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O00220

- TR10A_HUMAN

UniProt

O00220 - TR10A_HUMAN

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Protein

Tumor necrosis factor receptor superfamily member 10A

Gene

TNFRSF10A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. death receptor activity Source: ProtInc
  2. protease binding Source: UniProtKB
  3. receptor activity Source: UniProtKB
  4. TRAIL binding Source: UniProtKB
  5. transcription factor binding Source: UniProtKB

GO - Biological processi

  1. activation of NF-kappaB-inducing kinase activity Source: UniProtKB
  2. apoptotic process Source: UniProtKB
  3. cellular response to mechanical stimulus Source: UniProtKB
  4. extrinsic apoptotic signaling pathway Source: UniProtKB
  5. extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
  6. signal transduction Source: ProtInc
  7. TRAIL-activated apoptotic signaling pathway Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

SignaLinkiO00220.

Names & Taxonomyi

Protein namesi
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 namesi
Name:TNFRSF10A
Synonyms:APO2, DR4, TRAILR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:11904. TNFRSF10A.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 239216ExtracellularSequence AnalysisAdd
BLAST
Transmembranei240 – 26223HelicalSequence AnalysisAdd
BLAST
Topological domaini263 – 468206CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36597.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 468445Tumor necrosis factor receptor superfamily member 10APRO_0000034579Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi132 ↔ 145PROSITE-ProRule annotation
Disulfide bondi148 ↔ 164PROSITE-ProRule annotation
Glycosylationi156 – 1561N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi167 ↔ 180PROSITE-ProRule annotation
Disulfide bondi170 ↔ 188PROSITE-ProRule annotation
Disulfide bondi190 ↔ 204PROSITE-ProRule annotation
Disulfide bondi207 ↔ 221PROSITE-ProRule annotation
Disulfide bondi211 ↔ 229PROSITE-ProRule annotation
Modified residuei463 – 4631Phosphoserine1 Publication
Modified residuei466 – 4661Phosphoserine2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO00220.
PaxDbiO00220.
PRIDEiO00220.

PTM databases

PhosphoSiteiO00220.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiO00220.
CleanExiHS_TNFRSF10A.
ExpressionAtlasiO00220. baseline and differential.
GenevestigatoriO00220.

Organism-specific databases

HPAiHPA054475.

Interactioni

Subunit structurei

Can interact with TRADD and RIPK1. Interacts with ARAP1. Interacts with HCMV protein UL141; this interaction prevents TNFRSF10A cell surface expression.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARAP1Q96P484EBI-518861,EBI-710003
CASP8Q147909EBI-518861,EBI-78060
TNFSF10P505914EBI-518861,EBI-495373

Protein-protein interaction databases

BioGridi114325. 16 interactions.
IntActiO00220. 11 interactions.
MINTiMINT-99073.
STRINGi9606.ENSP00000221132.

Structurei

3D structure databases

ProteinModelPortaliO00220.
SMRiO00220. Positions 131-233.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati107 – 14539TNFR-Cys 1Add
BLAST
Repeati147 – 18842TNFR-Cys 2Add
BLAST
Repeati189 – 22941TNFR-Cys 3Add
BLAST
Domaini365 – 44884DeathPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi29 – 324Poly-Ala

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 3 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG131298.
GeneTreeiENSGT00730000110985.
HOGENOMiHOG000142423.
HOVERGENiHBG061626.
InParanoidiO00220.
KOiK04722.
OMAiNTACQCK.
OrthoDBiEOG71VSSN.
PhylomeDBiO00220.
TreeFamiTF333916.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020465. TNFR_10.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PIRSFiPIRSF037867. CD261_antigen. 1 hit.
PRINTSiPR01956. TNFACTORR10.
SMARTiSM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O00220-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAPPPARVHL GAFLAVTPNP GSAASGTEAA AATPSKVWGS SAGRIEPRGG
60 70 80 90 100
GRGALPTSMG QHGPSARARA GRAPGPRPAR EASPRLRVHK TFKFVVVGVL
110 120 130 140 150
LQVVPSSAAT IKLHDQSIGT QQWEHSPLGE LCPPGSHRSE HPGACNRCTE
160 170 180 190 200
GVGYTNASNN LFACLPCTAC KSDEEERSPC TTTRNTACQC KPGTFRNDNS
210 220 230 240 250
AEMCRKCSRG CPRGMVKVKD CTPWSDIECV HKESGNGHNI WVILVVTLVV
260 270 280 290 300
PLLLVAVLIV CCCIGSGCGG DPKCMDRVCF WRLGLLRGPG AEDNAHNEIL
310 320 330 340 350
SNADSLSTFV SEQQMESQEP ADLTGVTVQS PGEAQCLLGP AEAEGSQRRR
360 370 380 390 400
LLVPANGADP TETLMLFFDK FANIVPFDSW DQLMRQLDLT KNEIDVVRAG
410 420 430 440 450
TAGPGDALYA MLMKWVNKTG RNASIHTLLD ALERMEERHA REKIQDLLVD
460
SGKFIYLEDG TGSAVSLE
Length:468
Mass (Da):50,089
Last modified:November 30, 2010 - v3
Checksum:i7E96619D0BDC0CD4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti281 – 2811W → C in BAF83988. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti11 – 111G → V.
Corresponds to variant rs34737614 [ dbSNP | Ensembl ].
VAR_052349
Natural varianti33 – 331T → I.
Corresponds to variant rs20577 [ dbSNP | Ensembl ].
VAR_016149
Natural varianti105 – 1051P → R.
Corresponds to variant rs11986840 [ dbSNP | Ensembl ].
VAR_052350
Natural varianti141 – 1411H → R.2 Publications
Corresponds to variant rs6557634 [ dbSNP | Ensembl ].
VAR_016150
Natural varianti209 – 2091R → T.2 Publications
Corresponds to variant rs20575 [ dbSNP | Ensembl ].
VAR_016151
Natural varianti228 – 2281E → A.
Corresponds to variant rs20576 [ dbSNP | Ensembl ].
VAR_016152
Natural varianti297 – 2971N → H.
Corresponds to variant rs17088980 [ dbSNP | Ensembl ].
VAR_052351
Natural varianti441 – 4411R → K.5 Publications
Corresponds to variant rs2230229 [ dbSNP | Ensembl ].
VAR_052352

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6039.1.
RefSeqiNP_003835.3. NM_003844.3.
UniGeneiHs.213467.
Hs.591834.

Genome annotation databases

EnsembliENST00000221132; ENSP00000221132; ENSG00000104689.
GeneIDi8797.
KEGGihsa:8797.
UCSCiuc003xda.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS6039.1.
RefSeqi NP_003835.3. NM_003844.3.
UniGenei Hs.213467.
Hs.591834.

3D structure databases

ProteinModelPortali O00220.
SMRi O00220. Positions 131-233.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114325. 16 interactions.
IntActi O00220. 11 interactions.
MINTi MINT-99073.
STRINGi 9606.ENSP00000221132.

Chemistry

BindingDBi O00220.
ChEMBLi CHEMBL3551.
GuidetoPHARMACOLOGYi 1879.

PTM databases

PhosphoSitei O00220.

Proteomic databases

MaxQBi O00220.
PaxDbi O00220.
PRIDEi O00220.

Protocols and materials databases

DNASUi 8797.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000221132 ; ENSP00000221132 ; ENSG00000104689 .
GeneIDi 8797.
KEGGi hsa:8797.
UCSCi uc003xda.3. human.

Organism-specific databases

CTDi 8797.
GeneCardsi GC08M023048.
H-InvDB HIX0022944.
HGNCi HGNC:11904. TNFRSF10A.
HPAi HPA054475.
MIMi 603611. gene.
neXtProti NX_O00220.
PharmGKBi PA36597.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG131298.
GeneTreei ENSGT00730000110985.
HOGENOMi HOG000142423.
HOVERGENi HBG061626.
InParanoidi O00220.
KOi K04722.
OMAi NTACQCK.
OrthoDBi EOG71VSSN.
PhylomeDBi O00220.
TreeFami TF333916.

Enzyme and pathway databases

SignaLinki O00220.

Miscellaneous databases

GeneWikii TNFRSF10A.
GenomeRNAii 8797.
NextBioi 32996.
PROi O00220.
SOURCEi Search...

Gene expression databases

Bgeei O00220.
CleanExi HS_TNFRSF10A.
ExpressionAtlasi O00220. baseline and differential.
Genevestigatori O00220.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
InterProi IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020465. TNFR_10.
[Graphical view ]
Pfami PF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view ]
PIRSFi PIRSF037867. CD261_antigen. 1 hit.
PRINTSi PR01956. TNFACTORR10.
SMARTi SM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
PROSITEi PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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, 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.
  11. Cited for: INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL141.

Entry informationi

Entry nameiTR10A_HUMAN
AccessioniPrimary (citable) accession number: O00220
Secondary accession number(s): A8K5I4, Q53Y72, Q96E62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 30, 2010
Last modified: October 29, 2014
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3