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O00220 (TR10A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length468 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 468445Tumor necrosis factor receptor superfamily member 10A
PRO_0000034579

Regions

Topological domain24 – 239216Extracellular Potential
Transmembrane240 – 26223Helical; Potential
Topological domain263 – 468206Cytoplasmic Potential
Repeat107 – 14539TNFR-Cys 1
Repeat147 – 18842TNFR-Cys 2
Repeat189 – 22941TNFR-Cys 3
Domain365 – 44884Death
Compositional bias29 – 324Poly-Ala

Amino acid modifications

Modified residue4631Phosphoserine Ref.10
Modified residue4661Phosphoserine Ref.8 Ref.10
Glycosylation1561N-linked (GlcNAc...) Potential
Disulfide bond132 ↔ 145 By similarity
Disulfide bond148 ↔ 164 By similarity
Disulfide bond167 ↔ 180 By similarity
Disulfide bond170 ↔ 188 By similarity
Disulfide bond190 ↔ 204 By similarity
Disulfide bond207 ↔ 221 By similarity
Disulfide bond211 ↔ 229 By similarity

Natural variations

Natural variant111G → V.
Corresponds to variant rs34737614 [ dbSNP | Ensembl ].
VAR_052349
Natural variant331T → I.
Corresponds to variant rs20577 [ dbSNP | Ensembl ].
VAR_016149
Natural variant1051P → R.
Corresponds to variant rs11986840 [ dbSNP | Ensembl ].
VAR_052350
Natural variant1411H → R. Ref.1 Ref.3
Corresponds to variant rs6557634 [ dbSNP | Ensembl ].
VAR_016150
Natural variant2091R → T. Ref.1 Ref.3
Corresponds to variant rs20575 [ dbSNP | Ensembl ].
VAR_016151
Natural variant2281E → A.
Corresponds to variant rs20576 [ dbSNP | Ensembl ].
VAR_016152
Natural variant2971N → H.
Corresponds to variant rs17088980 [ dbSNP | Ensembl ].
VAR_052351
Natural variant4411R → K. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs2230229 [ dbSNP | Ensembl ].
VAR_052352

Experimental info

Sequence conflict2811W → C in BAF83988. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O00220 [UniParc].

Last modified November 30, 2010. Version 3.
Checksum: 7E96619D0BDC0CD4

FASTA46850,089
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.
RefSeqNP_003835.3. NM_003844.3.
UniGeneHs.213467.
Hs.591834.

3D structure databases

ProteinModelPortalO00220.
SMRO00220. Positions 131-233, 367-449.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114325. 14 interactions.
IntActO00220. 11 interactions.
MINTMINT-99073.
STRING9606.ENSP00000221132.

Chemistry

BindingDBO00220.
ChEMBLCHEMBL3551.
GuidetoPHARMACOLOGY1879.

PTM databases

PhosphoSiteO00220.

Proteomic databases

PaxDbO00220.
PRIDEO00220.

Protocols and materials databases

DNASU8797.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221132; ENSP00000221132; ENSG00000104689.
GeneID8797.
KEGGhsa:8797.
UCSCuc003xda.3. human.

Organism-specific databases

CTD8797.
GeneCardsGC08M023048.
H-InvDBHIX0022944.
HGNCHGNC:11904. TNFRSF10A.
HPAHPA054475.
MIM603611. gene.
neXtProtNX_O00220.
PharmGKBPA36597.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG131298.
HOGENOMHOG000142423.
HOVERGENHBG061626.
InParanoidO00220.
KOK04722.
OMANTACQCK.
OrthoDBEOG71VSSN.
PhylomeDBO00220.
TreeFamTF333916.

Enzyme and pathway databases

SignaLinkO00220.

Gene expression databases

ArrayExpressO00220.
BgeeO00220.
CleanExHS_TNFRSF10A.
GenevestigatorO00220.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020465. TNFR_10.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PIRSFPIRSF037867. CD261_antigen. 1 hit.
PRINTSPR01956. TNFACTORR10.
SMARTSM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTNFRSF10A.
GenomeRNAi8797.
NextBio32996.
PROO00220.
SOURCESearch...

Entry information

Entry nameTR10A_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries