O75509 (TNR21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 21

Alternative name(s):
Death receptor 6
CD_antigen=CD358

Gene names

Name:	TNFRSF21
Synonyms:	DR6
ORF Names:	UNQ437/PRO868

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	655 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	Associates with TRADD. Interacts with N-APP By similarity.
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.
Sequence similarities	Contains 1 death domain. Contains 4 TNFR-Cys repeats.
Caution	It is uncertain whether Met-1 or Met-25 is the initiator.
Sequence caution	The sequence AAH10241.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular lipid metabolic process Traceable author statement. Source: Reactome neuron apoptotic process Inferred from electronic annotation. Source: Compara signal transduction Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	axon Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay. Source: HPA integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	3	EBI-2313231,EBI-77613

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 41

41

Potential

Chain

42 – 655

614

Tumor necrosis factor receptor superfamily member 21

PRO_0000034602

Regions

Topological domain

42 – 349

308

Extracellular Potential

Transmembrane

350 – 370

21

Helical; Potential

Topological domain

371 – 655

285

Cytoplasmic Potential

Repeat

50 – 88

39

TNFR-Cys 1

Repeat

90 – 131

42

TNFR-Cys 2

Repeat

133 – 167

35

TNFR-Cys 3

Repeat

170 – 211

42

TNFR-Cys 4

Domain

415 – 498

84

Death

Amino acid modifications

Glycosylation

82

1

N-linked (GlcNAc...) Potential

Glycosylation

141

1

N-linked (GlcNAc...) Potential

Glycosylation

252

1

N-linked (GlcNAc...) Potential

Glycosylation

257

1

N-linked (GlcNAc...) Potential

Glycosylation

278

1

N-linked (GlcNAc...) Potential

Glycosylation

289

1

N-linked (GlcNAc...) Potential

Disulfide bond

67 ↔ 80

By similarity

Disulfide bond

70 ↔ 88

By similarity

Disulfide bond

91 ↔ 106

By similarity

Disulfide bond

109 ↔ 123

By similarity

Disulfide bond

113 ↔ 131

By similarity

Disulfide bond

133 ↔ 144

By similarity

Disulfide bond

150 ↔ 168

By similarity

Disulfide bond

171 ↔ 186

By similarity

Disulfide bond

192 ↔ 211

By similarity

Secondary structure

1

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655

Helix Strand Turn

Details...

Beta strand

53 – 57

5

Turn

59 – 61

3

Beta strand

64 – 68

5

Beta strand

74 – 78

5

Beta strand

82 – 84

3

Beta strand

87 – 90

4

Beta strand

99 – 101

3

Beta strand

118 – 121

4

Beta strand

130 – 132

3

Beta strand

137 – 140

4

Beta strand

143 – 146

4

Beta strand

154 – 158

5

Beta strand

162 – 164

3

Beta strand

167 – 170

4

Beta strand

181 – 183

3

Helix

193 – 195

3

Beta strand

198 – 201

4

Beta strand

205 – 207

3

Beta strand

210 – 212

3

Beta strand

571 – 573

3

Helix

579 – 591

13

Helix

598 – 606

9

Helix

609 – 616

8

Helix

621 – 635

15

Helix

637 – 650

14

Helix

652 – 654

3

Sequences

	Sequence		Length	Mass (Da)
	O75509 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 48939391C4852A33	FASTA	655	71,845
	10 20 30 40 50 60 MGTSPSSSTA LASCSRIARR ATATMIAGSL LLLGFLSTTT AQPEQKASNL IGTYRHVDRA 70 80 90 100 110 120 TGQVLTCDKC PAGTYVSEHC TNTSLRVCSS CPVGTFTRHE NGIEKCHDCS QPCPWPMIEK 130 140 150 160 170 180 LPCAALTDRE CTCPPGMFQS NATCAPHTVC PVGWGVRKKG TETEDVRCKQ CARGTFSDVP 190 200 210 220 230 240 SSVMKCKAYT DCLSQNLVVI KPGTKETDNV CGTLPSFSSS TSPSPGTAIF PRPEHMETHE 250 260 270 280 290 300 VPSSTYVPKG MNSTESNSSA SVRPKVLSSI QEGTVPDNTS SARGKEDVNK TLPNLQVVNH 310 320 330 340 350 360 QQGPHHRHIL KLLPSMEATG GEKSSTPIKG PKRGHPRQNL HKHFDINEHL PWMIVLFLLL 370 380 390 400 410 420 VLVVIVVCSI RKSSRTLKKG PRQDPSAIVE KAGLKKSMTP TQNREKWIYY CNGHGIDILK 430 440 450 460 470 480 LVAAQVGSQW KDIYQFLCNA SEREVAAFSN GYTADHERAY AALQHWTIRG PEASLAQLIS 490 500 510 520 530 540 ALRQHRRNDV VEKIRGLMED TTQLETDKLA LPMSPSPLSP SPIPSPNAKL ENSALLTVEP 550 560 570 580 590 600 SPQDKNKGFF VDESEPLLRC DSTSSGSSAL SRNGSFITKE KKDTVLRQVR LDPCDLQPIF 610 620 630 640 650 DDMLHFLNPE ELRVIEEIPQ AEDKLDRLFE IIGVKSQEAS QTLLDSVYSH LPDLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and functional characterization of DR6, a novel death domain-containing TNF receptor." Pan G., Bauer J.H., Haridas V., Wang S., Liu D., Yu G., Vincenz C., Aggarwal B.B., Ni J., Dixit V.M. FEBS Lett. 431:351-356(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Colon and Eye.
[7]	"Solution structure of the carboxyl-terminal CARD-like domain in human TNFR-related death receptor-6." RIKEN structural genomics initiative (RSGI) Submitted (DEC-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 562-655.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF068868 mRNA. Translation: AAC34583.1.
AY358304 mRNA. Translation: AAQ88671.1.
AK315560 mRNA. Translation: BAG37936.1.
BT007420 mRNA. Translation: AAP36088.1.
AL096801 Genomic DNA. Translation: CAB75692.1.
BC010241 mRNA. Translation: AAH10241.1. Different initiation.
BC017730 mRNA. Translation: AAH17730.1.
BC021572 mRNA. Translation: AAH21572.1.

IPI

IPI00004413.

RefSeq

NP_055267.1. NM_014452.3.

UniGene

Hs.443577.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DBH	NMR	-	A	567-655	[»]
3QO4	X-ray	2.20	A	42-218	[»]
3U3P	X-ray	2.09	A	42-349	[»]
3U3Q	X-ray	2.70	A	42-349	[»]
3U3S	X-ray	2.70	A	42-349	[»]
3U3T	X-ray	3.21	A	42-349	[»]
3U3V	X-ray	2.96	A	42-349	[»]

ProteinModelPortal

O75509.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-53299N.

IntAct

O75509. 1 interaction.

STRING

9606.ENSP00000296861.

PTM databases

PhosphoSite

O75509.

Proteomic databases

PaxDb

O75509.

PRIDE

O75509.

Protocols and materials databases

DNASU

27242.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296861; ENSP00000296861; ENSG00000146072.

GeneID

27242.

KEGG

hsa:27242.

UCSC

uc003oyv.3. human.

Organism-specific databases

CTD

27242.

GeneCards

GC06M047246.

HGNC

HGNC:13469. TNFRSF21.

HPA

CAB009805.
HPA006746.

MIM

605732. gene.

neXtProt

NX_O75509.

PharmGKB

PA37775.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42658.

HOGENOM

HOG000136852.

HOVERGEN

HBG054218.

InParanoid

O75509.

KO

K05157.

OMA

GLKKSMT.

OrthoDB

EOG47SSDR.

PhylomeDB

O75509.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

O75509.

CleanEx

HS_TNFRSF21.

Genevestigator

O75509.

GermOnline

ENSG00000146072. Homo sapiens.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.

InterPro

IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022330. TNFR_21.
[Graphical view]

Pfam

PF00531. Death. 1 hit.
[Graphical view]

PRINTS

PR01971. TNFACTORR21.

SMART

SM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TNFRSF21. human.

EvolutionaryTrace

O75509.

GenomeRNAi

27242.

NextBio

50139.

SOURCE

Search...

Entry information

Entry name

TNR21_HUMAN

Accession

Primary (citable) accession number: O75509
Secondary accession number(s): B2RDI9, Q0D2P5, Q96D86

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.