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Protein

Tumor necrosis factor receptor superfamily member 25

Gene

TNFRSF25

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

Functioni

Receptor for TNFSF12/APO3L/TWEAK. Interacts directly with the adapter TRADD. Mediates activation of NF-kappa-B and induces apoptosis. May play a role in regulating lymphocyte homeostasis.

GO - Molecular functioni

  • receptor activity Source: UniProtKB
  • tumor necrosis factor-activated receptor activity Source: ProtInc

GO - Biological processi

  • apoptotic process Source: ProtInc
  • apoptotic signaling pathway Source: ProtInc
  • cell surface receptor signaling pathway Source: ProtInc
  • immune response Source: GO_Central
  • inflammatory response Source: GO_Central
  • multicellular organism development Source: GO_Central
  • regulation of apoptotic process Source: GO_Central
  • regulation of cell proliferation Source: GO_Central
  • response to lipopolysaccharide Source: GO_Central
  • signal transduction Source: ProtInc
  • tumor necrosis factor-mediated signaling pathway Source: Reactome

Keywordsi

Molecular functionReceptor
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiQ93038.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 25
Alternative name(s):
Apo-3
Apoptosis-inducing receptor AIR
Apoptosis-mediating receptor DR3
Apoptosis-mediating receptor TRAMP
Death receptor 3
Lymphocyte-associated receptor of death
Short name:
LARD
Protein WSL
Protein WSL-1
Gene namesi
Name:TNFRSF25
Synonyms:APO3, DDR3, DR3, TNFRSF12, WSL, WSL1
ORF Names:UNQ455/PRO779
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000215788.9.
HGNCiHGNC:11910. TNFRSF25.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 199ExtracellularSequence analysisAdd BLAST175
Transmembranei200 – 220HelicalSequence analysisAdd BLAST21
Topological domaini221 – 417CytoplasmicSequence analysisAdd BLAST197

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi354L → A: Suppresses homodimerization, TNFR1 interaction, and apoptosis induction. 1 Publication1
Mutagenesisi356L → A: Suppresses homodimerization, and TNFR1 interaction. 1 Publication1
Mutagenesisi373D → A: Suppresses homodimerization, and TNFR1 interaction. 1 Publication1

Organism-specific databases

DisGeNETi8718.
OpenTargetsiENSG00000215788.
PharmGKBiPA36603.

Polymorphism and mutation databases

BioMutaiTNFRSF25.
DMDMi2501233.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000003460625 – 417Tumor necrosis factor receptor superfamily member 25Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 47PROSITE-ProRule annotation
Disulfide bondi48 ↔ 61PROSITE-ProRule annotation
Disulfide bondi51 ↔ 70PROSITE-ProRule annotation
Glycosylationi67N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi73 ↔ 89PROSITE-ProRule annotation
Disulfide bondi92 ↔ 107PROSITE-ProRule annotation
Disulfide bondi95 ↔ 115PROSITE-ProRule annotation
Glycosylationi106N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi117 ↔ 130PROSITE-ProRule annotation
Disulfide bondi138 ↔ 155PROSITE-ProRule annotation
Disulfide bondi141 ↔ 162PROSITE-ProRule annotation
Disulfide bondi165 ↔ 176PROSITE-ProRule annotation
Disulfide bondi179 ↔ 191PROSITE-ProRule annotation
Disulfide bondi187 ↔ 195PROSITE-ProRule annotation

Post-translational modificationi

Glycosylated.Curated

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PeptideAtlasiQ93038.
PRIDEiQ93038.

Expressioni

Tissue specificityi

Abundantly expressed in thymocytes and lymphocytes. Detected in lymphocyte-rich tissues such as thymus, colon, intestine, and spleen. Also found in the prostate.

Gene expression databases

BgeeiENSG00000215788.
ExpressionAtlasiQ93038. baseline and differential.
GenevisibleiQ93038. HS.

Organism-specific databases

HPAiHPA077620.

Interactioni

Subunit structurei

Homodimer. Interacts strongly via the death domains with TNFRSF1 and TRADD to activate at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4.1 Publication

Protein-protein interaction databases

BioGridi114258. 9 interactors.
DIPiDIP-59563N.

Structurei

3D structure databases

ProteinModelPortaliQ93038.
SMRiQ93038.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati34 – 71TNFR-Cys 1Add BLAST38
Repeati72 – 115TNFR-Cys 2Add BLAST44
Repeati116 – 163TNFR-Cys 3Add BLAST48
Repeati164 – 192TNFR-Cys 4Add BLAST29
Domaini332 – 413DeathPROSITE-ProRule annotationAdd BLAST82

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00530000064001.
HOVERGENiHBG058493.
InParanoidiQ93038.
KOiK05160.
OMAiGWRQMFW.
OrthoDBiEOG091G07LE.
PhylomeDBiQ93038.
TreeFamiTF333916.

Family and domain databases

CDDicd13420. TNFRSF25. 1 hit.
InterProiView protein in InterPro
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022329. TNFR_25.
IPR034050. TNFRSF25_N.
PfamiView protein in Pfam
PF00531. Death. 1 hit.
PF00020. TNFR_c6. 1 hit.
PRINTSiPR01972. TNFACTORR25.
SMARTiView protein in SMART
SM00005. DEATH. 1 hit.
SM00208. TNFR. 2 hits.
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiView protein in PROSITE
PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 1 hit.

Sequences (12)i

Sequence statusi: Complete.

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

This entry describes 12 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q93038-1) [UniParc]FASTAAdd to basket
Also known as: WSL-1, LARD-1A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEQRPRGCAA VAAALLLVLL GARAQGGTRS PRCDCAGDFH KKIGLFCCRG
60 70 80 90 100
CPAGHYLKAP CTEPCGNSTC LVCPQDTFLA WENHHNSECA RCQACDEQAS
110 120 130 140 150
QVALENCSAV ADTRCGCKPG WFVECQVSQC VSSSPFYCQP CLDCGALHRH
160 170 180 190 200
TRLLCSRRDT DCGTCLPGFY EHGDGCVSCP TSTLGSCPER CAAVCGWRQM
210 220 230 240 250
FWVQVLLAGL VVPLLLGATL TYTYRHCWPH KPLVTADEAG MEALTPPPAT
260 270 280 290 300
HLSPLDSAHT LLAPPDSSEK ICTVQLVGNS WTPGYPETQE ALCPQVTWSW
310 320 330 340 350
DQLPSRALGP AAAPTLSPES PAGSPAMMLQ PGPQLYDVMD AVPARRWKEF
360 370 380 390 400
VRTLGLREAE IEAVEVEIGR FRDQQYEMLK RWRQQQPAGL GAVYAALERM
410
GLDGCVEDLR SRLQRGP
Length:417
Mass (Da):45,385
Last modified:November 1, 1997 - v2
Checksum:i5226319DFDB46706
GO
Isoform 2 (identifier: Q93038-2) [UniParc]FASTAAdd to basket
Also known as: LARD-1B

The sequence of this isoform differs from the canonical sequence as follows:
     236-236: A → AA

Show »
Length:418
Mass (Da):45,456
Checksum:i54B48F8B35C620E2
GO
Isoform 3 (identifier: Q93038-3) [UniParc]FASTAAdd to basket
Also known as: WSL-S1, LARD-3

The sequence of this isoform differs from the canonical sequence as follows:
     182-218: STLGSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGA → VLGPGAPGWPCGPPPAWGHPDLHIPPLLASQAPGYCR
     219-417: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:218
Mass (Da):23,198
Checksum:i9B416919AFA442F6
GO
Isoform 4 (identifier: Q93038-4) [UniParc]FASTAAdd to basket
Also known as: WSL-S2, LARD-2

The sequence of this isoform differs from the canonical sequence as follows:
     200-253: MFWVQVLLAG...LTPPPATHLS → SRWCAGNARG...LWSPSCLGPP
     254-417: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:253
Mass (Da):27,004
Checksum:i50A06775B68FC3D7
GO
Isoform 5 (identifier: Q93038-5) [UniParc]FASTAAdd to basket
Also known as: LARD-4, LARD-11

The sequence of this isoform differs from the canonical sequence as follows:
     182-417: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:181
Mass (Da):19,432
Checksum:i59AAFEDBBB46E369
GO
Isoform 6 (identifier: Q93038-6) [UniParc]FASTAAdd to basket
Also known as: LARD-5

The sequence of this isoform differs from the canonical sequence as follows:
     54-98: Missing.
     182-417: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:136
Mass (Da):14,439
Checksum:i6846913006EEE40A
GO
Isoform 7 (identifier: Q93038-7) [UniParc]FASTAAdd to basket
Also known as: LARD-6

The sequence of this isoform differs from the canonical sequence as follows:
     54-98: Missing.
     156-171: SRRDTDCGTCLPGFYE → HPSVTLGQRPHPSSTS
     172-417: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:126
Mass (Da):13,349
Checksum:iEBAC98D7FB3EDB68
GO
Isoform 8 (identifier: Q93038-8) [UniParc]FASTAAdd to basket
Also known as: LARD-7

The sequence of this isoform differs from the canonical sequence as follows:
     54-236: Missing.

Show »
Length:234
Mass (Da):25,373
Checksum:iD082A4552EDF7531
GO
Isoform 9 (identifier: Q93038-9) [UniParc]FASTAAdd to basket
Also known as: LARD-8

The sequence of this isoform differs from the canonical sequence as follows:
     54-98: Missing.

Show »
Length:372
Mass (Da):40,391
Checksum:iD4F87353AB7F40F6
GO
Isoform 10 (identifier: Q93038-10) [UniParc]FASTAAdd to basket
Also known as: LARD-9

The sequence of this isoform differs from the canonical sequence as follows:
     200-237: MFWVQVLLAGLVVPLLLGATLTYTYRHCWPHKPLVTAD → N

Show »
Length:380
Mass (Da):41,193
Checksum:iED19B586ADD947B7
GO
Isoform 11 (identifier: Q93038-11) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     182-200: STLGSCPERCAAVCGWRQM → PPPSLAGAPWGAVQSAVPLSVAGGRVGV

Show »
Length:426
Mass (Da):45,928
Checksum:i292A9B2899F3AE1F
GO
Isoform 12 (identifier: Q93038-12) [UniParc]FASTAAdd to basket
Also known as: Beta soluble

The sequence of this isoform differs from the canonical sequence as follows:
     182-277: STLGSCPERC...SEKICTVQLV → PPPSLAGAPW...LASQAPGYCR
     278-417: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:277
Mass (Da):29,111
Checksum:i3D19F3E847BFC093
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4 – 6RPR → AAA in AAC51192 (PubMed:9052839).Curated3
Sequence conflicti4 – 6RPR → AAA in AAC51193 (PubMed:9052839).Curated3
Sequence conflicti60P → H in AAB41435 (Ref. 13) Curated1
Sequence conflicti167P → L (PubMed:9052839).Curated1
Sequence conflicti167P → L (Ref. 13) Curated1
Sequence conflicti312A → R (PubMed:8934525).Curated1
Sequence conflicti312A → R (PubMed:9446802).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01882623R → Q1 PublicationCorresponds to variant dbSNP:rs35771371Ensembl.1
Natural variantiVAR_018827159D → G2 PublicationsCorresponds to variant dbSNP:rs11800462Ensembl.1
Natural variantiVAR_018828254P → R1 PublicationCorresponds to variant dbSNP:rs34529016Ensembl.1
Natural variantiVAR_011814370R → L. Corresponds to variant dbSNP:rs1064590Ensembl.1
Natural variantiVAR_011815381R → H. Corresponds to variant dbSNP:rs1059333Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00649254 – 236Missing in isoform 8. 1 PublicationAdd BLAST183
Alternative sequenceiVSP_00649154 – 98Missing in isoform 6, isoform 7 and isoform 9. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_006493156 – 171SRRDT…PGFYE → HPSVTLGQRPHPSSTS in isoform 7. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_006494172 – 417Missing in isoform 7. 1 PublicationAdd BLAST246
Alternative sequenceiVSP_006495182 – 417Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST236
Alternative sequenceiVSP_006499182 – 277STLGS…TVQLV → PPPSLAGAPWGAVQSAVPLS VAGGRVGGVLGMRVGELGWT EGRRVRRGATTQHPPAAFSV LGPGAPGWPCGPPPAWGHPD LHIPPLLASQAPGYCR in isoform 12. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_006497182 – 218STLGS…LLLGA → VLGPGAPGWPCGPPPAWGHP DLHIPPLLASQAPGYCR in isoform 3. 2 PublicationsAdd BLAST37
Alternative sequenceiVSP_006496182 – 200STLGS…GWRQM → PPPSLAGAPWGAVQSAVPLS VAGGRVGV in isoform 11. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_006501200 – 253MFWVQ…ATHLS → SRWCAGNARGRTGMDRGEAG EEGGNHPTPTSCFQCSGSRC SWLALWSPSCLGPP in isoform 4. 2 PublicationsAdd BLAST54
Alternative sequenceiVSP_006503200 – 237MFWVQ…LVTAD → N in isoform 10. 2 PublicationsAdd BLAST38
Alternative sequenceiVSP_006498219 – 417Missing in isoform 3. 2 PublicationsAdd BLAST199
Alternative sequenceiVSP_006504236A → AA in isoform 2. 1 Publication1
Alternative sequenceiVSP_006502254 – 417Missing in isoform 4. 2 PublicationsAdd BLAST164
Alternative sequenceiVSP_006500278 – 417Missing in isoform 12. 1 PublicationAdd BLAST140

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09392 mRNA. Translation: CAA70561.1.
Y09392 mRNA. Translation: CAA70559.1.
Y09392 mRNA. Translation: CAA70560.1.
U72763 mRNA. Translation: AAC50819.1.
U83599 Genomic DNA. Translation: AAB41434.1.
U83600 Genomic DNA. Translation: AAB41435.1.
U78029 mRNA. Translation: AAB40918.1.
U74611 mRNA. Translation: AAB39714.1.
U94501 mRNA. Translation: AAC51306.1.
U94504 mRNA. Translation: AAC51309.1.
U94502 mRNA. Translation: AAC51307.1.
U94503 mRNA. Translation: AAC51308.1.
U94505 mRNA. Translation: AAC51310.1.
U94506 mRNA. Translation: AAC51311.1.
U94507 mRNA. Translation: AAC51312.1.
U94508 mRNA. Translation: AAC51313.1.
U94509 mRNA. Translation: AAC51314.1.
U94510 mRNA. Translation: AAC51315.1.
U94512 mRNA. Translation: AAC51316.1.
U83598 mRNA. Translation: AAB41433.1.
AF026070 mRNA. Translation: AAC39556.1.
AF026071 mRNA. Translation: AAB82288.1.
AB051850 Genomic DNA. Translation: BAB40662.1.
AB051851 Genomic DNA. Translation: BAB40663.1.
AY358309 mRNA. Translation: AAQ88676.1.
AY254324 Genomic DNA. Translation: AAO63495.1.
U75380 mRNA. Translation: AAC51192.1.
AL158217 Genomic DNA. Translation: CAI22153.1.
AL158217 Genomic DNA. Translation: CAI22154.1.
AL158217 Genomic DNA. Translation: CAI22155.1.
BC117189 mRNA. Translation: AAI17190.1.
BC143886 mRNA. Translation: AAI43887.1.
U75381 mRNA. Translation: AAC51193.1.
U83597 mRNA. Translation: AAB41432.1.
CCDSiCCDS71.1. [Q93038-1]
CCDS72.1. [Q93038-11]
CCDS73.1. [Q93038-10]
CCDS74.1. [Q93038-9]
CCDS75.1. [Q93038-8]
RefSeqiNP_001034753.1. NM_001039664.1. [Q93038-5]
NP_003781.1. NM_003790.2. [Q93038-1]
NP_683866.1. NM_148965.1. [Q93038-11]
NP_683867.1. NM_148966.1. [Q93038-10]
NP_683868.1. NM_148967.1. [Q93038-9]
NP_683871.1. NM_148970.1. [Q93038-8]
UniGeneiHs.462529.

Genome annotation databases

EnsembliENST00000348333; ENSP00000314451; ENSG00000215788. [Q93038-9]
ENST00000351748; ENSP00000326762; ENSG00000215788. [Q93038-8]
ENST00000351959; ENSP00000337713; ENSG00000215788. [Q93038-10]
ENST00000356876; ENSP00000349341; ENSG00000215788. [Q93038-1]
ENST00000377782; ENSP00000367013; ENSG00000215788. [Q93038-11]
ENST00000414040; ENSP00000404274; ENSG00000215788. [Q93038-3]
ENST00000485036; ENSP00000431554; ENSG00000215788. [Q93038-12]
ENST00000502588; ENSP00000423121; ENSG00000215788. [Q93038-6]
ENST00000502730; ENSP00000421976; ENSG00000215788. [Q93038-7]
ENST00000510563; ENSP00000424071; ENSG00000215788. [Q93038-5]
GeneIDi8718.
KEGGihsa:8718.
UCSCiuc001ana.4. human. [Q93038-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNR25_HUMAN
AccessioniPrimary (citable) accession number: Q93038
Secondary accession number(s): B1ALX2
, B1ALX3, B7ZLL7, O00275, O00276, O00277, O00278, O00279, O00280, O14865, O14866, P78507, P78515, Q17RU4, Q92983, Q93036, Q93037, Q99722, Q99830, Q99831, Q9BY86, Q9UME0, Q9UME1, Q9UME5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: September 27, 2017
This is version 170 of the entry and version 2 of the sequence. See 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 chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot