TNR21_RAT
ID TNR21_RAT Reviewed; 655 AA.
AC D3ZF92;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 21;
DE AltName: Full=Death receptor 6;
DE AltName: CD_antigen=CD358;
DE Flags: Precursor;
GN Name=Tnfrsf21; Synonyms=Dr6;
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 [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 [2]
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 [3]
RP FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=21725297; DOI=10.1038/nm.2373;
RA Mi S., Lee X., Hu Y., Ji B., Shao Z., Yang W., Huang G., Walus L.,
RA Rhodes K., Gong B.J., Miller R.H., Pepinsky R.B.;
RT "Death receptor 6 negatively regulates oligodendrocyte survival, maturation
RT and myelination.";
RL Nat. Med. 17:816-821(2011).
CC -!- FUNCTION: Promotes apoptosis, possibly via a pathway that involves the
CC activation of NF-kappa-B. Can also promote apoptosis mediated by BAX
CC and by the release of cytochrome c from the mitochondria into the
CC cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in
CC response to amyloid peptides derived from APP, and is required for both
CC normal cell body death and axonal pruning. Trophic-factor deprivation
CC triggers the cleavage of surface APP by beta-secretase to release sAPP-
CC beta which is further cleaved to release an N-terminal fragment of APP
CC (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and
CC degeneration of both neuronal cell bodies (via caspase-3) and axons
CC (via caspase-6). Plays a role in signaling cascades triggered by
CC stimulation of T-cell receptors, in the adaptive immune response and in
CC the regulation of T-cell differentiation and proliferation. Negatively
CC regulates T-cell responses and the release of cytokines such as IL4,
CC IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the
CC production of IgG, IgM and IgM in response to antigens. May inhibit the
CC activation of JNK in response to T-cell stimulation (By similarity).
CC Negatively regulates oligodendrocyte survival, maturation and
CC myelination. {ECO:0000250, ECO:0000269|PubMed:21725297}.
CC -!- SUBUNIT: Associates with TRADD. Interacts with NGFR. Interacts with N-
CC APP (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level). Detected in
CC corpus callosum oligodendrocytes. Detected in embryonic and adult
CC brain. {ECO:0000269|PubMed:21725297}.
CC -!- DEVELOPMENTAL STAGE: Detected at low levels in embryonic brain.
CC Expression is increased in newborns and during the first two weeks
CC after birth. Expression decreases thereafter and is low after three
CC weeks and in adult life. {ECO:0000269|PubMed:21725297}.
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DR EMBL; AABR06058936; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06058937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473987; EDM18686.1; -; Genomic_DNA.
DR RefSeq; NP_001101677.1; NM_001108207.1.
DR AlphaFoldDB; D3ZF92; -.
DR SMR; D3ZF92; -.
DR STRING; 10116.ENSRNOP00000015918; -.
DR GlyGen; D3ZF92; 4 sites.
DR PaxDb; D3ZF92; -.
DR PRIDE; D3ZF92; -.
DR Ensembl; ENSRNOT00000015918; ENSRNOP00000015918; ENSRNOG00000011517.
DR GeneID; 316256; -.
DR KEGG; rno:316256; -.
DR UCSC; RGD:1307308; rat.
DR CTD; 27242; -.
DR RGD; 1307308; Tnfrsf21.
DR eggNOG; ENOG502QVMX; Eukaryota.
DR GeneTree; ENSGT00940000156212; -.
DR HOGENOM; CLU_027496_0_0_1; -.
DR InParanoid; D3ZF92; -.
DR OMA; THQQGPH; -.
DR OrthoDB; 869160at2759; -.
DR PhylomeDB; D3ZF92; -.
DR TreeFam; TF331157; -.
DR PRO; PR:D3ZF92; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Proteomes; UP000234681; Chromosome 9.
DR Bgee; ENSRNOG00000011517; Expressed in adult mammalian kidney and 19 other tissues.
DR Genevisible; D3ZF92; RN.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0007413; P:axonal fasciculation; IMP:RGD.
DR GO; GO:0001783; P:B cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0006959; P:humoral immune response; ISS:UniProtKB.
DR GO; GO:0042552; P:myelination; ISS:UniProtKB.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032696; P:negative regulation of interleukin-13 production; ISS:UniProtKB.
DR GO; GO:0032714; P:negative regulation of interleukin-5 production; ISS:UniProtKB.
DR GO; GO:0031642; P:negative regulation of myelination; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0097252; P:oligodendrocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0048713; P:regulation of oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd08778; Death_TNFRSF21; 1.
DR CDD; cd10583; TNFRSF21; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR022330; TNFR_21.
DR InterPro; IPR034037; TNFRSF21_death.
DR InterPro; IPR034034; TNFRSF21_N.
DR PANTHER; PTHR46921; PTHR46921; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF00020; TNFR_c6; 1.
DR PRINTS; PR01971; TNFACTORR21.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00208; TNFR; 4.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS50050; TNFR_NGFR_2; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Apoptosis; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunity; Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..41
FT /evidence="ECO:0000255"
FT CHAIN 42..655
FT /note="Tumor necrosis factor receptor superfamily member
FT 21"
FT /id="PRO_0000425729"
FT TOPO_DOM 42..349
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 371..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 50..88
FT /note="TNFR-Cys 1"
FT REPEAT 90..131
FT /note="TNFR-Cys 2"
FT REPEAT 133..167
FT /note="TNFR-Cys 3"
FT REPEAT 170..211
FT /note="TNFR-Cys 4"
FT DOMAIN 415..498
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 214..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 214..231
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 368
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 67..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 70..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 91..106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 109..123
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 113..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 133..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 150..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 171..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 192..211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
SQ SEQUENCE 655 AA; 71870 MW; 9CC872C9B4DB8CD0 CRC64;
MGTSASSITA LASCSRIAGQ VGATMVAGSL LLLGFLSTIT AQPEQKTLSL TGTYRHVDRT
TGQVLTCDKC PAGTYVSEHC TNTSLRVCSS CPSGTFTRHE NGIERCHDCS QPCPRPMIER
LPCAALTDRE CICPPGMYQS NGTCAPHTVC PVGWGVRKKG TENEDVRCKQ CARGTFSDVP
SSVMKCRAHT DCLGQNLMVV KQGTKETDNV CGVHLSSSST TPSSPGIATF SHPEHTESHD
VPSSTYEPQG MNSTDSNSTA SVRTKVPSDI QEETVPDNTS STSGKESTNR TLPNPPQLTH
QQGPHHRHIL KLLPSSMEAT GEKSSTAIKA PKRGHPRQNP HKHFDINEHL PWMIVLFLLL
VLVLIVVCSI RKSSRTLKKG PRQDPSAIME KAGLKKSLTP TQNREKWIYY RNGHGIDILK
LVAAQVGSQW KDIYQFLCNA SEREVAAFSN GYTADHERAY AALQHWTIRG PEASLAQLIS
ALRQHRRNDV VEKIRGLMED TTQLETDKLA LPMSPSPLSP SPIPSPNVKL ENSTLLTVEP
SPLDKNKGFF VDESEPLLRC DSTSSGSSAL SRNGSFITKE KKDTVLRQVR LDPCDLQPIF
DDMLHILNPE ELRVIEEIPQ AEDKLDRLFE IIGVKSQEAS QTLLDSVYSH LPDLL
