Reviewed, UniProtKB/Swiss-Prot O14763 (TR10B_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 10B
Alternative name(s):
    Death receptor 5
    TNF-related apoptosis-inducing ligand receptor 2
      Short name=TRAIL receptor 2
      Short name=TRAIL-R2
    CD_antigen=CD262

Gene names

Name:	TNFRSF10B
Synonyms:	DR5, KILLER, TRAILR2, TRICK2, ZTNFR9
ORF Names:	UNQ160/PRO186

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	440 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	Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B.
Subunit structure	Homotrimer. Can interact with TRADD and RIP.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Widely expressed in adult and fetal tissues; very highly expressed in tumor cell lines such as HeLa S3, K562, HL-60, SW480, A549 and G361; highly expressed in heart, peripheral blood lymphocytes, liver, pancreas, spleen, thymus, prostate, ovary, uterus, placenta, testis, esophagus, stomach and throughout the intestinal tract; not detectable in brain.
Induction	TNFRSF10B is regulated by the tumor suppressor p53.
Involvement in disease	Defects in TNFRSF10B may be a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck.
Sequence similarities	Contains 1 death domain. Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	activation of NF-kappaB-inducing kinase activity Ref.7 Non-traceable author statement. Source: UniProtKB activation of caspase activity Non-traceable author statement. Source: UniProtKB activation of pro-apoptotic gene products Inferred from Experiment. Source: Reactome cell surface receptor linked signal transduction Ref.1 Traceable author statement. Source: ProtInc induction of apoptosis via death domain receptors Ref.1 Non-traceable author statement. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB
Cellular component	integral to membrane Ref.1 Inferred by curator. Source: UniProtKB plasma membrane Inferred from Experiment. Source: Reactome
Molecular function	TRAIL binding Ref.3 Non-traceable author statement. Source: UniProtKB caspase activator activity Non-traceable author statement. Source: UniProtKB receptor activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAP1	Q96P48	1	EBI-518882,EBI-710003

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: O14763-1)

Also known as: TRICK2B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform Short (identifier: O14763-2)

Also known as: TRICK2A;

The sequence of this isoform differs from the canonical sequence as follows:
     185-213: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 55

55

Chain

56 – 440

385

Tumor necrosis factor receptor superfamily member 10B

PRO_0000034580

Regions

Topological domain

56 – 210

155

Extracellular Potential

Transmembrane

211 – 231

21

Potential

Topological domain

232 – 440

209

Cytoplasmic Potential

Repeat

57 – 94

38

TNFR-Cys 1

Repeat

97 – 137

41

TNFR-Cys 2

Repeat

138 – 178

41

TNFR-Cys 3

Repeat

192 – 206

15

TAPE

Domain

339 – 422

84

Death

Compositional bias

250 – 253

4

Poly-Gly

Amino acid modifications

Disulfide bond

81 ↔ 94

Disulfide bond

97 ↔ 113

Disulfide bond

116 ↔ 129

Disulfide bond

119 ↔ 137

Disulfide bond

139 ↔ 153

Disulfide bond

156 ↔ 170

Disulfide bond

160 ↔ 178

Natural variations

Alternative sequence

185 – 213

29

Missing in isoform Short.

VSP_006490

Natural variant

32

1

P → L: dbSNP rs1129424. Ref.2 Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

VAR_016153

Natural variant

67

1

A → V: dbSNP rs1047266. Ref.2 Ref.3 Ref.6 Ref.7 Ref.9 Ref.11

VAR_016154

Natural variant

191

1

A → V: dbSNP rs13265018.

VAR_059831

Experimental info

Sequence conflict

439

1

M → L in AAB67103. Ref.8

Sequence conflict

439

1

M → L in AAQ88644. Ref.12

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

440

Helix Strand Turn

Details...

Beta strand

85 – 87

3

Beta strand

89 – 92

4

Beta strand

94 – 96

3

Turn

99 – 101

3

Beta strand

106 – 108

3

Beta strand

123 – 127

5

Beta strand

131 – 133

3

Beta strand

136 – 139

4

Beta strand

143 – 146

4

Beta strand

149 – 155

7

Beta strand

165 – 168

4

Beta strand

177 – 179

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long (TRICK2B) [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 603005AF2A8B4870	FASTA	440	47,850
	10 20 30 40 50 60 MEQRGQNAPA ASGARKRHGP GPREARGARP GPRVPKTLVL VVAAVLLLVS AESALITQQD 70 80 90 100 110 120 LAPQQRAAPQ QKRSSPSEGL CPPGHHISED GRDCISCKYG QDYSTHWNDL LFCLRCTRCD 130 140 150 160 170 180 SGEVELSPCT TTRNTVCQCE EGTFREEDSP EMCRKCRTGC PRGMVKVGDC TPWSDIECVH 190 200 210 220 230 240 KESGTKHSGE APAVEETVTS SPGTPASPCS LSGIIIGVTV AAVVLIVAVF VCKSLLWKKV 250 260 270 280 290 300 LPYLKGICSG GGGDPERVDR SSQRPGAEDN VLNEIVSILQ PTQVPEQEME VQEPAEPTGV 310 320 330 340 350 360 NMLSPGESEH LLEPAEAERS QRRRLLVPAN EGDPTETLRQ CFDDFADLVP FDSWEPLMRK 370 380 390 400 410 420 LGLMDNEIKV AKAEAAGHRD TLYTMLIKWV NKTGRDASVH TLLDALETLG ERLAKQKIED 430 440 HLLSSGKFMY LEGNADSAMS
	Isoform Short (TRICK2A). Checksum: 57D50020E72CC954	FASTA	411	45,083
	10 20 30 40 50 60 MEQRGQNAPA ASGARKRHGP GPREARGARP GPRVPKTLVL VVAAVLLLVS AESALITQQD 70 80 90 100 110 120 LAPQQRAAPQ QKRSSPSEGL CPPGHHISED GRDCISCKYG QDYSTHWNDL LFCLRCTRCD 130 140 150 160 170 180 SGEVELSPCT TTRNTVCQCE EGTFREEDSP EMCRKCRTGC PRGMVKVGDC TPWSDIECVH 190 200 210 220 230 240 KESGIIIGVT VAAVVLIVAV FVCKSLLWKK VLPYLKGICS GGGGDPERVD RSSQRPGAED 250 260 270 280 290 300 NVLNEIVSIL QPTQVPEQEM EVQEPAEPTG VNMLSPGESE HLLEPAEAER SQRRRLLVPA 310 320 330 340 350 360 NEGDPTETLR QCFDDFADLV PFDSWEPLMR KLGLMDNEIK VAKAEAAGHR DTLYTMLIKW 370 380 390 400 410 VNKTGRDASV HTLLDALETL GERLAKQKIE DHLLSSGKFM YLEGNADSAM S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL." Walczak H., Degli-Esposti M.A., Johnson R.S., Smolak P.J., Waugh J.Y., Boiani N., Timour M.S., Gerhart M.J., Schooley K.A., Smith C.A., Goodwin R.G., Rauch C.T. EMBO J. 16:5386-5397(1997) [PubMed: 9311998] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PROTEIN SEQUENCE OF N-TERMINUS. Tissue: Foreskin fibroblast.
[2]	"TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL." Screaton G.R., Mongkolsapaya J., Xu X.-N., Cowper A.E., McMichael A.J., Bell J.I. Curr. Biol. 7:693-696(1997) [PubMed: 9285725] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), ALTERNATIVE SPLICING, VARIANTS LEU-32 AND VAL-67.
[3]	"Characterization of two receptors for TRAIL." Schneider P., Bodmer J.-L., Thome M., Hofmann K., Holler N., Tschopp J. FEBS Lett. 416:329-334(1997) [PubMed: 9373179] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), CHARACTERIZATION, VARIANTS LEU-32 AND VAL-67. Tissue: Liver and Spleen.
[4]	"KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene." Wu G.S., Burns T.F., McDonald E.R. III, Jiang W., Meng R., Krantz I.D., Kao G., Gan D.D., Zhou J.Y., Muschel R., Hamilton S.R., Spinner N.B., Markowitz S., Wu G., el-Deiry W.S. Nat. Genet. 17:141-143(1997) [PubMed: 9326928] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Ovary.
[5]	"An antagonist decoy receptor and a death domain-containing receptor for TRAIL." Pan G., Ni J., Wei Y.-F., Yu G.-L., Gentz R., Dixit V.M. Science 277:815-818(1997) [PubMed: 9242610] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[6]	"Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL." MacFarlane M., Ahmad M., Srinivasula S.M., Fernandes-Alnemri T., Cohen G.M., Alnemri E.S. J. Biol. Chem. 272:25417-25420(1997) [PubMed: 9325248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANTS LEU-32 AND VAL-67.
[7]	"Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway." Chaudhary P.M., Eby M., Jasmin A., Bookwalter A., Murray J., Hood L. Immunity 7:821-830(1997) [PubMed: 9430227] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANTS LEU-32 AND VAL-67.
[8]	"Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors." Sheridan J.P., Marsters S.A., Pitti R.M., Gurney A., Skubatch M., Baldwin D.T., Ramakrishnan L., Gray C.L., Baker K., Wood W.I., Goddard A.D., Godowski P.J., Ashkenazi A. Science 277:818-821(1997) [PubMed: 9242611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANT LEU-32.
[9]	"Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in colorectal carcinomas." Arai T., Akiyama Y., Okabe S., Saito K., Iwai T., Yuasa Y. Cancer Lett. 133:197-204(1998) [PubMed: 10072170] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, VARIANTS LEU-32 AND VAL-67.
[10]	Cao X., Zhang W., Wan T. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[11]	"Homo sapiens homolog of tumor necrosis factor receptor." Farrah T., Vu T., Gilbert T., Gross J., O'Hara P. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANTS LEU-32 AND VAL-67.
[12]	"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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT), VARIANT LEU-32.
[13]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), VARIANT LEU-32. Tissue: Cervix.
[14]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[15]	"Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5." Hymowitz S.G., Christinger H.W., Fuh G., Ultsch M., O'Connell M., Kelley R.F., Ashkenazi A., de Vos A.M. Mol. Cell 4:563-571(1999) [PubMed: 10549288] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 54-183.
[16]	"Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation." Mongkolsapaya J., Grimes J.M., Chen N., Xu X.-N., Stuart D.I., Jones E.Y., Screaton G.R. Nat. Struct. Biol. 6:1048-1053(1999) [PubMed: 10542098] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 69-184.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF016849 mRNA. Translation: AAC51778.1.
AF018657 mRNA. Translation: AAB70577.1.
AF018658 mRNA. Translation: AAB70578.1.
AF016266 mRNA. Translation: AAB81180.1.
AF022386 mRNA. Translation: AAB71949.1.
AF012628 mRNA. Translation: AAB67109.1.
AF020501 mRNA. Translation: AAB71412.1.
AF016268 mRNA. Translation: AAC01565.1.
AF012535 mRNA. Translation: AAB67103.1.
AB014718 Genomic DNA. Translation: BAA33723.1.
AF153687 mRNA. Translation: AAF75587.1.
AF192548 mRNA. Translation: AAF07175.1.
AY358277 mRNA. Translation: AAQ88644.1.
BC001281 mRNA. Translation: AAH01281.1.

IPI

IPI00296379.
IPI00296380.

RefSeq

NP_003833.4.
NP_671716.2.

UniGene

Hs.521456

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D0G	X-ray	2.40	R/S/T	54-183	[»]
1D4V	X-ray	2.20	A	69-184	[»]
1DU3	X-ray	2.20	A/B/C/G/H/I	54-183	[»]
1ZA3	X-ray	3.35	R/S	54-183	[»]
2H9G	X-ray	2.32	R/S	54-183	[»]

SMR

O14763. Positions 69-184.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14763. 3 interactions.

STRING

O14763.

Proteomic databases

PRIDE

O14763.

Genome annotation databases

Ensembl

ENST00000276431; ENSP00000276431; ENSG00000120889; Homo sapiens. [Genome view]
ENST00000347739; ENSP00000317859; ENSG00000120889; Homo sapiens. [Genome view]

GeneID

8795.

KEGG

hsa:8795.

UCSC

uc003xct.1. human.
uc003xcu.1. human.

Organism-specific databases

CTD

8795.

GeneCards

GC08M022933.

H-InvDB

HIX0021066.

HGNC

HGNC:11905. TNFRSF10B.

HPA

HPA023625.

MIM

275355. phenotype.
603612. gene.

Orphanet

67037. Squamous cell carcinoma of head and neck.

PharmGKB

PA36598.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O14763.

HOVERGEN

O14763.

Enzyme and pathway databases

Pathway_Interaction_DB

trail_pathway. TRAIL signaling pathway.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

O14763.

Bgee

O14763.

CleanEx

HS_TNFRSF10B.

Genevestigator

O14763.

GermOnline

ENSG00000120889. Homo sapiens.

Family and domain databases

InterPro

IPR000488. Death.
IPR011029. DEATH-like.
IPR017301. TNF-rel_apoptosis-ind_lig_rcpt.
IPR001368. TNFR_Cys_rich_reg.
IPR020465. Tumour_necrosis_factor_rcpt_10.
[Graphical view]

Gene3D

G3DSA:1.10.533.10. DEATH_like. 1 hit.

Pfam

PF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]

PIRSF

PIRSF037867. CD261_antigen. 1 hit.

PRINTS

PR01956. TNFACTORR10.

SMART

SM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
[Graphical view]

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

32984.

SOURCE

Search...

Entry information

Entry name

TR10B_HUMAN

Accession

Primary (citable) accession number: O14763
Secondary accession number(s): O14720 , O15508, O15517, O15531, Q6UXM8, Q9BVE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	January 1, 1998
Last modified:	November 3, 2009
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.