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Protein

Tumor necrosis factor receptor superfamily member 21

Gene

Tnfrsf21

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). Negatively regulates oligodendrocyte survival, maturation and myelination. Plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation. Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the production of IgG, IgM and IgM in response to antigens. May inhibit the activation of JNK in response to T-cell stimulation.6 Publications

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • apoptotic process Source: MGI
  • apoptotic signaling pathway Source: GO_Central
  • B cell apoptotic process Source: UniProtKB
  • cellular response to tumor necrosis factor Source: MGI
  • humoral immune response Source: UniProtKB
  • inflammatory response Source: GO_Central
  • myelination Source: UniProtKB
  • negative regulation of B cell proliferation Source: UniProtKB
  • negative regulation of interleukin-10 secretion Source: UniProtKB
  • negative regulation of interleukin-13 secretion Source: UniProtKB
  • negative regulation of interleukin-5 secretion Source: UniProtKB
  • negative regulation of myelination Source: MGI
  • negative regulation of T cell proliferation Source: UniProtKB
  • neuron apoptotic process Source: UniProtKB
  • oligodendrocyte apoptotic process Source: UniProtKB
  • regulation of apoptotic process Source: GO_Central
  • regulation of oligodendrocyte differentiation Source: UniProtKB
  • response to lipopolysaccharide Source: GO_Central
  • T cell receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Adaptive immunity, Apoptosis, Immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 21
Alternative name(s):
Death receptor 6
CD_antigen: CD358
Gene namesi
Name:Tnfrsf21
Synonyms:Dr6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:2151075. Tnfrsf21.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini42 – 349ExtracellularSequence analysisAdd BLAST308
Transmembranei350 – 370HelicalSequence analysisAdd BLAST21
Topological domaini371 – 655CytoplasmicSequence analysisAdd BLAST285

GO - Cellular componenti

  • axon Source: UniProtKB
  • integral component of plasma membrane Source: MGI
  • intrinsic component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are born at the expected Mendelian rate, are viable and fertile. Mutant mice display an increased number of T-cells in the peripheral blood, but only a minor increase of the number of T-cells in spleen and thymus. T-cells from mutant mice show increased proliferative responses to antigens and produce higher levels of IL4, IL5, IL10, IL13 and IFNG. Mutant mice have normal serum levels of IgG and IgM in the absence of antigen, but produce higher levels of IgG, IgM and IgM in response to antigens. Likewise, B-cells from mutant mice display increased proliferation and decreased apoptosis in response to antigens. Mutant mice show increased levels of mature oligodendrocytes, decreased levels of apoptotic oligodendrocytes and increased myelination. Mutant mice are not susceptible to neuronal apoptosis triggered by exposure to amyloid peptides derived from APP.5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 41Sequence analysisAdd BLAST41
ChainiPRO_000003460342 – 655Tumor necrosis factor receptor superfamily member 21Add BLAST614

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi67 ↔ 80PROSITE-ProRule annotation
Disulfide bondi70 ↔ 88PROSITE-ProRule annotation
Glycosylationi82N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi91 ↔ 106PROSITE-ProRule annotation
Disulfide bondi109 ↔ 123PROSITE-ProRule annotation
Disulfide bondi113 ↔ 131PROSITE-ProRule annotation
Disulfide bondi133 ↔ 144PROSITE-ProRule annotation
Glycosylationi141N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi150 ↔ 168PROSITE-ProRule annotation
Disulfide bondi171 ↔ 186PROSITE-ProRule annotation
Disulfide bondi192 ↔ 211PROSITE-ProRule annotation
Glycosylationi252N-linked (GlcNAc...)Sequence analysis1
Glycosylationi257N-linked (GlcNAc...)Sequence analysis1
Glycosylationi278N-linked (GlcNAc...)Sequence analysis1
Glycosylationi289N-linked (GlcNAc...)Sequence analysis1
Lipidationi368S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiQ9EPU5.
PaxDbiQ9EPU5.
PRIDEiQ9EPU5.

PTM databases

iPTMnetiQ9EPU5.
PhosphoSitePlusiQ9EPU5.

Expressioni

Tissue specificityi

Detected in spleen B-cells (at protein level). Ubiquitous. Highly expressed in adult spleen, thymus, testis, prostate, ovary, small intestine, colon, brain, lung and kidney, and in fetal brain, liver and lung. Detected at lower levels in adult peripheral blood leukocytes, lung, and in fetal muscle, heart, kidney, small intestine and skin. Detected in T-cells, B-cells and monocytes. In T-cells expression is highest in Th0 cells, intermediate in Th2 cells and lower in Th1 cells. Expressed at low levels in proliferating progenitors in the spinal cord, but is highly expressed by differentiating neurons within the spinal cord and adjacent dorsal root ganglia. Expressed by developing neurons as they differentiate and enter a pro-apoptotic state. Expressed by both cell bodies and axons.4 Publications

Gene expression databases

BgeeiENSMUSG00000023915.
GenevisibleiQ9EPU5. MM.

Interactioni

Subunit structurei

Associates with TRADD. Interacts with NGFR (By similarity). Interacts with N-APP.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-59733N.
STRINGi10090.ENSMUSP00000024708.

Structurei

Secondary structure

1655
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi53 – 57Combined sources5
Turni59 – 61Combined sources3
Beta strandi64 – 68Combined sources5
Beta strandi74 – 78Combined sources5
Beta strandi82 – 84Combined sources3
Beta strandi87 – 90Combined sources4
Beta strandi118 – 121Combined sources4
Beta strandi130 – 132Combined sources3
Beta strandi137 – 140Combined sources4
Beta strandi143 – 146Combined sources4
Beta strandi154 – 158Combined sources5
Beta strandi162 – 164Combined sources3
Beta strandi167 – 170Combined sources4
Beta strandi181 – 183Combined sources3
Helixi193 – 195Combined sources3
Beta strandi198 – 201Combined sources4
Beta strandi205 – 207Combined sources3
Beta strandi210 – 212Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YN0X-ray2.20A42-220[»]
ProteinModelPortaliQ9EPU5.
SMRiQ9EPU5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati50 – 88TNFR-Cys 1Add BLAST39
Repeati90 – 131TNFR-Cys 2Add BLAST42
Repeati133 – 167TNFR-Cys 3Add BLAST35
Repeati170 – 211TNFR-Cys 4Add BLAST42
Domaini415 – 498DeathPROSITE-ProRule annotationAdd BLAST84

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 4 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHQ6. Eukaryota.
ENOG410YYKW. LUCA.
GeneTreeiENSGT00760000119204.
HOGENOMiHOG000136852.
HOVERGENiHBG054218.
InParanoidiQ9EPU5.
KOiK05157.
OMAiFSRPEHM.
OrthoDBiEOG091G03XW.
PhylomeDBiQ9EPU5.
TreeFamiTF331157.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022330. TNFR_21.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PRINTSiPR01971. TNFACTORR21.
SMARTiSM00005. DEATH. 1 hit.
SM01411. Ephrin_rec_like. 2 hits.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9EPU5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTRASSITA LASCSRTAGQ VGATMVAGSL LLLGFLSTIT AQPEQKTLSL
60 70 80 90 100
PGTYRHVDRT TGQVLTCDKC PAGTYVSEHC TNMSLRVCSS CPAGTFTRHE
110 120 130 140 150
NGIERCHDCS QPCPWPMIER LPCAALTDRE CICPPGMYQS NGTCAPHTVC
160 170 180 190 200
PVGWGVRKKG TENEDVRCKQ CARGTFSDVP SSVMKCKAHT DCLGQNLEVV
210 220 230 240 250
KPGTKETDNV CGMRLFFSST NPPSSGTVTF SHPEHMESHD VPSSTYEPQG
260 270 280 290 300
MNSTDSNSTA SVRTKVPSGI EEGTVPDNTS STSGKEGTNR TLPNPPQVTH
310 320 330 340 350
QQAPHHRHIL KLLPSSMEAT GEKSSTAIKA PKRGHPRQNA HKHFDINEHL
360 370 380 390 400
PWMIVLFLLL VLVLIVVCSI RKSSRTLKKG PRQDPSAIVE KAGLKKSLTP
410 420 430 440 450
TQNREKWIYY RNGHGIDILK LVAAQVGSQW KDIYQFLCNA SEREVAAFSN
460 470 480 490 500
GYTADHERAY AALQHWTIRG PEASLAQLIS ALRQHRRNDV VEKIRGLMED
510 520 530 540 550
TTQLETDKLA LPMSPSPLSP SPMPSPNVKL ENSTLLTVEP SPLDKNKCFF
560 570 580 590 600
VDESEPLLRC DSTSSGSSAL SRNGSFITKE KKDTVLRQVR LDPCDLQPIF
610 620 630 640 650
DDMLHILNPE ELRVIEEIPQ AEDKLDRLFE IIGVKSQEAS QTLLDSVYSH

LPDLL
Length:655
Mass (Da):71,983
Last modified:May 27, 2002 - v2
Checksum:i5EC7C51C7C99EFF7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti93A → T in BAE22249 (PubMed:16141072).Curated1
Sequence conflicti352W → L in AAG38115 (Ref. 1) Curated1
Sequence conflicti523M → I in AAH16420 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF322069 mRNA. Translation: AAG38115.1.
AY043489 mRNA. Translation: AAK74193.1.
AK043823 mRNA. Translation: BAC31664.1.
AK134704 mRNA. Translation: BAE22249.1.
BC016420 mRNA. Translation: AAH16420.1.
CCDSiCCDS28794.1.
RefSeqiNP_848704.1. NM_178589.3.
UniGeneiMm.200792.

Genome annotation databases

EnsembliENSMUST00000024708; ENSMUSP00000024708; ENSMUSG00000023915.
GeneIDi94185.
KEGGimmu:94185.
UCSCiuc008cov.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF322069 mRNA. Translation: AAG38115.1.
AY043489 mRNA. Translation: AAK74193.1.
AK043823 mRNA. Translation: BAC31664.1.
AK134704 mRNA. Translation: BAE22249.1.
BC016420 mRNA. Translation: AAH16420.1.
CCDSiCCDS28794.1.
RefSeqiNP_848704.1. NM_178589.3.
UniGeneiMm.200792.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YN0X-ray2.20A42-220[»]
ProteinModelPortaliQ9EPU5.
SMRiQ9EPU5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59733N.
STRINGi10090.ENSMUSP00000024708.

PTM databases

iPTMnetiQ9EPU5.
PhosphoSitePlusiQ9EPU5.

Proteomic databases

MaxQBiQ9EPU5.
PaxDbiQ9EPU5.
PRIDEiQ9EPU5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024708; ENSMUSP00000024708; ENSMUSG00000023915.
GeneIDi94185.
KEGGimmu:94185.
UCSCiuc008cov.1. mouse.

Organism-specific databases

CTDi27242.
MGIiMGI:2151075. Tnfrsf21.

Phylogenomic databases

eggNOGiENOG410IHQ6. Eukaryota.
ENOG410YYKW. LUCA.
GeneTreeiENSGT00760000119204.
HOGENOMiHOG000136852.
HOVERGENiHBG054218.
InParanoidiQ9EPU5.
KOiK05157.
OMAiFSRPEHM.
OrthoDBiEOG091G03XW.
PhylomeDBiQ9EPU5.
TreeFamiTF331157.

Miscellaneous databases

ChiTaRSiTnfrsf21. mouse.
PROiQ9EPU5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023915.
GenevisibleiQ9EPU5. MM.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022330. TNFR_21.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PRINTSiPR01971. TNFACTORR21.
SMARTiSM00005. DEATH. 1 hit.
SM01411. Ephrin_rec_like. 2 hits.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNR21_MOUSE
AccessioniPrimary (citable) accession number: Q9EPU5
Secondary accession number(s): Q3UYG3
, Q543Y9, Q91W77, Q91XH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: May 27, 2002
Last modified: November 30, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-25 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.