O00220 (TR10A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	468 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. Ref.7
Subunit structure	Can interact with TRADD and RIPK1. Interacts with ARAP1. Ref.9
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 K-562 erythroleukemia cells, MCF-7 breast carcinoma cells and activated T-cells.
Sequence similarities	Contains 1 death domain. Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of NF-kappaB-inducing kinase activity Non-traceable author statement PubMed 11464292Ref.7. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Non-traceable author statement. Source: UniProtKB cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB extrinsic apoptotic signaling pathway via death domain receptors Non-traceable author statement PubMed 9311998. Source: UniProtKB induction of apoptosis Non-traceable author statement PubMed 9311998. Source: UniProtKB
Cellular_component	integral to membrane Inferred by curator PubMed 9311998. Source: UniProtKB
Molecular_function	TRAIL binding Non-traceable author statement PubMed 9373179. Source: UniProtKB death receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAP1	Q96P48	4	EBI-518861,EBI-710003
CASP8	Q14790	9	EBI-518861,EBI-78060
TNFSF10	P50591	8	EBI-518861,EBI-495373

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	Helical; 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	463	1	Phosphoserine Ref.10
	Modified residue	466	1	Phosphoserine Ref.8 Ref.10
	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. Corresponds to variant rs34737614 [ dbSNP | Ensembl ].		VAR_052349
	Natural variant	33	1	T → I. Corresponds to variant rs20577 [ dbSNP | Ensembl ].		VAR_016149
	Natural variant	105	1	P → R. Corresponds to variant rs11986840 [ dbSNP | Ensembl ].		VAR_052350
	Natural variant	141	1	H → R. Ref.1 Ref.3 Corresponds to variant rs6557634 [ dbSNP | Ensembl ].		VAR_016150
	Natural variant	209	1	R → T. Ref.1 Ref.3 Corresponds to variant rs20575 [ dbSNP | Ensembl ].		VAR_016151
	Natural variant	228	1	E → A. Corresponds to variant rs20576 [ dbSNP | Ensembl ].		VAR_016152
	Natural variant	297	1	N → H. Corresponds to variant rs17088980 [ dbSNP | Ensembl ].		VAR_052351
	Natural variant	441	1	R → K. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs2230229 [ dbSNP | Ensembl ].		VAR_052352
Experimental info
	Sequence conflict	281	1	W → C in BAF83988. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O00220 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 7E96619D0BDC0CD4	FASTA	468	50,089
	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 REKIQDLLVD SGKFIYLEDG TGSAVSLE

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-141; THR-209 AND LYS-441.
[2]	"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], VARIANT LYS-441.
[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], VARIANTS ARG-141; THR-209 AND LYS-441. Tissue: Tongue.
[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], VARIANT LYS-441.
[5]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [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], VARIANT LYS-441. Tissue: Ovary.
[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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARAP1.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-466, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U90875 mRNA. Translation: AAC51226.1. BT006906 mRNA. Translation: AAP35552.1. AK291299 mRNA. Translation: BAF83988.1. EF064713 Genomic DNA. Translation: ABK41896.1. AC100861 Genomic DNA. No translation available. BC012866 mRNA. Translation: AAH12866.1.
IPI	IPI00021975.
RefSeq	NP_003835.3. NM_003844.3.
UniGene	Hs.213467. Hs.591834.
3D structure databases
ProteinModelPortal	O00220.
SMR	O00220. Positions 126-234.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00220. 11 interactions.
MINT	MINT-99073.
STRING	9606.ENSP00000221132.
PTM databases
PhosphoSite	O00220.
Proteomic databases
PaxDb	O00220.
PRIDE	O00220.
Protocols and materials databases
DNASU	8797.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221132; ENSP00000221132; ENSG00000104689.
GeneID	8797.
KEGG	hsa:8797.
UCSC	uc003xda.3. human.
Organism-specific databases
CTD	8797.
GeneCards	GC08M023048.
H-InvDB	HIX0022944.
HGNC	HGNC:11904. TNFRSF10A.
MIM	603611. gene.
neXtProt	NX_O00220.
PharmGKB	PA36597.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG131298.
HOGENOM	HOG000142423.
HOVERGEN	HBG061626.
InParanoid	O00220.
KO	K04722.
OMA	NTACQCK.
OrthoDB	EOG476K1M.
PhylomeDB	O00220.
Enzyme and pathway databases
Pathway_Interaction_DB	trail_pathway. TRAIL signaling pathway.
Gene expression databases
ArrayExpress	O00220.
Bgee	O00220.
CleanEx	HS_TNFRSF10A.
Genevestigator	O00220.
GermOnline	ENSG00000104689. 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. IPR020465. TNFR_10. [Graphical view]
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]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50017. DEATH_DOMAIN. 1 hit. PS00652. TNFR_NGFR_1. 2 hits. PS50050. TNFR_NGFR_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00220.
ChEMBL	CHEMBL3551.
GenomeRNAi	8797.
NextBio	32996.
SOURCE	Search...

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:	November 30, 2010
Last modified:	May 1, 2013
This is version 126 of the entry and version 3 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.