NRADD_RAT
ID NRADD_RAT Reviewed; 228 AA.
AC Q8K5A9; G3V8U7; Q8K5A8;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 2.
DT 03-AUG-2022, entry version 106.
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;
DE AltName: Full=P75-like apoptosis-inducing death domain protein;
DE Short=PLAIDD;
GN Name=Nradd; Synonyms=Nrh2, Plaidd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH
RP NGFR, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Embryonic brain;
RX PubMed=12095158; DOI=10.1385/nmm:1:3:153;
RA Frankowski H., Castro-Obregon S., del Rio G., Rao R.V., Bredesen D.E.;
RT "PLAIDD, a type II death domain protein that interacts with p75
RT neurotrophin receptor.";
RL NeuroMolecular Med. 1:153-170(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND INTERACTION WITH NGFR AND SORT1.
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).
CC -!- FUNCTION: Modulates NTRK1 signaling. Can activate several intracellular
CC signaling pathways, leading to activation of JUN. Promotes
CC translocation of SORT1 to the cell membrane, and thereby hinders
CC lysosomal degradation of SOTR1 and promotes its interaction with NGFR
CC (By similarity). Both isoform 1 and isoform 2 promote apoptosis.
CC {ECO:0000250, ECO:0000269|PubMed:12095158,
CC ECO:0000269|PubMed:19407813}.
CC -!- SUBUNIT: Interacts with NTRK1 (By similarity). Isoform 1 and isoform 2
CC interact with NGFR. Interacts with SORT1. {ECO:0000250,
CC ECO:0000269|PubMed:12095158, ECO:0000269|PubMed:19407813}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12095158};
CC Single-pass type III membrane protein {ECO:0000269|PubMed:12095158}.
CC Nucleus {ECO:0000250}. Note=Proteolytic processing gives rise to an
CC intracellular domain that translocates to the nucleus. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q8K5A9-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q8K5A9-2; Sequence=VSP_042237;
CC -!- TISSUE SPECIFICITY: Detected in embryo, including embryonic brain.
CC Detected at very low levels in adult testis, spleen, thymus and lung.
CC {ECO:0000269|PubMed:12095158}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in embryo. Expressed at very low
CC levels in adult. {ECO:0000269|PubMed:12095158}.
CC -!- PTM: Isoform 1 is N-glycosylated. Isoform 2 is not N-glycosylated.
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DR EMBL; AF497263; AAM28824.1; -; mRNA.
DR EMBL; AF497264; AAM28825.1; -; mRNA.
DR EMBL; AF534395; AAN05632.1; -; mRNA.
DR EMBL; CH473954; EDL77074.1; -; Genomic_DNA.
DR RefSeq; NP_640352.1; NM_139259.2.
DR RefSeq; XP_006243983.1; XM_006243921.2. [Q8K5A9-2]
DR AlphaFoldDB; Q8K5A9; -.
DR SMR; Q8K5A9; -.
DR IntAct; Q8K5A9; 2.
DR MINT; Q8K5A9; -.
DR STRING; 10116.ENSRNOP00000028416; -.
DR GlyGen; Q8K5A9; 2 sites.
DR iPTMnet; Q8K5A9; -.
DR PhosphoSitePlus; Q8K5A9; -.
DR PaxDb; Q8K5A9; -.
DR PRIDE; Q8K5A9; -.
DR GeneID; 246143; -.
DR KEGG; rno:246143; -.
DR UCSC; RGD:708524; rat. [Q8K5A9-1]
DR CTD; 67169; -.
DR RGD; 708524; Nradd.
DR VEuPathDB; HostDB:ENSRNOG00000020936; -.
DR eggNOG; ENOG502QRGT; Eukaryota.
DR HOGENOM; CLU_1229566_0_0_1; -.
DR InParanoid; Q8K5A9; -.
DR OMA; CAPSQGP; -.
DR OrthoDB; 1254770at2759; -.
DR PhylomeDB; Q8K5A9; -.
DR TreeFam; TF106466; -.
DR PRO; PR:Q8K5A9; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Proteomes; UP000234681; Chromosome 8.
DR Bgee; ENSRNOG00000020936; Expressed in ovary and 19 other tissues.
DR Genevisible; Q8K5A9; RN.
DR GO; GO:0044298; C:cell body membrane; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0032589; C:neuron projection membrane; IDA:RGD.
DR GO; GO:0005641; C:nuclear envelope lumen; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
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; IPI:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0001701; P:in utero embryonic development; IEP:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IDA:RGD.
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 Alternative splicing; Apoptosis; Cell membrane; Glycoprotein; Membrane;
KW Nucleus; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..228
FT /note="Death domain-containing membrane protein NRADD"
FT /id="PRO_0000415384"
FT TOPO_DOM 1..52
FT /note="Extracellular"
FT /evidence="ECO:0000255"
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:0000255"
FT DOMAIN 143..222
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 13..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12095158"
FT /id="VSP_042237"
FT CONFLICT 159
FT /note="Q -> R (in Ref. 1; AAM28824/AAM28825 and 2;
FT AAN05632)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 228 AA; 24400 MW; 8B9B243656DCC525 CRC64;
MLHNVSKGVV YSDTALKGQD GDREGMWVGA GGALAPNTSS LFPPEPPGAS SNIIPVYCAL
LATVVLGLLA YVAFKCWRSR KQRQQLAKAR TVELGDPDRD QRHGDSSVFV DSPHGLEPCI
PSQGPHADLG CRLYLHIPQQ QQEEVQRLLI LGEPAKGWQG LAGQLGYQAE AVETMACDQD
PAYALLRDWA AQEGSGATLR VLEDALTAIG REDVVQVLSS PAEGCSVV
