W., Willingham M., Xiao J., Kilpatrick T.J., Murray S.S.;
RT "Neurotrophin receptor homolog-2 regulates nerve growth factor signaling.";
RL J. Neurochem. 106:1964-1976(2008).
RN [7]
RP FUNCTION, INTERACTION WITH NGFR AND SORT1, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=19407813; DOI=10.1038/emboj.2009.118;
RA Kim T., Hempstead B.L.;
RT "NRH2 is a trafficking switch to regulate sortilin localization and permit
RT proneurotrophin-induced cell death.";
RL EMBO J. 28:1612-1623(2009).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-4.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [9]
RP STRUCTURE BY NMR OF 138-228.
RA Vilar M., Sung T.C., Lee K.F., Riek R.;
RT "Solution structure of p45 death domain.";
RL Submitted (SEP-2006) to the PDB data bank.
CC -!- FUNCTION: Modulates NTRK1 signaling. Can activate several intracellular
CC signaling pathways, leading to activation of JUN. Promotes apoptosis.
CC Promotes translocation of SORT1 to the cell membrane, and thereby
CC hinders lysosomal degradation of SOTR1 and promotes its interaction
CC with NGFR. {ECO:0000269|PubMed:12728256, ECO:0000269|PubMed:12843241,
CC ECO:0000269|PubMed:19407813}.
CC -!- SUBUNIT: Interacts with NGFR. Interacts with NTRK1. Interacts with
CC SORT1. {ECO:0000269|PubMed:18624909, ECO:0000269|PubMed:19407813}.
CC -!- INTERACTION:
CC Q8CJ26; Q6PHU5: Sort1; NbExp=5; IntAct=EBI-6985725, EBI-6985663;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type III membrane
CC protein. Nucleus. Note=Proteolytic processing gives rise to an
CC intracellular domain that translocates to the nucleus.
CC -!- TISSUE SPECIFICITY: Detected in lung and testis.
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DR EMBL; AF534394; AAN05631.1; -; mRNA.
DR EMBL; AK160222; BAE35698.1; -; mRNA.
DR EMBL; AC132103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069856; AAH69856.1; -; mRNA.
DR CCDS; CCDS23569.1; -.
DR RefSeq; NP_080288.1; NM_026012.2.
DR PDB; 2IB1; NMR; -; A=138-228.
DR PDB; 6HJ7; NMR; -; A=127-228.
DR PDBsum; 2IB1; -.
DR PDBsum; 6HJ7; -.
DR AlphaFoldDB; Q8CJ26; -.
DR SMR; Q8CJ26; -.
DR IntAct; Q8CJ26; 2.
DR MINT; Q8CJ26; -.
DR STRING; 10090.ENSMUSP00000035069; -.
DR GlyGen; Q8CJ26; 2 sites.
DR iPTMnet; Q8CJ26; -.
DR PhosphoSitePlus; Q8CJ26; -.
DR SwissPalm; Q8CJ26; -.
DR MaxQB; Q8CJ26; -.
DR PaxDb; Q8CJ26; -.
DR PeptideAtlas; Q8CJ26; -.
DR PRIDE; Q8CJ26; -.
DR ProteomicsDB; 293724; -.
DR DNASU; 67169; -.
DR Ensembl; ENSMUST00000035069; ENSMUSP00000035069; ENSMUSG00000032491.
DR GeneID; 67169; -.
DR KEGG; mmu:67169; -.
DR UCSC; uc009ruk.1; mouse.
DR CTD; 67169; -.
DR MGI; MGI:1914419; Nradd.
DR VEuPathDB; HostDB:ENSMUSG00000032491; -.
DR eggNOG; ENOG502QRGT; Eukaryota.
DR GeneTree; ENSGT00940000163571; -.
DR HOGENOM; CLU_1229566_0_0_1; -.
DR InParanoid; Q8CJ26; -.
DR OMA; CAPSQGP; -.
DR OrthoDB; 1254770at2759; -.
DR PhylomeDB; Q8CJ26; -.
DR TreeFam; TF106466; -.
DR BioGRID-ORCS; 67169; 0 hits in 72 CRISPR screens.
DR EvolutionaryTrace; Q8CJ26; -.
DR PRO; PR:Q8CJ26; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8CJ26; protein.
DR Bgee; ENSMUSG00000032491; Expressed in lip and 153 other tissues.
DR ExpressionAtlas; Q8CJ26; baseline and differential.
DR Genevisible; Q8CJ26; MM.
DR GO; GO:0044298; C:cell body membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0032589; C:neuron projection membrane; ISO:MGI.
DR GO; GO:0005641; C:nuclear envelope lumen; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IBA:GO_Central.
DR GO; GO:0005035; F:death receptor activity; IBA:GO_Central.
DR GO; GO:0048406; F:nerve growth factor binding; IBA:GO_Central.
DR GO; GO:0005166; F:neurotrophin p75 receptor binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR041448; TNFR16_TM.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF18422; TNFR_16_TM; 1.
DR SMART; SM00005; DEATH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cell membrane; Glycoprotein; Membrane; Nucleus;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..228
FT /note="Death domain-containing membrane protein NRADD"
FT /id="PRO_0000415383"
FT TOPO_DOM 1..52
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 53..73
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 143..222
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 87..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 92..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 121
FT /note="P -> H (in Ref. 2; BAE35698)"
FT /evidence="ECO:0000305"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:6HJ7"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:2IB1"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:2IB1"
FT HELIX 158..165
FT /evidence="ECO:0007829|PDB:2IB1"
FT HELIX 169..175
FT /evidence="ECO:0007829|PDB:2IB1"
FT HELIX 181..188
FT /evidence="ECO:0007829|PDB:2IB1"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:2IB1"
FT HELIX 201..207
FT /evidence="ECO:0007829|PDB:2IB1"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:2IB1"
FT HELIX 212..218
FT /evidence="ECO:0007829|PDB:2IB1"
SQ SEQUENCE 228 AA; 24727 MW; D46B7402D8362FDF CRC64;
MLYNVSKGVV YSDTALQGQD GDREGMWVGA GGALAPNTSS LFPPEPPGAS SNIIPVYCAL
LATVILGLLA YVAFKCWRSH KQRQQLAKAR TVELGDPDRD QRRGDSNVFV DSPPSLEPCI
PSQGPHPDLG CQLYLHIPQQ QQEEVQRLLM MGEPAKGWQE LAGHLGYQAE AVETMACDQM
PAYTLLRNWA AQEGNRATLR VLEDALAAIG REDVVQVLSS PAESSSVV
