Human Gene TNFRSF21 (ENST00000296861.2) from GENCODE V44
  Description: Homo sapiens TNF receptor superfamily member 21 (TNFRSF21), mRNA. (from RefSeq NM_014452)
RefSeq Summary (NM_014452): This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013].
Gencode Transcript: ENST00000296861.2
Gencode Gene: ENSG00000146072.6
Transcript (Including UTRs)
   Position: hg38 chr6:47,231,532-47,309,905 Size: 78,374 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg38 chr6:47,232,765-47,309,511 Size: 76,747 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:47,231,532-47,309,905)mRNA (may differ from genome)Protein (655 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TNR21_HUMAN
DESCRIPTION: RecName: Full=Tumor necrosis factor receptor superfamily member 21; AltName: Full=Death receptor 6; AltName: CD_antigen=CD358; Flags: Precursor;
FUNCTION: May activate NF-kappa-B and promote apoptosis. May activate JNK and be involved in T-cell differentiation. 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 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
SUBUNIT: Associates with TRADD. Interacts with N-APP (By similarity).
INTERACTION: P05067:APP; NbExp=3; IntAct=EBI-2313231, EBI-77613;
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Probable).
TISSUE SPECIFICITY: 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.
SIMILARITY: Contains 1 death domain.
SIMILARITY: Contains 4 TNFR-Cys repeats.
CAUTION: It is uncertain whether Met-1 or Met-25 is the initiator.
SEQUENCE CAUTION: Sequence=AAH10241.1; Type=Erroneous initiation;

-  Primer design for this transcript
 

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TNFRSF21
Diseases sorted by gene-association score: diffuse infiltrative lymphocytosis syndrome (16)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D013749 Tetrachlorodibenzodioxin
  • D001564 Benzo(a)pyrene
  • C006632 arsenic trioxide
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C548651 2-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • C023035 3,4,5,3',4'-pentachlorobiphenyl
  • C482492 3,4,5,4'-tetramethoxystilbene
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • C553817 7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one
  • C547126 AZM551248
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 59.25 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 571.28 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -197.30394-0.501 Picture PostScript Text
3' UTR -277.671233-0.225 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000488 - Death
IPR011029 - DEATH-like
IPR001368 - TNFR/NGFR_Cys_rich_reg
IPR022330 - TNFR_21

Pfam Domains:
PF00531 - Death domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2DBH - NMR MuPIT 3QO4 - X-ray MuPIT 3U3P - X-ray MuPIT 3U3Q - X-ray MuPIT 3U3S - X-ray MuPIT 3U3T - X-ray MuPIT 3U3V - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O75509
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005031 tumor necrosis factor-activated receptor activity

Biological Process:
GO:0001783 B cell apoptotic process
GO:0002250 adaptive immune response
GO:0002376 immune system process
GO:0006915 apoptotic process
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0006959 humoral immune response
GO:0007165 signal transduction
GO:0019216 regulation of lipid metabolic process
GO:0030889 negative regulation of B cell proliferation
GO:0031642 negative regulation of myelination
GO:0032496 response to lipopolysaccharide
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0042127 regulation of cell proliferation
GO:0042130 negative regulation of T cell proliferation
GO:0042552 myelination
GO:0042981 regulation of apoptotic process
GO:0048713 regulation of oligodendrocyte differentiation
GO:0050852 T cell receptor signaling pathway
GO:0051402 neuron apoptotic process
GO:0071356 cellular response to tumor necrosis factor
GO:0097190 apoptotic signaling pathway
GO:0097252 oligodendrocyte apoptotic process
GO:2000663 negative regulation of interleukin-5 secretion
GO:2000666 negative regulation of interleukin-13 secretion
GO:2001180 negative regulation of interleukin-10 secretion

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0031226 intrinsic component of plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AK025399 - Homo sapiens cDNA: FLJ21746 fis, clone COLF5076.
AF208860 - Homo sapiens BM-018 mRNA, complete cds.
BC015466 - Homo sapiens tumor necrosis factor receptor superfamily, member 21, mRNA (cDNA clone IMAGE:3903805).
BC010241 - Homo sapiens tumor necrosis factor receptor superfamily, member 21, mRNA (cDNA clone MGC:18151 IMAGE:4154494), complete cds.
AJ420531 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 2156033.
BC017730 - Homo sapiens tumor necrosis factor receptor superfamily, member 21, mRNA (cDNA clone MGC:21476 IMAGE:3847246), complete cds.
BC021572 - Homo sapiens tumor necrosis factor receptor superfamily, member 21, mRNA (cDNA clone MGC:31965 IMAGE:4874397), complete cds.
AY358304 - Homo sapiens clone DNA52594 DR6-TNFR (UNQ437) mRNA, complete cds.
AB209394 - Homo sapiens mRNA for tumor necrosis factor receptor superfamily, member 21 precursor variant protein.
BC005192 - Homo sapiens tumor necrosis factor receptor superfamily, member 21, mRNA (cDNA clone IMAGE:3684533).
JD486652 - Sequence 467676 from Patent EP1572962.
JD196513 - Sequence 177537 from Patent EP1572962.
JD350850 - Sequence 331874 from Patent EP1572962.
KJ906121 - Synthetic construct Homo sapiens clone ccsbBroadEn_15791 TNFRSF21 gene, encodes complete protein.
CR457190 - Homo sapiens full open reading frame cDNA clone RZPDo834E048D for gene TNFRSF21, tumor necrosis factor receptor superfamily, member 21; complete cds, incl. stopcodon.
JD092440 - Sequence 73464 from Patent EP1572962.
JD563539 - Sequence 544563 from Patent EP1572962.
JD048440 - Sequence 29464 from Patent EP1572962.
JD237877 - Sequence 218901 from Patent EP1572962.
JD224718 - Sequence 205742 from Patent EP1572962.
JD024143 - Sequence 5167 from Patent EP1572962.
JD027588 - Sequence 8612 from Patent EP1572962.
JD287156 - Sequence 268180 from Patent EP1572962.
JD433150 - Sequence 414174 from Patent EP1572962.
JD439981 - Sequence 421005 from Patent EP1572962.
JD298328 - Sequence 279352 from Patent EP1572962.
AK001504 - Homo sapiens cDNA FLJ10642 fis, clone NT2RP2005752, highly similar to Tumor necrosis factor receptor superfamily member 21 precursor.
JD552626 - Sequence 533650 from Patent EP1572962.
AF068868 - Homo sapiens TNFR-related death receptor-6 (DR6) mRNA, complete cds.
BT007420 - Homo sapiens tumor necrosis factor receptor superfamily, member 21 mRNA, complete cds.
DQ890769 - Synthetic construct clone IMAGE:100003399; FLH165802.01X; RZPDo839G11160D tumor necrosis factor receptor superfamily, member 21 (TNFRSF21) gene, encodes complete protein.
AK315560 - Homo sapiens cDNA, FLJ96631, Homo sapiens tumor necrosis factor receptor superfamily, member 21(TNFRSF21), mRNA.
KJ904728 - Synthetic construct Homo sapiens clone ccsbBroadEn_14122 TNFRSF21 gene, encodes complete protein.
DQ893930 - Synthetic construct Homo sapiens clone IMAGE:100008390; FLH165798.01L; RZPDo839G11159D tumor necrosis factor receptor superfamily, member 21 (TNFRSF21) gene, encodes complete protein.
AB590269 - Synthetic construct DNA, clone: pFN21AE1476, Homo sapiens TNFRSF21 gene for tumor necrosis factor receptor superfamily, member 21, without stop codon, in Flexi system.
AK025235 - Homo sapiens cDNA: FLJ21582 fis, clone COL06810, highly similar to AF068868 Homo sapiens TNFR-related death receptor-6 (DR6) mRNA.
JD519031 - Sequence 500055 from Patent EP1572962.
JD394220 - Sequence 375244 from Patent EP1572962.
JD355828 - Sequence 336852 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04060 - Cytokine-cytokine receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein O75509 (Reactome details) participates in the following event(s):

R-HSA-1989781 PPARA activates gene expression
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: B2RDI9, DR6, ENST00000296861.1, NM_014452, O75509, Q0D2P5, Q96D86, TNR21_HUMAN, uc003oyv.1, uc003oyv.2, uc003oyv.3, uc003oyv.4, uc003oyv.5, UNQ437/PRO868
UCSC ID: ENST00000296861.2
RefSeq Accession: NM_014452
Protein: O75509 (aka TNR21_HUMAN or TR21_HUMAN)
CCDS: CCDS4921.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.