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Protein

Tumor necrosis factor receptor superfamily member 21

Gene

TNFRSF21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.3 Publications

Caution

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Apoptosis, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-1989781 PPARA activates gene expression
SIGNORiO75509

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
ORF Names:UNQ437/PRO868
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000146072.6
HGNCiHGNC:13469 TNFRSF21
MIMi605732 gene
neXtProtiNX_O75509

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi82N → Q: Abolishes one glycosylation site and reduces total N-glycosylation; when associated with Q-252; Q-278 and Q-289. 1 Publication1
Mutagenesisi141N → Q: Abolishes one glycosylation site and reduces total N-glycosylation; when associated with Q-82; Q-252; Q-278 and Q-289. 1 Publication1
Mutagenesisi252N → Q: Abolishes one glycosylation site and reduces total N-glycosylation; when associated with Q-278 and Q-289. 1 Publication1
Mutagenesisi257N → Q: Abolishes one glycosylation site and reduces total N-glycosylation; when associated with Q-82; Q-141; Q-252; Q-278 and Q-289. 1 Publication1
Mutagenesisi278N → Q: Abolishes one glycosylation site and reduces total N-glycosylation. Abolishes one glycosylation site and reduces total N-glycosylation; when associated with Q-82; Q-141; Q-252; Q-257 and Q-289. 1 Publication1
Mutagenesisi289N → Q: Abolishes one glycosylation site and reduces total N-glycosylation; when associated with Q-278. 1 Publication1
Mutagenesisi368C → V: Abolishes palmitoylation. 1

Organism-specific databases

DisGeNETi27242
OpenTargetsiENSG00000146072
PharmGKBiPA37775

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 41Sequence analysisAdd BLAST41
ChainiPRO_000003460242 – 655Tumor necrosis factor receptor superfamily member 21Add BLAST614

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi67 ↔ 80
Disulfide bondi70 ↔ 88
Glycosylationi82N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi91 ↔ 106
Disulfide bondi109 ↔ 123
Disulfide bondi113 ↔ 131
Disulfide bondi133 ↔ 144
Glycosylationi141N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi150 ↔ 168
Disulfide bondi171 ↔ 186
Disulfide bondi192 ↔ 211
Glycosylationi252N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi257N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi278N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi289N-linked (GlcNAc...) asparagine1 Publication1
Lipidationi368S-palmitoyl cysteine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiO75509
PaxDbiO75509
PeptideAtlasiO75509
PRIDEiO75509

PTM databases

iPTMnetiO75509
PhosphoSitePlusiO75509
SwissPalmiO75509

Expressioni

Tissue specificityi

Detected in fetal spinal cord and in brain neurons, with higher levels in brain from Alzheimer disease patients (at protein level). Highly expressed in heart, brain, placenta, pancreas, lymph node, thymus and prostate. Detected at lower levels in lung, skeletal muscle, kidney, testis, uterus, small intestine, colon, spleen, bone marrow and fetal liver. Very low levels were found in adult liver and peripheral blood leukocytes.3 Publications

Inductioni

Up-regulated by TNF.2 Publications

Gene expression databases

BgeeiENSG00000146072
CleanExiHS_TNFRSF21
ExpressionAtlasiO75509 baseline and differential
GenevisibleiO75509 HS

Organism-specific databases

HPAiCAB009805
HPA006746

Interactioni

Subunit structurei

Interacts with N-APP (By similarity). Associates with TRADD. Interacts with NGFR.By similarity2 Publications

Protein-protein interaction databases

BioGridi118090, 9 interactors
CORUMiO75509
DIPiDIP-53299N
IntActiO75509, 6 interactors
MINTiO75509
STRINGi9606.ENSP00000296861

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 strandi99 – 101Combined sources3
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
Beta strandi571 – 573Combined sources3
Helixi579 – 591Combined sources13
Helixi598 – 606Combined sources9
Helixi609 – 616Combined sources8
Helixi621 – 635Combined sources15
Helixi637 – 650Combined sources14
Helixi652 – 654Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DBHNMR-A567-655[»]
3QO4X-ray2.20A42-218[»]
3U3PX-ray2.09A42-348[»]
3U3QX-ray2.70A42-348[»]
3U3SX-ray2.70A42-348[»]
3U3TX-ray3.21A42-348[»]
3U3VX-ray2.96A42-348[»]
ProteinModelPortaliO75509
SMRiO75509
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75509

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

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHQ6 Eukaryota
ENOG410YYKW LUCA
GeneTreeiENSGT00760000119204
HOGENOMiHOG000136852
HOVERGENiHBG054218
InParanoidiO75509
KOiK05157
OMAiLMEDTAQ
OrthoDBiEOG091G03XW
PhylomeDBiO75509
TreeFamiTF331157

Family and domain databases

CDDicd08778 Death_TNFRSF21, 1 hit
cd10583 TNFRSF21, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR022330 TNFR_21
IPR034037 TNFRSF21_death
IPR034034 TNFRSF21_N
IPR011641 Tyr-kin_ephrin_A/B_rcpt-like
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF00020 TNFR_c6, 3 hits
PRINTSiPR01971 TNFACTORR21
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM01411 Ephrin_rec_like, 2 hits
SM00208 TNFR, 4 hits
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS00652 TNFR_NGFR_1, 1 hit
PS50050 TNFR_NGFR_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

O75509-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTSPSSSTA LASCSRIARR ATATMIAGSL LLLGFLSTTT AQPEQKASNL
60 70 80 90 100
IGTYRHVDRA TGQVLTCDKC PAGTYVSEHC TNTSLRVCSS CPVGTFTRHE
110 120 130 140 150
NGIEKCHDCS QPCPWPMIEK LPCAALTDRE CTCPPGMFQS NATCAPHTVC
160 170 180 190 200
PVGWGVRKKG TETEDVRCKQ CARGTFSDVP SSVMKCKAYT DCLSQNLVVI
210 220 230 240 250
KPGTKETDNV CGTLPSFSSS TSPSPGTAIF PRPEHMETHE VPSSTYVPKG
260 270 280 290 300
MNSTESNSSA SVRPKVLSSI QEGTVPDNTS SARGKEDVNK TLPNLQVVNH
310 320 330 340 350
QQGPHHRHIL KLLPSMEATG GEKSSTPIKG PKRGHPRQNL HKHFDINEHL
360 370 380 390 400
PWMIVLFLLL VLVVIVVCSI RKSSRTLKKG PRQDPSAIVE KAGLKKSMTP
410 420 430 440 450
TQNREKWIYY CNGHGIDILK LVAAQVGSQW KDIYQFLCNA SEREVAAFSN
460 470 480 490 500
GYTADHERAY AALQHWTIRG PEASLAQLIS ALRQHRRNDV VEKIRGLMED
510 520 530 540 550
TTQLETDKLA LPMSPSPLSP SPIPSPNAKL ENSALLTVEP SPQDKNKGFF
560 570 580 590 600
VDESEPLLRC DSTSSGSSAL SRNGSFITKE KKDTVLRQVR LDPCDLQPIF
610 620 630 640 650
DDMLHFLNPE ELRVIEEIPQ AEDKLDRLFE IIGVKSQEAS QTLLDSVYSH

LPDLL
Length:655
Mass (Da):71,845
Last modified:November 1, 1998 - v1
Checksum:i48939391C4852A33
GO

Sequence cautioni

The sequence AAH10241 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068868 mRNA Translation: AAC34583.1
AY358304 mRNA Translation: AAQ88671.1
AK315560 mRNA Translation: BAG37936.1
BT007420 mRNA Translation: AAP36088.1
AL096801 Genomic DNA No translation available.
BC010241 mRNA Translation: AAH10241.1 Different initiation.
BC017730 mRNA Translation: AAH17730.1
BC021572 mRNA Translation: AAH21572.1
CCDSiCCDS4921.1
RefSeqiNP_055267.1, NM_014452.4
UniGeneiHs.443577

Genome annotation databases

EnsembliENST00000296861; ENSP00000296861; ENSG00000146072
GeneIDi27242
KEGGihsa:27242
UCSCiuc003oyv.5 human

Similar proteinsi

Entry informationi

Entry nameiTNR21_HUMAN
AccessioniPrimary (citable) accession number: O75509
Secondary accession number(s): B2RDI9, Q0D2P5, Q96D86
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: November 1, 1998
Last modified: May 23, 2018
This is version 170 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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