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UniProtKB - Q93038 (TNR25_HUMAN)

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Protein

Tumor necrosis factor receptor superfamily member 25

Gene

TNFRSF25

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • signaling receptor activity Source: UniProtKB
  • tumor necrosis factor-activated receptor activity Source: ProtInc
View the complete GO annotation on QuickGO ...

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
View the complete GO annotation on QuickGO ...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000215788.9
HGNCiHGNC:11910 TNFRSF25
MIMi603366 gene
neXtProtiNX_Q93038

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
ProteomicsDBi75674
75675 [Q93038-10]
75676 [Q93038-11]
75677 [Q93038-12]
75678 [Q93038-2]
75679 [Q93038-3]
75680 [Q93038-4]
75681 [Q93038-5]
75682 [Q93038-6]
75683 [Q93038-7]
75684 [Q93038-8]
75685 [Q93038-9]

PTM databases

iPTMnetiQ93038

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

HPAiHPA069834

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
IntActiQ93038, 1 interactor

Structurei

3D structure databases

ProteinModelPortaliQ93038
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_sf
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 No translation available.
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: June 20, 2018
This is version 176 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

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