Tumor necrosis factor receptor superfamily member 10A precursor

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 10A
Alternative name(s):
    Death receptor 4
    TNF-related apoptosis-inducing ligand receptor 1
      Short name=TRAIL receptor 1
      Short name=TRAIL-R1
    CD_antigen=CD261

Gene names

Name:	TNFRSF10A
Synonyms:	APO2, DR4, TRAILR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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. Ref.6
Subunit structure	Can interact with TRADD and RIP. Interacts with ARAP1. Ref.8
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Widely expressed. High levels are found in spleen, peripheral blood leukocytes, small intestine and thymus, but also in K562 erythroleukemia cells, MCF7 breast carcinoma cells and activated T-cells.
Sequence similarities	Contains 1 death domain. Contains 3 TNFR-Cys repeats.

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Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	activation of NF-kappaB-inducing kinase activity Ref.6 Non-traceable author statement. Source: UniProtKB activation of caspase activity Non-traceable author statement. Source: UniProtKB induction of apoptosis via death domain receptors Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Inferred by curator. Source: UniProtKB
Molecular function	TRAIL binding Non-traceable author statement. Source: UniProtKB caspase activator activity Non-traceable author statement. Source: UniProtKB death receptor activity Ref.1 Traceable author statement. Source: ProtInc transcription factor binding Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAP1	Q96P48	3	EBI-518861,EBI-710003

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Chain

24 – 468

445

Tumor necrosis factor receptor superfamily member 10A

PRO_0000034579

Regions

Topological domain

24 – 239

216

Extracellular Potential

Transmembrane

240 – 262

23

Potential

Topological domain

263 – 468

206

Cytoplasmic Potential

Repeat

107 – 145

39

TNFR-Cys 1

Repeat

147 – 188

42

TNFR-Cys 2

Repeat

189 – 229

41

TNFR-Cys 3

Domain

365 – 448

84

Death

Compositional bias

29 – 32

4

Poly-Ala

Amino acid modifications

Modified residue

83

1

Phosphoserine Ref.7

Modified residue

463

1

Phosphoserine Ref.7

Modified residue

466

1

Phosphoserine Ref.7

Glycosylation

156

1

N-linked (GlcNAc...) Potential

Disulfide bond

132 ↔ 145

By similarity

Disulfide bond

148 ↔ 164

By similarity

Disulfide bond

167 ↔ 180

By similarity

Disulfide bond

170 ↔ 188

By similarity

Disulfide bond

190 ↔ 204

By similarity

Disulfide bond

207 ↔ 221

By similarity

Disulfide bond

211 ↔ 229

By similarity

Natural variations

Natural variant

11

1

G → V: dbSNP rs34737614.

VAR_052349

Natural variant

33

1

T → I: dbSNP rs20577.

VAR_016149

Natural variant

105

1

P → R: dbSNP rs11986840.

VAR_052350

Natural variant

141

1

H → R: dbSNP rs6557634. Ref.1 Ref.2

VAR_016150

Natural variant

209

1

R → T: dbSNP rs20575. Ref.1 Ref.2

VAR_016151

Natural variant

228

1

E → A: dbSNP rs20576.

VAR_016152

Natural variant

297

1

N → H: dbSNP rs17088980.

VAR_052351

Natural variant

441

1

K → R: dbSNP rs2230229.

VAR_052352

Experimental info

Sequence conflict

281

1

W → C in BAF83988. Ref.2

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Sequences

Sequence

Length

Mass (Da)

Tools

O00220-1 [UniParc].

Last modified May 27, 2002. Version 2.
Checksum: 7E9661859A550CD4
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FASTA

468

50,061

        10         20         30         40         50         60 
MAPPPARVHL GAFLAVTPNP GSAASGTEAA AATPSKVWGS SAGRIEPRGG GRGALPTSMG 

        70         80         90        100        110        120 
QHGPSARARA GRAPGPRPAR EASPRLRVHK TFKFVVVGVL LQVVPSSAAT IKLHDQSIGT 

       130        140        150        160        170        180 
QQWEHSPLGE LCPPGSHRSE HPGACNRCTE GVGYTNASNN LFACLPCTAC KSDEEERSPC 

       190        200        210        220        230        240 
TTTRNTACQC KPGTFRNDNS AEMCRKCSRG CPRGMVKVKD CTPWSDIECV HKESGNGHNI 

       250        260        270        280        290        300 
WVILVVTLVV PLLLVAVLIV CCCIGSGCGG DPKCMDRVCF WRLGLLRGPG AEDNAHNEIL 

       310        320        330        340        350        360 
SNADSLSTFV SEQQMESQEP ADLTGVTVQS PGEAQCLLGP AEAEGSQRRR LLVPANGADP 

       370        380        390        400        410        420 
TETLMLFFDK FANIVPFDSW DQLMRQLDLT KNEIDVVRAG TAGPGDALYA MLMKWVNKTG 

       430        440        450        460 
RNASIHTLLD ALERMEERHA KEKIQDLLVD SGKFIYLEDG TGSAVSLE

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The receptor for the cytotoxic ligand TRAIL." Pan G., O'Rourke K., Chinnaiyan A.M., Gentz R., Ebner R., Ni J., Dixit V.M. Science 276:111-113(1997) [PubMed: 9082980] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-141 AND THR-209.
[2]	"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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-141 AND THR-209. Tissue: Tongue.
[3]	"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].
[4]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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]. Tissue: Ovary.
[6]	"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: FUNCTION.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-463 AND SER-466, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane." Simova S., Klima M., Cermak L., Sourkova V., Andera L. Apoptosis 13:423-436(2008) [PubMed: 18165900] [Abstract] Cited for: INTERACTION WITH ARAP1.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	U90875 mRNA. Translation: AAC51226.1. AK291299 mRNA. Translation: BAF83988.1. BT006906 mRNA. Translation: AAP35552.1. EF064713 Genomic DNA. Translation: ABK41896.1. BC012866 mRNA. Translation: AAH12866.1.
IPI	IPI00021975.
RefSeq	NP_003835.2.
UniGene	Hs.591834
3D structure databases
HSSP	HSSP built from PDB template 1D0G based on UniProtKB O14763.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00220. 2 interactions.
PTM databases
PhosphoSite	O00220.
Proteomic databases
PRIDE	O00220.
Genome annotation databases
Ensembl	ENSG00000104689. Homo sapiens. [Contig view]
GeneID	8797.
KEGG	hsa:8797.
Organism-specific databases
GeneCards	GC08M023104.
H-InvDB	HIX0022944.
HGNC	HGNC:11904. TNFRSF10A.
MIM	603611. gene.
PharmGKB	PA36597.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00220.
HOVERGEN	O00220.
Enzyme and pathway databases
Pathway_Interaction_DB	trail_pathway. TRAIL signaling pathway.
Gene expression databases
ArrayExpress	O00220.
Bgee	O00220.
CleanEx	HS_TNFRSF10A.
GermOnline	ENSG00000104689. Homo sapiens.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH-like. IPR017301. TNF-rel_apoptosis-ind_lig_rcpt. IPR001368. TNFR_Cys_rich_reg. [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.
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	32996.
SOURCE	Search...

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Entry information

Entry name

TR10A_HUMAN

Accession

Primary (citable) accession number: O00220
Secondary accession number(s): A8K5I4, Q53Y72, Q96E62

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	May 27, 2002
Last modified:	June 16, 2009
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents