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Death receptor 4

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From Wikipedia, the free encyclopedia

(Redirected fromTNFRSF10A)

Protein found in humans

TNFRSF10A

Identifiers

Aliases

TNFRSF10A, APO2, CD261, DR4, TRAILR-1, TRAILR1, tumor necrosis factor receptor superfamily member 10a, TNF receptor superfamily member 10a

External IDs

OMIM:603611;MGI:1341090;HomoloGene:129806;GeneCards:TNFRSF10A;OMA:TNFRSF10A - orthologs

Gene location (Human)

Chr.	Chromosome 8 (human)^[1]

Band	8p21.3	Start	23,190,452bp^[1]
Band	8p21.3	End	23,225,102bp^[1]

Gene location (Mouse)

Chr.	Chromosome 14 (mouse)^[2]

Band	14\|14 D2	Start	70,004,921bp^[2]
Band	14\|14 D2	End	70,021,860bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

buccal mucosa cell

nipple

pancreatic ductal cell

tendon of biceps brachii

pylorus

lymph node

superficial temporal artery

epithelium of colon

mucosa of pharynx

nasal epithelium

Top expressed in

urethra

female urethra

male urethra

genital tubercle

morula

endothelial cell of lymphatic vessel

tail of embryo

lens

embryo

embryo

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	TRAIL binding transcription factor binding protease binding protein binding tumor necrosis factor-activated receptor activity death receptor activity signaling receptor activity
Cellular component	membrane plasma membrane integral component of plasma membrane cell surface intracellular anatomical structure integral component of membrane
Biological process	activation of NF-kappaB-inducing kinase activity TRAIL-activated apoptotic signaling pathway multicellular organism development cell surface receptor signaling pathway response to lipopolysaccharide cellular response to mechanical stimulus regulation of cell population proliferation immune response regulation of extrinsic apoptotic signaling pathway via death domain receptors inflammatory response activation of cysteine-type endopeptidase activity involved in apoptotic process extrinsic apoptotic signaling pathway via death domain receptors signal transduction negative regulation of extrinsic apoptotic signaling pathway via death domain receptors extrinsic apoptotic signaling pathway tumor necrosis factor-mediated signaling pathway apoptotic process leukocyte migration regulation of apoptotic process negative regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of apoptotic process
Sources:Amigo /QuickGO

Orthologs

Species

Human

Mouse

Entrez


8797


21933

Ensembl


ENSG00000104689


ENSMUSG00000022074

UniProt


O00220


Q9QZM4

RefSeq (mRNA)


NM_003844


NM_020275

RefSeq (protein)


NP_003835


NP_064671

Location (UCSC)

Chr 8: 23.19 – 23.23 Mb

Chr 14: 70 – 70.02 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Death receptor 4 (DR4), also known asTRAIL receptor 1 (TRAILR1) andtumor necrosis factor receptor superfamily member 10A (TNFRSF10A), is acell surface receptor of theTNF-receptor superfamily that bindsTRAIL and mediatesapoptosis.^[5]^[6]

Function

[edit]

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis.^[7]

Studies with FADD-deficient mice suggested thatFADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.^[8]

Interactions

[edit]

TNFRSF10A has been shown tointeract withDAP3.^[9]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000104689 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000022074 –Ensembl, May 2017
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (Dec 1997)."TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL".EMBO J.16 (17):5386–97.doi:10.1093/emboj/16.17.5386.PMC 1170170.PMID 9311998.
^Pan G, O'Rourke K,Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (April 1997). "The receptor for the cytotoxic ligand TRAIL".Science.276 (5309):111–3.doi:10.1126/science.276.5309.111.PMID 9082980.S2CID 19984057.
^"Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a".
^Kuang AA, Diehl GE, Zhang J, Winoto A (2000)."FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts".J. Biol. Chem.275 (33):25065–8.doi:10.1074/jbc.C000284200.PMID 10862756.
^Miyazaki T, Reed J C (June 2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins".Nat. Immunol.2 (6):493–500.doi:10.1038/88684.ISSN 1529-2908.PMID 11376335.S2CID 6923467.

Kimberley FC, Screaton GR (2005)."Following a TRAIL: update on a ligand and its five receptors".Cell Res.14 (5):359–72.doi:10.1038/sj.cr.7290236.PMID 15538968.
Fleury S, Thibodeau J, Croteau G, et al. (1995)."HLA-DR polymorphism affects the interaction with CD4".J. Exp. Med.182 (3):733–41.doi:10.1084/jem.182.3.733.PMC 2192178.PMID 7650480.
MacFarlane M, Ahmad M, Srinivasula SM, et al. (1997)."Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL".J. Biol. Chem.272 (41):25417–20.doi:10.1074/jbc.272.41.25417.PMID 9325248.
Schneider P, Bodmer JL, Thome M, et al. (1997)."Characterization of two receptors for TRAIL"(PDF).FEBS Lett.416 (3):329–34.doi:10.1016/S0014-5793(97)01231-3.PMID 9373179.S2CID 83145771.
Marsters SA, Sheridan JP, Pitti RM, et al. (1998)."A novel receptor for Apo2L/TRAIL contains a truncated death domain".Curr. Biol.7 (12):1003–6.Bibcode:1997CBio....7.1003M.doi:10.1016/S0960-9822(06)00422-2.PMID 9382840.S2CID 21645158.
Chaudhary PM, Eby M, Jasmin A, et al. (1998)."Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway".Immunity.7 (6):821–30.doi:10.1016/S1074-7613(00)80400-8.PMID 9430227.
Schneider P, Thome M, Burns K, et al. (1998)."TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB".Immunity.7 (6):831–6.doi:10.1016/S1074-7613(00)80401-X.PMID 9430228.
Diab BY, Lambert NC, L'Faqihi FE, et al. (1999). "Human collagen II peptide 256-271 preferentially binds to HLA-DR molecules associated with susceptibility to rheumatoid arthritis".Immunogenetics.49 (1):36–44.doi:10.1007/s002510050461.PMID 9811967.S2CID 22393348.
Costanzo A, Guiet C, Vito P (1999)."c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB".J. Biol. Chem.274 (29):20127–32.doi:10.1074/jbc.274.29.20127.PMID 10400625.
Hymowitz SG, Christinger HW, Fuh G, et al. (1999)."Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5".Mol. Cell.4 (4):563–71.doi:10.1016/S1097-2765(00)80207-5.PMID 10549288.
Gibson SB, Oyer R, Spalding AC, et al. (2000)."Increased expression of death receptors 4 and 5 synergizes the apoptosis response to combined treatment with etoposide and TRAIL".Mol. Cell. Biol.20 (1):205–12.doi:10.1128/MCB.20.1.205-212.2000.PMC 85076.PMID 10594023.
Miyazaki T, Reed JC (2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins".Nat. Immunol.2 (6):493–500.doi:10.1038/88684.PMID 11376335.S2CID 6923467.
Trauzold A, Wermann H, Arlt A, et al. (2001)."CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells".Oncogene.20 (31):4258–69.doi:10.1038/sj.onc.1204559.PMID 11464292.
Dörr J, Bechmann I, Waiczies S, et al. (2002)."Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain".J. Neurosci.22 (4): RC209.doi:10.1523/JNEUROSCI.22-04-j0001.2002.PMC 6757573.PMID 11844843.
Koyama S, Koike N, Adachi S (2002). "Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor".J. Cancer Res. Clin. Oncol.128 (2):73–9.doi:10.1007/s004320100292.PMID 11862476.S2CID 19509629.
Guan B, Yue P, Lotan R, Sun SY (2002). "Evidence that the human death receptor 4 is regulated by activator protein 1".Oncogene.21 (20):3121–9.doi:10.1038/sj.onc.1205430.PMID 12082627.S2CID 6726601.
Söderström TS, Poukkula M, Holmström TH, et al. (2002)."Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8".J. Immunol.169 (6):2851–60.doi:10.4049/jimmunol.169.6.2851.PMID 12218097.

v t e Proteins:clusters of differentiation (see alsolist of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 -CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 -CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD327 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

Cytokine receptors

Chemokine receptor
(GPCRs)

CC	CCR1 /CCRL1 CCR2 CCRL2 CCR3 CCR4 CCR5 CCR6 CCR7 CCR8 CCR9 CCR10
CXC	IL-8 CXCR1 CXCR2 CXCR3 CXCR4 CXCR5 CXCR6 CXCR7
Other	CX3C CX3CR1 XC XCR1 CCBP2 CMKLR1

TNF receptor

1-10	TNFR1(TNFRSF1A) TNFR2(TNFRSF1B) LTBR(TNFRSF3) CD134(TNFRSF4) CD40(TNFRSF5) Fas receptor(TNFRSF6) DcR3(TNFRSF6B) CD27(TNFRSF7) CD30(TNFRSF8) CD137(TNFRSF9)
11-20	DR4(TNFRSF10A) DR5(TNFRSF10B) DcR1(TNFRSF10C) DcR2(TNFRSF10D) RANK(TNFRSF11A) Osteoprotegerin(TNFRSF11B) TweakR(TNFRSF12A) TACI(TNFRSF13B) BAFFR(TNFRSF13C) HVEM(TNFRSF14) NGFR(TNFRSF16) BCMA(TNFRSF17) GITR(TNFRSF18) TAJ/TROY(TNFRSF19)
21-27	DR6(TNFRSF21) DR3(TNFRSF25) EDA2R(TNFRSF27)

JAK-STAT

Type I

γ-chain	Interleukin receptors IL2R /IL2RA/IL2RB /IL15R IL4R /IL13R /IL13RA1 /IL13RA2 IL7R /IL7RA IL9R IL21R
β-chain	Interleukin receptors IL3R /IL3RA IL5R /IL5RA GM-CSF
gp130	Interleukin receptors IL6RA 11/IL11RA 27/IL27RA OSMR LIFR CNTFR
IL12RB1	Interleukin receptors IL12R/IL12RB1/IL12RB2 IL23R
Other	otherCSF receptors EPO G-CSF Thrombopoietin hormone receptor:GH prolactin

Type II

Interleukin receptors
- IL10R /IL10RA /IL10RB /IL22R /IL22RA1 /IL22RA2
- IL20R /IL20RA /IL20RB
- IL28R
Interferon receptors
- -α/β /IFNAR1/IFNAR2
- -γ/IFNGR1 /IFNGR2

Ig superfamily

IL1
- IL1R1
- IL1R2
IL18R /IL18R1

IL 17 family

IL17

Enzyme-linked receptor

Cytokine receptor modulators

Chemokine

Seehere instead.

CSF

Erythropoietin	Agonists:ARA-290 Asialo erythropoietin Carbamylated erythropoietin CNTO-530 Darbepoetin alfa Epoetin alfa Epoetin beta Epoetin delta Epoetin epsilon Epoetin gamma Epoetin kappa Epoetin omega Epoetin theta Epoetin zeta Erythropoietin (EPO) Erythropoietin-Fc Methoxy polyethylene glycol-epoetin beta (CERA/Mircera) Peginesatide Pegol sihematide (EPO-018B)
G-CSF (CSF3)	Agonists:Filgrastim Granulocyte colony-stimulating factor Lenograstim Leridistim Lipegfilgrastim Nartograstim Pegfilgrastim Pegnartograstim
GM-CSF (CSF2)	Agonists:Ecogramostim Granulocyte macrophage colony-stimulating factor Milodistim Molgramostim Regramostim Sargramostim Antibodies:Mavrilimumab Namilumab Otilimab
M-CSF (CSF1)	Agonists:Cilmostim Interleukin-34 Lanimostim Macrophage colony-stimulating factor Mirimostim Kinase inhibitors:Agerafenib
SCF (c-Kit)	Seehere instead.
Thrombopoietin	Agonists:Eltrombopag Pegacaristim Promegapoietin Romiplostim Thrombopoietin (THPO, MGDF)

Interferon

IFNAR (α/β, I)	Agonists:Albinterferon Interferon alpha (interferon alfa, IFN-α) Interferon alfa (IFNA1,IFNA2,IFNA4,IFNA5,IFNA6,IFNA7,IFNA8,IFNA10,IFNA13,IFNA14,IFNA16,IFNA17,IFNA21) Interferon alfa 2a Interferon alfa 2b Interferon alfa n1 Interferon alfacon-1 Interferon alpha-n3 Interferon beta (IFN-β) (IFNB1,IFNB3) Interferon beta 1a Interferon beta 1b Interferon kappa (IFN-ε/κ/τ/ζ, IFNK) Interferon omega (IFN-ω, IFNW1) Peginterferon alfa-2a Peginterferon alfa-2b Antibodies:Anifrolumab Faralimomab MEDI-545 Rontalizumab Sifalimumab Decoy receptors:Bifarcept
IFNGR (γ, II)	Agonists:Interferon gamma (IFN-γ) Interferon gamma 1b Antibodies:Emapalumab Fontolizumab
IFNLR (λ, III)	See IL-28R (IFNLR)here instead.

Interleukin

Seehere instead.

TGFβ

Seehere instead.

TNF

Seehere instead.

Others

JAK
(inhibitors)

JAK1	Abrocitinib Baricitinib Deuruxolitinib Filgotinib Momelotinib Oclacitinib Peficitinib Ruxolitinib Tofacitinib (tasocitinib) Upadacitinib
JAK2	Atiprimod AZD-1480 Baricitinib CHZ868 Cucurbitacin I (elatericin B, JSI-124) CYT387 Deuruxolitinib Lestaurtinib NSC-7908 NSC-33994 Pacritinib Peficitinib Ruxolitinib SD-1008 Tofacitinib (tasocitinib)
JAK3	Cercosporamide Decernotinib (VX-509) Peficitinib Ritlecitinib TCS-21311 Tofacitinib (tasocitinib) WHI-P 154 ZM-39923 ZM-449829
TYK2	Deucravacitinib

Others

Additional cytokine receptor modulators:Emfilermin
Lestaurtinib
Midostaurin
Quizartinib
Sorafenib
Sunitinib

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Interactions

References

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